Cryptocarya moschata extract decreases single and mixed biofilms on acrylic resins.

OBJECTIVE: This study proposed to assess the effect of Cryptocarya moschata extract on single and mixed biofilms formed on denture base and reline acrylic resin. MATERIALS AND METHODS: Single and mixed biofilms of Candida albicans and Streptococcus mutans were formed on the samples and treated with C. moschata extract; Nystatin solution at 100,000 IU/mL or Penicillin antibiotic solution at 100,000 IU/mL; or PBS solution. Antimicrobial activity was analyzed by counting colony-forming units, metabolism assay, assessment of protein components of the biofilm matrix, and of cell viability using confocal laser scanning microscopy (CLSM). Data were submitted to ANOVA and Tukey's post-test (α = 0.05). RESULTS: Cryptocarya moschata extract reduced cell viability of C. albicans and S. mutans single and mixed biofilms formed on samples. For all types of biofilms in the C. moschata group, there was a log reduction of the biofilm, proven by the Alamar Blue assay. Analyzing the extracellular matrix protein components, groups treated with the extract exhibited a lower level of fluorescence compared to the PBS groups. Reduction in thickness biofilm and viable cells was perceptible in the C. moschata group when assessing through CLSM. CONCLUSION: Cryptocarya moschata extract reduced the single and mixed biofilms of C. albicans and S. mutans on acrylic resins.

A systematic review and meta-analysis on the effects of phototherapy on postoperative pain in conventional endodontic reintervention.

OBJECTIVES: This systematic review and meta-analysis (SRM) aimed to evaluate the efficacy of laser phototherapy (LPT) on the reduction in postoperative pain (PP) of endodontic origin after conventional/non-surgical reintervention of root canals. METHODS: This SRM was registered with PROSPERO (CRD42021243500) and followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Meta-analysis was conducted using R software with the "META" package, the mean difference (MD) measure of effect was calculated, and the fixed effect model was applied with a 95% confidence interval (CI). The Cochrane collaboration scale was used to assess the risk of bias and the GRADE tool to assess the quality of evidence. RESULTS: Initially, 1028 articles were found, and five articles were included. Most studies were classified as "low" risk of bias. Of the five clinical studies, four showed a significant decrease in PP after endodontic reintervention in the LPT groups compared to the control group, especially in the first four days after the intervention. In symptomatic teeth with multiple roots, LPT led to less PP at 24 h (MD -0.52 [-1.03; -0.02] p = .04). However, no significant difference between the groups was found at 48 and 72 h (p > .05). The certainty of the evidence was classified as low. CONCLUSION: Despite the limitations of this SRM, LPT was shown to be a promising alternative for reducing and controlling PP in conventional endodontic reintervention. CLINICAL SIGNIFICANCE: The use of LPT in endodontic reintervention may be a safe and promising alternative to clinically efficacious agent for use in the management of PP in this procedure.

Influence of bioceramic sealers on dentinal tubule penetration and antimicrobial effectiveness: a systematic review and meta-analysis of in vitro studies.

The aim of this systematic review and meta-analysis (SRM) was to evaluate whether bioceramic sealers have better penetration capacity in dentinal tubules and antimicrobial activity when compared to AH Plus® sealer. This SRM was recorded in the Open Science Framework database and followed the guidelines of the PRISMA 2020. Five databases were searched by two independent reviewers. Only in vitro studies that evaluated the effects of bioceramic sealers on dentinal tubule penetration and antimicrobial activity outcomes compared to AH Plus® sealer were included. Meta-analysis was conducted using R software, using the effect measure of the standardized mean difference (SMD) and inverse variance method. A modified Joanna Briggs Institute's Checklist was used for the risk of bias assessment. A total of 1486 studies were identified, and only 54 studies that fulfilled our eligibility criteria were included in this review. There was no statistical difference between the sealers evaluated for dentinal tubule penetration, in the thirds evaluated: coronal SMD 0.58 [0.14; 1.31], p = 0.12; middle SMD 0.07 [0.54; 0.39], p = 0.75; and apical SMD 0.08 [0.73; 0.56], p = 0.80. Both sealers demonstrated similar antimicrobial action (SMD [3.42; 5.32], p = 0.67 and SMD 0.67 [1.89; 0.55], p = 0.28). The studies presented a low risk of bias. Based on the in vitro studies included and according to the limitations of the present review, the data suggest that bioceramic and AH Plus® sealers present similar penetration capacity in dentinal tubules and antimicrobial effect, making them suitable materials to be considered in clinical practice.

The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

High density of CD8 T cell and immune imbalance of T lymphocytes subsets are associated with proliferative verrucous leukoplakia.

Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.

Antimicrobial effectiveness of ultrasonic irrigation in root canal treatment: a systematic review of randomized clinical trials and meta-analysis.

OBJECTIVE: The objective of this systematic review and meta-analysis (SRM) was to answer the question as to whether the use of ultrasonic irrigation (UI) results in better antimicrobial activity in root canal disinfection compared to conventional irrigation (CI). METHODS: A literature search was performed in the main scientific databases, carried out until October 2021. The eligibility criteria were randomized clinical trials (RCTs). Two meta-analyses were conducted using R software with the "META" package. The mean difference (MD) and odds ratio (OR) measure of effect were calculated. The fixed effect model was applied with a 95% confidence interval. The Cochrane collaboration scale was used to assess risk of bias and the GRADE tool to assess the quality of evidence. RESULTS: A total of 1782 records were screened, and 12 studies meeting the criteria were included in this review. A low risk of bias was observed for most domains, except allocation concealment that was considered unclear. The certainty of evidence was classified as moderate in the OR meta-analyses and low in the MD meta-analyses. Ultrasonic irrigation resulted in a better antimicrobial effect in both meta-analyses, MD 1.42 [1.60; 1.23] p < 0.0001, I2 = 80%; and OR 3.86 [1.98; 7.53] p< 0.0001, I2 = 28.7%. CONCLUSION: Within the limitations of this SRM, UI presented better antimicrobial efficacy than CI. CLINICAL RELEVANCE: UI should be used by clinicians as it promotes better antimicrobial efficacy in patients undergoing endodontic treatment.

Postoperative pain after root canal filling with bioceramic sealers: a systematic review and meta-analysis of randomized clinical trials.

The aim of this systematic review and meta-analysis (SRM) was to assess postoperative pain (PP) after endodontic treatment with bioceramic root canal sealer compared to AH Plus® sealer. This SRM was carried out in accordance with the items on the PRISMA 2020 checklist and Cochrane guidelines and registered in PROSPERO (CRD42021259283). Only randomized clinical trials (RCTs) were included. Meta-analysis was conducted using R software, the standardized means difference (SMD) measure of effect was calculated for quantitative variables, and the odds ratio (OR) for binary variables. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Qualitative and quantitative analysis included 18 and 17 studies, respectively. For quantitative variables, the bioceramic root canal sealer presented less occurrence of postoperative pain than the AH Plus® sealer in 24 h (SMD - 0.17 [- 0.34; - 0.01], p = 0.0340). For binary variables, there was no difference observed between the sealers evaluated, except for sealer extrusion where the bioceramic group had lower post-filling material extrusion (OR 0.52 [0.32; 0.84], p = 0.007). Regarding the risk of bias analysis, low risk was observed for most domains, except allocation that was considered unclear, while the certainty of evidence ranged from moderate to low. The results showed that bioceramics sealers reduced postoperative endodontic pain only after 24 h and showed less sealer extrusion compared to the AH Plus® sealer. However, more robust and standardized clinical trials are needed to confirm the results with less heterogeneity and higher quality of evidence.

Macrophages CD163+ and Factor XIIIa+ Provide a First-Line Defence against Proliferative Verrucous Leukoplakia Antigens.

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.

In vivo antifungal activity and biocompatibility of Cryptocarya moschata.

The objective of this study was evaluate, in vivo model, the antifungal activity of Cryptocarya moschata extract against Candida albicans and its biocompatibility. The animals (N = 50) were divided into groups (n = 5): CI/CG: candidiasis was induced and treated with C. moschata extract (0.045 g/mL); CI/NG: candidiasis was induced and treated with nystatin; CI/NT: candidiasis was induced and no treated; CI/CG-2: candidiasis was induced and treated with C. moschata extract (0.045 g/mL), reapplied after 24 h; CI/NG-2: candidiasis was induced and treated with nystatin, reapplied after 24 h; NCI/NT: candidiasis was not induced and no treated; NCI/CG: candidiasis was not induced and treated with C. moschata extract (0.045 g/mL); NCI/NG: candidiasis was not induced treated with nystatin; NCI/CG-2: candidiasis was not induced and treated with C. moschata extract (0.045 g/mL), reapplied after 24 h; NCI/NG-2: candidiasis was not induced and treated with nystatin, reapplied after 24 h. The fungi present in the lingual dorsum of mice were collected and analyzed by the count of colony-forming units. In addition, histological analysis was performed. Histologically, there was no cell damage in the mice's tongue, and there was a decrease in Candida biofilm, similar to the use of nystatin. It was concluded that the C. moschata extract was effective against C. albicans and was biocompatible.

Photodynamic therapy associated with nanomedicine strategies for treatment of human squamous cell carcinoma: A systematic review and meta-analysis.

A systematic review and meta-analysis were conducted about photodynamic therapy (PDT) associated with nanomedicine approaches in the treatment of human squamous cell carcinoma (HSSC). Independent reviewers conducted all steps in the systematic review. For evaluating the risk of bias, RoB 2, OHAT and SYRCLE tools were used. Meta-analysis was performed using a random-effect model (α = 0.05). For PDT against HSSC, Protoporphyrin IX was the photosensitizer, and liposomes were the nanomaterial more frequently used. Photosensitizers conjugated with nanoparticles exhibited positive results against HSSC. Tumors treated with PDT in combination with a nanotechnology drug-delivery system had an increased capacity for inhibiting the tumor growth rate (51.93%/P < 0.0001) when compared with PDT only. Thus, the PDT associated with nanomedicine approaches against HSCC could be a significant option for use in future clinical studies, particularly due to improved results in tumor growth inhibition.

A systematic review and meta-analysis of the effect of thymol as an anti-inflammatory and wound healing agent: A review of thymol effect on inflammation and wound healing: A review of thymol effect on inflammation and wound healing.

Thymol (THY) exhibits antibacterial and antioxidant properties. Recent studies have also shown that THY presents anti-inflammatory and healing properties. This review focused on in vitro and in vivo investigations related to THY utilization, as an anti-inflammatory and/or wound healing agent. PubMed, WebOfScience, and Scopus were examined. Independent reviewers conducted all diagram steps. PRISMA was followed for data extraction. RoB 2 and SYRCLE were utilized to assess the risk of bias for in vitro and animal studies. Meta-analysis was performed for in vitro and in vivo articles that investigated THY as an anti-inflammatory agent. Thirty-six and 15 articles were included in the qualitative analysis and meta-analysis, respectively. Studies showed high risk of bias related to sampling, allocation procedures, randomization, and blinding. Even so, for in vitro studies, significant result was observed for IL-2. For in vivo studies, significant results were found for IL-1, IL-17, TNF-α, AST, MPO, and CRP, with higher levels noticed in control groups. THY presents significant properties as anti-inflammatory, ameliorating affections of the digestive system, cardiovascular problems, respiratory system and dermal damages, and burns. Researches are needed to clarify THY dose-response relationship and its mechanism of action, especially in the application of THY as a healing agent.

Does oral lichen planus aggravate the state of periodontal disease? A systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis (SRM) was to assess the evidence between the association of oral lichen planus and periodontal disease, evaluating the periodontal clinical parameters and biomarkers levels. METHODS: This systematic review and meta-analysis followed PRISMA and was registered in PROSPERO (CRD42020181513). Searches were accomplished in databases for articles published until June 2021. The meta-analysis was performed with the variables: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). The mean difference was applied with a 95% confidence interval. RESULTS: Six articles were included. Qualitative analysis showed the levels of biomarkers (matrix metalloproteinases, interleukins, and periodontal microbiological profile) are increased in subjects with periodontal disease and oral lichen planus. In the meta-analysis, these subjects also presented increases in all periodontal clinical parameters evaluated: GI-gingivitis 0.22 [0.14, 0.31] p < 0.0001 and periodontitis 0.12 [0.06, 0.19] p = 0.0003; PI-gingivitis 0.22 [0.12, 0.31] p < 0.0001 and periodontitis 0.15 [0.08, 0.23] p < 0.0001; PD-gingivitis 0.27 [0.06; 0.48] p = 0.0107 and periodontitis 0.11 [0.01; 0.21] p = 0.0299; and CA-periodontitis 0.06 [0.01, 0.12] p = 0.0176. CONCLUSIONS: Evidence suggests a significant relationship between the severity of periodontal disease and the presence of oral lichen planus. Although the association is biologically plausible, further studies are needed using populations and well-defined biochemical and clinical outcomes with consideration of potential confounding factors. CLINICAL RELEVANCE: This SRM provides information on the interaction between OLP and periodontal disease and guides clinicians to make evidence-based decisions and suggests recommendations for further high-quality studies.

Postoperative pain in root canal treatment with ultrasonic versus conventional irrigation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The objective of this systematic review and meta-analysis (SRM) was to answer the question whether the use of ultrasonic irrigation (UI) results in less postoperative pain (PP) compared to conventional irrigation (CI). METHODS: A literature search was performed within the main scientific databases carried out until May 2021. The eligibility criteria were randomized clinical trials (RCTs). Meta-analysis was conducted using R software with the "META" package, the mean difference (MD) measure of effect was calculated, and the fixed effect model was applied with a 95% confidence interval (CI). The Cochrane collaboration scale was used to assess risk of bias and the GRADE tool to assess the quality of evidence. RESULTS: Six RCTs were included for systematic review and four for meta-analysis. UI resulted in less PP in 3 of 5 periods, at 6 h (MD - 1.40 [CI - 2.38 to - 0.42] p = 0.0052), 24 h (MD - 0.73 [CI - 1.07 to - 0.39] p = 0.0001), and 48 h (MD - 0.36 [CI - 0.59 to - 0.13] p = 0.022). However, PP showed no significant differences between the groups at 72 h and 7 days (p > 0.05). A low risk of bias was observed for most domains, except allocation that was considered unclear. The certainty of evidence was classified as moderate (24 h, 48 h, and 7 days) and low (6 and 72 h). CONCLUSION: Within the limitations of this SRM, UI presented less occurrence of PP than CI. Further randomized clinical trials are needed to corroborate these findings. CLINICAL RELEVANCE: UI should be used by clinicians as it reduces postoperative pain in patients undergoing endodontic treatment.

Use of Photodynamic Therapy Associated with Antimicrobial Peptides for Bacterial Control: A Systematic Review and Meta-Analysis.

Considering the challenges related to antimicrobial resistance, other strategies for controlling infections have been suggested, such as antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides (AMP). This study aims to perform a systematic review and meta-analysis to obtain evidence on the antimicrobial effectiveness of aPDT associated with AMP and establish in vitro knowledge on this topic for further study designs. The PubMed, Scopus, Web of Science, Science Direct, Scielo, and Cochrane Library databases were searched. Two independent and calibrated researchers (Kappa = 0.88) performed all the systematic steps according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The odds ratio (OR) was used as the effect measure. The Peto method was used to perform the meta-analysis due to the sparse data. Twenty studies were included in the present review. The result was significant (OR = 0.14/p = 0.0235/I-squared = 0%), showing better outcomes of aPDT associated with peptides than those of aPDT alone for controlling the microbial load. Only 20% of the studies included evaluated this approach in a biofilm culture. Combined treatment with aPDT and AMP highly increased the ability of microbial reduction of Gram-positive and Gram-negative bacteria. However, additional blind studies are required to evaluate the efficacy of this therapy on microbial biofilms.

COVID-19 (SARS-CoV-2) infection and thrombotic conditions: A systematic review and meta-analysis.

BACKGROUND: COVID-19 is an infectious disease caused by SARS-CoV-2 associated with haematological manifestations (thrombolytic events). AIMS: Considering the high prevalence of the thrombotic scenarios associated with COVID-19, the aim of this study was to perform a systematic review of the available literature, concerning the relation of COVID-19 and the thrombotic events, and identify prognostic factors for these events. MATERIALS & METHODS: PubMed, Web of Science and Scopus databases were searched. Independent reviewers conducted all flow diagram steps. For qualitative analysis, Oxford level of evidence and Newcastle-Ottawa scale were used in the eligible articles. For the prognostic factors, a meta-analysis was conducted to age, number of neutrophils and platelets, and levels of ferritin, C-reactive protein, lactate dehydrogenase and D-dimer. Publication bias was accessed by funnel plot and by trim-and-fill test. Trim-and-fill test was also applied to evaluate meta-analysis bias. RESULTS: Twenty articles were included in the qualitative analysis, and 6 articles were included in the meta-analysis. Case-control studies showed bias related to exposure, and the main bias in cohort studies were related to selection and outcome. All articles received score 4 for the level of evidence. Hypertension and diabetes were the comorbidities more frequently associated with thrombolytic events. Significant results were found regarding D-dimer (P < .0001) and age (P = .0202) for thrombotic events in patients diagnosed with COVID-19. CONCLUSION: Patients older than 60 years, with hypertension, diabetes and D-Dimer values above 3.17 µg/mL, can be considered prognostic factors for developing thrombotic events due to COVID-19.

Concomitant endogenous and exogenous etiology for gingival pigmentation.

Oral pigmented lesions can be physiological or pathological, exogenous or endogenous, as well as focal, multifocal, or diffuse. Among them, the oral melanotic macule (OMM) is a small, well-delimited brown-to-black macule, often affecting the lip and gingiva. Amalgam tattoo (AT) is a grey or black area of discoloration on the oral mucosa as a result of entry of dental amalgam into the soft tissues, commonly gingiva and alveolar ridge. Herein, we present a patient with gingival pigmentation with features of both OMM and AT in the same location.

Odontogenic Myxoma: Systematic review and bias analysis.

BACKGROUND: Odontogenic myxoma (OM) is a rare neoplasm, which originates from odontogenic ectomesenchyme. There is no study in the literature that analyses the best standards for OM diagnosis and how the treatment modalities may influence the recurrence rates. OBJECTIVE: To evaluate the best standards for odontogenic myxoma (OM) diagnosis and treatment, and how these may influence the recurrence rates. STUDY DESIGN: Two independent researchers performed a systematic review in many databases. Fifty-two eligible studies were included for qualitative analysis. Bias analysis was conducted according to Oxford Centre for Evidence-Based Medicine. RESULTS: A total of 1363 OM cases were reported on, and female gender with average age of 27 years is the most common patient profile. Conventional microscopic findings were observed in 93.43% of the reported cases. In 57.49% of the cases, multilocular radiographic appearance was present, followed by unilocular appearance (32.87%). Posterior mandible was the site with the major prevalence, while surgical resection was the most common treatment modality, followed by enucleation. Recurrence rates for both treatment modalities were approximately close (13.04% and 25.0%, respectively). CONCLUSION: The correct diagnosis of OM relies on the association of clinical, radiographic and microscopic findings. About imaging examinations, panoramic radiography and computed tomography are sufficient for the evaluation of OM. Recurrence rates were closely among the two most used surgery treatments. So according to some clinical-radiological aspects, conservative surgery may be preferred than aggressive surgery modalities.

Effect of Photodynamic Therapy on Microorganisms Responsible for Dental Caries: A Systematic Review and Meta-Analysis.

The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries.

Bacterial resistance to antimicrobial photodynamic therapy: A critical update.

Bacterial antibiotic resistance is one of the most significant challenges for public health. The increase in bacterial resistance, mainly due to microorganisms harmful to health, and the need to search for alternative treatments to contain infections that cannot be treated by conventional antibiotic therapy has been aroused. An alternative widely studied in recent decades is antimicrobial photodynamic therapy (aPDT), a treatment that can eliminate microorganisms through oxidative stress. Although this therapy has shown satisfactory results in infection control, it is still controversial in the scientific community whether bacteria manage to develop resistance after successive applications of aPDT. Thus, this work provides an overview of the articles that performed successive aPDT applications in models using bacteria published since 2010, focusing on sublethal dose cycles, highlighting the main PSs tested, and addressing the possible mechanisms for developing tolerance or resistance to aPDT, such as efflux pumps, biofilm formation, OxyR and SoxRS systems, catalase and superoxide dismutase enzymes and quorum sensing.

Assessment of synergism between enzyme inhibition of Cu/Zn-SOD and antimicrobial photodynamic therapy in suspension and E. coli biofilm.

BACKGROUND: Antimicrobial Photodynamic Therapy (aPDT) is a treatment based on the interaction between a photosensitizer (PS), oxygen and a light source, resulting in the production of reactive oxygen species (ROS). There are two main types of reactions that can be triggered by this interaction: type I reaction, which can result in the production of hydrogen peroxide, superoxide anion and hydroxyl radical, and type II reaction, which is the Photodynamic Reaction, which results in singlet oxygen production. Antioxidant enzymes (e.g., catalase and superoxide dismutase) are agents that help prevent the damage caused by ROS and, consequently, reduce the effectiveness of aPDT. The aim of this study was to evaluate a possible synergism of the combined inhibition therapy of the enzyme Cu/Zn-Superoxide dismutase (SOD) and the methylene blue- and curcumin-mediated aPDT against Escherichia coli ATCC 25922, in suspension and biofilm. METHODS: Kinetic assay of antimicrobial activity of diethydithiocarbamate (DDC) and Minimum Bactericidal Concentration (MIC) of DDC were performed to evaluate the behavior of the compound on bacterial suspension. Inhibition times of Cu/Zn-SOD, as well as DDC concentration, were evaluated via bacterial susceptibility to combined therapy in suspension and biofilm. RESULTS: DDC did not present MIC at the evaluated concentrations. The inhibition time and Cu/Zn-SOD concentration with the highest bacterial reductions were 30 minutes and 1.2 µg/mL, respectively. Synergism occurred between DDC and MB-mediated aPDT, but not with CUR-mediated aPDT. CONCLUSIONS: The synergism between Cu/Zn-SOD inhibition and aPDT has been confirmed, opening up a new field of study full of possibilities.