Plos One
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SLURP-1 is a secreted toxin-like Ly-6/uPAR protein found in epithelium, sensory neurons and immune cells. Point mutations in the slurp-1 gene cause the autosomal inflammation skin disease Mal de Meleda. SLURP-1 is considered an autocrine/paracrine hormone that regulates growth and differentiation of keratinocytes and controls inflammation and malignant cell transformation. ⋯ Contrary to rSLURP-1, other inhibitors of α7-nAChRs (mecamylamine, α-bungarotoxin and Lynx1) did not suppress the proliferation of keratinocytes. Moreover, the co-application of α-bungarotoxin with rSLURP-1 did not influence antiproliferative activity of the latter. This supports the hypothesis that the antiproliferative activity of SLURP-1 is related to 'metabotropic' signaling pathway through α7-nAChR, that activates intracellular signaling cascades without opening the receptor channel.
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Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. ⋯ We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil. Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy.
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To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. ⋯ Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance.
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Although production of polybrominated diphenyl ethers (PBDEs) is now banned, release from existing products will continue for many years. The PBDEs are assumed to be neurotoxic and toxic to endocrine organs at low concentrations. Their effect on the immune system has not been investigated thoroughly. We aimed to investigate the influence of DE-71 on cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with Escherichia Coli lipopolysaccharide (LPS) or phytohaemagglutinin-L (PHA-L). ⋯ We demonstrate an enhancing effect of DE-71 on cytokine production by normal human PBMCs stimulated with LPS or PHA-L ex vivo.
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To examine whether elevated anxiety and/or depressive symptoms are related to all-cause mortality in people with Type 2 diabetes, not using insulin. ⋯ Elevated depressive symptoms were associated with excess mortality risk in people with Type 2 diabetes not using insulin. No significant association with mortality was found among people with elevated anxiety symptoms. Having both elevated anxiety and depressive symptoms was not associated with mortality. The hypothesis that elevated levels of anxiety symptoms leads to behavior that counteracts the adverse health effects of Type 2 diabetes needs further investigation.