Int J Med Sci
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Background: Estrogens are involved in glycemic regulation, playing an important role in the development and/or progression of insulin resistance. For that, estrogens regulate the expression of the glucose transporter protein GLUT4 (codified by the solute carrier family 2 member 4 gene, Slc2a4), thus modulating adipose and muscle glucose disposal. This regulation is a balance between ESR1-mediated enhancer effect and ESR2-mediated repressor effect on Slc2a4 gene. ⋯ Conclusions: ESR1 activation in adipocytes increased the nuclear content of SP1 protein, the SP1/ESR1 interaction and SP1 binding into the Slc2a4 gene promoter, culminating with increased Slc2a4/GLUT4 expression. No involvement of SP1 seems to occur in ESR2-mediated repressor effect on Slc2a4. We expect that this ESR1/SP1 cooperative effect can contribute to the development of new approaches for prevention or treatment of insulin resistance and diabetes mellitus.
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Background: The study examined the difference in the expression of the receptor for activated C kinase 1 (RACK1) between anaesthesia with propofol and isoflurane in rats with myocardial ischemia-reperfusion injury (IRI). Methods: Male Sprague-Dawley rats were studied. Anaesthesia was induced with xylazine 20 µg/g by intraperitoneal injection and maintained with propofol or isoflurane. ⋯ However, the heart injury scores in the two groups did not differ significantly (3.56 ± 0.29 vs. 4.33 ± 0.23 in the propofol and isoflurane groups, respectively, p=0.33). Conclusion: There were significant differences in inflammation and apoptosis, including the expression of RACK1 and TLR4, after myocardial IRI between the propofol and isoflurane groups. However, both groups had similar heart injury scores.
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Autophagy is a catabolic process to maintain intracellular homeostasis via removal of cytoplasmic macromolecules and damaged cellular organelles through lysosome-mediated degradation. Trehalose is often regarded as an autophagy inducer, but we reported previously that it could prevent ischemic insults-induced autophagic death in neurons. Thus, we further investigated in this study whether trehalose could protect human dopaminergic SH-SY5Y cells against H2O2-induced lethal autophagy. ⋯ Notably, we found that trehalose inhibited H2O2-induced increase of intracellular ROS and reduction in the activities of CAT and SOD. Consistently, our data revealed as well that mitigation of intracellular ROS levels with antioxidant NAC markedly attenuated H2O2-induced AMPK activation and ER stress. Therefore, we demonstrated in this study that trehalose prevented H2O2-induced autophagic death in SH-SY5Y cells via mitigation of ROS-dependent endoplasmic reticulum stress and AMPK activation.
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Cardiac glycosides are natural compounds used for the treatment of congestive heart failure and cardiac arrhythmias. Recently, they have been reported to exhibit anticancer activity. Proscillaridin A (PSN-A), a cardiac glycoside constituent of Urginea maritima has been shown to exhibit anticancer activity. ⋯ Of note, LNCaP cells were found to be more sensitive to PSN-A treatment as compared to DU145 cells. Taken together, the data provided first evidence of the anticancer activity and possible molecular mechanism of PSN-A in prostate cancer. Further study is needed to develop PSN-A into a potential lead compound for the treatment of prostate cancer.
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Chemotherapy is one of effective methods for the treatment of tumor. Patients often develop drug resistance after chemotherapic cycles. Salmonella has potential as antitumor agent. ⋯ In addition, Salmonella significant reduced the protein express the expression levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), and phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells. The Salmonella-induced downregulation of P-gp was rescued by transfection of cells with active P-AKT. Our results demonstrate that Salmonella in tumor sites leads to decrease the expression of P-gp and enhances the combination of Salmonella and 5-Fluorouracil therapeutic effects.