IL-6 treatment increases the survival of retinal ganglion cells in vitro: The role of adenosine A1 receptor

AbstractIL-6 is a pleiotropic cytokine classically denominated pro-inflammatory. It has been already demonstrated that IL-6 can increase the survival of retinal ganglion cells (RGC) in culture. In this work, we show that the trophic effect of IL-6 is mediated by adenosine receptor (A1R) activation. The neutralization of extracellular BDNF abolished the IL-6 effect and the treatment with IL-6 and CHA (an agonist of A1R) modulated BDNF expression as well as pCREB and pTrkB levels

Muscarinic receptors and chronic obstructive pulmonary disease: From Biology to clinical practice

A doença pulmonar obstrutiva crônica (DPOC) caracteriza-se por persistente e geralmente progressiva limitação do fluxo de ar associada com uma resposta inflamatória crônica nas vias aéreas e pulmões em resposta a partículas ou gases nocivos. A prescrição de medicamentos como os antimuscarínicos é um item importante para a reabilitação pulmonar em pacientes com DPOC porque melhoram os sintomas, particularmente a dispneia e a capacidade de fazer as atividades diárias. Há evidências de alguns estudos de que também reduzam a tendência a exacerbações. Não há evidências de que broncodilatadores reduzam complicações sistêmicas, comorbidades ou tenham influência sobre a mortalidade.The chronic obstructive pulmonary disease (COPD) is characterized by persistent and often progressive airflow limitation associated with a chronic severe inflammatory response in the airways and lungs in response to noxious particles or gases. The prescription of drugs such a muscarinic antagonist is an important step for pulmonary rehabilitation in patients with COPD because they improve symptoms, particularly dyspnea and the ability to do daily activities. There is evidence of some studies also tend to reduce exacerbations. There is no evidence that bronchodilators reduce systemic complications, comorbidities or have influence on mortality

Insulin-like growth factor-1 stimulates retinal cell proliferation via activation of multiple signaling pathways

Insulin-like growth factor-1 (IGF-1) plays critical roles in the development of the central nervous system (CNS), including the retina, regulating cell proliferation, differentiation, and survival. Here, we investigated the role of IGF-1 on retinal cell proliferation using primary cultures from rat neural retina. Our data show that IGF-1 stimulates retinal cell proliferation and regulates the expression of neurotrophic factors, such as interleukin-4 and brain-derived neurotrophic factor. In addition, our results indicates that IGF-1-induced retinal cell proliferation requires activation of multiple signaling pathways, including phosphatidylinositol 3-kinase, protein kinase Src, phospholipase-C, protein kinase C delta, and mitogen-activated protein kinase pathways. We further show that activation of matrix metalloproteinases and epidermal growth factor receptor is also necessary for IGF-1 enhancing retinal cell proliferation. Overall, these results unveil potential mechanisms by which IGF-1 ensures retinal cell proliferation and support the notion that manipulation of IGF-1 signaling may be beneficial in CNS disorders associated with abnormal cell proliferation

Psycho-Neuriendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. We discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host can also trigger changes in the brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in the endocrine and immune response in the periphery or in the central nervous system. The article highlights the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation in psychiatric issues.Si

Increased Cytokeratin 19 Fragment Levels Are Positively Correlated with Adenosine Deaminase Activity in Malignant Pleural Effusions from Adenocarcinomas

Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P=0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas

Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients’ survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain’s effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile