Immunoexpression of PD-L1, CD4+ and CD8+ cell infiltrates and tumor-infiltrating lymphocytes (TILs) in the microenvironment of actinic cheilitis and lower lip squamous cell carcinoma

Lower lip squamous cell carcinomas (LLSCC) could be associated with a previous history of potentially malignant oral diseases (PMOD), especially actinic cheilitis (AC), with high sun exposure being a well-described risk factor. Immune evasion mechanisms, such as the PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) pathway has been gaining prominence since immunotherapy with immune checkpoint inhibitors showed a positive effect on the survival of patients with different types of neoplasms. Concomitant with the characterization of the tumor microenvironment, the expression of either or both PD-1 and PD-L1 molecules may estimate mutual relations of progression or regression of the carcinoma and prognostic values of the patient. Objective: Considering the importance of tumor microenvironment characterization, this study aims to determine the immunoexpression of PD-L1 and correlate with the frequency of CD4+ and CD8+ cells in AC and LLSCC lesions and with tumor-infiltrating lymphocytes (TILs) in LLSCC and its relationship with histopathological characteristics. Methodology: This sample includes 33 cases of AC and 17 cases of LLSCC. The cases were submitted to histopathological analysis and to CD4+, CD8+, and PD-L1+ cell determination by immunohistochemistry. Results: There was a significant difference among the frequencies of CD4+, CD8+, and PD-L1+ cells between AC and LSCC cases, higher in the last group. Moreover, histopathological and atypical changes in AC and LLSCC were correlated with the frequencies of PD-L1+, CD4+, and CD8+ cells. In AC, PD-L1+ cases had a low frequency of CD4+ cells, but on the other hand, PD-L1+ cases of LLSCC had a higher frequency of CD4+ and CD8+ cells. Conclusion: Therefore, the PD-L1 molecule may be a potential escape route for the immune response in oral lesions, but the mechanisms differ between AC and LLSCC. Future studies related to immune evasion and immunotherapy in oral lesions should consider the analysis of inflammatory infiltrate and TILs

The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis

Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria. The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107–121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107–121) significantly reduced worm burden (48–50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107–121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis

Synergetic action of atorvastatin and fluconazole against fluconazole-resistant Candida albicans in vitro and in a murine model for intra-abdominal Candidiasis / Ação sinérgica da atorvastatina e fluconazol contra Candida albicans resistente ao fluconazol in vitro e em um modelo murino contra Candidíase intra-abdominal

Introduction: Candida albicans is the most common causative agent of Intra-abdominal Candidiasis (IAC) and it is resistant to most antifungal drugs currently available. Here we investigated atorvastatin in vitro and in vivo antifungal activities against a fluconazole-resistant C. albicans strain as a potential repurposed drug. The following tests were carried out: antifungal susceptibility tests to determine minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC), determination of time-kill curve, biofilm assays, Candida albicans yeast-hyphae transition inhibition assay, murine model of Intra-abdominal candidiasis, survival curve, fungal load quantification, histopathology analysis, quantification of TNF-α and IL-17 cytokines, quantification of N-acetyl-β-D-glucosaminidase. In vitro assays showed the synergetic action of atorvastatin and fluconazole against C. albicans growth and biofilm maturation while the time-kill curve assay revealed their fungicidal effect after 24 h of treatment. When yeast-to-hyphae transition was assessed, the synergetic effect of atorvastatin and fluconazole reduced C. albicans filamentation significantly. In vivo tests showed that one of the most noticeable signs of IAC is the intense systemic inflammation. However, our survival curve test showed that despite being ill, animals exhibited little to no clinical signs of systemic inflammation when treatment included a combination of atorvastatin and fluconazole. Altogether, these findings suggest that atorvastatin could be feasibly used in the treatment fluconazole-resistant C. albicans strains, showing that drug repurposing is an important strategy when considering the limited number of antifungal drugs available for treatment in addition to financial hardship experienced in research and development of new antifungal drugs.

Annona coriacea Mart. fractions promote cell cycle arrest and inhibit autophagic flux in human cervical cancer cell lines

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.e FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/ 2013—FP XII-BIOPLAT), Barretos Cancer Hospital, CAPES, CNPq, FAPEMIG, UFSJ. RMR is a recipient of CNPq Productivity Gran

ELABORAÇÃO DE AÇÃO EDUCATIVA SOBRE CÂNCER DE BOCA PARA ESCOLARES EM DIVINÓPOLIS, MINAS GERAIS: UM RELATO DE EXPERIÊNCIA

A ação educativa é essencial para consolidar a promoção de saúde na Atenção Primária, e tem grande potencial para melhorar os índices de saúde da população, desde que planejada, elaborada e executada segundo referencial teórico consistente. Este relato de experiência descreve todo o processo de elaboração de uma ação educativa sobre câncer de boca direcionada à escolares do 7º ao 9º ano do ensino fundamental das escolas municipais de Divinópolis, Minas Gerais. Os resultados deste estudo mostraram que cada fase – planejamento, revisão de literatura, estudo piloto com realização de pré-teste e pós-teste - foi essencial para garantir a qualidade da fase subsequente e, por conseguinte, da ação como um todo

Antibacterial activity of Baccharis trimera (Less.) DC. (carqueja) against bacteria of medical interest

Baccharis trimera (Less.) (Asteraceae), popularly know as "carqueja", is a species commonly used in folk medicine for the treatment or prevention of diseases. In this context, the purpose of this work was to study the antibacterial activity of crude hydroalcoholic extract from Baccharis trimera against Gram-positive bacterial strains (Staphylococcus aureus ATCC 29213, Staphylococcus saprophyticus ATCC 15305, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 19433) and Gram-negative bacteria (Escherichia coli EHEC ATCC 43895, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 27736, Salmonella typhi ATCC 19430) of clinical interest. Antibacterial susceptibility was evaluated by broth microdilution assay following the CLSI (formerly the NCCLS) guidelines. The extract from B. trimera showed antibacterial activity against Gram-positive bacteria and the most interesting result was obtained against S. epidermidis that presented Minimal Inhibitory Concentration of 250μg/mL. These results indicate that B. trimera have bacterisostatic potential against Gram-positive bacterial strains of medical interest and could serve as a base for further studies on the use of isolated compounds from this species as future antimicrobials

Expressão de metaloproteinases de matriz e de seus inibidores teciduais em carcinomas basocelulares

INTRODUÇÃO: Aproximadamente 80% das neoplasias malignas de pele não-melanomas são carcinomas basocelulares (CBC). Apesar das raras metástases, esses tumores são localmente agressivos. As metaloproteinases de matriz (MMPs), especialmente as MMP-2 e 9, são importantes no processo de invasão. Em contrapartida, os inibidores teciduais das MMPs (TIMPs) têm como principal função a inibição dessas enzimas. OBJETIVO: Investigar a associação de variáveis clinicopatológicas de pacientes portadores de CBC com a expressão de MMP-2, MMP-9, TIMP-1 e TIMP-2. MATERIAL E MÉTODOS: Foram selecionados 31 casos de CBC, sendo então obtidos, retrospectivamente, os dados referentes a idade, sexo e tamanho da lesão. Cortes histológicos das lesões foram submetidos a reação imuno-histoquímica pela técnica estreptavidina-biotina-peroxidase para detecção dos antígenos de interesse. Índices de imunomarcação foram construídos e comparados com os dados previamente obtidos. RESULTADOS: Observou-se correlação significativa entre idade e tamanho da lesão (R = 0,532; p = 0,008). Não foram observadas correlações significativas entre as outras variáveis e a expressão imuno-histoquímica dos antígenos de interesse. CONCLUSÃO: A expressão das metaloproteinases e de seus inibidores teciduais não parece ser influenciada pelos parâmetros investigados. Estudos adicionais são necessários para melhor compreensão de sua associação com o comportamento biológico do CBC