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Objective: Evaluation of the effect of phycocyanin (PC) and toluidine blue (TBO) along with sodium fluoride varnish (FV) or titanium tetrafluoride (TiF4) under the conditions of antimicrobial photodynamic therapy (PDT) on a dual-species cariogenic biofilm and on remineralization process. Design: After the development of Streptococcus mutansStreptococcus mutans and Lactobacillus acidophilus dual-species biofilms on the human enamel disks, they were divided into 11 groups (n = 9): Control (0.9 % saline), PC, TBO, FV, and TiF4 alone, PC and TBO in combination with a 635 nm diode laser (PDT treatment), PC-PDT+ (PC + FV or TiF4 + 635 nm diode laser), and TBO-PDT+ (TBO + FV or TiF4 + 635 nm diode laser). After the treatment, crystal violet assay was performed to determine the reduction of cariogenic biofilms. Enamel remineralization changes were analyzed using energy dispersive X-ray spectroscopy (EDX) and field emission scanning electron microscopy (FESEM) for the calcium and phosphorus (Ca/P) ratio. Results: Only TBO-PDT+ showed superior antibiofilm activity when TiF4 was applied. Furthermore, the highest Ca/P ratio was found after treatment of enamel surfaces with TiF4-TBO-PDT+. The FESEM images showed that the enamel disks treated with TiF4 plus TBO-mediated PDT exhibited surface coating. However, TiF4 plus PC-mediated PDT cannot repair demineralized enamel. Conclusions: These data suggest that TBO-PDT along with TiF4 can effectively reduce cariogenic biofilms and significantly remineralize enamel disks, opening new avenues in caries prevention.

Background: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. Methods: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. Results: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. Conclusion: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

Background: Biofilms are a potential harbor for many microorganisms. The aim of this study was to test the efficacy of riboflavin (Rib), nano-micelle curcumin (NC), and hydrogen peroxide (HP), alone and in combination with the respective light (light-emitting diode (LED) or 980 nm diode laser) on the reduction of Streptococcus mutans and Lactobacillus acidophilus dual-species biofilms and their effect on the enamel mineral loss., Materials and Methods: The biofilms were formed on saliva-coated enamel slabs. Then, the biofilms were treated with antimicrobial photodynamic therapy (PDT) based on LED, Rib, and NC photosensitizers and with HP also based on a 980 nm diode laser (n = 8 per group). A crystal violet assay was performed to determine the reduction of the dual-species biofilms. The enamel slabs were analyzed for calcium and phosphorus content by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX)., Results: While HP-PDT showed a reduction of 37% (p < 0.001), PDT with NC resulted in an even greater reduction of dual-species biofilms (40%, p < 0.001) than HP- and Rib-mediated PDT. In the EDX test, no significant difference was found between the control group and the treatment groups., Conclusions: The use of natural photosensitizers such as NC in PDT has an effect that may be potentially important in reducing caries-causing bacteria., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Our previous clinical trial demonstrated that antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) and potassium iodide (KI) effectively killed Candida albicans (C. albicans) in adult AIDS patients with oral candidiasis, regardless of biofilm formation or 25S rDNA genotype. This study evaluated changes in antifungal susceptibility and virulence gene expression in C. albicans before and after aPDT, and explored factors related to clinical aPDT efficacy., Methods: Twenty-one adult AIDS patients with C. albicans oral candidiasis were divided into Group a (400 μM MB, N = 11) and Group b (600 μM MB, N = 10). Both groups received two aPDT treatments, where MB was applied for 5 min, followed by 300 mM KI, and illuminated for 30 min (37.29 J/cm²). C. albicans isolates were collected before and after treatment to assess antifungal susceptibility (fluconazole, itraconazole, flucytosine, amphotericin B) and gene expression (CAT1, HWP1). Peripheral blood tests were analyzed for correlations with aPDT efficacy., Results: aPDT reduced minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, and flucytosine, with significant reductions primarily after the first treatment. MIC reductions differed between groups, with Group a showing greater decreases in flucytosine and fluconazole MICs, and Group b in amphotericin B MICs. No significant changes in CAT1 or HWP1 expression were observed. Clinical efficacy of aPDT negatively correlated with leukocyte and neutrophil levels., Conclusions: aPDT effectively reduces MICs of antifungal drugs against C. albicans isolated from treated patients, particularly after the first treatment. The concentration of MB required to reduce MICs varies among different antifungal drugs. aPDT does not alter CAT1 or HWP1 expression, and its clinical efficacy in eradicating C. albicans is negatively associated with leukocyte and neutrophil levels., Competing Interests: Declaration of competing interest MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. The other authors declare there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Evaluation of the effect of phycocyanin (PC) and toluidine blue (TBO) along with sodium fluoride varnish (FV) or titanium tetrafluoride (TiF 4 ) under the conditions of antimicrobial photodynamic therapy (PDT) on a dual-species cariogenic biofilm and on remineralization process., Design: After the development of Streptococcus mutans and Lactobacillus acidophilus dual-species biofilms on the human enamel disks, they were divided into 11 groups (n = 9): Control (0.9 % saline), PC, TBO, FV, and TiF 4 alone, PC and TBO in combination with a 635 nm diode laser (PDT treatment), PC-PDT + (PC + FV or TiF 4 + 635 nm diode laser), and TBO-PDT + (TBO + FV or TiF 4 + 635 nm diode laser). After the treatment, crystal violet assay was performed to determine the reduction of cariogenic biofilms. Enamel remineralization changes were analyzed using energy dispersive X-ray spectroscopy (EDX) and field emission scanning electron microscopy (FESEM) for the calcium and phosphorus (Ca/P) ratio., Results: Only TBO-PDT + showed superior antibiofilm activity when TiF 4 was applied. Furthermore, the highest Ca/P ratio was found after treatment of enamel surfaces with TiF 4 -TBO-PDT + . The FESEM images showed that the enamel disks treated with TiF 4 plus TBO-mediated PDT exhibited surface coating. However, TiF 4 plus PC-mediated PDT cannot repair demineralized enamel., Conclusions: These data suggest that TBO-PDT along with TiF 4 can effectively reduce cariogenic biofilms and significantly remineralize enamel disks, opening new avenues in caries prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated., Methods: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm 2 ) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen ( 1 O 2 ), free iodine (I 2 ), hydrogen peroxide (H 2 O 2 ), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed., Results: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I 2 and H 2 O 2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Characterized by an immune reaction to medications, toxic epidermal necrolysis (TEN) and Steven-Johnson Syndrome (SJS) are potentially fatal mucocutaneous reactions, and their management remains challenging. Considering the promising studies regarding the use of laser in managing orofacial lesions, this study aimed to report two cases in which children presenting with TEN and SJS were treated using a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) concurrently with conventional supportive care. The treatment proposed herein resulted in significant clinical improvement of the children's oral condition within a few days, enabling the reintroduction of oral feeding. Within the limitations of the study, the cases reported suggest that the adjuvant combination of PBMT and aPDT may be beneficial for improving the oral condition of children afflicted with oral injuries induced by TEN and SJS., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The aim was to systematically review clinical studies that investigated the efficacy of antimicrobial photodynamic therapy (aPDT) in reducing oral yeasts growth (OYG) in individuals wearing implant overdentures (IO)., Methods: The focused question was "Is aPDT effective in reducing OYG in patients wearing IO?" Literature search was performed in accordance with PRISMA guidelines. Indexed databases were searched without time and language restrictions up to and including January 2024. Clinical studies were included; and letters to the Editor, case-reports/case-series, perspectives/commentaries, in-vitro/ex-vivo studies, studies on animal models and expert opinions were excluded. The risk of bias was also assessed., Results: Two clinical studies were included and processed for data extraction. The study population comprised of 100 (mean age: 58.5 years) and 53 (mean age: 58.5 years) individuals. The numbers of males and females included in these studies ranged between 33 and 35 males and 18-67 females, respectively. In both studies, follow-up evaluations were performed after 60 days. In both studies, aPDT was performed using a 660 nm diode laser at a power of 100 mW and using methylene-blue as photosensitizer. Results from both studies showed that aPDT is effective in significantly reducing oral yeasts CFU/ml and improvement of OHRQoL of individuals using IO., Conclusion: The aPDT is useful in reducing OYG on IO; however, further well-designed and power-adjusted studies are needed in this area of research., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Streptococcus mutans and Candida albicans are associated with caries recurrence. Therefore, this study evaluated the combination of a Ru(II)-loaded resin-based dental material (RDM) and antimicrobial photodynamic therapy (aPDT) against a dual-species biofilm of S. mutans and C. albicans., Methods: An aPDT protocol was established evaluating Ru(II)'s photocatalytic activity and antimicrobial potential under blue LED irradiation (440-460 nm, 22.55 mW/cm 2 ) at different energy densities (0.00, 6.25, 20.25, 40.50 J/cm2). This evaluation involved singlet oxygen quantification and determination of minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). The biofilm was grown (72 h) on resin disks prepared with Ru(II)-doped RDM (0.00, 0.56, or 1.12 %) and samples were exposed to aPDT or dark conditions. The biofilm was then harvested to analyze cell viability (CFU counts) and formation of soluble and insoluble exopolysaccharides., Results: The photocatalytic activity of Ru(II) was concentration and energy density dependent (p < 0.05), and MIC/MBC values were reduced for the microorganisms after LED irradiation (40.5 J/cm 2 ); therefor, this energy density was chosen for aPDT. Although incorporation of Ru(II) into RDM reduced the biofilm growth compared to Ru(II)-free RDM for both species in dark conditions (p < 0.05), aPDT combined with an Ru(II)-loaded RDM (0.56 or 1.12 %) potentialized CFU reductions (p < 0.05). Conversely, only 1.12 % Ru(II) with LED irradiation showed lower levels of both soluble and insoluble exopolysaccharides compared to Ru(II)-free samples in dark conditions (p < 0.05)., Conclusions: When the Ru(II)-loaded RDM was associated with blue LED, aPDT reduced cell viability and lower soluble and insoluble exopolysaccharides were found in the cariogenic dual-species biofilm., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: This study aimed to evaluate the effectiveness of nano-emodin (n-Emo) mediated photodynamic therapy (PDT) as an adjunctive therapy to conventional wound care in patients undergoing free gingival graft (FGG) treatment. The study employed a single-center, parallel, two-blind, randomized, controlled trial design., Method and Material: A total of 53 patients requiring FGG treatment were randomly assigned to one of three groups: the n-Emo mediated PDT group, the n-Emo gel group, and the control group. The n-Emo mediated PDT group received n-Emo gel on donor site followed by LED (450 nm, 1000 ± 1400 mW/cm 2 , 60-80 J/cm 2 , 60 s), the n-Emo gel group received only n-Emo gel on donor site, and the control group received a placebo gel on donor site. All groups received treatment immediately and 48 h after FGG surgery. Wound healing was assessed based on wound area, bleeding, color match, and epithelialization. Postoperative pain perception was evaluated using a Visual Analogue Scale (VAS), and the number of non-steroidal anti-inflammatory drug (NSAID) intakes was recorded., Results: The results showed that all groups demonstrated significant improvement in wound healing by day 28, with the n-Emo mediated PDT exhibiting significantly better healing on the 14th, 21st, and 28th day compared to the control group. Additionally, on the 28th day, the n-Emo mediated PDT showed significantly better healing than the n-Emo gel group. The n-Emo mediated PDT also had significantly lower pain scores than the control group. There were no significant differences in the number of NSAID intakes, bleeding, or color match among the groups, but all groups showed improved color match during follow-up. By the third week, all groups had fully epithelialized without significant differences, and no secondary bleeding incidents were reported., Conclusion: The study concludes that n-Emo mediated PDT is an effective adjunctive therapy to conventional wound care for managing complication after surgery at donor site after FGG surgery., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: The presence of peri‑implant inflammation including peri‑implant mucositis and peri‑implantitis, is a crucial factor that impacts the long-term stability and success of dental implants. This review aimed to evaluate the safety and effectiveness of antimicrobial photodynamic therapy (aPDT) as an adjuvant therapy option for managing peri‑implant mucositis and peri‑implantitis., Methods: We systematically searched the PubMed/MEDLINE, Cochrane Library, Scopus, and Google Scholar databases (no time limitation). The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the quality of the studies was assessed using the Cochrane Collaboration tool., Results: Of 322 eligible articles, 14 studies were included in this review. The heterogeneity and poor quality of the articles reviewed prevented a meta-analysis. The reviewed articles used a light source (60 s, 1 session) with a wavelength of 635 to 810 nm for optimal tissue penetration. These studies showed improved clinical parameters such as probing depth, bleeding on probing (BOP), and plaque index after aPDT treatment. However, in smokers, BOP increased after aPDT. Compared to conventional therapy, aPDT had a longer-term antimicrobial effect and reduced periopathogens like Porphyromonas gingivalis, as well as inflammatory factors such as Interleukin (IL)-1β, IL-6, and Tumor necrosis factor alpha (TNF-α). No undesired side effects were reported in the studies., Conclusion: Although the reviewed articles had limitations, aPDT showed effectiveness in improving peri‑implant mucositis and peri‑implantitis. It is recommended as an adjunctive strategy for managing peri‑implant diseases, but further high-quality research is needed for efficacy and long-term outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The aim of this study was to investigate the effects of antimicrobial photodynamic therapy (PDT) using 635 nm diode laser irradiation with an energy density of 6 to 30 J/cm 2 and toluidine blue O (TBO) as a photosensitizer on the viability of Aggregatibacter actinomycetemcomitans attached to the surface of titanium implants., Materials and Methods: Titanium implants contaminated with A. actinomycetemcomitans were treated with TBO alone or in combination with different exposure parameters (light doses of 6 - 30 J/cm 2 at 635 nm) and 0.2 % chlorhexidine (CHX). After treatment, colony forming units (CFUs)/ml were determined to assess PDT efficacy. The structure of the biofilm of A. actinomycetemcomitans was analyzed by field emission scanning electron microscopy (FESEM)., Results: Under optimal conditions, the colony count was reduced by ∼90 %. Treatment with CHX was somewhat more effective (colony formation was reduced by ∼95 %), but this agent has adverse effects that can be avoided with PDT., Conclusion: This study confirms the efficacy of PDT against A. actinomycetemcomitans depending on the light dose. Treatment with TBO + 635 nm diode laser has an effect that may be equivalent to that of CHX, but perhaps with fewer adverse effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Peri-implantitis is a destructive inflammatory disease affecting both hard and soft tissues of the osseointegrated implant and causing bone loss and envelope surrounding the implant. The study aimed at evaluating the effect of Photodynamic therapy with Curcumin and Riboflavin on the level of decontamination of implant surface impregnated with Aggregatibacter actinomycetemcomitans (A.a) biofilm., Materials and Methods: In this experimental and laboratory study, 42 implants (4.3 mm in diameter and 8 mm in length) were infected with A.a. bacterial suspension. Then, the implants carrying A.a biofilm were randomly divided into seven groups (n = 6). The groups included: 1- a negative control group (without treatment), 2- a positive control group of Chlorhexidine 0.12 %, 3- a Curcumin (5 mg/ ml) group, 4- a Riboflavin (0.5 %) group, 5- an LED irradiation group (390-480 nm), 6- a photodynamic therapy with Curcumin group, and 7- a photodynamic therapy with Riboflavin group. Then, the implants were sonicated and the amount of CFU/mL of each sample was calculated. One-way ANOVA and Tamhane tests were used to analyze the data., Results: The lowest mean number of colonies of A.a (CFU/ mL) were seen in the following groups, respectively: the positive control group of Chlorhexidine 0.12 %, the photodynamic therapy with Curcumin group, the photodynamic therapy with Riboflavin group, the Curcumin (5 mg/ ml) group, the Riboflavin (0.5 %) group, the LED radiation group, and the negative control group. The use of photodynamic therapy with Curcumin significantly reduced the number of colonies of A.a (CFU/ mL) in comparison with the photodynamic therapy with Riboflavin group (p = 0.004), the Riboflavin group (p = 0.045), the LED radiation group (p = 0.012), and the negative control group (p = 0.007)., Conclusion: aPDT with Curcumin and LED can reduce A.a biofilm on implant surfaces and can be used as a safe and non-invasive disinfection method to reduce A.a biofilm on implant surfaces., (Copyright © 2023. Published by Elsevier B.V.)

Background: The development of multidrug resistance (MDR) in infectious agents is one of the most serious global problems facing humanity. Antimicrobial photodynamic therapy (APDT) shows encouraging results in the fight against MDR pathogens, including those in biofilms., Methods: Photosensitizers (PS), monocationic methylene blue, polycationic and polyanionic derivatives of phthalocyanines, electroneutral and polycationic derivatives of bacteriochlorin were used to study photodynamic inactivation of Gram-positive and Gram-negative planktonic bacteria and biofilms under LED irradiation. Zeta potential measurements, confocal fluorescence imaging, and coarse-grained modeling were used to evaluate the interactions of PS with bacteria. PS aggregation and photobleaching were studied using absorption and fluorescence spectroscopy., Results: The main approaches to ensure high efficiency of bacteria photosensitization are analyzed., Conclusions: PS must maintain a delicate balance between binding to exocellular and external structures of bacterial cells and penetration through the cell wall so as not to get stuck on the way to photooxidation-sensitive structures of the bacterial cell., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Periodontitis is a chronic inflammatory disease that leads to the loss of tooth-supporting structures. Porphyromonas gingivalis is one of the main pathogens responsible for periodontitis. Because of the limitations of antibiotic use, various alternative approaches have been developed. Antimicrobial photodynamic therapy uses photosensitizers and light to eliminate pathogens. Curcumin is a promising photosensitizer, but has low bioavailability and water solubility. However, dendrosomes can efficiently encapsulate curcumin, overcoming these obstacles. This study aimed to evaluate the efficacy of photodynamic therapy with blue laser and dendrosomal curcumin against Porphyromonas gingivalis., Methods: In this in vitro experiment, the minimum inhibitory concentration (MIC) of dendrosomal curcumin was determined using a serial dilution approach. Porphyromonas gingivalis suspensions were subjected to blue laser irradiation (447 nm, output power 100 mW) for 30 to 180 s. Finally, several subMIC dendrosomal curcumin concentrations and blue laser irradiation periods were applied to the bacterial suspensions. The negative control group received no therapy, whereas the positive control group was treated with 0.2% chlorhexidine. Consequently, the colony count of each group was calculated., Results: Treatment of Porphyromonas gingivalis with dendrosomal Curcumin at concentrations of 8-250 μg/mL significantly reduced bacterial growth compared to untreated group. 90 second exposure to a blue laser (31.8 J/cm2) completely inhibited the growth of Porphyromonas gingivalis. Blue laser irradiation for 60 s (21.2 J/cm2) markedly reduced bacterial growth but did not completely prevent its survival. Photodynamic therapy using dendrosomal curcumin at concentrations of 2-4 μg/mL and irradiation for 30-90 s resulted in complete eradication of Porphyromonas gingivalis compared to controls (P < 0.05)., Conclusion: The reduction in survival of Porphyromonas gingivalis following photodynamic therapy with dendrosomal curcumin and blue laser indicates that this technique could be a useful approach to eradicate Porphyromonas gingivalis infections., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2023. Published by Elsevier B.V.)

Background: The aim of this study was to evaluate the inactivation potency of riboflavin and curcumin plus blue diode laser against Streptococcus mutans with different power densities., Materials and Methods: In this in vitro study, standard-strain S. mutans was exposed to curcumin and riboflavin plus blue diode laser with different power densities (0.4-1.0 W/cm 2 ) as well as chlorhexidine (CHX). The colony forming units (CFUs)/mL was calculated. Data were analyzed by one-way ANOVA., Results: Antibacterial analysis indicated that the blue diode laser irradiation with curcumin and riboflavin provided a satisfactory reduction of the S. mutans level. In addition, S. mutans was more affected by curcumin + blue diode laser when the power density was set to 1.0 W/cm 2 (P < 0.0001). Meanwhile, bacterial suspensions treated with CHX showed maximum colony number reduction, compared with the control (P < 0.0001)., Conclusion: This study showed the blue diode laser along with curcumin had strong bactericidal effect on S. mutans, and this effect improved by increasing the power density., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form - the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O 2  to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Polymethylmethacrylate (PMMA)-based removable orthodontic appliances are susceptible to microbial colonization due to the surface porosity, and accumulating the biofilms causes denture stomatitis. the present study evaluated the anti-biofilm and antiinflammatory effects of antimicrobial photo-sonodynamic therapy (aPSDT) against multispecies microbial biofilms (Candida albicans, Staphylococcus aureus, Streptococcus sobrinus, and Actinomyces naeslundii) formed on acrylic resin modified with nanoresveratrol (NR)., Materials and Methods: Following the determination of the minimum biofilm inhibitory concentration (MBIC) of NR, in vitro anti-biofilm activity of NR was evaluated. The antibiofilm efficacy against multispecies microbial biofilm including C. albicans, S. aureus, S. sobrinus, and A. naeslundii, were assessed by biofilm inhibition test and the results were measured. To reveal the anti-inflammatory effects of aPSDT on human gingival fibroblast (HGF) cells, the gene expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were evaluated via quantitative real-time polymerase chain reaction (qRT-PCR)., Results: According to the results, the MBIC dose of NR against multispecies microbial biofilm was considered 512 µg/mL. The highest biofilm reduction activity was observed in MBIC treated with aPSDT and 2 × MBIC exposed to light emitting diode (LED) and ultrasound waves (UW). The expression level of TNF-α and IL-6 genes were significantly increased when HGF cells were exposed to multispecies microbial biofilms (P<0.05), while after treatment with aPSDT, the expression levels of genes were significantly downregulated in all groups (P<0.05)., Conclusion: Overall, NR-mediated aPSDT reduced the growth of the multispecies microbial biofilm and downregulated the expression of TNF-α and IL-6 genes. Therefore, modified PMMA with NR can be serving as a promising new orthodontic acrylic resin against multispecies microbial biofilms and the effect of this new material is amplified when exposed to LED and UW., Competing Interests: Declarations of Competing Interest The authors declare to have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Monkeypox is a viral zoonotic disease that has emerged as a threat to public health. Currently, there is no treatment approved specifically targeting Monkeypox disease. Hence, it is essential to identify and develop therapeutic approaches to the Monkeypox virus. In the current in silico paper, we comprehensively involve using computer simulations and modeling to insights and predict hypotheses on the potential of natural photosensitizers-mediated targeted antimicrobial photodynamic therapy (aPDT) against D8L as a Monkeypox virus protein involved in viral cell entry., Materials and Methods: In the current study, computational techniques such as molecular docking were combined with in silico ADMET predictions to examine how Curcumin (Cur), Quercetin (Qct), and Riboflavin (Rib) as the natural photosensitizers bind to the D8L protein in Monkeypox virus, as well as to determine pharmacokinetic properties of these photosensitizers., Results: The three-dimensional structure of the D8L protein in the Monkeypox virus was constructed using homology modeling (PDB ID: 4E9O). According to the physicochemical properties and functional characterization, 4E9O was a stable protein with the nature of a hydrophilic structure. The docking studies employing a three-dimensional model of 4E9O with natural photosensitizers exhibited good binding affinity. D8L protein illustrated the best docking score (-7.6 kcal/mol) in relation to the Rib and displayed good docking scores in relation to the Cur (-7.0 kcal/mol) and Qct (-7.5 kcal/mol)., Conclusions: The findings revealed that all three photosensitizers were found to obey the criteria of Lipinski's rule of five and displayed drug-likeness. Moreover, all the tested photosensitizers were found to be non-hepatotoxic and non-cytotoxic. In summary, our investigation identified Cur, Qct, and Rib could efficiently interact with D8L protein with a strong binding affinity. It can be concluded that aPDT using these natural photosensitizers may be considered an adjuvant treatment against Monkeypox disease., Competing Interests: Declaration of Competing Interest There is no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Although Candida albicans is the most frequent etiological agent of candidiasis, it has been reported a sizable number of infections related to the non-albicans Candida (NAC) species, Candida krusei. In addition, dual biofilms (biofilms composed by two species) may easily occur in vivo, becoming even more challenging the treatment of an infection. The fungicide effect of Photodynamic Therapy (PDT), using toluidine blue O (TBO) on both C. albicans and C. krusei development has been demonstrated. Thus, the objective of this study was to investigate the effects of PDT on dual-species biofilms of Candida albicans and Candida krusei., Methods: The effect of PDT was observed on the metabolic activity of mature dual-species biofilms of Candida albicans and Candida krusei by a metabolic assay based on the reduction of XTT (2,3-bis(2‑methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and the identification of Candida albicans and Candida krusei was performed on CHROMagar Candida medium., Results: it was observed a reduction of ∼30% in the metabolic activity of a mature biofilm treated with PDT, using 0.05 mg·mL -1 TBO and during biofilm formation a predominance of C. albicans on C. krusei was observed. The inhibition observed was related to reduction in the number of Colony Forming Units (CFU) of Candida albicans from 31.33 ± 3.7 to 17.0 ± 1.5. The number of CFU of C. krusei was not significantly modified., Conclusions: These results demonstrated the efficiency of PDT in inhibiting the dual-species biofilms of Candida albicans and Candida krusei by reducing C. albicans development., Competing Interests: Declaration of Competing Interest The authors have no financial, personal, or other conflicts of interest related to this work., (Copyright © 2023. Published by Elsevier B.V.)

Antimicrobial photodynamic therapy (aPDT) has been studied as an alternative to combat bacterial resistance to the commonly used antibiotics. aPDT requires the use of a photosensitizer and curcumin is one of the more promising, though the usage of natural curcumin can be inconsistent in certain biomedical uses due to differences in soil condition and turmeric age, besides a large quantity of the plant is necessary to obtain useful amounts of the actual molecule. As such, a synthetic analogue is preferred as it is pure, and its components are better characterized. The present work studied photophysical differences in both natural and synthetic curcumin using photobleaching experiments and searched for whether differences existed in aPDT studies against Staphylococcus aureus. The results showed a faster O 2 consumption and a singlet oxygen's generation rate lower by the synthetic curcumin, in comparison with the natural derivative. However, no statistical difference was observed when inactivating S. aureus and these results were following a concentration-based pattern. Thus, the use of synthetic curcumin is indicated, as it can be obtained in controlled amounts and with less environmental impact. Although there are small changes in a photophysical context comparing natural versus synthetic curcumins, we did not observe statistical differences in the photoinactivation of S.aureus bacteria, and reproducibility in biomedical contexts is better achieved with the synthetic analogue., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The eradication of C. albicans is difficult due to the organization of the yeast in biofilms. Photodynamic therapy (PDT) has been proposed as an alternative to antifungals. Phenothiazinium dyes, e.g. methylene blue (MB), have been proposed as photosensitizing agents (PS), and their association with sodium dodecyl sulfate (SDS) has recently been shown to improve the effectiveness of PDT in planktonic culture. In this sense, the objective of this work was to evaluate the effect of PDT with phenothiazinium dyes associated to SDS in biofilms at the different stages of growth., Methods: Experiments were carried out to evaluate the effects of PDT on biofilm formation and on established biofilms of C. albicans ATCC 10231. Samples were exposed to PS 50 mg/L (MB, Azure A - AA, Azure B - AB and dimethyl methylene blue - DMMB) dissolved in water or 0.25% SDS, for 5 min in the dark. After irradiation at 660 nm, 37.3mW/cm 2 for 27 min, 60.4J/cm 2 colony forming units count assay (CFU/mL) was performed. One or two irradiations were applied. Statistical methods were used to assess effectiveness., Results: PSs showed low toxicity in the dark. An application of PDT irradiation was not able to reduce the CFU/mL both in mature biofilms (24h) and in biofilms in the dispersion phase (48h), only in the adherence phase did PDT prevent the formation of biofilms. With two successive applications of PDT irradiation in the dispersion phase, PDT with MB, AA, and DMMB completely inactivated C. albicans. The similar was not observed with mature biofilms., Conclusions: Different stages of biofilm growth respond differently to PDT, with the greatest inhibitory effect found in the adhesion stage. Mature and dispersed biofilms are less susceptible to PDT. The use of two successive applications of PDT with PSs associated with SDS may be a useful approach to inactivate C. albicans biofilms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The growth of resistant microorganisms has been a challenge for health systems. Antimicrobial Photodynamic Therapy (aPDT) has gained attention due to its effects on resistant strains. Recently, it was shown that the association of methylene blue (MB) and sodium dodecyl sulfate (SDS) are an effective strategy to increase the effect of aPDT; however, it is unknown which are the best light parameters (such as irradiance and radiant exposure, RE), to reach the most effective protocols. This work aimed to evaluate the light parameters, irradiance, and radiant exposure, in aPDT with MB when conveyed in water compared to MB associated with SDS., Methods: Tests were carried out to quantify the colony-forming units (CFU) of ATCC 10,231 strain of Candida albicans when using MB in different media and with different light parameters: Control (water), SDS (0.25%), MB (20 mg/mL), and the MB/SDS at irradiances of 3.7; 11.2; 18.6, and 26.1 mW/cm 2 and varied irradiation times to reach radiant exposures of 4.4; 17.8; 26.7, and 44 J/cm²., Results: The results showed that aPDT with MB/SDS had a higher antimicrobial effect than MB when conveyed in water. Furthermore, for the highest irradiance studied (26.1 mW/cm 2 ), CFU decreases exponentially with increasing RE from 4.4 up to 44 J/cm 2 . Similarly, at a fixed RE, the higher the irradiance used, the higher the antimicrobial effect was observed, except for the lowest RE studied (4.4 J/cm 2 )., Conclusions: aPDT with MB/SDS had a greater antimicrobial action at the lower light parameters when compared to MB conveyed in water. The authors suggest the use of RE above 18 J/cm 2 and irradiance above 26 mW/cm 2 since at the mentioned parameters the increase in its value caused a greater antimicrobial effect., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The objective of this short-term follow-up study was to evaluate the influence of antimicrobial photodynamic therapy (aPDT) as an adjuvant to mechanical debridement (MD) in reducing soft-tissue inflammation and subgingival yeasts colonization (SYC) in patients with peri‑implant mucositis (PiM)., Methods: Individuals diagnosed with PiM were included. Demographic data was collected using a questionnaire. Peri-implant plaque index (PI), bleeding index (BI), probing depth (PD), crestal bone levels and SYC were measured at baseline. Therapeutically, these individuals were divided into test and control groups. In the control-group patients underwent MD and in the test-group patients underwent MD with adjunct single session of aPDT. Clinical peri‑implant parameters and SYC were reassessed after 12-weeks. Correlation between age, gender and duration of implants with SYC and clinical peri‑implant status was assessed using logistic regression models. P < 0.05 was selected as an indicator of statistical significance., Results: The test and control-groups comprised of 24 and 23 individuals, respectively. In the test and control groups, toothbrushing twice daily was reported by 7 (29.2%) and 5 (21.7%) individuals, respectively. None of the individuals had ever used a dental floss. At baseline, there was no difference in peri‑implant PI, BI, PD and CBL in the test and control groups. At follow-up, peri‑implant PI (P < 0.01), BI (P < 0.01) and PD (P < 0.01) were significantly higher in the control compared with the test-group. At baseline, SYC in the test and control groups were 1865.3 ± 403.4 CFU/ml and 1963.7 ± 512.4 CFU/ml, respectively. At 90 days' follow-up, SYC in the test and control groups were 1472 ± 202.7 and 1538.4 ± 331.7 CFU/ml, respectively. There was no significant difference in SYC in both groups when baseline values were compared with 90 days' follow-up., Conclusion: One session of aPDT after MC with adjunct aPDT is effective in reducing soft tissue inflammation but not SYC in patients with PiM., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023. Published by Elsevier B.V.)

Background: Antimicrobial photodymanic therapy mediated by methylene blue has been investigated as an adjunctive to periodontal treatment but the dimerization of photosensitizer molecules reduces the phototoxic effects. Sodium dodecyl sulfate is a surfactant that may control this aggregation. The aim of this study was evaluated the photodynamic effect of methylene blue in sodium dodecyl sulfate in periodontitis., Methods: 36 participants with periodontitis were selected and allocated randomly in two group for intervention and other two for control - all of them were treated with scaling and root planing before aPDT. Three periodontal evaluations were done: at the selection time, at the day of intervention and thirty-day after this. Pre-irradiation time was 1 min and 2 min for irradiation. Laser (Therapy XT, DMC, São Carlos, Brazil) with wavelength of 660 nm and 100 mW of power was used. Two photosensitizer solutions with 100 µM methylene blue was used, one of them was in water and other in 0,25% of sodium dodecyl sulfate. Two sites of each participant were selected for the experimental procedures. Microbiological evaluations were performed to quantify microorganisms before and immediately after intervention. Quantitative microbiological evaluation was the primary outcome; morphological aspects of bacterial colony, and clinical probing depth was the secondary one., Results: There was no significant difference between the groups in both bacterial reduction and the clinical parameter evaluated., Conclusion: The effect of methylene blue in surfactant did not cause enough phototoxic effects that could promote reduction of periodontal pocket depth., (Copyright © 2022. Published by Elsevier B.V.)

Background: The present study evaluated the anti-biofilm and bystander effects of antimicrobial photo-sonodynamic therapy (aPSDT) on the polymicrobial periopathogenic biofilms formed on mini-screws coated with zinc oxide nanoparticles (ZnONPs)., Materials and Methods: Thirty orthodontic identical mini-screws were divided into 6 groups (n = 5) as follows: 1. negative control: uncoated mini-screw + phosphate-buffered saline (PBS), 2. positive control: uncoated mini-screw + 0.2% CHX, 3. coating control: coated mini-screw + PBS, 4. antimicrobial photodynamic therapy (aPDT): coated mini-screw+light emitting diode (LED), 5. Antimicrobial sonodynamic therapy (aSDT): coated mini-screw+ultrasound waves, and 6. aPSDT: coated mini-screw+LED+ultrasound waves. Electrostatic spray-assisted vapor deposition was employed to coat ZnONPs on titanium mini-screws. The biofilm inhibition test was used to assess the anti-biofilm efficacy against polymicrobial periopathogenic biofilms including Porphyromonas gingivitis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, and the results were shown as the percent reduction of Log 10 colony-forming unit (CFU)/mL. Following each treatment, the gene expression levels of TNF-α, IL-1β, and IL-6 were evaluated on human gingival fibroblast (HGF) cells via quantitative real-time polymerase chain reaction (qRT-PCR) to reveal the bystander effects of aPSDT on HGF cells., Results: A significant reduction in log 10 CFU/mL of periopathogens was observed in groups treated with aPDT, aSDT, aPSDT, and 0.2% CHX up to 6.81, 6.63, 5.02, and 4.83 log, respectively, when compared with control groups (P<0.05). 0.2% CHX and aPSDT groups demonstrated significantly higher capacity in eliminating the periopathogen biofilm compared with other groups (P<0.05). The qRT-PCR showed that the expression level of inflammatory cytokines was significantly down regulated in aPDT, aSDT, and aPSDT groups (P<0.05)., Conclusion: It was found that the ZnONPs-mediated aPSDT could significantly reduce periopathogen biofilm as well as the expression level of inflammatory cytokines., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: One critical issue that impairs the therapeutic effects of antimicrobial photodynamic therapy (aPDT) in root canal disinfection is the insufficient penetration of photosensitizer into dentinal tubules. Therefore, this study aimed to compare the treatments in enhancing photosensitizers' penetrability for aPDT in root canal therapy., Methods: Thirty premolars with a single root canal were randomly divided into three groups (n = 10), using Methylene blue (MB) as a photosensitizer and treated with different approaches: sonic-assisted diffusing group, ultrasonic-assisted diffusing group and the control without treatment. All specimens were observed by stereomicroscope to measure the penetration depth of MB into dentinal tubules., Results: Both sonic and ultrasonic treatments substantially improved the penetrability of MB. The former achieved a deeper penetration depth than the latter did in the same region of root (P<0.05). Regarding the dye penetration depths at different root regions, the control group showed a declining trend from coronal to apical. In contrast, the penetration depths of sonic and ultrasonic-assisted diffusing groups from highest to lowest were middle > coronal > apical (P<0.05)., Conclusions: This study showed that both sonic and ultrasonic treatments remarkably promoted MB's penetration depth into dentinal tubules. Maximum penetration was achieved when treated with a sonic approach., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2022. Published by Elsevier B.V.)

Background: Monkeypox is a viral zoonotic disease and there are no available treatments that specifically target the monkeypox virus. Antimicrobial photodynamic therapy (aPDT) is a non-invasive approach that has been introduced as a targeted adjuvant treatment against various microbial infections. In this study, we used a computational strategy to investigate the potential of aPDT using propolis-benzofuran A against the Monkeypox virus., Methods: In this in silico study, the evaluation of drug-likeness, molecular properties, and bioactivity of propolis-benzofuran A was carried out using SwissADME. Pro-Tox II and OSIRIS servers were used to identify the organ toxicities and toxicological endpoints of propolis-benzofuran A. Molecular docking approach was employed to screen the potential binding modes of propolis-benzofuran A ligand with the Monkeypox virus A48R protein (PDB ID: 2V54)., Results: The results of the computational investigation revealed that propolis-benzofuran A obeyed all the criteria of Lipinski's rule of five and exhibited drug-likeness. The photosensitizing agent tested was categorized as toxicity class-5 and was found to be non-hepatotoxic, non-carcinogenic, non-mutagenic, and non-cytotoxic. The docking studies employing a predicted three-dimensional model of Monkeypox virus A48R protein with propolis-benzofuran A ligand exhibited good binding affinity (-7.84 kcal/mol)., Discussion: The computational simulation revealed that propolis-benzofuran A had a strong binding affinity with the Monkeypox virus A48R protein. Hence, aPDT based on this natural photosensitizer can be proposed as an adjuvant treatment against the Monkeypox virus., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effectiveness of supplemental photodynamic therapy for improving the bacterial removal and the levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by conducting a clinical trial., Methodology: Twenty-four root canals with pulp necrosis and periapical lesion were selected and randomly divided into conventional group using endodontic treatment with chemo-mechanical preparation (CMP) alone (n = 12) and a group using antimicrobial photodynamic therapy (aPDT) after CMP (n = 12). The samples were collected before and after CMP (conventional group) and after photodynamic therapy (aPDT group). A photosensitizer (0.005% methylene blue) was applied to the root canal for 3 minutes after CMP, whereas aPDT was performed by using a red laser with a power of 30Mw and energy density of 9J/cm 2 for 90 s per root canal. Culture technique was performed to determine the bacterial colony forming units. LPS and LTA levels were quantified by using limulus amoebocyte lysate (LAL) assay and enzyme-linked immunosorbent assay (ELISA), respectively., Results: All samples showed growth of viable bacteria on Fastidious Anaerobe Agar (FAA), with an average of 5.19 × 10 5 CFU/ mL. CMP was effective in decreasing viable bacteria (p < 0.05), whereas there was a significant decrease (p < 0.05) in the samples treated with aPDT compared to those submitted to CMP. LPS and LTA were detected in all initial samples, with mean values of 20.561 EU/mL and 430.91 pg/mL, respectively. Both CMP and aPDT groups significantly decreased the levels of LPS and LTA (p < 0.05), with a statistical difference between the groups regarding aPDT (p < 0.05)., Conclusion: Photodynamic therapy as an adjunct to CMP proved to be effective in improving root canal disinfection and reducing the LPS and LTA levels in teeth with primary endodontic infection., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2023. Published by Elsevier B.V.)

Background: Treatment of aggressive periodontitis (stage III, grade C periodontitis) represents a challenge. The aim of the study was to compare the long-term results of antimicrobial photodynamic therapy (aPDT) and antibiotic therapy as an adjunct to conventional non-surgical therapy in patients with aggressive periodontitis., Materials and Methods: Twenty subjects with untreated aggressive periodontitis (stage III, grade C periodontitis) were divided into two groups: the test group (TG) received non-surgical therapy and two sessions of aPDT using a laser (HELBO TheraLite laser) with a wavelength of 670 nm associated with HELBO Blue photosensitizer, and the control group (CG) received non-surgical therapy and antibiotics (amoxicillin 500 mg and metronidazole 400 mg, 7 days). Clinical parameters of probing depth, clinical attachment level and bleeding on probing (BOP) were assessed at baseline, 3, 6, 9 and 12 months after treatment., Results: The mean probing pocket depths at baseline were 3.68 mm in TG and 3.51 mm in CG. These values decreased to 2.77 mm (p < 0.05) and 2.54 mm (p < 0.05) 3 months after treatment and stayed decreased after 12 months. Clinical attachment levels at baseline were 3.88 mm in TG and 3.70 mm in CG. These values decreased to 3.06 mm (p < 0.05) and 2.80 mm (p < 0.05) after 3 months and stayed decreased after 12 months. We also found a decrease in BOP after 3, 6, 9 and 12 months in TG and in CG., Conclusions: aPDT and antibiotics as an adjunct to non-surgical periodontal treatment lead to a comparable improvement in long term periodontal parameters., Competing Interests: Declaration of Competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To evaluate the clinical and biochemical peri‑implant parameters using chloro‑aluminum phthalocyanine-(CAP) mediated antimicrobial photodynamic therapy (PDT) as an adjunct to non-surgical mechanical debridement (NSD) in cigarette smokers (CS) and never-smokers (NS) with peri‑implantitis., Materials and Methods: Thirty-two patients with peri‑implantitis [Group CS - 16 and Group NS - 16] were recruited for the trial. The study participants underwent two therapies: PDT + NSD and NSD alone. The clinical peri‑implant parameters assessed in this clinical trial were bleeding on probing (BP), crestal bone loss (CBL) peri‑implant pocket depth (PD), and peri‑implant plaque scores (PS), respectively. Peri-implant crevicular fluid was sampled and the quantification of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α) was performed using enzyme linked immunosorbent assay (ELISA)., Results: BP was significantly reduced at 6 months after PDT+NSD in CS groups. Mean PD significantly reduced after both PDT+NSD and NSD subgroups within both NS and CS groups. Only at 6 months did PDT+NSD showed statistically significantly reduced IL-1β levels in the NS group. TNF-α levels significantly reduced in CS group with PDT+NSD and NSD alone at both 3 months and 6 months follow up., Conclusion: CAP-assisted PDT helped to improve the clinical and cytokine levels after non-surgical peri‑implant mechanical debridement in treating peri‑implantitis patients in smokers., Competing Interests: Declaration of Competing Interest The authors report there are no competing interests to declare., (Copyright © 2022. Published by Elsevier B.V.)

Background: The spread of Acinetobacter baumannii strains has become a global concern due to its extensive antibiotic resistance and biofilm formation. To overcome it, new antimicrobial strategies have been needed. Among them, antimicrobial photodynamic therapy (aPDT) is an efficient approach against various microorganisms. This study was focused on the use of curcumin (Cur) and quercetin (Qct) as natural photosensitive compounds to improve the activity of aPDT against A. baumannii biofilm-associated protein (Bap)., Materials and Methods: In this in silico and in vitro study, after determining drug-likeness property, ADME/Toxicity profile, and pharmacological activity of Cur and Qct, virtual screening and molecular docking were assessed to determine the potential binding modes of Cur and Qct to Bap. Then, the anti-biofilm potential of natural photosensitizers-mediated aPDT against A. baumannii was evaluated after the determination of minimum inhibitory concentration (MIC). Subsequently, reverse transcription-quantitative real-time PCR (RT-qPCR) was used to exhibit the anti-virulent effect of aPDT against the gene involved in the biofilm formation of A. baumannii RESULTS: Cur and Qct showed almost similar pharmacokinetic and pharmacodynamics properties. These natural photosensitizers obeyed all the criteria of Lipinski's rule of five principles. According to the molecular docking analysis of protein-ligand complexes, Qct and Cur with a high affinity for Bap showed binding affinity of -6.34 and -6.98 kcal/mol, respectively. According to the findings, aPDT using 4 ×, and 8 × MIC of Cur and Qct could significantly reduce A. baumannii growth in biofilm structures in comparison with the control group (P < 0.05). Also, a significant downregulation by 3.7-, and 5.2-fold in gene expression of bap was observed after treatment with sub-MIC doses of Cur- and Qct-mediated aPDT, respectively (P < 0.05)., Conclusions: In summary, the in silico analysis showed that Cur and Qct had strong binding affinity with Bap as a stable protein of A. baumannii. Furthermore, in vitro results displayed that targeted aPDT based on these natural photosensitizers can be considered a treatment against A. baumannii infections by reducing the growth of microbial biofilm and reducing the expression of bap as a gene involved in A. baumannii biofilm formation., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) is a method for the treatment of cancer. Furthermore, PDT can also be used for the eradication of bacteria. The photo-sensitizing drug, a.k.a photosensitizer, is critical for the success of PDT. Although norsquaraines are analogs of squaraine dyes, they are overlooked as photosensitizers., Methods: In this work, synthesis, characterization, bioimaging and in vitro PDT applications of a new norsquaraine dye 1 were described. We also prepared nanoparticles from norsquaraine 1 and Pluronic F127 to obtain 1@F127., Results: Norsquaraine 1 boosted the generation of reactive oxygen species over a wide range of pH (pH 8.0, 7.0, 6.0, and 2.2.). Furthermore, 1 was internalized by epidermoid laryngeal carcinoma Hep-2 (Hep-2) cells and used for fluorescence imaging. Remarkably, norsquaraine 1 destroyed most of the cancer cells (ca. 77% to 89%) after illumination with red light. Most strikingly, 1 successfully inhibited the growth of Methicillin-resistant Staphylococcus aureus (MRSA) upon illumination. Last but not least, photodynamic sterilization of tomato juice, an acidic beverage, was feasible using 1 as a photo sterilizer. Nano formulation of 1 with Pluronic F127 provided 1@F127 nanoparticles. It is lucid that 1@F127 nanoparticles permeate into Hep-2 cells and boost the generation of ROS upon illumination., Conclusion: Norsquaraine 1 shows superior features as a photosensitizer pertinent to PDT in a wide range of pH. This norsquaraine is endowed with anticancer and antibacterial activities. Which should be further evaluated., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice., Methods: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light., Results: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same., Conclusions: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate in vitro the efficacy of ultrasound device to remove caries-like dentin and the curcumin-mediated antimicrobial photodynamic therapy (aPDT) to decontaminate the affected dentin., Methods: Bovine dentin specimens (n = 173) of 4 × 4 × 2 mm were first submitted to Knoop surface microhardness to standardize the specimens (29 ± 3 KHN). Artificial caries lesion was induced by Streptococcus mutans strain by biological model for 7 days. Infected dentin was removed (1 min) with the following techniques: dentin excavator, bur at low-speed rotation and ultrasound device. After that, aPDT application was performed using blue LED under 460 nm. Polarized light microscopy (PLM), removal rate (n = 10), cross-sectional microhardness (n = 10), colony forming units per milliliter (CFU) (n = 9) and confocal laser microscopy (CM) (n = 2) were performed. ANOVA with Welch correction, post-hoc Games-Howell and two-way ANOVA followed by Tukey's post-hoc tests were used., Results: PLM confirmed the caries lesion formation with a depth of ∼147.9 µm. Groups treated with ultrasound showed lower removal rate (p = 0.001). Regardless of the treatment, the microhardness values increased as function of depth (p ≤ 0.05). Carbide bur showed the highest microhardness value, followed by ultrasound and excavator. CFU and CM showed a significant reduction in S. mutans after aPDT application., Conclusion: Ultrasound was efficient, since it removed infected dentin, preserving the affected dentin and aPDT can be used as a complementary therapy to decontaminate the affected dentin., Clinical Significance: Ultrasound device may help the clinician to remove dentin caries-like lesions since it is a conservative technique and provided the removal of infected dentin, preserving the affected dentin. aPDT application may be used as a complimentary technique to promote antibacterial effect and possibly minimize the risk of secondary caries., Competing Interests: Declaration of Competing Interest The authors deny any conflict of interest in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background/purpose: The formation of white spot lesions (WSLs) around fixed orthodontic appliances is a major complication during treatment. The current double-blind, randomized clinical trial (RCT) study aims to investigate the varying effects of nanomicelle curcumin-based photodynamic therapy (NMCur-aPDT) on microbial count and virulence of Streptococcus mutans as well as the number and dynamics of WSLs., Materials and Methods: Double-blind prospective RCT, comprised of 48 patients with fixed orthodontic appliances, were recruited for the current study. The patients were divided into four groups according to the type of the treatment (NMCur, LED, NMCur-aPDT or VITIS® anti-caries mouthwash), using block randomization. Antimicrobial and anti-virulence activities of the treatments against isolated S. mutans were assessed via colony counting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The visual inspection using the International Caries Detection and Assessment System (ICDAS II) score and laser fluorescence (LF) detection using a DIAGNOdent device were used for the detection and assessment of the dynamics of WSLs, respectively, on the labial surface in four areas (i.e., gingival, incisal, mesial, and distal) of the upper and lower anterior teeth at 30-, 60-, 90-, and 120-days follow-up after bonding of the lower and upper arches., Results: The antimicrobial properties of NMCur, VITIS®, and NMCur-aPDT were time-dependent so the highest reduction in S. mutans population was observed following NMCur-aPDT (99.98%) on day 120 of the study. The gtfB gene expression levels in S. mutans isolates from the NMCur-aPDT group on days 60, 90, and 120 decreased by 2.07-, 2.32-, and 3.01-fold more than in S. mutans isolates from the VITIS® group, respectively (all P < 0.05), while NMCur and LED treatments could not significantly reduce gtfB gene expression up to 120 days of follow-up (P > 0.05). In patients who were treated with LED, an increase in the mean number of WSLs per patient (mean increase, 1.8; P < 0.05) was found, while in NMCur-aPDT and VITIS® groups, not only no increases were observed, but the mean number of WSLs per patient decreased (mean reductions, 0.5 and 0.9, respectively; not significant). LED treatment caused significant increases (P < 0.05) in the mean LF values at 90-and 120-days of follow-up in comparison with the baseline (mean increases, 5.1 and 6.5, respectively) while, in NMCur-aPDT, VITIS®, and NMCur groups 11.8-, 7.1-, and 4.4-reductions in the mean LF values were observed, respectively (all, P < 0.05)., Conclusions: The antimicrobial and anti-virulence activities of NMCur-aPDT against S. mutans were higher than the other treatment groups. In patients who were treated with NMCur-aPDT, the mean number and LF values of WSLs per patient were significantly lower than the other groups in 90-and 120-days of follow-up., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests concerning the current study., (Copyright © 2022 Elsevier B.V. All rights reserved.)