Adjuvant antimicrobial photodynamic therapy improves periodontal health and reduces inflammatory cytokines in patients with type 1 diabetes mellitus.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) is an adjuvant treatment to scaling and root planing (SRP) which improves periodontal health. It may be beneficial to patients with systemic diseases, such as type 1 diabetes mellitus. OBJECTIVE: This randomized clinical trial evaluated the adjunctive effect of aPDT on the periodontal treatment of patients with type 1 diabetes (T1D). METHODOLOGY: 38 patients were included in the study and divided into four groups: DSRP - T1D patients treated with SRP; CSRP - normoglycemic patients treated with SRP; DPDT - T1D patients treated with SRP + aPDT (methylene blue and red laser); CPDT - normoglycemic patients treated with SRP + aPDT. , Periodontal clinical parameters and inflammatory cytokines in crevicular fluid were recorded at baseline and then after 1, 3 and 6 months. The clinical endpoint for treatment was evaluated after 6 months. RESULTS: Adjuvant aPDT treatment resulted in reduction of probing depth after 3 months (0.38 mm - p<0.05) on T1D patients and in control group after 6 months (0.66 mm - p<0.05). Reduction of clinical attachment levels was similar for both treatments in control patients (p>0.05). There was a significant reduction of TNF-α in crevicular fluid in both groups treated with aPDT (p<0.05). The T1D (65%) and normoglycemic (72%) groups achieved the clinical endpoint after both treatments (p>0.05). CONCLUSIONS: Adjuvant aPDT provided additional benefits in improving periodontal clinical parameters and reducing inflammatory cytokines in both T1D and normoglycemic patients. However, normoglycemic patients showed greater clinical improvements compared to T1D patients following adjuvant aPDT treatment.

Laser NIR Irradiation Enhances Antimicrobial Photodynamic Inactivation of Biofilms of Staphylococcus aureus.

OBJECTIVES: Photodynamic inactivation (PDI) is a powerful technique for eradicating microorganisms, and our group previously demonstrated its effectiveness against planktonic cultures of Staphylococcus aureus bacteria using 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]porphyrin (TAPP) and visible light irradiation. However, biofilms exhibit a lower sensitivity to PDI, mainly due to limited penetration of the photosensitizer (PS). In the context of emerging antibacterial strategies, near-infrared treatments (NIRTs) have shown promise, especially for combating resistant strains. NIRT can act either through photon absorption by water, causing a thermal effect on bacteria, or by specific chromophores without a significant temperature increase. Our objective was to enhance biofilm sensitivity to TAPP-PDI by pretreatment with NIRT. This combined approach aims to disrupt biofilms and increase the efficacy of TAPP-PDI against bacterial biofilms. MATERIALS AND METHODS: In vitro biofilm models of S. aureus RN6390 were utilized. NIRTs involved a 980 nm laser (continuous mode, 7.5 W/cm2, 30 s, totaling 225 J/cm2) post-TAPP exposure to enhance photosensitizer accumulation. Subsequent visible light irradiation at 180 J/cm2 was employed to perform PDI. Colony-forming unit counts evaluated the synergistic effect on bacterial viability. Scanning electron microscopy visualized the architectural changes in the biofilm structure. TAPP was extracted from bacteria to estimate the impact of NIRT on biofilm penetration. RESULTS: Using in vitro biofilm models, NIRT application following biofilm exposure to TAPP increased PS accumulation per bacteria. Under these conditions, NIRT induced a transient increase in the temperature of PBS to 46.0 ± 2.6°C (ΔT = 21.5°C). Following exposure to visible light, a synergistic effect emerged, yielding a substantial 4.4 ± 0.1-log CFU reduction. In contrast, the PDI and NIRT treatments individually caused a decrease in viability of 0.9 ± 0.1 and 0.8 ± 0.2-log respectively. Interestingly, preheating TAPP-PBS to 46°C had no significant impact on TAPP-PDI efficacy, suggesting the involvement of thermal and nonthermal effects of NIR action. In addition to the enhanced TAPP penetration, NIRT dispersed the biofilms and induced clefts in the biofilm matrix. CONCLUSION: Our findings suggest that NIR irradiation serves as a complementary treatment to PDI. This combined strategy reduces bacterial numbers at lower PS concentrations than standalone PDI treatment, highlighting its potential as an effective and resource-efficient antibacterial approach.

Assessment of photodynamic therapy with annatto and led for the treatment of halitosis in mouth-breathing children: Randomized controlled clinical trial.

OBJECTIVE: To assess the effectiveness of antimicrobial photodynamic therapy (aPDT) employing an annatto-based (20%) dye combined with blue LED for the treatment of halitosis in mouth-breathing children. MATERIALS AND METHODS: Fifty-two children six to twelve years of age with diagnoses of mouth breathing and halitosis (score of ≥ 3 on portable breath meter) Breath Alert™ (Tanita Corporation®-Japan), were randomly allocated to two groups (n = 26). Group 1: brushing, dental floss and aPDT applied to middle third of the dorsum of the tongue. Group 2: brushing, dental floss and tongue scraper. Breath meter results before, immediately after treatment as well as seven and 30 days after treatment were compared. The hypothesis of normality in the data was discarded by the Shapiro-Wilk test (p < 0.05) and for statistical analysis the Wilcoxon and Mann-Whitney tests were used. RESULTS: A significant difference was found between the pre-treatment reading and all other readings (p < 0.05) in both groups, suggesting the effectiveness of the proposed treatments. No significant difference was found between the post-treatment reading and two follow-up readings, suggesting the maintenance of the effect of treatment over time (p > 0.05). However, significant differences were found between groups for all post-treatment assessments (p < 0.0001 for all comparisons), indicating greater effectiveness with aPDT. No association was found between the initial reading and the presence of coated tongue. CONCLUSION: Antimicrobial photodynamic therapy using annatto and blue LED proved to be a viable therapeutic option for the treatment of halitosis in mouth-breathing children.

Multiple PDT sessions with chlorin-e6 and LL-37 loaded-nanoemulsion provide limited benefits to periodontitis in rats.

BACKGROUND: The combination of photodynamic therapy (PDT) and LL-37 has never been tested in an animal study and our research team background suggests this strategy might be a promising alternative to intensify periodontitis resolution. This study aimed to assess the effects of multiple sessions of PDT with chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion, as adjunctive therapy in experimental periodontitis in rats. METHODS: Experimental periodontitis was induced in 81 rats. After disease establishment, animals were assigned to three groups: SRP (scaling and root planning); SRP + 1PDT, SRP followed by a single PDT session; SRP + 4PDT (n = 27), SRP followed by four PDT sessions at 0, 24, 48 and 72 h after SRP. Animals were subjected to euthanasia at 7, 14 and 28 days, and samples were submitted to osteoclast quantification, immunological and microtomography analysis. RESULTS: All treatments resulted in significant periodontal improvements and there was no significant difference between the groups in both local inflammatory response and healing process. Minimal adjunctive effects could be found for the combined therapy in terms of cytokine levels (IL-1ß and IL-10), with no statistical significance. However, the number of TRAP-positive osteoclasts per mm of alveolar bone linear surface for the group treated with PDT sessions was significantly lower than those treated with SRP only. CONCLUSIONS: Multiple PDT sessions with chlorin-e6 and LL-37 nanoemulsion as an adjunct to scaling and root planning reduced the presence of osteoclast in the local site but did not contribute towards bone regeneration and IL-1ß and IL-10 levels.

Near infrared photothermal inactivation of Candida albicans assisted by plasmonic nanorods.

The use of photothermal processes has been proven effective in the control of microbial infections. Simultaneously, the localized surface plasmon resonance phenomena in metallic nanoparticles have been explored as an alternative strategy to achieve highly efficient localized heating. In this work, we propose the use of selected nanoheaters to improve the efficiency of fungal photothermal inactivation of Candida albicans through size optimization of plasmonic gold nanorods. Here, the optical heating of polyethylene glycol coated gold nanorods of varying sizes is evaluated, both theoretically and experimentally. A size-dependent computational approach was applied to identify metallic nanorods with maximized thermal performance at 800 nm, followed by the experimental comparison of optimal and suboptimal nanoheaters. Comparison among samples show temperatures of up to 53.0 °C for 41×10 nm gold nanorods against 32.3 °C for 90×25 nm, a percentage increase of ∼63% in photothermal inactivation assessments. Our findings reveal that gold nanorods of 41×10 nm exhibit superior efficiency in near-infrared (800 nm) photothermal inactivation of fungi, owing to their higher light-thermal conversion efficiency. The identification of high performance metallic nanoheaters may lead to the reduction of the nanoparticle dose used in plasmonic-based procedures and decrease the laser exposure time needed to induce cell death. Moreover, our results provide insights to better exploit plasmonic nanoparticles on photothermal inactivation protocols.

Use of photodynamic therapy to combat recurrent pharyngotonsillitis: Three case reports.

BACKGROUND: Pharyngotonsillitis (PT) is an inflammatory and infectious condition affecting the tonsils in the oropharynx, predominantly caused by a variety of viral, fungal, and bacterial pathogens, including Streptococcus pyogenes. With the increasing challenge of antibiotic resistance, alternative therapeutic approaches are needed. METHODS: This study explores the effectiveness and safety of Photodynamic Therapy (PDT) as a therapeutic approach for managing acute PT. PDT involves the use of a photosensitizer, light, and molecular oxygen. We utilized a curcumin-based photosensitizer incorporated into a gum formulation, followed by exposure to blue LED irradiation (455 ± 30 nm, intensity of 200 mW for 6 min) with 1 to 2 PDT sessions depending on the clinical case. RESULTS: The treatment's impact was assessed through systematic monitoring of clinical progression post-treatment, encompassing clinical history, examination, and follow-up. In all three cases examined, PDT was observed to effectively eradicate the infection and prevent its recurrence during the period evaluated. CONCLUSION: Photodynamic Therapy, using a curcumin-based photosensitizer and blue LED light, appears to be a promising alternative to traditional antibiotics for the treatment of PT, demonstrating both efficacy in infection eradication and safety in application. Further studies are recommended to substantiate these findings and explore long-term outcomes.

Photodynamic therapy on mRNA levels in bacteria.

Antimicrobial photodynamic therapy (aPDT) has shown efficacy in inactivating different bacterial species by photosensitizer-induced free radical production. Despite aPDT is considered unable to cause resistant strains, enzymatic pathways for detoxification of reactive oxygen species and transmembrane photosensitizer efflux systems could cause resistance to aPDT. Resistance mechanisms can be evaluated by measurement of mRNA from by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Thus, the aim of this study was to access the mRNA level data obtained by RT-qPCR in bacterial cells submitted to photodynamic therapy. Studies performed on mRNA levels in bacteria after PDT were assessed on MEDLINE/Pubmed. The mRNA levels from genes related to various functions have been successfully evaluated in both Gram-positive and -negative bacteria after aPDT by RT-qPCR. Such an approach has improved the understanding of aPDT-induced effects, and reinforced the effectiveness of aPDT on bacteria, which can cause infections in different human tissues.

In Vitro Effect of Epigallocatechin Gallate on Heme Synthesis Pathway and Protoporphyrin IX Production.

Photodynamic therapy (PDT) treats nonmelanoma skin cancer. PDT kills cells through reactive oxygen species (ROS), generated by interaction among cellular O2, photosensitizer and specific light. Protoporphyrin IX (PpIX) is a photosensitizer produced from methyl aminolevulinate (MAL) by heme group synthesis (HGS) pathway. In PDT-resistant cells, PDT efficacy has been improved by addition of epigallocatechin gallate (EGCG). Therefore, the aim of this work is to evaluate the effect of EGCG properties over MAL-TFD and PpIX production on A-431 cell line. EGCG's role over cell proliferation (flow cytometry and wound healing assay) and clonogenic capability (clonogenic assay) was evaluated in A-431 cell line, while the effect of EGCG over MAL-PDT was determined by cell viability assay (MTT), PpIX and ROS detection (flow cytometry), intracellular iron quantification and gene expression of HGS enzymes (RT-qPCR). Low concentrations of EGCG (<50 µM) did not have an antiproliferative effect over A-431 cells; however, EGCG inhibited clonogenic cell capability. Furthermore, EGCG (<50 µM) improved MAL-PDT cytotoxicity, increasing PpIX and ROS levels, exerting a positive influence on PpIX synthesis, decreasing intracellular iron concentration and modifying HGS enzyme gene expression such as PGB (upregulated) and FECH (downregulated). EGCG inhibits clonogenic capability and modulates PpIX synthesis, enhancing PDT efficacy in resistant cells.

Efficiency of the photodynamic therapy on viability of Streptococcus mutans in the oral cavity using chitosan nanoparticles: an in vitro study.

PURPOSE: This study aimed to investigate the efficiency of antimicrobial photodynamic therapy (aPDT) on Streptococcus mutans biofilm in the oral cavity using the photosensitizer chloroaluminum phthalocyanine encapsulated in chitosan nanoparticles (ClAlPc/Ch) at three preirradiation times. METHODS: Biofilms of Streptococcus mutans strains (ATCC 25,175) were cultivated on bovine tooth blocks and exposed to a 10% sucrose solution three times a day for 1 min over three consecutive days. The samples were randomly distributed into five treatment groups (n = 5): (I) aPDT with ClAlPc/Ch with a preirradiation time of 5 min (F5), (II) aPDT with ClAlPc/Ch with a preirradiation time of 15 min (F15), (III) aPDT with ClAlPc/Ch with a preirradiation time of 30 min (F30), (IV) 0.12% chlorhexidine digluconate (CHX), and (V) 0.9% saline solution (NaCl). After treatment, the S. mutans biofilms formed on each specimen were collected to determine the number of viable bacteria (colony-forming units (CFU)/mL). Data were analyzed for normality using the Shapiro-Wilk test and the analysis of variance (ANOVA) and Tukey HSD tests to analyze the number of viable bacteria (α = 0.05). RESULTS: The one-way ANOVA showed a difference between the groups (p = 0.0003), and the Tukey HSD posttest showed that CHX had the highest microbial reduction of S. mutans, not statistically different from the F5 and F15 groups, whereas the NaCl group had the lowest microbial reduction statistically similar to the F30 group. CONCLUSION: The results demonstrate that aPDT mediated by ClAlPc/Ch when used at preirradiation times of 5-15 min can be an effective approach in controlling cariogenic biofilm of S. mutans, being an alternative to 0.12% CHX.

Effectiveness of antimicrobial photodynamic therapy in the treatment of peri-implantitis: systematic review and meta-analysis.

The purpose of this study was to evaluate the current scientific evidence on the effectiveness of antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to mechanical debridement in the treatment of peri-implantitis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses was followed. A protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO #CRD42022361684). The search was carried out in seven databases, with no restrictions regarding language or year of publication. Our work included studies that compared clinical periodontal parameters between individuals treated with mechanical debridement associated with aPDT and a control group of patients who had undergone mechanical debridement alone. Study selection, data extraction, and risk of bias assessment (RoB 2.0) were performed by two review authors. Meta-analysis was performed. The mean difference (MD) and a 95% confidence interval (CI) were provided. Four hundred and seven-four studies were identified, of which five studies were included. The meta-analysis demonstrated that aPDT adjunctive to mechanical debridement in subjects with peri-implantitis resulted in greater reduction in probing depth 3 months after treatment than among subjects receiving treatment with mechanical debridement. Most of the included studies exhibit a low risk of bias. Adjunctive aPDT to mechanical debridement contributes to the improvement of peri-implant clinical parameters in individuals with peri-implantitis, in particular probing depth.

Enhancing Therapeutic Approaches in Glioblastoma with Pro-Oxidant Treatments and Synergistic Combinations: In Vitro Experience of Doxorubicin and Photodynamic Therapy.

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, which complicates treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is involved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. Evaluating pro-oxidant therapies in brain tumors is crucial due to their potential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were analyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Short term effect of antimicrobial photodynamic therapy and probiotic L. salivarius WB21 on halitosis: A controlled and randomized clinical trial.

OBJECTIVE: This study aimed to evaluate the effect of antimicrobial photodynamic therapy (aPDT) and the use of probiotics on the treatment of halitosis. METHODS: Fifty-two participants, aged from 18 to 25 years, exhaling sulfhydride (H2S) ≥ 112 ppb were selected. They were allocated into 4 groups (n = 13): Group 1: tongue scraper; Group 2: treated once with aPDT; Group 3: probiotic capsule containing Lactobacillus salivarius WB21 (6.7 x 108 CFU) and xylitol (280mg), 3 times a day after meals, for 14 days; Group 4: treated once with aPDT and with the probiotic capsule for 14 days. Halimetry with gas chromatography (clinical evaluation) and microbiological samples were collected from the dorsum of the tongue before and after aPDT, as well as after 7, 14, and 30 days. The clinical data failed to follow a normal distribution; therefore, comparisons were made using the Kruskal-Wallis test (independent measures) and Friedman ANOVA (dependent measures) followed by appropriate posthoc tests, when necessary. For the microbiological data, seeing as the data failed to follow a normal distribution, the Kruskal-Wallis rank sum test was performed with Dunn's post-test. The significance level was α = 0.05. RESULTS: Clinical results (halimetry) showed an immediate significant reduction in halitosis with aPDT (p = 0.0008) and/or tongue scraper (p = 0.0006). Probiotics showed no difference in relation to the initial levels (p = 0.7530). No significant differences were found in the control appointments. The amount of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were not altered throughout the analysis (p = 0.1616, p = 0.2829 and p = 0.2882, respectively). CONCLUSION: There was an immediate clinical reduction of halitosis with aPDT and tongue scraping, but there was no reduction in the number of bacteria throughout the study, or differences in the control times, both in the clinical and microbiological results. New clinical trials are necessary to better assess the tested therapies. TRIAL REGISTRATION: Clinical Trials NCT03996044.

Antimicrobial photodynamic therapy in the nonsurgical treatment of periodontitis in patients with HIV infection: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis (SRM) was to evaluate the effectiveness of the adjunctive use of antimicrobial photodynamic therapy (aPDT) in non-surgical periodontal treatment (NSPT) in subjects with Human Immunodeficiency Virus (HIV) and periodontitis. This SRM was registered in PROSPERO (CRD42023410180) and followed the guidelines of PRISMA 2020. Searches were performed in different electronic databases. Risk of bias was performed using the Cochrane Risk of Bias tool (RoB 2.0) for randomized clinical trials (RCT). Meta-analysis was performed using Rev Man software. The mean difference (MD) measure of effect was calculated, the random effect model was applied with a 95% confidence interval, and heterogeneity was tested by the I2 index. The certainty of the evidence was rated using GRADE. A total of 1118 records were screened, and four studies were included. There was a greater reduction in the microbial load of periodontopathogens after NSPT with aPDT. Meta-analysis showed that probing depth (post 3 and 6 months) and clinical attachment loss (post 6 months) were lower for the aPDT-treated group than the NSPT alone: MD -0.39 [-0.74; -0.05], p = 0.02; MD -0.70 [-0.99; -0.41], p < 0.0001; MD -0.84 [-1,34; -0.34], p = 0.0001, respectively. Overall, the studies had a low risk of bias and, the certainty of evidence was rated as moderate. It is suggested that aPDT is a promising adjuvant therapy, showing efficacy in the reduction of the microbial load and in some clinical parameters of individuals with periodontitis and HIV.

Photodynamic therapy offers a novel approach to managing miltefosine-resistant cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected disease caused by Leishmania parasites. The oral drug miltefosine is effective, but there is a growing problem of drug resistance, which has led to increasing treatment failure rates and relapse of infections. Photodynamic therapy (PDT) combines a light source and a photoactive drug to promote cell death by oxidative stress. Although PDT is effective against several pathogens, its use against drug-resistant Leishmania parasites remains unexplored. Herein, we investigated the potential of organic light-emitting diodes (OLEDs) as wearable light sources, which would enable at-home use or ambulatory treatment of CL. We also assessed its impact on combating miltefosine resistance in Leishmania amazonensis-induced CL in mice. The in vitro activity of OLEDs combined with 1,9-dimethyl-methylene blue (DMMB) (OLED-PDT) was evaluated against wild-type and miltefosine-resistant L. amazonensis strains in promastigote (EC50 = 0.034 µM for both strains) and amastigote forms (EC50 = 0.052 µM and 0.077 µM, respectively). Cytotoxicity in macrophages and fibroblasts was also evaluated. In vivo, we investigated the potential of OLED-PDT in combination with miltefosine using different protocols. Our results demonstrate that OLED-PDT is effective in killing both strains of L. amazonensis by increasing reactive oxygen species and stimulating nitric oxide production. Moreover, OLED-PDT showed great antileishmanial activity in vivo, allowing the reduction of miltefosine dose by half in infected mice using a light dose of 7.8 J/cm2 and 15 µM DMMB concentration. In conclusion, OLED-PDT emerges as a new avenue for at-home care and allows a combination therapy to overcome drug resistance in cutaneous leishmaniasis.

Antimicrobial photodynamic therapy with methylene blue and its derivatives in animal studies: Systematic review.

BACKGROUND: Infections are complications in the wound healing process, and their treatment can lead to antibiotic overuse and bacterial resistance. Antimicrobial photodynamic therapy (aPDT) is used to treat infectious diseases caused by fungi, viruses, or bacteria. Methylene blue (MB) and its derivatives are commonly used dyes in antimicrobial photodynamic therapy (aPDT-MB). METHODS: This study is a PRISMA systematic review of animal models used to discuss the usefulness and therapeutic parameters of aPDT-MB or its derivatives for treating infected skin wounds. RESULTS: After an extensive literature review, 13 controlled trials totaling 261 animals were selected to evaluate skin infection by leishmaniasis and cutaneous bacterial and fungal infections. All studies found results favoring the use of aPDT-MB. Great variability in parameters was found for radiant exposure from 12 to 360 J/cm2, MB diluted in saline solution or distilled water, irradiation time from 40 to 3600 s, irradiance most commonly at a maximum of 100 mW/cm2, and wavelength used mainly in the 630-670 nm range. CONCLUSION: MB is a safe and promising agent used as a photosensitizer in aPDT for skin-infected lesions. There is great variability in the parameters found. Comparisons concerning concentration, irradiation time, and light intensity need to be performed.

Association of 5-aminolevulinic acid fluorescence guided resection with photodynamic therapy in recurrent glioblastoma: a matched cohort study.

PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.

CLINICAL EFFICACY OF PHOTODYNAMIC THERAPY IN MANAGEMENT OF ORAL POTENTIALLY MALIGNANT DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%. CONCLUSIONS: PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.

Modulation of heat shock protein expression and cytokine levels in MCF-7 cells through photodynamic therapy.

In this study, we assess the impact of photodynamic therapy (PDT) using aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability and cellular stress responses of MCF-7 breast cancer cells. Specifically, we investigate changes in cell viability, cytokine production, and the expression of stress-related genes. Experimental groups included control cells, those treated with AlPcS4 only, light-emitting diode (LED) only, and combined PDT. To evaluate these effects on cell viability, cytokine production, and the expression of stress-related genes, techniques such as 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT‒qPCR) were employed. Our findings reveal how PDT with AlPcS4 modulates mitochondrial activity and cytokine responses, shedding light on the cellular pathways essential for cell survival and stress adaptation. This work enhances our understanding of PDT's therapeutic potential and mechanisms in treating breast cancer.

Photodynamic therapy repairs medication-related osteonecrosis of the jaw by reducing NF-kB protein in rats.

OBJECTIVE: To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. METHODOLOGY: Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). RESULTS: Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). CONCLUSION: PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.

Reduction of microorganisms in carious dentin by photodynamic therapy mediated by potassium iodide added to methylene blue and red laser.

OBJECTIVE: To evaluate the effect of the association of potassium iodide to antimicrobial photodynamic therapy on human carious dentin produced with a microcosm biofilm model. METHODS: A microcosm biofilm model was used to generate a caries lesion on human dentin. Pooled human saliva diluted with glycerol was used as an inoculum on specimens immersed on McBain artificial saliva enriched with 1 % sucrose (24 h at 37 °C in 5 % CO2). After refreshing culture media for 7 days, the dentin specimens were divided in 5 groups (3 specimens per group, in triplicate; n = 9): C (NaCl 0.9 %), CX (2 % chlorhexidine), PKI (0.01 % methylene blue photosensitizer+50 mM KI), L (laser at 15 J, 180 s, 22.7 J/cm2), and PKIL (methylene blue + KI + Laser). After the treatments, dentin was collected, and a 10-fold serial dilution was performed. The number of total microorganisms, total lactobacilli, total streptococci, and Streptococcus mutans was analyzed by microbial counts (CFU/mL). After normality and homoscedasticity analysis, the Welch's ANOVA and Dunnett's tests were used for CFU. All tests used a 5 % significance level. RESULTS: CX and PKIL groups showed significant bacterial decontamination of dentin, compared to group C (p < 0.05) reaching reductions up to 3.8 log10 for CX for all microorganisms' groups and PKIL showed 0.93, 1.30, 1.45, and 1.22 log10 for total microorganisms, total lactobacilli, total streptococci, and S. mutans, respectively. CONCLUSION: aPDT mediated by the association of KI and methylene blue with red laser reduced the viability of microorganisms from carious dentin and could be a promising option for cavity decontamination.