Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

New Oxazolidines Inhibit the Secretion of IFN-γ and IL-17 by PBMCS from Moderate to Severe Asthmatic Patients.

BACKGROUND: Moderate to severe asthma could be induced by diverse proinflammatory cytokines, as IL-17 and IFN-γ, which are also related to treatment resistance and airway hyperresponsiveness. Oxazolidines emerged as a novel approach for asthma treatment, since some chemical peculiarities were suggested by previous studies. OBJECTIVE: The present study aimed to evaluate the IL-17A and IFN-γ modulatory effect of two new oxazolidine derivatives (LPSF/NB-12 and -13) on mononucleated cells of patients with moderate and severe asthma. METHODS: The study first looked at potential targets for oxazolidine derivatives using SWISS-ADME. After the synthesis of the compounds, cytotoxicity and cytokine levels were analyzed. RESULTS: We demonstrated that LPSF/NB-12 and -13 reduced IFN-γ and IL-17 production in peripheral blood mononucleated cells from asthmatic patients in a concentrated manner. Our in silico analysis showed the neurokinin-1 receptor as a common target for both compounds, which is responsible for diverse proinflammatory effects of moderate and severe asthma. CONCLUSION: The work demonstrated a novel approach against asthma, which deserves further studies of its mechanisms of action.

Covid-19, the anti-vaccine movement and immunization challenges in Brazil: a review / Covid-19, o movimento anti-vacina e os desafios da imunização no Brasil: uma revisão

AIMS: The COVID-19 pandemic suddenly and significantly increased hospitalizations for pneumonia with systemic inflammatory disease. Since its appearance, COVID-19 has affected more than 200 countries, with more than 90 million cases and almost 2 million deaths. So far, there is no quality evidence regarding the specific pharmacological therapy for COVID-19; most treatments usually involve off-label use of existing drugs and have unproven efficacy. The global effort converges on the development of a vaccine; however, the greatest challenge is to achieve collective immunization in the face of increasing vaccination hesitancy. METHODS: This study investigated the impact of vaccine hesitancy movements on the goal of COVID-19 immunization in Brazil. An integrative bibliographic review was performed with an electronic search on PubMed and SciELO that yielded 13.535 articles. Inclusion and exclusion criteria were applied which included 29 interventional and descriptive studies. RESULTS: The results of the 29 studies revealed that the most frequent reasons for hesitation is skepticism about the true interests of the industry and politicians, the lack of trust in research, and inaccurate information on social media. CONCLUSION: The main factors that lead the population not to believe in vaccines were the real interests of industry and politicians, lack of confidence in research, and the amount of false information that circulates massively on social media and because of that it is possible that Brazil will face some challenges in achieving collective immunity due to the anti-vaccine movement.

OBJETIVOS: A pandemia de COVID-19 aumentou repentina e significativamente as hospitalizações por pneumonia com doença inflamatória sistêmica. Desde o seu surgimento, a COVID-19 afetou mais de 200 países, com mais de 90 milhões de casos e quase 2 milhões de mortes. Até o momento, não há evidências de qualidade em relação à terapia farmacológica específica para COVID-19; a maioria dos tratamentos geralmente envolve o uso off-label de medicamentos existentes e sem eficácia comprovada. O esforço global converge para o desenvolvimento de uma vacina; entretanto, o maior desafio é conseguir a imunização coletiva diante do aumento da recusa à vacinação. MÉTODOS: Este estudo investigou o impacto dos movimentos de recusa à vacina no objetivo de imunização com COVID-19 no Brasil. Foi realizada uma revisão bibliográfica integrativa com busca eletrônica no PubMed e SciELO que resultou em 13.535 artigos. Foram aplicados os critérios de inclusão e exclusão que incluíram 29 estudos de intervenção e descritivos. RESULTADOS: Os resultados dos 29 estudos revelaram que os motivos de hesitação mais frequentes são o ceticismo sobre os verdadeiros interesses da indústria e dos políticos, a falta de confiança em pesquisas e informações imprecisas nas redes sociais. CONCLUSÃO: Os principais fatores que levaram a população a não acreditar nas vacinas foram os reais interesses da indústria e dos políticos, a falta de confiança nas pesquisas e a quantidade de informações falsas que circulam massivamente nas redes sociais e por isso é possível que o Brasil enfrente alguns desafios para alcançar a imunidade coletiva devido ao movimento anti-vacinas.

Potential Therapeutic Agents Against Par-4 Target for Cancer Treatment: Where Are We Going?

One of the greatest challenges of cancer therapeutics nowadays is to find selective targets successfully. Prostate apoptosis response-4 (Par-4) is a selective tumor suppressor protein with an interesting therapeutic potential due to its specificity on inducing apoptosis in cancer cells. Par-4 activity and levels can be downregulated in several tumors and cancer cell types, indicating poor prognosis and treatment resistance. Efforts to increase Par-4 expression levels have been studied, including its use as a therapeutic protein by transfection with adenoviral vectors or plasmids. However, gene therapy is very complex and still presents many hurdles to be overcome. We decided to review molecules and drugs with the capacity to upregulate Par-4 and, thereby, be an alternative to reach this druggable target. In addition, Par-4 localization and function are reviewed in some cancers, clarifying how it can be used as a therapeutic target.