Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis

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Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm2, laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis, respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis, respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis. These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-142/v5", "name": "Comparison of the antimicrobial reduction effect of photodynamic inactivation..." } } ] } Home Browse Comparison of the antimicrobial reduction effect of photodynamic inactivation... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Arifianto D, Astuti SD, Medyaz SR et al. Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.12688/f1000research.128483.5 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] Deny Arifianto https://orcid.org/0000-0003-2276-4290 1,2 , Suryani Dyah Astuti https://orcid.org/0000-0002-0729-0237 3 , Sarah Ratri Medyaz 3 , [...] Septia Budi Lestari 3 , Samian Samian 3 , Dezy Zahrotul Istiqomah Nurdin https://orcid.org/0000-0002-0729-0237 4 , Dita Ayu Hariyani 3 , Yunus Susilo 5 , Ardiansyah Syahrom 6 Deny Arifianto https://orcid.org/0000-0003-2276-4290 1,2 , Suryani Dyah Astuti https://orcid.org/0000-0002-0729-0237 3 , [...] Sarah Ratri Medyaz 3 , Septia Budi Lestari 3 , Samian Samian 3 , Dezy Zahrotul Istiqomah Nurdin https://orcid.org/0000-0002-0729-0237 4 , Dita Ayu Hariyani 3 , Yunus Susilo 5 , Ardiansyah Syahrom 6 PUBLISHED 14 Nov 2025 Author details Author details 1 Doctoral Degree, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 2 Department of Engineering, Faculty of Vocational, Universitas Airlangga, Surabaya, Indonesia 3 Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 4 Magister of Biomedical Engineering, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 5 Faculty of Engineering, Dr Soetomo University, Surabaya, East Java, 60115, Indonesia 6 Medical Devices and Technology Centre, Universiti Teknologi Malaysia, Johor Bahru, Johor, 81310, Malaysia Deny Arifianto Roles: Data Curation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Suryani Dyah Astuti Roles: Conceptualization, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Sarah Ratri Medyaz Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Septia Budi Lestari Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Samian Samian Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dezy Zahrotul Istiqomah Nurdin Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dita Ayu Hariyani Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Yunus Susilo Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Ardiansyah Syahrom Roles: Conceptualization, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Plant Science gateway. Abstract Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm 2 , laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. READ ALL READ LESS Keywords Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, photodynamic inactivation, diode laser, diseases, periodontitis, curcumin, chlorophyll Corresponding Author(s) Suryani Dyah Astuti ( [email protected] ) Close Corresponding author: Suryani Dyah Astuti Competing interests: No competing interests were disclosed. Grant information: This work was supported by Grant Support International Collaborative Research Scheme [175/UN3.15/PT/2022]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Arifianto D et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Arifianto D, Astuti SD, Medyaz SR et al. Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.12688/f1000research.128483.5 ) First published: 07 Feb 2023, 12 :142 ( https://doi.org/10.12688/f1000research.128483.1 ) Latest published: 14 Nov 2025, 12 :142 ( https://doi.org/10.12688/f1000research.128483.5 ) Revised Amendments from Version 4 The manuscript has been substantially revised to address reviewer and editorial feedback. The introduction has been expanded to include updated literature on the relationship between periodontitis, peri-implant diseases, and systemic health, with particular attention to recent studies (Isola et al., 2025; Isola et al., 2025). The rationale and aim of the study have been clarified at the end of the introduction to better define the study’s objectives and relevance. The abstract has been reformulated to clearly state the background, aim, methods, key findings, and conclusion. It now emphasizes the comparative efficacy of curcumin and chlorophyll as natural photosensitizers in photodynamic inactivation against Aggregatibacter actinomycetemcomitans and Enterococcus faecalis . In the Materials and Methods section, inclusion and exclusion criteria for the bacterial samples and experimental conditions have been more explicitly described to enhance methodological transparency. The Results section has been refined for clarity and precision, and numerical values have been clearly presented to highlight the significant antibacterial effects observed with curcumin-mediated photodynamic inactivation. In the Discussion, an additional paragraph was included to explicitly summarize the main findings at the beginning, and further elaboration was added on the relationship between periodontitis and oxidative stress mechanisms, supported by relevant literature. The Conclusion has been strengthened to reflect the findings and potential implications for future research and clinical applications. Minor textual edits were made throughout the manuscript to improve coherence, scientific tone, and readability. No changes were made to the title, author list, figures, or tables. The manuscript has been substantially revised to address reviewer and editorial feedback. The introduction has been expanded to include updated literature on the relationship between periodontitis, peri-implant diseases, and systemic health, with particular attention to recent studies (Isola et al., 2025; Isola et al., 2025). The rationale and aim of the study have been clarified at the end of the introduction to better define the study’s objectives and relevance. The abstract has been reformulated to clearly state the background, aim, methods, key findings, and conclusion. It now emphasizes the comparative efficacy of curcumin and chlorophyll as natural photosensitizers in photodynamic inactivation against Aggregatibacter actinomycetemcomitans and Enterococcus faecalis . In the Materials and Methods section, inclusion and exclusion criteria for the bacterial samples and experimental conditions have been more explicitly described to enhance methodological transparency. The Results section has been refined for clarity and precision, and numerical values have been clearly presented to highlight the significant antibacterial effects observed with curcumin-mediated photodynamic inactivation. In the Discussion, an additional paragraph was included to explicitly summarize the main findings at the beginning, and further elaboration was added on the relationship between periodontitis and oxidative stress mechanisms, supported by relevant literature. The Conclusion has been strengthened to reflect the findings and potential implications for future research and clinical applications. Minor textual edits were made throughout the manuscript to improve coherence, scientific tone, and readability. No changes were made to the title, author list, figures, or tables. See the authors' detailed response to the review by Chenyu Jiang See the authors' detailed response to the review by Gaetano Isola See the authors' detailed response to the review by Shima Afrasiabi See the authors' detailed response to the review by Min Wu READ REVIEWER RESPONSES Introduction The oral cavity is one of the most important parts of the body that must be maintained. Infectious diseases of the teeth and mouth that are often found are periodontitis and endodontics. Periodontitis is a bacterial infection of the teeth that causes inflammation of the supporting tissues of the teeth, which include the gingiva, ligaments, cement, and alveolar bone. 1 Periodontitis is caused by pathogenic bacteria, predominantly gram-negative, anaerobic, or microaerophilic in the subgingival area. 2 Aggregatibacter actinomycetemcomitans bacteria are found in dental plaque, periodontal pockets, and buccal mucosa in up to 36% of the normal population. 3 Aggregatibacter actinomycetemcomitans bacteria can infect patients when the human immune system decreases and inhibits other organisms’ growth in the oral mucosa, teeth, and nasopharynx. In general, gram-positive bacteria, Enterococcus faecalis ( E. faecalis ), are found in the root canals of teeth. The bacterium Enterococcus faecalis is ovoid, with a diameter between 0.5 and 1 μm. 4 These bacteria are facultative anaerobes and can survive in extreme environments such as highly alkaline pH and high salt concentration conditions. The number of these bacteria in the human body can be minimized by paying attention to the food consumed and environmental conditions such as humidity. Furthermore, E. faecalis bacteria resist calcium hydroxide and antibiotics such as tetracycline. 5 Systemic treatment in the form of antibiotics has been widely used to treat periodontitis. However, several studies have reported cases of antimicrobial resistance to certain types of antibiotics. 6 So alternative therapy is needed that is effective and does not cause antibiotic resistance. 7 Therefore, the recommended alternative therapy in this study is photodynamic inactivation (PDI). Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. 8 This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. 9 The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Photodynamic inactivation (PDI) is a method of inactivating microorganisms by utilizing light to activate a photosensitizer (PS) agent that produces reactive oxygen species (ROS), causing cell lysis. 10 , 11 The suitability of the light spectrum with the PS absorption spectrum is the key to photophysical reactions, namely the absorption of light energy by PS agents, which will trigger photochemical and photobiological reactions to produce antimicrobial effects 12 , 13 and biomodulation. 14 PS is a light-sensitive molecule that plays a role in absorbing light energy. 15 PS is divided into two types, namely endogenous and exogenous photosensitizers. The addition of exogenous PS aims to increase the effectiveness of light energy absorption. 16 Some natural ingredients that are exogenous PS include chlorophyll and curcumin. Chlorophyll is a green substance found in green plants that photosynthesizes. 17 In photosynthesis, chlorophyll acts as a light catcher, energy transfer, and light conversion and can absorb a maximum wavelength range of 400-700 nm. 18 Chlorophyll acts as a photosensitizer because it is naturally able to absorb light. 19 The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways. 20 Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective. 21 The absorption spectrum of curcumin is in the wavelength range of 375-475 nm. 22 The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and the biological membranes of bacteria because the attachment of hydrogen groups plays an important role. 23 Previous studies have reported the effectiveness of using PS chlorophyll in alfalfa leaves with a blue LED activator of 20.48 J/cm 2 for the inactivation of A. actinomycetemcomitans bacteria by 81%. 24 The results of another study with the addition of PS curcumin and diode laser activator 403 nm 15.83 J/cm 2 in Staphylococcus aureus resulted in a mortality rate of 85.48%. 23 Then, another study using curcumin and blue LEDs on S. aureus bacteria resulted in a mortality rate of 91.49%. 25 Continuing previous studies, 21 , 22 , 24 this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely 30, 60, 90, 120, 150, and 180 seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. Methods Bacterial culture Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37°C until the colonies reached ~10 8 CFU/mL or 1.0 McFarland standard. Photosensitizer (PS) Chlorophyll was extracted from Medicago sativa L (K-Link liquid, Indonesia) and Curcuma standard (Sigma Aldrich) with a concentration of 1.6 mg/mL diluted with sterile normal saline. The absorption spectra of chlorophyll and curcuma were measured using a Shimadzu UV-VIS 1800 spectrophotometer. Light source The light source of a diode laser is 405 nm, and characterization was carried out using Jasco CT-10 monochromators to determine the peak wavelength. The power output was 2.49 mW, measured with the power meter OMM-6810B-220V. The spot beam area size is 0.28 cm 2 . Diode laser irradiation was carried out with variations in the length of the irradiation time of 30, 60, 90, 120, 150, and 180 seconds. The energy density value can be calculated using equation 1 12 : (1) Energy Density J . cm − 2 = Intensity W . m − 2 × Irradiation Time s PDI treatment The treatment samples consisted of two types of bacteria, A. actinomycetemcomitans and E. faecalis. The bacterial PDI treatment consisted of a negative control group without treatment (T0), a positive control group with the addition of chlorophyll and curcumin (T1), a 405 nm diode laser treatment group at various energy densities of 0.26; 0.53; 0.79; 1.06; 1.32; 1.59 J/cm 2 (S1), a 405 nm diode laser treatment group with the addition of chlorophyll Medicago sativa L 1.6 mg/ml (S2), and a 405 nm diode laser treatment group with the addition of curcumin PS 1.6 mg/ml (S3). In groups S2 and S3, samples were given chlorophyll or curcumin, and they were incubated for 10 minutes, then irradiated with a 405 nm diode laser with an exposure time of 30, 60, 90, 120, 150, and 180 seconds. The treated samples were grown on TSA media, incubated for 24 hours at 37°C, and the number of bacterial colonies grown was counted by the total plate count (TPC) method. Statistical analysis CFU/mL was calculated for each treatment using equation 2. Furthermore, the percentage of bacterial reduction was calculated using equation 3 based on the control group. The results of bacterial reduction were statistically analyzed by a two-way Anova factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey’s post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. (2) CFU ml = number of colonies × dilution factor volume of culture plate (3) %Viability reduction of bacteria = ∑ CFU ml control − ∑ kCFU ml treatment ∑ CFU ml control × 100 % Results The chlorophyll and curcumin extracts were tested using UV-Vis at a wavelength range of 325 nm to 705 nm to determine the absorption spectrum of light. Then, the results of characterizing the absorption spectrum of chlorophyll and curcumin to light are obtained, as shown in Figure 1 . Based on Table 1 , the characterization results show the peak wavelength of the diode laser at 405 nm with the stability of the output power at a distance of 1 cm (2.49 ±0.07) mW. The temperature characterization showed the optimum temperature stability (26.60±0.01) °C for bacterial growth. Thus, the irradiation energy density of the diode laser is 405 nm with an output power of 2.49 mW and a beam area of 0.28 at various exposure times (30, 60, 90, 120, 150, 180) seconds are 0.26, 0.53, 0.79, 1.06, 1.32, and 1.59 J/cm 2 . Figure 1. Graph of curcumin and chlorophyll absorption spectrum. Table 1. Laser energy density at various time exposure. Laser parameters Parameter Value Emitter type Laser Diode Center wavelength 405 ± 0,02 nm Operating mode Continuous wave (CW) Polarization Linear Beam spot size at target ≈ 2.80 ± 0.01 mm 2 Beam divergence ≈ 12 o parallel to beam ≈ 26 o perpendicular to the beam Application technique Distance 1 cm Aperture diameter 1.89 mm Power 2.49 ± 0,01 mW Beam shape elliptical Variation in laser exposure time 30; 60; 90; 120; 150 and 180 s Spectral bandwidth 10 nm Average radiant power 2.49 ± 0,01 mW Variation in radiant exposure/energy density 0.26; 0.53; 0.79; 1.06; 1.32; 1.59 J/cm 2 Area irradiated 2.80 mm 2 Variation in radiant energy 0.075; 0.15; 0.22; 0.29; 0.37; 0.45 J After that, antibacterial tests were carried out on Aggregatibacter actinomycetemcomitans and Enterococcus faecalis bacteria, which were exposed to a diode laser with and without a photosensitizer. So, the viability of the bacteria Aggregatibacter actinomycetemcomitans and Enterococcus faecalis is shown in Figures 2 and 3 . Based on bacterial viability, the percentages of death of A. actinomycetemcomitans and E. faecalis bacteria by diode laser irradiation with the addition of curcumin photosensitizer and Medicago sativa L chlorophyll treatment are shown in Tables 2 and 3 . Figure 2. Graph of bacterial viability of A. actinomycetemcomitans in various treatments with and without the addition of curcumin and chlorophyll Medicago sativa L. Figure 3. Graph of bacterial viability of E. faecalis in various treatments with and without the addition of curcumin and chlorophyll Medicago sativa L. Table 2. Results of statistical analysis of Enterococcus faecalis bacteria. Group Irradiation time (s) Energy density (J/cm 2) N % Bacterial death Anova Mean Std. Sig. Conclusion Laser 30 0.264 (1) 4 2.61 0.90 0.00 There is a difference in meaning 60 0.529 (1.2) 4 4.83 1.74 90 0.794 (2) 4 7.99 2.06 120 1.059 (3.4) 4 15.65 1.46 150 1.324 (5) 4 23.39 1.40 180 1.589 (7) 4 35.81 2.09 Lasers and Chlorophyll 30 0.264 (3) 4 13.89 0.63 0.00 60 0.529 (4) 4 18.68 1.69 90 0.794 (6) 4 27.95 1.22 120 1.059 (7) 4 39.35 0.75 150 1.324 (8) 4 54.69 0.83 180 1.589 (9) 4 69.27 1.74 Lasers and Curcumin 30 0.264 (10) 4 73.20 0.17 0.00 60 0.529 (10) 4 73.29 0.28 90 0.794 (11) 4 80.31 0.33 120 1.059 (12) 4 88.12 0.33 150 1.324 (13) 4 89.25 0.28 180 1.589 (13) 4 89.42 0.20 Table 3. Results of statistical analysis of Aggregatibacter actinomycetemcomitans bacteria. Group Irradiation time (s) Energy density (J/cm 2) N % Bacterial death Anova Mean Std. Sig. Conclusion Laser 30 0.264 (1) 4 1.45 2.57 0.00 There is a difference in meaning 60 0.529 (2) 4 8.82 1.58 90 0.794 (2.3) 4 12.99 0.91 120 1.059 (3.4) 4 16.73 1.07 150 1.324 (5) 4 26.48 2.83 180 1.589 (7) 4 41.99 1.24 Lasers and Chlorophyll 30 0.264 (2) 4 8.39 1.33 0.00 60 0.529 (4) 4 20.80 2.49 90 0.794 (6) 4 34.12 2.00 120 1.059 (6.7) 4 37.96 2.46 150 1.324 (8) 4 51.46 3.14 180 1.589 (9) 4 62.96 2.01 Lasers and Curcumin 30 0.264 (10) 4 85.00 0.18 0.00 60 0.529 (11) 4 86.14 0.20 90 0.794 (12) 4 87.89 0.35 120 1.059 (12) 4 88.68 0.18 150 1.324 (13) 4 89.74 0.18 180 1.589 (13) 4 89.82 0.29 Based on the results of statistical tests, it was shown that diode laser irradiation with an energy density of 1.59 J/cm 2 gave a percentage of E. faecalis bacteria death of 36.7% without adding a photosensitizer. Then, the percentage of death of E. faecalis bacteria was 69.30% with the addition of PS chlorophyll Medicago sativa L. and 89.42% with the addition of PS curcumin. Meanwhile, the results of statistical tests on bacteria A. actinomycetemcomitans with diode laser irradiation at an energy density of 1.59 J/cm 2 gave the percentage of bacterial death of 35.81% without the addition of PS. Then, the death of A. actinomycetemcomitans was 64.39% with the addition of PS chlorophyll and 89.82% with the addition of PS curcumin. Discussion The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . This research was conducted using the PDI technique using a blue diode laser as a light source, chlorophyll Medicago sativa L and curcumin as PS to reduce bacteria E. faecalis and A. actinomycetemcomitans. The wavelength of light is an important factor in the photoinactivation process. The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. The results of the characterization of power against time and temperature show the stability of power and temperature so that the temperature factor does not cause the death of bacteria. PS is a light-sensitive molecule. Exogenous PS is PS that is added to assist the photoinactivation process. This study used exogenous PS chlorophyll Medicago sativa L and curcumin. Medicago sativa L chlorophyll absorbance used for a laser wavelength of 405 nm was 85.1% and for curcumin it was 80.64%. 25 The photoinactivation process occurs due to a photophysical mechanism initiated by the absorption of light by PS. The energy of the absorbed photon will cause the excitation of the electron to increase to a higher energy level. If the energy excitation state overlaps with the triplet excitation state, an intersystem crossing occurs, a spin reversal that places the electron in a triplet excited state and triggers a photochemical reaction. The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 4 . During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizer is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis. 25 The photochemical reactions in PDI are generally of the second type. Figure 4. Mechanism of bacterial inactivation. The study’s results on E. faecalis bacteria showed a significant difference between treatments. Diode laser irradiation with an energy density of 1.59 J/cm 2 gave the percentage of bacterial death of E. faecalis 36.7% without the addition of PS, 69.30% with the addition of PS chlorophyll Medicago sativa L and 89.42% with the addition of PS curcumin. Meanwhile, in A. actinomycetemcomitans bacteria with energy density diode laser irradiation of 1.59 J/cm 2 , the percentage of bacterial death was 35.81% with the addition of PS, 64.39% with the addition of PS chlorophyll Medicago sativa L and 89.82% with the addition of PS curcumin. The results showed that adding PS curcumin increased the effectiveness of reducing E. faecalis and A. actinomycetemcomitans bacteria. PDI with PS curcumin was effectively used to reduce bacteria because its absorption followed endogenous porphyrins. 26 The addition of energy density will increase the reduction effect without and with the addition of PS Medicago sativa L 19 and curcumin. 21 In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than that of A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 μm × 1.0-1.5 μm. 27 Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm. 28 The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell. 27 In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused. 23 Research conducted by Balhaddad et al. (2020) showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm 2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death. 29 Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al . (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm 2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans. 30 In addition, Ashtiani et al . (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm 2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm 2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria. 31 In vivo studies are found in other journals. 32 , 33 The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95%. 33 Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria. 34 Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals. 33 , 34 The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT. 33 The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes of irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation. 35 Conclusion Based on statistical tests, the results of research on E. faecalis bacteria showed that laser irradiation with an energy density of 1.59 J/cm 2 gave a percentage of E. faecalis bacteria mortality of 36.7% without the addition of PS, 69.30% with the addition of PS chlorophyll Medicago sativa L and 89.42% with the addition of PS curcumin. Meanwhile, A. actinomycetemcomitans showed that the energy density diode laser irradiation of 1.59 J/cm 2 gave the percentage of bacterial death 35.81% without the addition of PS, 64.39% with the addition of PS chlorophyll Medicago sativa L and 89.82% with the addition of PS curcumin. So it can be concluded that the role of PS is significant for the success of PDI. The addition of PS curcumin increased the effectiveness of reducing bacteria E. faecalis and A. actinomycetemcomitans compared to chlorophyll Medicago sativa L. Author contributions DA contributes to the data curation, methodology, validation, original draft preparation of the work and editing of the work. SDA contributes to the conception, methodology, analysis, funding acquisitions, project administration, supervision, validation, review, original draft preparation of the work and editing of the work. SRM, SBL, DZIN, and DAH contribute to the conception, data curation, methodology, investigation, validation, original draft preparation of the work and editing of the work. S contributes to the conception, methodology, investigation, analysis, supervision, validation, review, original draft preparation of the work and editing of the work. YS contributes to the conception, data curation, methodology, investigation, validation, original draft preparation of the work and editing of the work. AS contributes to the conception, methodology, analysis, supervision, validation, review, original draft preparation of the work and editing of the work. Data availability Underlying data Open Science Framework: Antimicrobial Reduction Effect of Photodynamic Inactivation with The Addition Photosensitizer. https://doi.org/10.17605/OSF.IO/BEZ2R . 36 This project contains the following files: • Table 1. Laser energy density at various time exposure.docx (The laser parameters used in this research) • Table 2. Results of statistical analysis of Enterococcus faecalis bacteria.docx • Table 3. Results of statistical analysis of Aggregatibacter actinomycetemcomitans bacteria.docx • Bacterial Treatment Group Aggregatibacter actinomycetemcomitant ○ CFU Calculation Aggregatibacter actinomycetemcomitant.xlsx ○ Excel of Bacterial Viability.xls ○ Graph of Bacterial Viability.jpg • Bacterial Treatment Group Enterococcus faecalis ○ CFU Calculation Bacterial Treatment Group Enterococcus faecalis.xlsx ○ Excel of Bacterial Viability.xls ○ Graph of Bacterial Viabilty.jpg Extended data Open Science Framework: Antimicrobial Reduction Effect of Photodynamic Inactivation with The Addition Photosensitizer. https://doi.org/10.17605/OSF.IO/BEZ2R . 36 This project contains the following extended data: • Figure 1. Graph of curcumin and chlorophyll absorption spectrum.jpg • Figure 2. Graph of bacterial viability of A. actinomycetemcomitans in various treatments with and without the addition of curcumin and chlorophyll Medicago sativ.jpg • Figure 3. Graph of bacterial viability of E. faecalis in various treatments with and without photosensitizer.jpg • Figure 4. Mechanism of Bacterial Inactivation.png • Equipment used during the research.docx • The materials used during the research.docx • Treatment process.docx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgements We would like to thank Dr Riries Rulaningtyas for providing advice and supervision for this manuscript. References 1. Könönen E, Gursoy M, Gursoy UK: Periodontitis: A multifaceted disease of tooth-supporting tissues. J. Clin. Med. Aug. 01, 2019; vol. 8 (no.8). MDPI. 31370168 Publisher Full Text | Free Full Text , PubMed Abstract | 2. 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Avianti RS, Kunarti S, Subiyanto A:comparative study of the E. faecalis antibiofilm efficacy of photoactivated curcumin, chlorophyll and riboflavin. Dent. J. 2020; 53 : 62–66. Publisher Full Text 24. Astuti SD, Mawaddah A, Nasution AM, et al. :Effectiveness of photodynamic inactivation with exogenous photosensitizer Curcuma longa extract activated by laser diode 403 nm on staphylococcus aureus. J. Int. Dent. Med. Res. https://www.jidmr.com/journal/wp-content/uploads/2020/04/28.D19_918_Suryani_Dyah_Astuti_Indonesia-28.pdf 25. Setiawatie EM, Astuti SD, Zaidan AH:An in vitro Anti-microbial Photodynamic Therapy (aPDT) with Blue LEDs to Activate Chlorophylls of Alfalfa Medicago sativa L on Aggregatibacter actinomycetemcomitans. J. Int. Dent. Med. Res. 9 (2): 118–125. 26. Hakimiha N, Khoei F, Bahador A:The susceptibility of Streptococcus mutans to antibacterial photodynamic therapy: a comparison of two different photosensitizers and light sources. J. Appl. Oral Sci. 2014; 22 (2): 80–84. PubMed Abstract | Publisher Full Text | Free Full Text 27. Nørskov-Lauritsen N, Claesson R, Jensen AB, et al. :Aggregatibacter actinomycetemcomitans: Clinical significance of a pathobiont subjected to ample changes in classification and nomenclature. Pathogens. 2019; 8 (4): 243. PubMed Abstract | Publisher Full Text | Free Full Text 28. Jaafar SS:Enterococcus faecalis: A Mini-Review. J. Univ. Babylon Pure Appl. Sci. 2022; 30 (2): 191–200. Publisher Full Text 29. Balhaddad AA, AlQranei MS, Ibrahim MS, et al. :Light energy dose and photosensitizer concentration are determinants of effective photo-killing against caries-related biofilms. Int. J. Mol. Sci. 2020; 21 (20): 7612. PubMed Abstract | Publisher Full Text | Free Full Text 30. Pordel E, Ghasemi T, Afrasiabi S, et al. :The effect of different output powers of blue diode laser along with curcumin and riboflavin against Streptococcus mutans around orthodontic brackets: An in vitro study. Biomedicines. 2023; 11 (8): 2248. PubMed Abstract | Publisher Full Text | Free Full Text https://www.mdpi.com/2227-9059/11/8/2248 31. Ashtiani AS, Jafari Z, Chiniforush N, et al. :In vitro antibiofilm effect of different irradiation doses in infected root canal model. Photodiagnosis Photodyn. Ther. 2024; 46 (104053): 104053. PubMed Abstract | Publisher Full Text 32. Astuti SD, Ardyana Y, Arifianto D, et al. : Antimicrobial Photodynamic Effectiveness of Light Emitting Diode (Led) For Inactivation on Staphylococcus aureus Bacteria and Wound Healing in Infectious Wound Mice. J. Phys.: Conf. Ser. 2020, March; 1505 (1): 012060. IOP Publishing. Publisher Full Text 33. Astuti SD, Pertiwi WI, Wahyuningsih SPA, et al. :Effectiveness of ozone-laser photodynamic combination therapy for healing wounds infected with methicillin-resistant Staphylococcus aureus in mice. Vet. World. 2023; 16 (5): 1176–1184. Publisher Full Text 34. Puspita PS, Astuti SD, Nasution AM, et al. :Photodynamic therapy with ozone aids to Staphylococcus aureus biofilm reduction. Indian Vet. J. 2020; 97 (2): 24–26. 35. Astuti SD, Drantantiyas NDG, Putra AP, et al. :Photodynamic effectiveness of laser diode combined with ozone to reduce Staphylicoccus aureus biofilm with exogenous chlorophyll of Dracaena angustifolia leaves. Biomed. Photonics. 2019; 8 (2): 4–13. Publisher Full Text 36. Astuti SD: Antimicrobial Reduction Effect of Photodynamic Inactivation with The Addition Photosensitizer. [Dataset]. 2022, December 13. Publisher Full Text Comments on this article Comments (0) Version 5 VERSION 5 PUBLISHED 07 Feb 2023 ADD YOUR COMMENT Comment Author details Author details 1 Doctoral Degree, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 2 Department of Engineering, Faculty of Vocational, Universitas Airlangga, Surabaya, Indonesia 3 Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 4 Magister of Biomedical Engineering, Faculty of Science and Technology, Airlangga University, Surabaya, East Java, 60115, Indonesia 5 Faculty of Engineering, Dr Soetomo University, Surabaya, East Java, 60115, Indonesia 6 Medical Devices and Technology Centre, Universiti Teknologi Malaysia, Johor Bahru, Johor, 81310, Malaysia Deny Arifianto Roles: Data Curation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Suryani Dyah Astuti Roles: Conceptualization, Formal Analysis, Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Sarah Ratri Medyaz Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Septia Budi Lestari Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Samian Samian Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dezy Zahrotul Istiqomah Nurdin Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dita Ayu Hariyani Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Yunus Susilo Roles: Conceptualization, Data Curation, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Ardiansyah Syahrom Roles: Conceptualization, Investigation, Methodology, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This work was supported by Grant Support International Collaborative Research Scheme [175/UN3.15/PT/2022]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (5) version 5 Revised Published: 14 Nov 2025, 12:142 https://doi.org/10.12688/f1000research.128483.5 version 4 Revised Published: 04 Apr 2025, 12:142 https://doi.org/10.12688/f1000research.128483.4 version 3 Revised Published: 09 Oct 2024, 12:142 https://doi.org/10.12688/f1000research.128483.3 version 2 Revised Published: 29 Feb 2024, 12:142 https://doi.org/10.12688/f1000research.128483.2 version 1 Published: 07 Feb 2023, 12:142 https://doi.org/10.12688/f1000research.128483.1 Copyright © 2025 Arifianto D et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Arifianto D, Astuti SD, Medyaz SR et al. Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.12688/f1000research.128483.5 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 5 VERSION 5 PUBLISHED 14 Nov 2025 Revised Views 0 Cite How to cite this report: Isola G. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.189529.r432692 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v5#referee-response-432692 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 19 Nov 2025 Gaetano Isola , University of Catania, Catania, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.189529.r432692 The authors have well addressed ... Continue reading READ ALL The authors have well addressed all issues raised by the reviewer. Competing Interests: No competing interests were disclosed. Reviewer Expertise: periodontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Isola G. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.189529.r432692 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v5#referee-response-432692 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 4 VERSION 4 PUBLISHED 04 Apr 2025 Revised Views 0 Cite How to cite this report: Isola G. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.179507.r382890 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v4#referee-response-382890 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 May 2025 Gaetano Isola , University of Catania, Catania, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.179507.r382890 In the manuscript entitled: “Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis" the authors aimed to assess PDI method with a 405 nm diode laser ... Continue reading READ ALL In the manuscript entitled: “Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis" the authors aimed to assess PDI method with a 405 nm diode laser at various energy density with the addition PS curcumin or chlorophyll Alfalfa, as much as 1.6 mg/ml on A. actinomycetemcomitans and E. faecalis bacteria. The authors found that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of E. faecalis bacteria death 36.7% without PS, 69.30% with the addition of chlorophyll Medicago sativa L and 89.42% with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of bacterial death 35.81% without PS, 64.39% with the addition of chlorophyll Medicago sativa L and 89.82% with the addition of curcumin. PS was critical to the success of the PDI. The authors concluded that the addition of PS curcumin increased the effectiveness of reducing bacteria E. faecalis and A. actinomycetemcomitans compared to chlorophyll Medicago sativa L. Major comments: In general, the idea and innovation of this study regards the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Introduction: Please refer to major comments Discussion Please add a specific sentence that clarifies the results obtained in the first part of the discussion Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Isola G, Polizzi A, Serra S, Boato M, et al.: Relationship between periodontitis and systemic diseases: A bibliometric and visual study. Periodontol 2000 . 2025. PubMed Abstract | Publisher Full Text 2. Isola G, Polizzi A, Santagati M, Alibrandi A, et al.: Effect of Nonsurgical Mechanical Debridement With or Without Chlorhexidine Formulations in the Treatment of Peri-Implant Mucositis. A Randomized Placebo-Controlled Clinical Trial. Clin Oral Implants Res . 2025; 36 (5): 566-577 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: periodontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Isola G. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.179507.r382890 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v4#referee-response-382890 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 14 Nov 2025 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 14 Nov 2025 Author Response Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because ... Continue reading Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Response to reviewer: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Response to reviewer: Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm², laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. Introduction: Please refer to major comments Response to reviewer: Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Discussion: Please add a specific sentence that clarifies the results obtained in the first part of the discussion Response to reviewer: The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Response to reviewer: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Response to reviewer: Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm², laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. Introduction: Please refer to major comments Response to reviewer: Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Discussion: Please add a specific sentence that clarifies the results obtained in the first part of the discussion Response to reviewer: The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 14 Nov 2025 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 14 Nov 2025 Author Response Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because ... Continue reading Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Response to reviewer: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Response to reviewer: Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm², laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. Introduction: Please refer to major comments Response to reviewer: Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Discussion: Please add a specific sentence that clarifies the results obtained in the first part of the discussion Response to reviewer: The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Response to reviewer: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Response to reviewer: Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm², laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. Introduction: Please refer to major comments Response to reviewer: Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Discussion: Please add a specific sentence that clarifies the results obtained in the first part of the discussion Response to reviewer: The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 3 VERSION 3 PUBLISHED 09 Oct 2024 Revised Views 0 Cite How to cite this report: Afrasiabi S. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.171310.r330190 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v3#referee-response-330190 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Dec 2024 Shima Afrasiabi , Tehran University of Medical Sciences, Tehran, Iran Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.171310.r330190 -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. ... Continue reading READ ALL -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. - There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Afrasiabi S. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.171310.r330190 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v3#referee-response-330190 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 04 Apr 2025 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 04 Apr 2025 Author Response 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. ... Continue reading 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. This research only aims to determine the effect of irradiation or PDI treatment. So this study did not consider the incubation time or culture conditions of A. actinomycetemcomitans and E. faecalis bacteria. 2. There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. This research only aims to determine the effect of irradiation or PDI treatment. So this study did not consider the incubation time or culture conditions of A. actinomycetemcomitans and E. faecalis bacteria. 2. There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 04 Apr 2025 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 04 Apr 2025 Author Response 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. ... Continue reading 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. This research only aims to determine the effect of irradiation or PDI treatment. So this study did not consider the incubation time or culture conditions of A. actinomycetemcomitans and E. faecalis bacteria. 2. There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. This research only aims to determine the effect of irradiation or PDI treatment. So this study did not consider the incubation time or culture conditions of A. actinomycetemcomitans and E. faecalis bacteria. 2. There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 29 Feb 2024 Revised Views 0 Cite How to cite this report: Jiang C. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308148 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308148 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 21 Aug 2024 Chenyu Jiang , School of Optical and Electronic Information, Suzhou City University, Suzhou, China Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.163153.r308148 This paper studied the photodynamic inactivation of chlorophyll and curcumin against two oral cavity related pathogens: Aggregatibacter actinomycetemcomitans and Enterococcus faecalis and found that E. faecalis bacteria exhibited 69.30% inactivation with the addition of chlorophyll Medicago sativa L and 89.42% ... Continue reading READ ALL This paper studied the photodynamic inactivation of chlorophyll and curcumin against two oral cavity related pathogens: Aggregatibacter actinomycetemcomitans and Enterococcus faecalis and found that E. faecalis bacteria exhibited 69.30% inactivation with the addition of chlorophyll Medicago sativa L and 89.42% inactivation with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans presented 64.39% inactivation with the addition of chlorophyll Medicago sativa L and 89.82% inactivation with the addition of curcumin. PS was critical to the success of the PDI. Here are some comments: The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Photodynamic inactivation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Jiang C. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308148 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308148 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Oct 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 09 Oct 2024 Author Response Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged ... Continue reading Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. Response to reviewer : Chlorophyll acts as a photosensitizer because it is naturally able to absorb light [17]. The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework, and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways [18]. Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective [19]. The absorption spectrum of curcumin is in the wavelength range of 375-475 nm [20]. The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and biological membranes of bacteria, because the attachment of hydrogen groups plays an important role [21]. 2. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. Response to reviewer : We have transformed Images 1 and 2 into one image. Figure 1. Graph of curcumin and chlorophyll absorption spectrum 3. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. Response to reviewer : Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37 o C until the colonies reached ~108 CFU/mL or 1.0 McFarland standard. 4. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizers is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. Response to reviewer : Chlorophyll acts as a photosensitizer because it is naturally able to absorb light [17]. The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework, and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways [18]. Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective [19]. The absorption spectrum of curcumin is in the wavelength range of 375-475 nm [20]. The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and biological membranes of bacteria, because the attachment of hydrogen groups plays an important role [21]. 2. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. Response to reviewer : We have transformed Images 1 and 2 into one image. Figure 1. Graph of curcumin and chlorophyll absorption spectrum 3. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. Response to reviewer : Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37 o C until the colonies reached ~108 CFU/mL or 1.0 McFarland standard. 4. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizers is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Oct 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 09 Oct 2024 Author Response Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged ... Continue reading Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. Response to reviewer : Chlorophyll acts as a photosensitizer because it is naturally able to absorb light [17]. The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework, and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways [18]. Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective [19]. The absorption spectrum of curcumin is in the wavelength range of 375-475 nm [20]. The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and biological membranes of bacteria, because the attachment of hydrogen groups plays an important role [21]. 2. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. Response to reviewer : We have transformed Images 1 and 2 into one image. Figure 1. Graph of curcumin and chlorophyll absorption spectrum 3. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. Response to reviewer : Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37 o C until the colonies reached ~108 CFU/mL or 1.0 McFarland standard. 4. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizers is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. Response to reviewer : Chlorophyll acts as a photosensitizer because it is naturally able to absorb light [17]. The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework, and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways [18]. Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective [19]. The absorption spectrum of curcumin is in the wavelength range of 375-475 nm [20]. The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and biological membranes of bacteria, because the attachment of hydrogen groups plays an important role [21]. 2. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. Response to reviewer : We have transformed Images 1 and 2 into one image. Figure 1. Graph of curcumin and chlorophyll absorption spectrum 3. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. Response to reviewer : Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37 o C until the colonies reached ~108 CFU/mL or 1.0 McFarland standard. 4. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizers is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Afrasiabi S. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308151 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308151 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Aug 2024 Shima Afrasiabi , Tehran University of Medical Sciences, Tehran, Iran Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.163153.r308151 I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis . The authors have not considered this case. -In the discussion section, studies that share common characteristics such as similar ... Continue reading READ ALL I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis . The authors have not considered this case. -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Discussion Line 3; “The laser diode used in this study” should be diode laser. Photodynamic Inactivation, please use lowercase letters. - The manuscript contains many writing problems. Is the work clearly and accurately presented and does it cite the current literature? No Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Balhaddad AA, AlQranei MS, Ibrahim MS, Weir MD, et al.: Light Energy Dose and Photosensitizer Concentration Are Determinants of Effective Photo-Killing against Caries-Related Biofilms. Int J Mol Sci . 2020; 21 (20). PubMed Abstract | Publisher Full Text 2. Pordel E, Ghasemi T, Afrasiabi S, Benedicenti S, et al.: The Effect of Different Output Powers of Blue Diode Laser along with Curcumin and Riboflavin against Streptococcus mutans around Orthodontic Brackets: An In Vitro Study. Biomedicines . 2023; 11 (8). PubMed Abstract | Publisher Full Text 3. Ashtiani AS, Jafari Z, Chiniforush N, Afrasiabi S: In vitro antibiofilm effect of different irradiation doses in infected root canal model. Photodiagnosis Photodyn Ther . 2024; 46 : 104053 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Photodynamic therapy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Afrasiabi S. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308151 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308151 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Oct 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 09 Oct 2024 Author Response Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this ... Continue reading Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 µm × 1.0-1.5 µm. [25]. Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm [26]. The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell [25]. Reviewer Comment For Author: -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] Response to reviewer : In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused [21]. Research conducted by Balhaddad et al. (2020), showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death [27]. Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al. (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans [28]. In addition, Ashtiani et al. (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria [29]. Reviewer Comment For Author: - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Response to reviewer : We have added 2 Tables to summarize the data from Figures 3,4,5, and 6. Reviewer Comment For Author: Discussion Line 3; “The laser diode used in this study” should be diode laser. Response to reviewer : The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. Reviewer Comment For Author: Photodynamic Inactivation, please use lowercase letters. Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. Reviewer Comment For Author: - The manuscript contains many writing problems. Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 µm × 1.0-1.5 µm. [25]. Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm [26]. The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell [25]. Reviewer Comment For Author: -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] Response to reviewer : In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused [21]. Research conducted by Balhaddad et al. (2020), showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death [27]. Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al. (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans [28]. In addition, Ashtiani et al. (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria [29]. Reviewer Comment For Author: - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Response to reviewer : We have added 2 Tables to summarize the data from Figures 3,4,5, and 6. Reviewer Comment For Author: Discussion Line 3; “The laser diode used in this study” should be diode laser. Response to reviewer : The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. Reviewer Comment For Author: Photodynamic Inactivation, please use lowercase letters. Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. Reviewer Comment For Author: - The manuscript contains many writing problems. Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Oct 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 09 Oct 2024 Author Response Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this ... Continue reading Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 µm × 1.0-1.5 µm. [25]. Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm [26]. The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell [25]. Reviewer Comment For Author: -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] Response to reviewer : In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused [21]. Research conducted by Balhaddad et al. (2020), showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death [27]. Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al. (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans [28]. In addition, Ashtiani et al. (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria [29]. Reviewer Comment For Author: - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Response to reviewer : We have added 2 Tables to summarize the data from Figures 3,4,5, and 6. Reviewer Comment For Author: Discussion Line 3; “The laser diode used in this study” should be diode laser. Response to reviewer : The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. Reviewer Comment For Author: Photodynamic Inactivation, please use lowercase letters. Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. Reviewer Comment For Author: - The manuscript contains many writing problems. Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 µm × 1.0-1.5 µm. [25]. Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm [26]. The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell [25]. Reviewer Comment For Author: -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] Response to reviewer : In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused [21]. Research conducted by Balhaddad et al. (2020), showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death [27]. Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al. (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans [28]. In addition, Ashtiani et al. (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria [29]. Reviewer Comment For Author: - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Response to reviewer : We have added 2 Tables to summarize the data from Figures 3,4,5, and 6. Reviewer Comment For Author: Discussion Line 3; “The laser diode used in this study” should be diode laser. Response to reviewer : The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. Reviewer Comment For Author: Photodynamic Inactivation, please use lowercase letters. Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. Reviewer Comment For Author: - The manuscript contains many writing problems. Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 07 Feb 2023 Views 0 Cite How to cite this report: Wu M. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.141076.r221717 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v1#referee-response-221717 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 13 Feb 2024 Min Wu , Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Harvard University, Boston, Massachusetts, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.141076.r221717 This paper is about comparison of the antimicrobial reduction effect of two PSs in different bacteria related to oral cavity causing various diseases such as periodontitis and endodontics. I think the purpose and ... Continue reading READ ALL This paper is about comparison of the antimicrobial reduction effect of two PSs in different bacteria related to oral cavity causing various diseases such as periodontitis and endodontics. I think the purpose and design of this manuscript is quite clear but a little bit too simple. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. This manuscript focused on two pathogens highly related to various oral diseases. They used photodynamic inactivation (PDI) to deal with these pathogens. The photosensitizer are chlorophyll and curcumin. The light source is aBL (405nm), and treatment is aPDI. The data only include CFU which is gold standard and survival rate. They compared between different groups including light alone and negative control. The conclusions are also very clear. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Light-based therapy for both bench work and clinical work I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Wu M. Reviewer Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.141076.r221717 ) The direct URL for this report is: https://f1000research.com/articles/12-142/v1#referee-response-221717 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 13 Apr 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 13 Apr 2024 Author Response Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been ... Continue reading Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been changed. 1. The purpose and design of this manuscript is quite clear but a little bit too simple. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The purpose of this manuscript: Continuing previous studies [15,16,18], this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely (30, 60, 90, 120, 150, and 180) seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. The design of this manuscript: CFU/ml was calculated for each treatment using Equation 2. Furthermore, the percentage of bacterial reduction was calculated using Equation 3 based on the control group. The results of bacterial reduction were statistically analyzed using the Two Way Anova Factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey's post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. 2. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The mechanism of Photodynamic Inactivation (PDI) is illustrated in Figure 7. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is a radical. Reactive Oxygen Species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. In vivo studies are found in other journals [20,21]. The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95% [20]. Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria [21]. Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals [22,23]. The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT [22]. The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation [24]. Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been changed. 1. The purpose and design of this manuscript is quite clear but a little bit too simple. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The purpose of this manuscript: Continuing previous studies [15,16,18], this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely (30, 60, 90, 120, 150, and 180) seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. The design of this manuscript: CFU/ml was calculated for each treatment using Equation 2. Furthermore, the percentage of bacterial reduction was calculated using Equation 3 based on the control group. The results of bacterial reduction were statistically analyzed using the Two Way Anova Factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey's post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. 2. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The mechanism of Photodynamic Inactivation (PDI) is illustrated in Figure 7. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is a radical. Reactive Oxygen Species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. In vivo studies are found in other journals [20,21]. The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95% [20]. Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria [21]. Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals [22,23]. The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT [22]. The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation [24]. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 13 Apr 2024 Suryani Dyah Astuti , Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 13 Apr 2024 Author Response Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been ... Continue reading Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been changed. 1. The purpose and design of this manuscript is quite clear but a little bit too simple. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The purpose of this manuscript: Continuing previous studies [15,16,18], this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely (30, 60, 90, 120, 150, and 180) seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. The design of this manuscript: CFU/ml was calculated for each treatment using Equation 2. Furthermore, the percentage of bacterial reduction was calculated using Equation 3 based on the control group. The results of bacterial reduction were statistically analyzed using the Two Way Anova Factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey's post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. 2. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The mechanism of Photodynamic Inactivation (PDI) is illustrated in Figure 7. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is a radical. Reactive Oxygen Species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. In vivo studies are found in other journals [20,21]. The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95% [20]. Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria [21]. Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals [22,23]. The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT [22]. The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation [24]. Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been changed. 1. The purpose and design of this manuscript is quite clear but a little bit too simple. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The purpose of this manuscript: Continuing previous studies [15,16,18], this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely (30, 60, 90, 120, 150, and 180) seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. The design of this manuscript: CFU/ml was calculated for each treatment using Equation 2. Furthermore, the percentage of bacterial reduction was calculated using Equation 3 based on the control group. The results of bacterial reduction were statistically analyzed using the Two Way Anova Factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey's post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. 2. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The mechanism of Photodynamic Inactivation (PDI) is illustrated in Figure 7. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is a radical. Reactive Oxygen Species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. In vivo studies are found in other journals [20,21]. The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95% [20]. Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria [21]. Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals [22,23]. The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT [22]. The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation [24]. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 5 VERSION 5 PUBLISHED 07 Feb 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 Version 5 (revision) 14 Nov 25 read Version 4 (revision) 04 Apr 25 read Version 3 (revision) 09 Oct 24 read Version 2 (revision) 29 Feb 24 read read Version 1 07 Feb 23 read Min Wu , Harvard University, Boston, USA Shima Afrasiabi , Tehran University of Medical Sciences, Tehran, Iran Chenyu Jiang , Suzhou City University, Suzhou, China Gaetano Isola , University of Catania, Catania, Italy Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Isola G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Nov 2025 | for Version 5 Gaetano Isola , University of Catania, Catania, Italy 0 Views copyright © 2025 Isola G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors have well addressed all issues raised by the reviewer. Competing Interests No competing interests were disclosed. Reviewer Expertise periodontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Isola G. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.189529.r432692) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v5#referee-response-432692 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Isola G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 May 2025 | for Version 4 Gaetano Isola , University of Catania, Catania, Italy 0 Views copyright © 2025 Isola G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions In the manuscript entitled: “Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis" the authors aimed to assess PDI method with a 405 nm diode laser at various energy density with the addition PS curcumin or chlorophyll Alfalfa, as much as 1.6 mg/ml on A. actinomycetemcomitans and E. faecalis bacteria. The authors found that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of E. faecalis bacteria death 36.7% without PS, 69.30% with the addition of chlorophyll Medicago sativa L and 89.42% with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of bacterial death 35.81% without PS, 64.39% with the addition of chlorophyll Medicago sativa L and 89.82% with the addition of curcumin. PS was critical to the success of the PDI. The authors concluded that the addition of PS curcumin increased the effectiveness of reducing bacteria E. faecalis and A. actinomycetemcomitans compared to chlorophyll Medicago sativa L. Major comments: In general, the idea and innovation of this study regards the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Introduction: Please refer to major comments Discussion Please add a specific sentence that clarifies the results obtained in the first part of the discussion Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Isola G, Polizzi A, Serra S, Boato M, et al.: Relationship between periodontitis and systemic diseases: A bibliometric and visual study. Periodontol 2000 . 2025. PubMed Abstract | Publisher Full Text 2. Isola G, Polizzi A, Santagati M, Alibrandi A, et al.: Effect of Nonsurgical Mechanical Debridement With or Without Chlorhexidine Formulations in the Treatment of Peri-Implant Mucositis. A Randomized Placebo-Controlled Clinical Trial. Clin Oral Implants Res . 2025; 36 (5): 566-577 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise periodontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 14 Nov 2025 Suryani Dyah Astuti, Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia Reviewer Comment for Author: Major comments: In general, the idea and innovation of this study regard the analysis of the link between mediator and periodontitis is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. Moreover, there are few reports in the literature that studied this interesting topic with this kind of study design. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the relationship between periodontitis and systemic diseases. However, as the importance of the topic, the reviewer strongly recommends, before a further re-evaluation of the manuscript, to update the literature through read, discuss and must cites in the references with great attention all of those recent interesting articles, that helps the authors to better introduce and discuss the relationship and mediators of periodontitis peri-implant diseases and systemic diseases and how periodontal treatment could improve microbiome outcomes: 1) Isola G, et al.: 2025 (Ref 1) 2) Isola G, Polizzi A, Santagati M, Alibrandi A, et al 2025 (Ref 2) The authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the study. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the by periodontitis in and risk of oxidative stress evolution in periodontitis patients. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol. However, this study, in my view does not in its current form satisfy a very high scientific requirement for indexing in this journal and requests a revision before a further re-evaluation of the manuscript. Response to reviewer: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. Minor Comments: Abstract: Better formulate the abstract section by better describing the aim of the study Response to reviewer: Background Antibiotic resistance in oral pathogens such as Aggregatibacter actinomycetemcomitans and Enterococcus faecalis necessitates alternative antimicrobial strategies. Photodynamic inactivation (PDI) is a promising approach that utilizes a photosensitizer (PS), light, and oxygen to generate cytotoxic reactive oxygen species. This study evaluated the efficacy of two natural photosensitizers, curcumin and chlorophyll (from Medicago sativa L.), for the photodynamic inactivation of these bacteria. Methods Planktonic cultures of A. actinomycetemcomitans and E. faecalis were subjected to PDI using a 405 nm diode laser at various energy densities. The bacteria were treated with either curcumin (1.6 mg/mL) or chlorophyll (1.6 mg/mL) prior to laser irradiation. Bacterial viability was assessed using the colony-forming unit (CFU) assay. Groups without PS and without light served as controls. Results At an energy density of 1.59 J/cm², laser irradiation resulted in a reduction of 35.8% and 36.7% for A. actinomycetemcomitans and E. faecalis , respectively. The addition of chlorophyll significantly enhanced bacterial reduction to 64.4% and 69.3%. Curcumin demonstrated superior efficacy, achieving bacterial reduction of 89.8% and 89.4% for A. actinomycetemcomitans and E. faecalis , respectively. The differences between the PS groups and the control groups were statistically significant (p < 0.05). Conclusions Curcumin is a significantly more effective natural photosensitizer than chlorophyll from Medicago sativa L. for the photodynamic inactivation of A. actinomycetemcomitans and E. faecalis . These findings point to the prospect of curcumin-based PDI as a potent therapeutic alternative for combating resistant oral infections. Introduction: Please refer to major comments Response to reviewer: Periodontitis, a chronic inflammatory disease triggered by dysbiotic oral microbiome, has implications that extend far beyond the oral cavity. A recent bibliometric analysis highlights the deep and growing research interest in the strong relationship between periodontitis and systemic diseases, such as diabetes, cardiovascular disease, and adverse pregnancy outcomes. This well-established systemic relationship confirms that effective periodontitis management is not merely a dental concern but a critical component of overall public health. Consequently, there is an urgent need to develop innovative and effective therapeutic strategies to control periodontal biofilm and reduce the associated local and systemic inflammatory burden. Conventional treatments for inflammatory conditions, including peri-implant mucositis, often consist of non-surgical mechanical debridement enhanced with antiseptics like chlorhexidine. The limitations of these conventional treatments emphasize the necessity for exploring alternate therapy methods, including antimicrobial photodynamic inactivation. Discussion: Please add a specific sentence that clarifies the results obtained in the first part of the discussion Response to reviewer: The results of this study indicate that photodynamic inactivation (PDI) using curcumin as a photosensitizer (PS) is the most effective strategy for significantly reducing the viability of both E. faecalis and A. actinomycetemcomitans . View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Isola G. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.179507.r382890) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v4#referee-response-382890 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Afrasiabi S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Dec 2024 | for Version 3 Shima Afrasiabi , Tehran University of Medical Sciences, Tehran, Iran 0 Views copyright © 2024 Afrasiabi S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. - There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 04 Apr 2025 Suryani Dyah Astuti, Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia 1. The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : Thank you for your suggestion. This research only aims to determine the effect of irradiation or PDI treatment. So this study did not consider the incubation time or culture conditions of A. actinomycetemcomitans and E. faecalis bacteria. 2. There is a duplicate data. Graph of the percentage of death of bacteria should be removed. (Fig 4, 5) Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Afrasiabi S. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.171310.r330190) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v3#referee-response-330190 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Jiang C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 21 Aug 2024 | for Version 2 Chenyu Jiang , School of Optical and Electronic Information, Suzhou City University, Suzhou, China 0 Views copyright © 2024 Jiang C. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This paper studied the photodynamic inactivation of chlorophyll and curcumin against two oral cavity related pathogens: Aggregatibacter actinomycetemcomitans and Enterococcus faecalis and found that E. faecalis bacteria exhibited 69.30% inactivation with the addition of chlorophyll Medicago sativa L and 89.42% inactivation with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans presented 64.39% inactivation with the addition of chlorophyll Medicago sativa L and 89.82% inactivation with the addition of curcumin. PS was critical to the success of the PDI. Here are some comments: The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Photodynamic inactivation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 09 Oct 2024 Suryani Dyah Astuti, Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia Reviewer 3: Reviewer Comment For Author: 1. The introduction did mention brief introduction of chlorophyll and curcumin but advantages of both compound as PS compared to other PS are encouraged to include in the introduction. Response to reviewer : Chlorophyll acts as a photosensitizer because it is naturally able to absorb light [17]. The chemical structure of chlorophyll consists of a porphyrin ring that serves as the core framework, and long hydrophobic side chains. The bioactivity of chlorophyll is due to its ability to act as an antioxidant, antimutagen, and anticarcinogen. Its unique chemical structure allows chlorophyll to capture harmful free radicals, reduce DNA damage, and modulate cellular processes involved in disease progression. In addition, its hydrophobic side chains facilitate interactions with biological membranes, affecting cellular uptake and signaling pathways [18]. Curcumin is a curcuminoid compound with yellow pigment in turmeric rhizome, which is antitumor, antioxidant, anticarcinogenic, anti-inflammatory, antiviral, antifungal, antispasmodic, and hepatoprotective [19]. The absorption spectrum of curcumin is in the wavelength range of 375-475 nm [20]. The advantage of curcumin as PS is that there are reactive functional groups, including ketone and phenol groups, that play a role in phototherapeutic activity. Phenol groups play an important role in the interaction of curcumin and biological membranes of bacteria, because the attachment of hydrogen groups plays an important role [21]. 2. The figure 1 and figure 2 can be combined into one figure and distinguish two sample with different color or shape considering both figures are the absorption property. Response to reviewer : We have transformed Images 1 and 2 into one image. Figure 1. Graph of curcumin and chlorophyll absorption spectrum 3. The author did mention the there is a dilution factor but also mentioned that the treated sample was placed into incubator overnight directly. Please clarify this part. Response to reviewer : Bacteria A. actinomycetemcomitans ATCC 43718 and E. faecalis ATCC 29212 were cultured in tryptone soy broth (TSB). Then, it was incubated for 24 hours at 37 o C until the colonies reached ~108 CFU/mL or 1.0 McFarland standard. 4. The generation of ROS is encouraged to confirm via whatever chemical method, EPR, or photoluminescence. This study did mention that there are two type of ROS but none of them are confirmed under chlorophyll and curcumin illuminated by diode laser Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. During photodynamic therapy, chlorophyll and curcumin act as photosensitizers. A photosensitizers is a solution that is able to absorb laser light optimally through a photophysical process. The first process that occurs is that the photosensitizer absorbs photon energy from a 405 nm laser diode, causing excitation from a low state ( 1 PS) to an excited state ( 1 PS*). In the 1 PS* state, the photosensitizer can return to the 1 PS state by emitting fluorescence or internal conversion. In addition, the photosensitizer can also convert to a more stable T nearest excitation level before finally returning to the 1 PS state by emitting energy in the form of phosphorescence. This energy conversion is what requires oxygen through the photochemical process. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is radical. Reactive oxygen species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Jiang C. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308148) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308148 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Afrasiabi S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Aug 2024 | for Version 2 Shima Afrasiabi , Tehran University of Medical Sciences, Tehran, Iran 0 Views copyright © 2024 Afrasiabi S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis . The authors have not considered this case. -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Discussion Line 3; “The laser diode used in this study” should be diode laser. Photodynamic Inactivation, please use lowercase letters. - The manuscript contains many writing problems. Is the work clearly and accurately presented and does it cite the current literature? No Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Balhaddad AA, AlQranei MS, Ibrahim MS, Weir MD, et al.: Light Energy Dose and Photosensitizer Concentration Are Determinants of Effective Photo-Killing against Caries-Related Biofilms. Int J Mol Sci . 2020; 21 (20). PubMed Abstract | Publisher Full Text 2. Pordel E, Ghasemi T, Afrasiabi S, Benedicenti S, et al.: The Effect of Different Output Powers of Blue Diode Laser along with Curcumin and Riboflavin against Streptococcus mutans around Orthodontic Brackets: An In Vitro Study. Biomedicines . 2023; 11 (8). PubMed Abstract | Publisher Full Text 3. Ashtiani AS, Jafari Z, Chiniforush N, Afrasiabi S: In vitro antibiofilm effect of different irradiation doses in infected root canal model. Photodiagnosis Photodyn Ther . 2024; 46 : 104053 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Photodynamic therapy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 09 Oct 2024 Suryani Dyah Astuti, Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia Reviewer 2: Reviewer Comment For Author: I have the following comments: -The culture conditions of A. actinomycetemcomitans differ from those of E. faecalis. The authors have not considered this case. Response to reviewer : In addition, the results showed that the administration of Medicago chlorophyll PS was more effective in reducing E. faecalis bacteria than A. actinomycetemcomitans. This is because the wall structure of E. faecalis bacteria is thinner than A. actinomycetemcomitans. A. actinomycetemcomitans is a Gram-negative bacterium measuring 0.4-0.5 µm × 1.0-1.5 µm. [25]. Enterococcus faecalis bacteria are Gram-positive bacteria with a cell wall thickness of about 40 nm [26]. The cell wall structure of gram-negative bacteria consists of lipopolysaccharides. lipoproteins, lipopolysaccharides, and peptidoglycans. The cell wall of gram-negative bacteria is more complex, so it is more difficult to penetrate antibacterial compounds. The cell wall structure of gram-positive bacteria is relatively simpler so that antibacterial compounds easily enter the cell [25]. Reviewer Comment For Author: -In the discussion section, studies that share common characteristics such as similar PS or similar bacteria should be used. In addition, the use of different energy doses is not discussed. Please search again and refer to the articles below; (i) Balhaddad AA et al. (2020 [Ref-1]) [doi.org/10.3390/ijms21207612] (ii) Pordel E et al. (2023 [Ref - 2]) [doi.org/10.3390/biomedicines11082248] (iii) Ashtiani AS et al. (2024 [Ref - 3]) [doi.org/10.1016/j.pdpdt.2024.104053] Response to reviewer : In this study, PS curcumin has a higher percentage of bacterial death than PS chlorophyll (Medicago sativa L). This is in accordance with research conducted by Avianti et al. (2020) that PS curcumin in photodynamic therapy has a greater bacterial death effect than PS chlorophyll on E. faecalis. In addition, the research by Avianti et al. (2020) was also conducted at 60 and 90 seconds of irradiation duration. Then, it was proven that the duration of 90 seconds on all PS proved effective in increasing the death of E. faecalis bacteria. This is related to the nature of curcumin and its molecular structure, which enhances its function in photodynamic therapy. It shows that the longer the duration of laser irradiation given, the greater the bacterial death caused [21]. Research conducted by Balhaddad et al. (2020), showed that irradiation of S. mutans biofilm through 100 μg/mL TBO and an energy dose of ≈180 J/cm2 resulted in a higher number of dead S. mutans colonies compared to the control (p < 0.001). Light energy dose and PS concentration optimize bacterial death [27]. Later, Pordel et al. (2023) reported that chlorhexidine and curcumin with a blue diode laser at 500 mW output power had the highest reduction in the number of S. mutans colonies (p < 0.001). The curcumin group was more effective than the riboflavin group. The results of the study by Pordel et al. (2023) showed that aPDT using curcumin as a photosensitizer plus a blue diode laser with an output power of 500 mW and a power density of 1.0 W/cm2 at a wavelength of 445 nm can effectively reduce the colonies of S. mutans [28]. In addition, Ashtiani et al. (2024) also reported the results of their research that toluidine blue O (TBO) and phycocyanin (PC) activated with a 635 nm diode laser with a power density of 1592 W/cm2 were more efficient in increasing the death of E. faecalis bacteria compared to a 636 W/cm2 diode laser (p = 0.00). Light power density optimizes the reduction of E. faecalis bacteria [29]. Reviewer Comment For Author: - Figures 3, 4, 5, and 6 should be summarized in a Table by mentioning SD. Response to reviewer : We have added 2 Tables to summarize the data from Figures 3,4,5, and 6. Reviewer Comment For Author: Discussion Line 3; “The laser diode used in this study” should be diode laser. Response to reviewer : The diode laser used in this study has a wavelength of 405 nm and an output power of 2.49 mW. Reviewer Comment For Author: Photodynamic Inactivation, please use lowercase letters. Response to reviewer : The mechanism of photodynamic inactivation (PDI) is illustrated in Figure 6. Reviewer Comment For Author: - The manuscript contains many writing problems. Response to reviewer : Thank you for your suggestion. We have changed it as you suggested. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Afrasiabi S. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.163153.r308151) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v2#referee-response-308151 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Wu M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Feb 2024 | for Version 1 Min Wu , Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Harvard University, Boston, Massachusetts, USA 0 Views copyright © 2024 Wu M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This paper is about comparison of the antimicrobial reduction effect of two PSs in different bacteria related to oral cavity causing various diseases such as periodontitis and endodontics. I think the purpose and design of this manuscript is quite clear but a little bit too simple. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. This manuscript focused on two pathogens highly related to various oral diseases. They used photodynamic inactivation (PDI) to deal with these pathogens. The photosensitizer are chlorophyll and curcumin. The light source is aBL (405nm), and treatment is aPDI. The data only include CFU which is gold standard and survival rate. They compared between different groups including light alone and negative control. The conclusions are also very clear. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Light-based therapy for both bench work and clinical work I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 13 Apr 2024 Suryani Dyah Astuti, Department of Physics, Faculty of Science and Technology, Airlangga University, Surabaya, 60115, Indonesia Thanks for valuable comments and suggestions for our manuscript. We have revised the manuscript according to the reviewers’ comments and answered them accurately. Some parts of the manuscript have been changed. 1. The purpose and design of this manuscript is quite clear but a little bit too simple. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The purpose of this manuscript: Continuing previous studies [15,16,18], this study aims to compare the effectiveness of antimicrobial reduction from photodynamic inactivation (PDI) on bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. using a 405 nm diode laser. Diode laser irradiation was carried out at various lengths of irradiation time, namely (30, 60, 90, 120, 150, and 180) seconds. In addition, this study aims to determine the effective laser irradiation time to reduce the bacteria A. actinomycetemcomitans and E. faecalis with PS curcumin and chlorophyll Medicago sativa L. The design of this manuscript: CFU/ml was calculated for each treatment using Equation 2. Furthermore, the percentage of bacterial reduction was calculated using Equation 3 based on the control group. The results of bacterial reduction were statistically analyzed using the Two Way Anova Factorial test using IBM SPSS Statistics Version 21 to determine the effect of each factor and its interaction between factors. The test usually requires distributed and at least interval scale data, with significant differences determined as P<α=0.05. Tukey's post hoc test and Kolmogorov-Smirnov test were used to check the normality of the data. 2. I think it would be better if in vivo study is included to make the work more solid. For in vitro study, I think the authors can also add different types of ROS probe and even perform the biofilm experiment to support their conclusions. Provide further comments here: We would like to say thank you for your valuable suggestion and the opportunity to revise the manuscript. We already revised it. The mechanism of Photodynamic Inactivation (PDI) is illustrated in Figure 7. Photochemical reactions are divided into two types. The first type is the transfer of electrons to a biological substrate in the form of a redox reaction and produces singlet oxygen. The second type is the transfer of energy to the triplet electrons to produce singlet oxygen. Singlet oxygen is a radical. Reactive Oxygen Species (ROS) can damage the bacterial cell membrane and cause lysis. This is the earliest stage in bacterial cell death. Photochemical activity generates ROS and triplet oxygen radicals that oxidize unsaturated fatty acids, producing hydroperoxides. These radicals interfere with the synthesis of saturated fatty acids, causing harmful hydroperoxides known as lipid peroxidation. This disruption of the bacterial cell wall leads to cell lysis [18]. The photochemical reactions in PDI are generally of the second type. In vivo studies are found in other journals [20,21]. The effect of bacterial photoinactivation on wounds in vivo due to photodynamic therapy in the red LED exposure group was 88%, the blue LED exposure group was 94%, and the red and blue LED combination exposure group was 95% [20]. Blue and red lasers combined with ozone treatment effectively accelerated wound healing of incisions infected with MRSA bacteria [21]. Thus, LED antimicrobial photodynamic therapy is effective for bacterial inactivation and accelerates wound healing in mice. Biofilm research is also found in other journals [22,23]. The difference in the reduction rate of PDT increased when ozone was added, thus helping biofilm reduction compared to PDT [22]. The results showed that the Chlo+Ozon+Laser combination treatment at 20 seconds of ozone exposure with 4 minutes irradiation time caused a decrease in biofilm activity by 80.26%, which was the highest efficacy of all treatment groups. The combination of laser, chlorophyll, and lower ozone concentration increased the effectiveness of photodynamic inactivation [24]. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Wu M. Peer Review Report For: Comparison of the antimicrobial reduction effect of photodynamic inactivation with the addition of chlorophyll and curcumin photosensitizer in Aggregatibacter actinomycetemcomitans and Enterococcus faecalis [version 5; peer review: 1 approved, 3 approved with reservations] . F1000Research 2025, 12 :142 ( https://doi.org/10.5256/f1000research.141076.r221717) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-142/v1#referee-response-221717 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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