Application of photosensitive dental materials as a novel antimicrobial option in dentistry: A literature review.

The formation of dental plaque is well-known for its role in causing various oral infections, such as tooth decay, inflammation of the dental pulp, gum disease, and infections of the oral mucosa like peri-implantitis and denture stomatitis. These infections primarily affect the local area of the mouth, but if not treated, they can potentially lead to life-threatening conditions. Traditional methods of mechanical and chemical antimicrobial treatment have limitations in fully eliminating microorganisms and preventing the formation of biofilms. Additionally, these methods can contribute to the development of drug-resistant microorganisms and disrupt the natural balance of oral bacteria. Antimicrobial photodynamic therapy (aPDT) is a technique that utilizes low-power lasers with specific wavelengths in combination with a photosensitizing agent called photosensitizer to kill microorganisms. By inducing damage through reactive oxygen species (ROS), aPDT offers a new approach to addressing dental plaque and associated microbial biofilms, aiming to improve oral health outcomes. Recently, photosensitizers have been incorporated into dental materials to create photosensitive dental materials. This article aimed to review the use of photosensitive dental materials for aPDT as an innovative antimicrobial option in dentistry, with the goal of enhancing oral health.

Application of antimicrobial sonodynamic therapy as a potential treatment modality in dentistry: A literature review.

The accumulation of dental plaque is a precursor to various dental infections, including lesions, inflammation around dental implants, and inflammation under dentures. Traditional cleaning methods involving physical removal and chemical agents often fall short of eliminating bacteria and their protective biofilms. These methods can also inadvertently lead to bacteria that resist drugs and upset the mouth's microbial harmony. To counter these issues, a new approach is needed that can target and clear away dental plaque, minimize biofilms and bacteria, and thus support sustained dental health. Enter antimicrobial sonodynamic therapy (aSDT), a supplementary treatment that uses gentle ultrasound waves to trigger a sonosensitizer compound, destroying bacterial cells. This process works by generating heat, mechanical pressure, initiating chemical reactions, and producing reactive oxygen species (ROS), offering a fresh tactic for managing dental plaque and biofilms. The study reviews how aSDT could serve as an innovative dental treatment option to enhance oral health.

Bioinformatics analysis of photoexcited natural flavonoid glycosides as the inhibitors for oropharyngeal HPV oncoproteins.

The presence of oropharyngeal human papillomavirus (HPV)-18 E6 and E7 oncoproteins is highly significant in the progression of oropharyngeal cancer. Natural flavonoid compounds have potential as photosensitizers for light-activated antimicrobial therapy against HPV-associated oropharyngeal cancer. This study evaluated five natural flavonoid glycosides including Fisetin, Kaempferol, Morin, Myricetin, and Quercetin as photosensitizers against HPV-18 E6 and E7 oncoproteins using computational methods. After obtaining the amino acid sequences of HPV-18 E6 and E7, various tools were used to predict and verify their properties. The PubChem database was then examined to identify potential natural flavonoid glycosides, followed by predictions of their drug-likeness and ADMET properties. Subsequently, molecular docking was conducted to enhance the screening accuracy and to gain insights into the interactions between the natural compounds and the active sites of HPV-18 E6 and E7 oncoproteins. The protein structures of E6 and E7 were predicted and validated to be reliable. The results of molecular docking demonstrated that Kaempferol exhibited the highest binding affinity to both E6 and E7. All compounds satisfied Lipinski's rules of drug-likeness, except Myricetin. They showed high absorption, distribution volume and similar ADMET profiles with no toxicity. In summary, natural flavonoid glycosides, especially Kaempferol, show potential as photosensitizers for antimicrobial photodynamic therapy against HPV-associated oropharyngeal cancer through inhibition of E6 and E7 oncoproteins. These findings provide insights into the development of novel therapeutic strategies based on antimicrobial photodynamic therapy.

Periodontal ligament stem cell-derived exosome-loaded Emodin mediated antimicrobial photodynamic therapy against cariogenic bacteria.

BACKGROUND: This study was conducted to investigate the efficiency of periodontal ligament (PDL) stem cell-derived exosome-loaded Emodin (Emo@PDL-Exo) in antimicrobial photodynamic therapy (aPDT) on Streptococcus mutans and Lactobacillus acidophilus as the cariogenic bacteria. MATERIALS AND METHODS: After isolating and characterizing PDL-Exo, the study proceeded to prepare and verify the presence of Emo@PDL-Exo. The antimicrobial effect, anti-biofilm activity, and anti-metabolic potency of Emo, PDL-Exo, and Emo@PDL-Exo were then evaluated with and without irradiation of blue laser at a wavelength of 405 ± 10 nm with an output intensity of 150 mW/cm2 for a duration of 60 s. In addition, the study assessed the binding affinity of Emodin with GtfB and SlpA proteins using in silico molecular docking. Eventually, the study examined the generation of endogenous reactive oxygen species (ROS) and changes in the gene expression levels of gelE and sprE. RESULTS: The study found that using Emo@PDL-Exo-mediated aPDT resulted in a significant decrease in L. acidophilus and S. mutans by 4.90 ± 0.36 and 5.07 log10 CFU/mL, respectively (P < 0.05). The study found that using Emo@PDL-Exo for aPDT significantly reduced L. acidophilus and S. mutans biofilms by 44.7% and 50.4%, respectively, compared to untreated biofilms in the control group (P < 0.05). Additionally, the metabolic activity of L. acidophilus and S. mutans decreased by 58.3% and 71.2%, respectively (P < 0.05). The molecular docking analysis showed strong binding affinities of Emodin with SlpA and GtfB proteins, with docking scores of -7.4 and -8.2 kcal/mol, respectively. The study also found that the aPDT using Emo@PDL-Exo group resulted in the most significant reduction in gene expression of slpA and gtfB, with a decrease of 4.2- and 5.6-folds, respectively, compared to the control group (P < 0.05), likely due to the increased generation of endogenous ROS. DISCUSSION: The study showed that aPDT using Emo@PDL-Exo can effectively reduce the cell viability, biofilm activity, and metabolic potency of S. mutans and L. acidophilus. aPDT also significantly reduced the expression levels of gtfB and slpA mRNA due to the increased endogenous ROS generation. The findings suggest that Emo@PDL-Exo-mediated aPDT could be a promising antimicrobial approach against cariogenic microorganisms.

The effects of antimicrobial photocatalytic nanoparticles on the flexural strength of orthodontic acrylic resins: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: Orthodontic acrylic resins containing antimicrobial photocatalytic nanoparticles aims to reduce oral lesions including denture stomatitis and white spot lesions but they should not imperil its mechanical properties. This systematic review was done to evaluate the effect of various photocatalytic nanoparticles on the flexural strength (FS) of acrylic resins. MATERIALS AND METHODS: We systematically searched the PubMed/Medline, Cochrane Library, and Scopus databases from January 2018 to October 2023. 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 evaluated using the QUIN tool, which is specifically designed to assess the risk of bias in vitro studies. RESULTS: Following screening of 1016 initial records, 23 studies were deemed eligible for inclusion. The addition of photocatalytic nanoparticles, such as emodin (Emo), curcumin (Cur), Cur nisin (CurNis), zeolite/zinc oxide (Zeo/ZnO), and Ulva lactuca (U. lactuca), to acrylic resins resulted in a reduction in FS, with the extent of reduction dependent on the nanoparticle concentration. Specifically, the addition of Emo (≥0.5 %), Cur (≥0.5 %), CurNis (≥5 %), Zeo/ZnO (≥2), and U. lactuca (≥1 %) to acrylic resins significantly decreased FS. Conversely, the inclusion of ZnO and titanium dioxide (TiO2) in acrylic resins improved FS, but higher concentrations (≥5 % for TiO2) had a limited positive effect. CONCLUSION: Our study supports the use of low concentrations of photocatalytic nanoparticles, such as ZnO (≤2 %), TiO2 (≤3 %), Emo (≤0.5 %), Cur (≤0.5 %), CurNis (≤5 %), and U. lactuca (≤1 %), in orthodontic acrylic resins without compromising FS.

The flexural strength of orthodontic acrylic resin containing resveratrol nanoparticles as antimicrobial agent: An in vitro study.

OBJECTIVE: This study aimed to evaluate how the addition of resveratrol nanoparticles (RNPs), which act as an antimicrobial agent, affects the strength of acrylic resin used in orthodontics. METHODS: According to ISO 20795-1-2013, 76 cold cure acrylic resin samples (65×10×3.3mm) were prepared. The samples were divided into four groups (19 samples in each group) based on RN concentrations added to 1mL acrylic monomer (0 for control, 256, 512, and 1024µg/mL). Flexural strength was assessed in megapascal (MPa) using a universal testing machine. Data analysis involved nonparametric Kruskal-Wallis analysis of variance and pairwise post-hoc Dunn's test. RESULTS: The flexural strength decreased as the concentration of RNPs increased, with the lowest value observed at 1024µg/mL (63.06±5.33MPa). The control group exhibited the highest mean of flexural strength (88.43±4.41MPa), followed by the groups with RNPs at the concentrations of 256µg/mL (82.69±4.41MPa) and 512µg/mL (76.02±4.59MPa). CONCLUSION: In conclusion, the addition of RNs to orthodontic acrylic resin had a dose-dependent impact on its flexural strength. Based on the findings, we recommend incorporating RNs at a concentration of 256µg/mL as an antimicrobial agent in orthodontic acrylic resin. However, further research is necessary to assess the long-term effects and clinical applications of this approach.

Exosomes: Friends or Foes in Microbial Infections?

The use of new approaches is necessary to address the global issue of infections caused by drug-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) is a promising approach that reduces the emergence of drug resistance, and no resistance has been reported thus far. APDT involves using a photosensitizer (PS), a light source, and oxygen. The mechanism of aPDT is that a specific wavelength of light is directed at the PS in the presence of oxygen, which activates the PS and generates reactive oxygen species (ROS), consequently causing damage to microbial cells. However, due to the PS's poor stability, low solubility in water, and limited bioavailability, it is necessary to employ drug delivery platforms to enhance the effectiveness of PS in photodynamic therapy (PDT). Exosomes are considered a desirable carrier for PS due to their specific characteristics, such as low immunogenicity, innate stability, and high ability to penetrate cells, making them a promising platform for drug delivery. Additionally, exosomes also possess antimicrobial properties, although in some cases, they may enhance microbial pathogenicity. As there are limited studies on the use of exosomes for drug delivery in microbial infections, this review aims to present significant points that can provide accurate insights.

Synergistic effects of nano curcumin mediated photodynamic inactivation and nano-silver@colistin against Pseudomonas aeruginosa biofilms.

BACKGROUND: Patients with burn injuries colonized by multidrug-resistant Pseudomonas aeruginosa face increased mortality risk. The efficacy of colistin, a last-resort treatment, is declining as resistance levels rise. P. aeruginosa's robust biofilm exacerbates antibiotic resistance. Photodynamic Inactivation (PDI) shows promise in fighting biofilm. MATERIALS AND METHODS: Nano curcumin (nCur) particles were synthesized, and their chemical characteristics were determined using zeta potential (ZP), dynamic light scattering analysis (DLS), energy-dispersive X-ray (EDX) analysis, and fourier transform infrared (FTIR). We conducted an MTT assay to assess the cytotoxicity of nCur-mediated PDI in combination with nanosilver colistin. The fractional biofilm inhibitory concentration (FBIC) of two P. aeruginosa clinical isolates and P. aeruginosa ATCC 27853 during nCur-mediated PDI@AgNPs@CL was determined using a 3-dimensional (3-D) checkerboard assay. To study the effect of nCur-mediated PDI@AgNPs@CL on lasI, lasR, rhlI, rhlR, pelA, and pslA gene expression, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted at each isolate's FBIC. The impact of treatments was also investigated using scanning electron microscopy (SEM). RESULTS: The ZP and mean DLS values of the nCur were 10.3 mV and 402.6 ± 24.6 nm, respectively. The distinct functional groups of nCur corresponded with the peaks of FTIR absorption. Moreover, the EDX analysis showed the ratios of different metals in nCur. Cell viability percentages of nCur-mediated PDI@AgNPs@CL at FBIC concentrations of clinical isolates Nos. 30, 354, and P. aeruginosa ATCC 27853 were 91.36 %, 83.20 %, and 92.48 %, respectively. nCur-mediated PDI@AgNPs@CL treatment showed synergistic effects in clinical isolates and P. aeruginosa ATCC 27853 in a 3-D checkerboard assay. All six of the investigated genes showed down-regulation after nCur-mediated PDI@AgNPs@CL treatment. The most suppressed gene during nCur-mediated PDI@AgNPs@CL treatment was the rhlR gene (-11.9-fold) of P. aeruginosa ATCC 27853. The SEM micrographs further proved the connecting cement reduction and biofilm mass mitigation following nCur-mediated PDI@AgNPs@CL treatments. CONCLUSIONS: The combined effect of nCur-mediated PDI and AgNPs@CL synergistically reduce the formation of biofilm in P. aeruginosa. This may be attributable to the suppression of the genes responsible for regulating the production of biofilms.

Antimicrobial photodynamic therapy for managing the peri-implant mucositis and peri-implantitis: A systematic review of randomized clinical trials.

BACKGROUND: The presence of peri­implant inflammation including peri­implant mucositis and peri­implantitis, 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 peri­implant mucositis and peri­implantitis. 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)-1ß, 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 peri­implant mucositis and peri­implantitis. It is recommended as an adjunctive strategy for managing peri­implant diseases, but further high-quality research is needed for efficacy and long-term outcomes.

Photoinactivation of Enterococcus faecalis Biofilm: In Vitro Antimicrobial Effect of Photoexcited Rutin-Gallium(III) Complex via Visible Blue Light.

INTRODUCTION: Endodontic infection is a common problem that can result in tooth loss if not effectively treated. This study focused on investigating the use of rutin-gallium (Ga)(III) complex-mediated antimicrobial photodynamic therapy (aPDT) for the photoinactivation of Enterococcus faecalis biofilm. METHODS: The minimum biofilm eradication concentration of the rutin-Ga(III) complex and the minimum biofilm eradication dose of light-emitting diode against E. faecalis were evaluated. The antimicrobial effect of rutin-Ga(III) complex-mediated aPDT against E. faecalis was assessed. Additionally, the expression of genes associated with E. faecalis virulence, such as ace, gelE, and esp, as well as the production of reactive oxygen species within the cells were evaluated. RESULTS: The minimum biofilm eradication concentration of the rutin-Ga(III) complex was determined to be 25 µmol/L, whereas the minimum biofilm eradication dose of light-emitting diode irradiation was defined as 5 minutes with an energy density of 300-420 J/cm2. Rutin-Ga(III) complex-mediated aPDT demonstrated a significant dose-dependent reduction in the growth of E. faecalis biofilms. Moreover, aPDT led to increased intracellular reactive oxygen species generation in treated E. faecalis cells. Furthermore, the messenger RNA levels of ace, gelE, and esp genes were significantly down-regulated in E. faecalis treated with rutin-Ga(III) complex-mediated aPDT (P < .05). CONCLUSIONS: Rutin-Ga(III) complex-mediated aPDT effectively reduces E. faecalis biofilm growth by disrupting biofilm structure and down-regulating virulence genes. These findings highlight the potential of aPDT with the rutin-Ga(III) complex as an adjuvant therapeutic approach against E. faecalis biofilms.

Anti-leishmanial effects of Eryngium planum and Ecbilliun elaterum methanolic extract against Leishmania major.

Leishmaniasis is a vector-borne disease, one of the most important neglected tropical diseases. Existing anti-leishmanial treatments are not effective for a long time and associated with toxic side effects so searching for a new, effective and safe alternative treatments against infectious diseases is greatly needed. This study is aimed to assess the leishmaniacidal effects of methanolic extracts of Eryngium planum (E. planum) and Ecbilliun elaterum (E. elaterum) on Leishmania major (L. major), In vitro. The selected plants were collected from northern areas of Iran. The methanolic extract from the aerial parts of plants were prepared using maceration methods. GC- Mass analysis was used to determine the compounds of the plants. Promastigotes of L. major was cultured in RPMI-1640 medium and the anti-leishmanial and cytotoxicity effects of extracts at concentrations of 100, 200, 400 and 800 µg/ml were assessed using MTT assay. The data obtained from gas chromatography revealed that α-Pinene, Caryophyllene oxide, ß-Caryophyllene, Bicyclogermacrene and α-Bisabolol are the main compounds extracted from E. planum and α-Pinene, Germacrene D, Caryophyllene oxide, γ-Eudesmol and α-Bisabolol are the main components of E. elaterum. The results of MTT Assay revealed that E. planum at concentrations of 800 µg/ml after 24 h at 400 µg/ml after 48 h and the E. elaterium at concentrations of 800 µg/ml after 48 h at 400 µg/ml after 72 h had similar anti-leishmanial effects to the positive control. These results indicated that E. planum and E. elaterum are the potential sources for the discovery of novel anti-leishmanial treatments.

Characteristics and Applications of Peptide Nucleic Acid in the Treatment of Infectious Diseases and the Effect of Antimicrobial Photodynamic Therapy on Treatment Effectiveness.

Antibiotic resistance is a growing global problem, so there is an urgent need for new antimicrobial agents and strategies. Peptide nucleic acid (PNA) oligomers could be designed and utilized as gene-specific oligonucleotides to target any infectious agents. Selectivity and high-affinity binding are the main properties of PNA. However, in therapeutic applications, intracellular delivery of peptide nucleic acids is still a challenge. In photodynamic therapy (PDT), which could be a useful adjunct to mechanical and antibiotics in removing pathogenic agents, low-power lasers are used in appropriate wavelength for killing the microorganisms that have been treated with a photosensitizer drug. Antimicrobial photodynamic therapy (aPDT) in combination with lipid-charged nanoparticles of PNA is a promising alternative therapy proposed to control infectious diseases. This review summarizes progress in the uptake of peptide nucleic acids at intracellular targets. In addition, we focus on recent nanoparticle- based strategies to efficiently deliver conventional and chemically modified peptide nucleic acids. The likely impact of using two treatment methods simultaneously, i.e., PNP and PDT, has already been discussed.

Antimicrobial photodynamic therapy for the management of gingivitis and white spot lesions in fixed orthodontic patients: A systematic review.

AIM: We conducted this review to evaluate the safety and efficacy of antimicrobial photodynamic therapy (aPDT) for the management of gingivitis and white spot lesions (WSLs) in fixed orthodontic patients. METHODS: The PubMed/MEDLINE, Cochrane Library, Scopus, and Google Scholar databases were searched for randomized controlled trials and clinical trials assessing the clinical effectiveness of aPDT for the management of gingivitis and WSLs in fixed orthodontic patients without time limitation. Primary outcomes were the changes in clinical parameters such as DIAGNOdent, plaque index (PI), bleeding on probing (BOP), and gingival index (GI). Secondary outcomes included measurements of microbial and inflammatory factors, such as cytokine levels (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1ß], and interleukin-6 [IL-6]), and bacterial counts. RESULTS: Our search yielded a total of 12 studies that met the inclusion criteria. Among the 11 studies that evaluated gingivitis, the majority employed a diode laser (670nm, 150 mW, 22J/cm2, 60seconds) as the light source and methylene blue at a concentration of 0.0005% (applied for 3minutes) as the photosensitizer in a single treatment session. The included studies reported positive effects of aPDT on gingivitis management, with more improvements observed in PI, BOP, and GI following aPDT treatment. Additionally, aPDT was found to reduce the counts of periopathogens such as Porphyromonas gingivalis, as well as inflammatory factors (TNF-α, IL-1ß, and IL-6). Two studies demonstrated that aPDT, particularly when administered in multiple sessions, effectively controlled the extent of WSLs during orthodontic treatment and yielded favorable outcomes that persisted for several months after treatment. CONCLUSION: Based on the available evidence, aPDT appears to be a safe and effective treatment option for managing WSLs and gingivitis in patients with fixed orthodontic appliances. However, further high-quality RCTs are necessary to investigate the impact of potential confounding factors on the efficacy of aPDT.

Monitoring Over a Decade in the Serotype Prevalence of Streptococcus pneumoniae in Iran: A Systematic Review and Meta-analysis.

BACKGROUND: There is no comprehensive information about the circulating serotypes of Streptococcus pneumoniae in Iran in recent years. This study aimed to summarize information about the changes over a decade in the serotype prevalence of S. pneumoniae in Iran. METHODS: We performed a comprehensive search in PubMed/Medline, Web of Science, Science Direct, and the Iranian Database, such as Magiran and SID, from January 2011 to February 2023. The systematic process, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was carried out by two researchers who were both independent and calibrated. Statistical analyses were carried out using Comprehensive Meta-Analysis software. Identifying and measuring heterogeneity were done using I2 and the chi-square test. Finally, Begg's rank correlation test was used in combination with a funnel plot to evaluate any possible publication bias. RESULTS: The search returned 16 relevant results, with a total of 1575 isolates. Of those studies, eight studies reported the distribution of S. pneumoniae serotypes among patients, three studies among healthy individuals, and five studies among both groups. As the meta-analysis revealed, the most common serotypes were 23F (n = 299, 14.1% [95% CI: 9.7-19.9]; I2 = 84.3%; P<0.001 for heterogeneity), 19F (n = 221, 13.4% [95% CI: 9.9-17.9; I2 = 76.7%; P<0.001 for heterogeneity]), and 19A (n = 102, 8.7% [95% CI: 6.5-11.7; I2 = 54.3%; P<0.001 for heterogeneity]). Moreover, Begg's test (P = 0.160, 0.173, and 0.176 for 23F, 19F, and 19A, respectively) showed no evidence of publication bias. CONCLUSION: Based on our pooled results, the majority of the serotypes of pneumococci in the Iranian population were 23F, 19F, and 19A, respectively, over the last decade. The findings can be valuable in selecting effective pneumococcal vaccine candidates and targeted antibiotics in Iranian patients.

Nano-emodin mediated photodynamic therapy for wound healing of donor site after free gingival graft: A parallel clinical trial.

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/cm2, 60-80 J/cm2, 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.

In vitro effects of antimicrobial properties and shear bond strength of different concentrations of Emodin nanoparticles incorporated orthodontic composites.

OBJECTIVE: Fixed appliances used in orthodontic treatment are accompanied by some drawbacks, including the development of white spots or enamel demineralization in the vicinity of the brackets and bonding failures. This study aims to evaluate the effect of combining different wt.% of Emodin nanoparticles (ENPs) with orthodontic adhesives to attain adhesives with improved antimicrobial and mechanical properties. METHODS: ENPs were synthesized and added to orthodontic composite at different concentrations (0.5%, 1%, and 2%). The distribution of ENPs within the composite was evaluated using a field emission scanning electron microscope (FESEM). A total of 216 disks were prepared, with 144 subjected to an eluted components test, 36 used for disk agar diffusion (DAD) test, and 36 for biofilm inhibition test. These tests aimed to assess the antimicrobial activity of the composites against Streptococcus mutans, Lactobacillus acidophilus, and Candida albicans. Additionally, the bond strength between stainless-steel brackets and teeth was evaluated using the shear bond strength (SBS) test, and the adhesive remnant index (ARI) score was determined. One-way analysis of variance and Kruskal-Wallis test were used to analyse the SBS and ARI, respectively. For pairwise group comparison concerning the biofilm inhibition, DAD, and eluted components tests, the Tamhane and Games-Howell tests for data with unequal variances and the post-hoc Tukey's HSD and Scheffe tests for data with equal variances were used. RESULTS: The FESEM results confirmed the synthesis and even distribution of ENPs in the composite. Only the 2% group showed significant biofilm inhibition against all microorganisms studied (P<0.05). The DAD test revealed that a 1% concentration of ENPs is sufficient to inhibit growth for all microorganisms. The eluted components test demonstrated that the 2% concentration of ENPs performed significantly better against S. mutans compared to the control group (P<0.05). The highest mean SBS was observed with the 0.5% ENP concentration, while no significant differences in SBS and ARI were found among the groups (P>0.05). CONCLUSIONS: This in vitro study showed that the 2% concentration of ENP produced significantly improved antimicrobial activity without adversely affecting SBS and ARI score. This would support the addition of 2% ENP to orthodontic adhesives.

Effects of Kojic Acid-mediated Sonodynamic Therapy as a Matrix Metalloprotease-9 Inhibitor against Oral Squamous Cell Carcinoma: A Bioinformatics Screening and in vitro Analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a type of cancer that is responsible for a significant amount of morbidity and mortality worldwide. Researchers are searching for promising therapeutic methods to manage this cancer. In this study, an in silico approach was used to evaluate the activity of sonodynamic therapy (SDT) based on the use of Kojic acid as a sonosensitizer to inhibit matrix metalloprotease-9 (MMP-9) in OSCC. MATERIALS AND METHODS: The three-dimensional structure of MMP-9 was predicted and validated by computational approaches. The possible functional role of MMP-9 was determined in terms of Gene Ontology (GO) enrichment analysis. In silico, molecular docking was then performed to evaluate the binding energies of Kojic acid with MMP-9, and ADME parameters and toxicity risks were predicted. The pharmacokinetics and drug-likeness properties of Kojic acid were assessed. Moreover, after the determination of the cytotoxicity effect of Kojic acid-mediated SDT, the change of mmp-9 gene expression was assessed on OSCC cells. RESULTS: The results of the study showed that Kojic acid could efficiently interact with MMP-9 protein with a strong binding affinity. Kojic acid obeyed Lipinski's rule of five without violation and exhibited drug-likeness. The cytotoxic effects of Kojic acid and ultrasound waves on the OSCC cells were dose-dependent, and the lowest expression level of the mmp-9 gene was observed in SDT. CONCLUSIONS: Overall, Kojic acid-mediated SDT as an MMP-9 inhibitor can be a promising adjuvant treatment for OSCC. The study highlights the potential of in silico approaches to evaluate therapeutic methods for cancer treatment.

Evaluation of anti-biofilm effect of antimicrobial sonodynamic therapy-based periodontal ligament stem cell-derived exosome-loaded kojic acid on Enterococcus faecalis biofilm.

Introduction. Antimicrobial sonodynamic therapy (aSDT) is an approach that uses ultrasound waves (UWs) and a sonosensitizer to generate reactive oxygen species (ROS) to damage microbial cells in biofilms. Using nano-carriers, such as exosomes (Exos), to deliver the sonosensitizer can potentially enhance the effectiveness of aSDT.Hypothesis/Gap Statement. aSDT can downregulate the expression of gelE and sprE genes, increasing the production of endogenous ROS and degradation of pre-formed Enterococcus faecalis biofilms.Aim. This study investigated the anti-biofilm effect of aSDT-based periodontal ligament stem cell-derived exosome-loaded kojic acid (KA@PDL-Exo) on pre-formed E. faecalis biofilms in root canals.Methodology. Following the isolation and characterization of PDL-Exo, KA@PDL-Exo was prepared and confirmed. The minimal biofilm inhibitory concentration (MBIC) of KA, PDL-Exo, KA@PDL-Exo and sodium hypochlorite (NaOCl) was determined, and their anti-biofilm effects were assessed with and without UWs. The binding affinity of KA with GelE and SprE proteins was evaluated using in silico molecular docking. Additionally, the study measured the generation of endogenous ROS and evaluated changes in the gene expression levels of gelE and sprE.Results. The results revealed a dose-dependent decrease in the viability of E. faecalis cells within biofilms. KA@PDL-Exo was the most effective, with an MBIC of 62.5 µg ml-1, while NaOCl, KA and PDL-Exo had MBIC values of 125, 250 and 500 µg ml-1, respectively. The use of KA@PDL-Exo-mediated aSDT resulted in a significant reduction of the E. faecalis biofilm (3.22±0.36 log10 c.f.u. ml-1; P<0.05). The molecular docking analysis revealed docking scores of -5.3 and -5.2 kcal mol-1 for GelE-KA an SprE-KA, respectively. The findings observed the most significant reduction in gene expression of gelE and sprE in the KA@PDL-Exo group, with a decrease of 7.9- and 9.3-fold, respectively, compared to the control group (P<0.05).Conclusion. The KA@PDL-Exo-mediated aSDT was able to significantly reduce the E. faecalis load in pre-formed biofilms, decrease the expression of gelE and srpE mRNA, and increase the generation of endogenous ROS. These findings imply that KA@PDL-Exo-mediated aSDT could be a promising anti-biofilm strategy that requires additional in vitro and in vivo investigations.

Physico-mechanical and antimicrobial properties of an elastomeric ligature coated with reduced nanographene oxide-nano curcumin subjected to dual-modal photodynamic and photothermal inactivation against Streptococcus mutans biofilms.

BACKGROUND: White spot lesions (WSLs) are a common side effect of fixed orthodontic treatment. Streptococcus mutans is the primary causative agent of WSLs and dental caries on the teeth during treatment. According to the unique features of reduced graphene oxide-nano curcumin (rGO-nCur), this study aimed to investigate the mechanical properties and antimicrobial potency of rGO-nCur coated orthodontic elastomeric ligatures as a novel coating composite following dual-modal photodynamic inactivation (PDI) and photothermal inactivation (PTI) against S. mutans biofilms. METHODS: After confirmation of rGO-nCur synthesis and coating elastomeric ligatures with different concentration levels of 1.25, 2.5, 5, 7.5, and 10 % of rGO-nCur, tensile strength, force decay, extension to tensile strength, and contact angle of the coated elastomeric ligatures were measured using universal testing machine and sessile drop method, respectively. To investigate the mechanism through which irradiated rGO-nCur can inhibit the formation of S. mutans biofilms, intracellular reactive oxygen species (ROS) generation, and increase in temperature of rGO-nCur solutions under the 450 and 980 nm laser irradiation, respectively, were measured. The anti-biofilm activity and inhibition of water-insoluble extracellular polysaccharide (EPS) production ability of irradiated rGO-nCur coated elastomeric ligatures using a 450 nm diode laser (195 J/cm2), a 980 nm diode laser (195 J/cm2), and a combination of both (78 J/cm2 of irradiation from each one) (i.e., PDI, PTI, and dual-modal PDI/PTI, respectively) were determined. Also, the expression of virulence genes involved in biofilm formation (comDE, gtfD, and smuT) was assessed by quantitative real-time polymerase chain reaction (RT-qPCR) following the mentioned treatment. One-way ANOVA test and Tukey post-hoc test at a p-value equal to/or less than 0.05 were used to analyze the obtained data. RESULTS: The synthesis of GO nano-sheets in a layered structure with a thickness of 0.76 nm was confirmed by AFM analysis. FESEM showed that the exfoliated sheet of synthesized GO had several micrometers in lateral size. DLS revealed that the mean particle size and density index of synthesized nCur were 57.47 ± 2.14 nm and 10 % respectively. In DLS analysis, rGO-nCur showed more positive surface charge (24 mV) than the nano-sheets of GO. FESEM confirmed the coating of rGO-nCur on elastomeric ligatures. ANOVA revealed that tensile strength of 1.25, 2.5, and 5 % rGO-nCur coated elastomeric ligatures were not decreased statistically significantly (P > 0.05). Mean tensile strength and recorded force of 7.5 and 10 % rGO-nCur coated elastomeric ligatures decreased significantly after 14 days' immersion in the artificial saliva (P < 0.05). On the 28th day of the study, the mean of the tensile strength of elastomeric ligatures coated with 10 % rGO-nCur (13.03 ± 0.10 N) was recorded as 55.90 % of the initial tensile strength (23.31 ± 0.41 N in uncoated elastomeric ligatures), while the mean tensile strength of elastomeric ligatures coated with 7.5 % rGO-nCur (16.01 ± 0.10 N) was measured as 68.94 % of the initial tensile strength (23.22 ± 0.09 N in uncoated elastomeric ligatures). When comparing the coated elastomeric ligatures at 7.5 % and 10 % to the original uncoated elastomeric ligatures at similar time intervals, statistically significant decreases in extension to tensile strength (0.42 to 0.71 mm or 3.02 to 5.05 %; all P < 0.05) were observed. The largest contact angle was measured in elastomeric ligatures coated by 10 % rGO-nCur followed by 7.5 and 5 % rGO-nCur (128 ± 2.19°, 117 ± 2.23°, and 99 ± 1.83°; respectively). The results revealed a rise of 6.4-fold in intracellular ROS and an 11.2 °C increase in the temperature of rGO-nCur solutions following the 450 nm and 980 nm laser irradiation, respectively. The 5 % rGO-nCur coated elastomeric ligature mediated dual-modal PDI/PTI showed the most inhibition of the biofilm formation of S. mutans by 83.62 % (P = 0.00). Significant reductions in water-insoluble EPS were detected in biofilm cultures of S. mutans on 1.25 % rGO-nCur coated elastomeric ligatures following irradiation with dual waves of the 450 nm and 980 nm diode lasers (i.e., dual-modal PDI/PTI; 96.17 %; P = 0.00). The expression levels of comDE, gtfD, and smuT virulence genes were significantly downregulated (7.52-, 13.92-, and 8.23-fold, respectively) in the biofilm cultures of S. mutans on 1.25 % rGO-nCur coated elastomeric ligatures following dual-modal PDI/PTI in comparison with biofilm cultures on non-coated elastomeric ligatures. CONCLUSION: 5 % rGO-nCur coated elastomeric ligatures following irradiation with dual waves of the 450 and 980 nm diode lasers (dual-modal PDI/PTI), without adverse effects on the physico-mechanical properties of elastomeric ligatures, can be used to inhibit the formation of S. mutans biofilms on the coated elastomeric ligatures around orthodontic brackets.