Um esclarecimento sobre a real necessidade de realizar a reposição hormonal de testosterona no homem / A clarification on the real need for testosterone hormone replacement in men / Una aclaración sobre la necesidad real de sustituir la hormona testosterona en los hombres

O artigo é uma revisão sobre os aspectos relacionados ao envelhecimento masculino e necessidades de tratamentos, com ênfase no hipogonadismo tardio, baixa produção de testosterona e possível desenvolvimento do Distúrbio Androgênico do Envelhecimento Masculino (DAEM). O objetivo foi apresentar o DAEM e suas implicações sobre a qualidade de vida do paciente para promover e validar o tratamento, quando realmente for apropriado, para esse quadro clínico. Utilizou-se como a fonte de pesquisa Google Acadêmico, banco de dados Biblioteca Virtual em Saúde e do PubMed foram obtidos artigos com as aplicações dos seguintes filtros: 2010-2023 e descritores em saúde (andropausa, reposição hormonal, testosterona, DAEM, hipogonadismo e síndromes metabólicas). Os critérios de inclusão utilizados foram a disponibilidade integral dos artigos, ter os idiomas inglês e português, e abordar o tema da Doença Androgênica do Envelhecimento, todas as suas repercussões sobre a qualidade de vida do homem e, sobretudo, o seu tratamento. Para excluir artigos encontrados na busca, foram observadas obras que apenas tangenciam o tema e tinham enfoque em outros aspectos, como: estética e esporte. Após a aplicação do método, 14 trabalhos foram selecionados por estabelecerem grande relação com o tema. Esse distúrbio acarreta para o indivíduo um conjunto de sinais e sintomas capazes de comprometer sua qualidade de vida: disfunção erétil, baixa libido, obesidade, redução de massa magra ou sarcopenia, osteoporose e distúrbios do humor. O diagnóstico é feito clinicamente e através de exames laboratoriais de dosagem sérica de testosterona. Perante a confirmação diagnóstica e sem patologizar processos fisiológicos do envelhecimento, o tratamento indicado é a reposição de testosterona que tende a normalizar o quadro do idoso por amenizar ou finalizar os sinais e sintomas desse paciente, proporcionando-o uma terceira idade com qualidade de vida. Vale destacar que as disposições de formulações de testosterona são inúmeras: orais, transdérmicas, intramusculares ou injetáveis. A via de administração depende da situação individual de cada paciente e cada tipo de medicamento tem seus benefícios se comparado aos outros, seja por comparação entre efeitos colaterais, estabilidade de níveis séricos hormonais, custo e acesso. O DAEM precisa ser identificado e diagnosticado naqueles pacientes que necessitam de um tratamento por apresentar sinais e sintomas prejudiciais ao bem-estar. Para isso, a indústria farmacêutica disponibiliza uma gama de formas de administração de testosterona. Entretanto, é preciso ter clareza sobre a real necessidade de medicar um paciente.

The article is a review of aspects related to male aging and treatment needs, with an emphasis on late-onset hypogonadism, low testosterone production and the possible development of Androgenic Male Aging Disorder (AMAD). The aim was to present the AMAD and its implications for the patient's quality of life in order to promote and validate treatment, where appropriate, for this clinical condition. The search source used was Google Scholar, the Virtual Health Library database and PubMed, where articles were obtained using the following filters: 2010-2023 and health descriptors (andropause, hormone replacement, testosterone, AMAD, hypogonadism and metabolic syndromes). The inclusion criteria used were that the articles were available in full, that they were in English and Portuguese, and that they dealt with the subject of Androgenic Ageing Disorder, all its repercussions on men's quality of life and, above all, its treatment. To exclude articles found in the search, we looked at works that only touched on the subject and focused on other aspects, such as aesthetics and sport. After applying the method, 14 articles were selected because they were closely related to the topic. This disorder leads to a set of signs and symptoms that can compromise the individual's quality of life: erectile dysfunction, low libido, obesity, reduced lean mass or sarcopenia, osteoporosis and mood disorders. The diagnosis is made clinically and through laboratory tests of serum testosterone levels. Once the diagnosis has been confirmed and without pathologizing the physiological processes of ageing, the treatment indicated is testosterone replacement, which tends to normalize the condition of the elderly by easing or ending the signs and symptoms of the patient, providing them with a quality old age. It's worth noting that there are many different formulations of testosterone: oral, transdermal, intramuscular or injectable. The route of administration depends on the individual situation of each patient and each type of medication has its benefits compared to the others, whether it's a comparison of side effects, stability of serum hormone levels, cost and accessibility. AMAD needs to be identified and diagnosed in those patients who need treatment because they have signs and symptoms that are detrimental to their well-being. To this end, the pharmaceutical industry offers a range of forms of testosterone administration. However, it is necessary to be clear about the real need to medicate a patient.

El artículo es una revisión de los aspectos relacionados con el envejecimiento masculino y las necesidades de tratamiento, con énfasis en el hipogonadismo de inicio tardío, la baja producción de testosterona y el posible desarrollo del Trastorno Androgénico del Envejecimiento Masculino (TAME). El objetivo fue presentar el TAME y sus implicaciones en la calidad de vida del paciente, con el fin de promover y validar el tratamiento de esta condición clínica, cuando sea apropiado. La fuente de búsqueda utilizada fue Google Scholar, la base de datos de la Biblioteca Virtual de Salud y PubMed, donde se obtuvieron artículos utilizando los siguientes filtros: 2010-2023 y descriptores de salud (andropausia, reemplazo hormonal, testosterona, TAME, hipogonadismo y síndromes metabólicos). Los criterios de inclusión utilizados fueron que los artículos estuvieran disponibles en su totalidad, en inglés y portugués, y que abordaran el tema del Trastorno Androgénico del Envejecimiento, todas sus repercusiones en la calidad de vida de los hombres y, sobre todo, su tratamiento. Para excluir los artículos encontrados en la búsqueda, se consideraron los trabajos que sólo tocaban el tema y se centraban en otros aspectos, como la estética y el deporte. Tras aplicar el método, se seleccionaron 14 artículos por estar estrechamente relacionados con el tema. Este trastorno conlleva un conjunto de signos y síntomas que pueden comprometer la calidad de vida del individuo: disfunción eréctil, libido baja, obesidad, reducción de la masa magra o sarcopenia, osteoporosis y trastornos del estado de ánimo. El diagnóstico se realiza clínicamente y mediante pruebas de laboratorio de los niveles séricos de testosterona. Una vez confirmado el diagnóstico y sin patologizar los procesos fisiológicos del envejecimiento, el tratamiento indicado es el reemplazo de testosterona, que tiende a normalizar la condición del anciano, aliviando o terminando con sus signos y síntomas, proporcionándole una vejez con calidad de vida. Cabe destacar que existen diversas formulaciones de testosterona: oral, transdérmica, intramuscular o inyectable. La vía de administración depende de la situación individual de cada paciente y cada tipo de medicación tiene sus ventajas frente a las demás, ya sea en comparación con los efectos secundarios, la estabilidad de los niveles séricos de la hormona, el coste y la accesibilidad. Es necesario identificar y diagnosticar el TAME en aquellos pacientes que necesitan tratamiento porque presentan signos y síntomas perjudiciales para su bienestar. Para ello, la industria farmacéutica ofrece diversas formas de administración de testosterona. Sin embargo, es necesario tener clara la necesidad real de medicar a un paciente.

5-ALA mediated photodynamic therapy increases natural killer cytotoxicity against oral squamous cell carcinoma cell lines.

Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.

The Potential of Photodynamic Therapy Using Solid Lipid Nanoparticles with Aluminum Phthalocyanine Chloride as a Nanocarrier for Modulating Immunogenic Cell Death in Murine Melanoma In Vitro.

Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells (DCs) and consequently modulate the immune response in the tumor microenvironment. However, PDT still has limitations, such as the activity of photosensitizers in aqueous media and poor bioavailability. Therefore, a new photosensitizer system, SLN-AlPc, has been developed to improve the therapeutic efficacy of PDT. In vitro experiments showed that the light-excited nanocarrier increased ROS production in murine melanoma B16-F10 cells and modulated the profile of DCs. PDT induced cell death accompanied by the exposure of DAMPs and the formation of autophagosomes. In addition, the DCs exposed to PDT-treated B16-F10 cells exhibited morphological changes, increased expression of MHCII, CD86, CD80, and production of IL-12 and IFN-γ, suggesting immune activation towards an antitumor profile. These results indicate that the SLNs-AlPc protocol has the potential to improve PDT efficacy by inducing ICD and activating DCs.

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.

Unveiling novel targets in melanoma under melanogenesis stimulation and photodynamic therapy by redox proteomics.

Melanogenesis-stimulated B16-F10 cells enter in a quiescent state, present inhibited mitochondrial respiration and increased reactive oxygen species levels. These alterations suggest that these cells may be under redox signaling, allowing tumor survival. The aim of this study was to evaluate redox-modified proteins in B16-F10 cells after melanogenesis stimulation and rose bengal-photodynamic therapy (RB-PDT). A redox proteomics label-free approach based on the biotin switch assay technique with biotin-HPDP and N-ethylmaleimide was used to assess the thiol-oxidized protein profile. Aconitase was oxidized at Cys-448 and Cys-451, citrate synthase was oxidized at Cys-202 and aspartate aminotransferase (Got2) was oxidized at Cys-272 and Cys-274, exclusively after melanogenesis stimulation. After RB-PDT, only guanine nucleotide-binding protein subunit beta-2-like 1 (Gnb2l1) was oxidized (Cys-168). In contrast, melanogenesis stimulation followed by RB-PDT led to the oxidation of different cysteines in Gnb2l1 (Cys-153 and Cys-249). Besides that, glyceraldehyde-3-phosphate dehydrogenase (Gapdh) presented oxidation at Cys-245, peptidyl-prolyl cis-trans isomerase A (Ppia) was oxidized at Cys-161 and 5,6-dihydroxyindole-2-carboxylic acid oxidase (Tyrp1) was oxidized at Cys-65, Cys-30, and Cys-336 after melanogenesis stimulation followed by RB-PDT. The redox alterations observed in murine melanoma cells and identification of possible target proteins are of great importance to further understand tumor resistance mechanisms.

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 the efficacy of antimicrobial photodynamic therapy through curcumin modifications.

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm2. Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule.

Use of parvovirus B19-like particles in self-illuminated photodynamic therapy for solid tumors.

Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.

The Effect of Photodynamic Therapy on Enterococcus spp. and Its Application in Dentistry: A Scoping Review.

Enterococci spp. are Gram-positive bacteria that cause mild to severe infections, many associated with the oral cavity, such as periapical infections and healthcare-associated infections (HAIs). Many of these infections become serious diseases that are difficult to resolve, specifically when multidrug-resistant (MDR) strains cause them. In recent years, the number of MDR strains of Enterococcus spp. has increased significantly. This increased prevalence of MDR strains produces significant pressure to generate more antimicrobial therapies, but there is a decline in the production of new antibiotics, driving the development of complementary therapies, such as photodynamic therapy (PDT). PDT combines a photosensitizer agent (PS), light, and oxygen to cause photooxidative stress in bacterial cells. PDT can eradicate Enterococcus spp. contaminations, improve the classic cleaning processes, and eradicate the bacteria in dental pieces. PDT's effectiveness can be improved with nanoparticles that function as carriers. Our work aims to describe the advances in PDT against Enterococcus spp. as a complement to antibiotic therapy, focusing on infections by Enterococcus faecium and Enterococcus faecalis, dental hygiene, and using nanoparticles to improve the antimicrobial effect. A systematic bibliographic search without a meta-analysis was conducted on various databases, using inclusion and exclusion criteria to identify the most relevant research. Of the 193 non-redundant articles found, 65 were selected for a systematic review, from which a summary table was created and a manual description was made. Photodynamic therapy for treating E. faecium and E. faecalis is a widely studied area, with promising results concerning bactericidal effectiveness and reductions in biofilm formation, particularly in regard to dental hygiene. Because most of the studies were conducted in vitro or ex vivo, the results indicated that there were not sufficient data to initiate clinical trials for safety and efficacy studies on humans.

Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

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.

Evaluation of the Oral Microbiome before and after Treatments for Halitosis with Photodynamic Therapy and Probiotics-Pilot Study.

BACKGROUND: To compare photodynamic therapy and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. METHODS: Participants aged from 18 to 25 years showing sulfide (SH2) ≥ 112 ppb on gas chromatography were selected. They were divided into four treatment groups: Group 1-Tongue Scraping; Group 2-Antimicrobial Photodynamic Therapy (aPDT); Group 3-Probiotics; and Group 4-Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, and 7 days, 14 days, and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry for microbiome analysis. RESULTS: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. CONCLUSIONS: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

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.

Root Canal Disinfection in Permanent Molars with Apical Lesion by Antimicrobial Photodynamic Therapy: Protocol for a Blind Randomized Clinical Trial.

Objective: The proposed study aims to compare the effectiveness of conventional endodontic treatment (ET) with that of ET associated with antimicrobial photodynamic therapy (aPDT) in patients with apical lesion. Methods: Controlled, double-blind, randomized clinical trial (RCT); superiority study with three parallel arms. Randomization will be conducted in exchange blocks of six, with allocation 1:1:1. The control group will receive conventional ET, while experimental group 1 (EG1) will receive conventional ET + aPDT with laser at 660 nm, fluence of 600 J/cm2; EG2 will receive conventional ET + aPDT with laser at 660 nm, fluence of 1200 J/cm2. The primary outcome will be canal disinfection before treatment, measured by analysis of colony formation (CFU/mL) and the success rate measured after 6 months on the clinical and radiographic evaluations. The mean and standard deviation will be calculated for continuous outcomes, and the CFU/mL mean between groups will be evaluated by ANOVA test. The Chi-squared test will be calculated for binary outcomes. A logistic regression analysis will be performed to assess differences in the success rate between groups, adjusted for the covariates. The Stata 18 software will be used, with a significance threshold of 5%. Conclusions: Few RCTs have evaluated the effectiveness of aPDT in root canal disinfection in patients with permanent dentition presenting apical lesion. New RCTs with larger numbers of participants are needed to support using aPDT as an adjuvant to conventional ET in root canal disinfection for routine use in clinical practice. The trial was registered prospectively in ClinicalTrials.gov (NCT05916859).

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.

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.

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.

Evaluation of antifungal activity of visible light-activated doped TiO2 nanoparticles.

Titanium dioxide (TiO2) is a well-known material for its biomedical applications, among which its implementation as a photosensitizer in photodynamic therapy has attracted considerable interest due to its photocatalytic properties, biocompatibility, high chemical stability, and low toxicity. However, the photoactivation of TiO2 requires ultraviolet light, which may lead to cell mutation and consequently cancer. To address these challenges, recent research has focused on the incorporation of metal dopants into the TiO2 lattice to shift the band gap to lower energies by introducing allowed energy states within the band gap, thus ensuring the harnessing of visible light. This study presents the synthesis, characterization, and application of TiO2 nanoparticles (NPs) in their undoped, doped, and co-doped forms for antimicrobial photodynamic therapy (APDT) against Candida albicans. Blue light with a wavelength of 450 nm was used, with doses ranging from 20 to 60 J/cm2 and an NP concentration of 500 µg/ml. It was observed that doping TiO2 with Cu, Fe, Ag ions, and co-doping Cu:Fe into the TiO2 nanostructure enhanced the visible light photoactivity of TiO2 NPs. Experimental studies were done to investigate the effects of different ions doped into the TiO2 crystal lattice on their structural, optical, morphological, and chemical composition for APDT applications. In particular, Ag-doped TiO2 emerged as the best candidate, achieving 90-100% eradication of C. albicans.

Multi-targets of antimicrobial photodynamic therapy mediated by erythrosine against Staphylococcus aureus identified by proteomic approach.

Staphylococcus aureus is a global challenge to the clinical field and food industry. Therefore, the development of antimicrobial photodynamic therapy (aPDT) has become one of the valuable methods to control this pathogen. The antibacterial activity of photoinactivation by erythrosine (Ery) against S. aureus has been reported, but its modes of action are unclear. This study aimed to employ a proteomic approach to analyze modes of action of Ery-aPDT against S. aureus. We determined the antibacterial effect by Ery-aPDT assays, quantified reactive oxygen species (ROS) and injury to the cell membrane, and determined protein expression using a proteomic approach combined with bioinformatic tools. Ery-aPDT was effective in reducing S. aureus to undetectable levels. In addition, the increment of ROS accompanied the increase in the reduction of cell viability, and damage to cellular membranes was shown by sublethal injury. In proteomic analysis, we found 17 differentially expressed proteins. These proteins revealed changes mainly associated with defense to oxidative stress, energy metabolism, translation, and protein biosynthesis. Thus, these results suggest that the effectiveness of Ery-aPDT is due to multi-targets in the bacterial cell that cause the death of S. aureus.