Exploring the interplay between miRNAs, apoptosis and viral load, in Dengue virus infection.

Dengue virus (DENV) is a major global health concern, causing millions of infections annually. Understanding the cellular response to DENV infection is crucial for developing effective therapies. This study provides an in-depth analysis of the cellular response to Dengue virus (DENV) infection, with a specific focus on the interplay between microRNAs (miRNAs), apoptosis, and viral load across different DENV serotypes. Utilizing a variety of cell lines infected with four DENV serotypes, the research methodically quantifies viral load, and the expression levels of miRNA-15, miRNA-16, and BCL2 protein, alongside measuring apoptosis markers. Methodologically, the study employs quantitative PCR for viral load and miRNA expression analysis, and Western blot for apoptosis and BCL2 detection, with a statistical framework that includes ANOVA and correlation analysis to discern significant differences and relationships. The findings reveal that despite similar viral loads across DENV serotypes, DENV-2 exhibits a marginally higher load. A notable upregulation of miRNA-15 and miRNA-16 correlates positively with increased viral load, suggesting their potential role in modulating viral replication. Concurrently, a marked activation of caspases 3 and 7, along with changes in BCL2 protein levels, underscores the role of apoptosis in the cellular response to DENV infection. Conclusively, the study enhances the understanding of miRNA involvement in DENV pathogenesis, highlighting miRNA-15 and miRNA-16 as potential regulatory agents in viral replication and apoptosis. These findings pave the way for further exploration into miRNA-based therapeutic strategies against DENV infection.

Role of Bcl-2, p53, and Ki-67 expression in basal cell carcinoma and their association with aggressive and non-aggressive histological phenotypes.

Introduction: There is increasing evidence that immunohistochemical expression of p53, Ki-67, and Bcl-2 is associated with aggressive (aBCC) and less aggressive (nBCC) histological subtypes and may have a prognostic role. Aim: To investigate the clinicopathological features and immunohistochemical expressions of p53, Ki-67, and Bcl-2 in cutaneous basal cell carcinoma focusing on histological subtypes. Their roles and possible interactions in the development and progression of BCC are discussed. Material and methods: A total of 50 BCC samples from 50 patients from Western Mexico between June 2018 and June 2019 were included. Paraffin-embedded samples were immunostained with p53, Ki-67, and Bcl-2 antibodies. Semi-quantitative analysis was performed to determine the intensity and positivity of immunostained cells. Parametrical and non-parametrical tests were performed according to the sample's distribution. Results: Samples included 21 nBCC and 29 aBCC. The statistical analysis showed statistical association when grouped as non-aggressive and aggressive subtypes for p53 (p = 0.04) and Bcl-2 (p < 0.01). An inverse negative correlation was found between age and Bcl-2 expression. No statistical association was found between Ki-67 immunoreactivity and any of the other variables. Conclusions: We found that a high expression of Bcl-2 and a low expression of p53 was associated with more indolent histopathological features of BCC and therefore better outcomes. These findings suggest that examination of p53 and Bcl-2 expression in BCC patients may provide valuable prognostic information. These biomarkers may play a role in the development and progression of some cases of BCC.

Estudio descriptivo sobre Cáncer Colorrectal en Cova da Beira, Portugal y el valor pronóstico de BCL2 en asociación con la localización del tumor, Estadificación TNM, y tipo histológico / A descriptive study on Colorectal Cancer in Cova da Beira Portugal and the prognostic value of BCL2 in association with tumor location, TNM Staging, and histological type

Objetivo: realizar un estudio descriptivo sobre Cáncer Colorrectal en Cova da Beira Portugal y el valor pronóstico de BCL2 en asociación con la localización del tumor,Estadificación TNM, y tipo histológico. Materiales y Métodos: se realizó un estudio en 29 pacientes que tuvieron cirugía curativa para la escisión de Cáncer Colon Rectal (CCR) en Centro Hospitalario Cova da Beira con el objetivo de verificar si la presencia de la oncoproteína BCL2 en células neoplásicas es un factor predictivo del pronóstico,verificando también si es predictivo de la estadificación TNM, localización y diferenciación celular en el Cáncer Colon Rectal. Resultados: los hallazgos de este estudio coinciden con lo reportado en la literatura, se encontró que la incidencia del CCR es mayor en hombres que en mujeres, el riesgo de la enfermedad aumenta con la edad y la localización más frecuente de lesión neoplásica es en la porción izquierda del colon,con un total de 26 casos (89,65%). Además, se encontró asociación estadística de la expresión de BCL2 con el pronóstico y con la diferenciación histológica. Conclusión:a pesar de las limitaciones de este estudio, los datos hallados guardan relación con lo reportado en la literatura y establecen una asociación estadística de la expresión de BCL2 con el pronóstico y con la diferenciación histológica..(AU)

Objective: to carry out a descriptive study on Colorectal Cancer in Cova da Beira Portugal and the prognostic value of BCL2 in association with tumor location, TNM Staging, and histological type.Materials and Methods: a study was conducted in 29 patients who had curative surgery for Rectal Colon Cancer (CRC) excision in the Cova da Beira Hospital Center with the objective of verifying whether the presence of the BCL2 oncoprotein in neoplastic cells is a predictive factor of the prognosis, also verifying if it is predictive of TNM staging, localization and cell differentiation in Rectal Colon Cancer. Results: the findings of this study coincide with that reported in the literature,it was found that the incidence of CRC is higher in men than in women, the risk of the disease increases with age and the most frequent location of neoplastic lesion is in the left portion of the colon, with a total of 26 cases (89.65%). In addition, statistical association of BCL2 expression with prognosis and with histological differentiation was found. Conclusion: despite the limitations of this study, the data found are related to that reported in the literature and establish a statistical association of BCL2 expression with prognosis and histological differentiation..(AU)

Proteínas pro-apoptóticas y anti-apoptóticas como factores de pronóstico en Linfoma B difuso de célula grande en adultos / Pro-apoptotic and anti-apoptotic proteins as prognostic factors in diffuse large B-cell lymphoma in adults / Proteínas pró-apoptóticas e anti-apoptóticas como fatores de prognóstico no Linfoma B difuso de célula grande em adultos

Objetivo. El propósito de este estudio fue evaluar en pacientes con LBDCG la expresión de las proteínas anti-apoptóticas Bcl-2 y Bcl-X L y de las proteínas pro-apoptóticas Bad y Bax y su asociación con la supervivencia. Materiales y métodos. Se analizaron biopsias de 28 pacientes con diagnóstico de LBDCG. La expresión de los reguladores apoptóticos se evaluó mediante western blot. La asociación entre la expresión de las proteínas y la supervivencia fue analizada mediante el método de Kaplan-Meier y la prueba log-rank. Resultados. Las proteínas Bcl-2, Bak, Bad y Bcl-xL se encontraron expresadas en el 78,8%; 71,4%; 64,3% y 50% de los casos de LBDCG respectivamente. No encontramos asociación entre la presencia de las proteínas o sus niveles de expresión y la supervivencia total. La presencia de las proteínas Bad y Bcl-xL se asoció con una mayor supervivencia libre de enfermedad (33,3% vs. 20,0%, p LR test= 0,003; 42,9% vs. 14,3%, p LR test= 0,03 respectivamente). Niveles altos de expresión de Bad y de Bcl-X L se asociaron con una supervivencia libre de enfermedad mayor (35,7% vs. 21,4%, p LR test= 0,012 y 42,9% vs. 14,3%, p LR test= 0,045 respectivamente). Conclusión. Dado que la expresión de la proteína Bad en los tumores se asoció con una mayor supervivencia libre de enfermedad, los pacientes con bajos niveles de expresión de esta proteína podrían ser beneficiados en un futuro con terapias orientadas a inhibir las moléculas anti apoptóticas Bcl-xL y Bcl-2 mediante el empleo de moléculas que se unen específicamente al dominio BH3.

Objective. Our purpose was to evaluate the expression of antiapoptotic proteins Bcl-2 and Bcl-xL, and pro-apoptotic proteins Bad and Bax and their association with survival, in patients with DLBCL. Materials and methods. We analyzed biopsies from 28 patients diagnosed with DLBCL. The expression of the apoptotic regulators was assessed by western blot. The association between protein expression and survival was analyzed by the Kaplan-Meier method and the log-rank test. Results. Bcl-2, Bak, Bad and Bcl-xL proteins were expressed in 78.8, 71.4, 64.3 and 50% of the DLBCL cases, respectively. We found no association between the presence of proteins or their expression levels and overall survival. Both Bad and Bcl-xL were associated with higher disease-free survival (33.3% vs. 20.0%, p LR test= 0,003; 42.9% vs. 14.3%, p LR test= 0.03, respectively). High expression levels of Bad and Bcl-xL were associated with a higher disease-free survival (35.7% vs. 21.4%, p LR test= 0.012 y 42.9% vs. 14.3%, p LR test= 0.045, respectively). Conclusion. Given that expression of the Bad protein in tumors was related to a higher disease-free survival, patients with low expression levels of Bad could be candidates in future therapies oriented towards the inhibition of the anti-apoptotic proteins Bcl-xL and Bcl-2 by using molecules that bind specifically to the BH3 domain.

Objetivo. O objetivo deste estudo foi avaliar em pacientes com LBDCG a expressão das proteínas anti-apoptótica Bcl-2 e Bcl-X L e das proteínas pró-apoptóticas Bad e Bax e sua associação com a sobrevivência. Materiais e métodos. Foram analisadas biópsias de 28 pacientes com diagnóstico de LBDCG. A expressão de reguladores de apoptose foi avaliada por Western blot. A associação entre a expressão das proteínas e a sobrevivência foi analisada pelo método de Kaplan-Meier e o teste log-rank. Resultados. As proteína Bcl-2, Bak, Bad e Bcl-xL foram expressas em 78,8%, 71,4%, 64,3% e 50% dos casos de LBDCG, respectivamente. Nós não encontramos associação entre a presença das proteínas ou de seus níveis de expressão e a sobrevivência total. A presença das proteínas Bad e Bcl-xL foi associada à maior sobrevivência livre da doença (33,3% vs. 20,0%, p LR teste= 0,003; 42,9% vs. 14,3%, p LR teste= 0,03, respectivamente). Altos níveis de expressão de Bad e de Bcl-X L foram associados com uma sobrevivência livre da doença maior (35,7% vs. 21,4%, p LR teste= 0,012 e 42,9% vs. 14,3%, p LR teste= 0,045, respectivamente). Conclusão. Uma vez que a expressão da proteína Bad em tumores foi associada com uma maior sobrevivência livre de doença, os pacientes com baixos níveis de expressão dessa proteína poderiam ser beneficiados num futuro com terapias orientadas a inibir as moléculas anti-apoptóticas Bcl-xL e Bcl-2 utilizando moléculas que se ligam especificamente ao domínio BH3.

The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.

The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.