Translational research : the journal of laboratory and clinical medicine
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Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor highly expressed in coronary plaques, particularly in macrophages, and in activated platelets. Thus, a possible role in the pathogenesis of acute coronary syndrome (ACS) has been suggested. We evaluated systemic BDNF levels according to the different clinical presentations of ACS. ⋯ At multivariate regression analysis BDNF levels independently predicted the presence of MØI (odds ratio [OR] = 2.856; 95% confidence interval [CI] [1.151-7.090], P = 0.024) and the absence of healed plaques (OR = 0.438, 95% CI [0.185-0.992], P= 0.050). Among ACS patients, BDNF levels were higher in patients with STEMI. Moreover, BDNF levels were independently associated with MØI and with the absence of healed plaques along the culprit vessel, suggesting a possible role of BDNF in promoting plaque inflammation, destabilization and occlusive thrombosis.
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Gastric cancer (GC) is a highly prevalent malignancy featured by dismal oncological outcomes. Accumulating pieces of evidence have consensus over the therapeutic significance of extracellular vesicles (EVs) and its role in carcinogenesis. Here, we planned to uncover EVs' role in GC by shuttling microRNA-1290 (miR-1290) and to identify the possible molecular mechanism associated with Grhl2, PD-L1, and ZEB1. ⋯ Moreover, we also developed a mouse model of GC and injected the EVs derived from miR-1290-inhibitor-treated GC cells into the tumor-bearing mice for further validation of mechanism in vivo. Intriguingly, the pivotal role of EVs-shuttled miR-1290 as an oncomiR was demonstrated in vivo. Collectively, we found that miR-1290 in EVs secreted from GC cells contributed to immune escape through the Grhl2/ZEB1/PD-L1 axis.
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Obesity has become a common rising health care problem, especially in "modern" societies. Obesity is considered a low-grade systemic inflammation, partly linked to leaky gut. Circadian rhythm disruption, a common habit in modern life, has been reported to cause gut barrier impairment. ⋯ Analysis of gut microbiota and their metabolites, as important regulators of barrier homeostasis, revealed that abnormal food timing reduced relative abundance of butyrate-producing bacteria, and the colonic butyrate level. Overall, our data supported that dysbiosis was characterized by increased intestinal permeability and decreased beneficial barrier butyrate-producing bacteria and/or metabolite to mechanistically link the time of eating to obesity. This data provides basis for noninvasive microbial-targeted interventions to improve intestinal barrier function as new opportunities for combating circadian rhythm disruption induced metabolic dysfunction.
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Diabetes mellitus (DM) is a devastating metabolic disease. Recently, the cross-talk between insulin-secreting-β-cells and various organs has sparked much interest. SerpinB1 emerged as a novel hepatokine inducing β-cell proliferation. ⋯ Higher serum serpinB1 levels were found to be associated with lower susceptibility for T2DM. Conclusively, serpinB1 is associated with various aspects of β-cell dysfunction, glycemic-control, and dyslipidemia with a possible role in β-cell compensation in obese nondiabetic subjects. The results of the current study shed lights on potential novel roles of serpinB1 in T2DM besides its action as an inducer for β-cell proliferation.
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Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. ⋯ The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.