Bro Acosta (heliumcorn35)

BACKGROUND MicroRNAs (miRNAs) are a class of critical epigenetic regulators involved in several autoimmune diseases. Our previous study reported an miR-326-induced increase in T helper (Th) 17 cells in a mouse model of Hashimoto's thyroiditis (HT), but the pathogenic effect of miR-326 in HT patients has not been verified. The goal of the present study was to explore the pathogenic role of miR-326 and its underlying molecular mechanism in HT patients. METHODS A total of 58 HT patients and 55 normal controls were enrolled in this study. We examined whether Th17 cells and miR-326 were aberrantly altered in the peripheral blood mononuclear cells (PBMCs) of HT patients with flow cytometry and real-time PCR. Levels of membrane IL-23R (mIL-23R) were determined by flow cytometry and western blot to explore the critical role of mIL-23R in the development of Th17 cells. Isolated CD3+ T cells were employed to further investigate the ectodomain shedding of mIL-23R by a disintegrin and metalloprotease (ADAM17). Furthermore, miR-326 inhibitor and mimics were transfected into PBMCs derived from HT patients and healthy controls to verify the regulation of ADAM17 by miR-326. RESULTS We observed elevated miR-326 levels in the PBMCs of HT patients compared with those in the PBMCs of healthy controls. Consistent with IL-23-induced STAT3 overactivation, substantially more HT patient-derived PBMCs differentiated into Th17 cells under polarization culture conditions, which may, at least in part, have resulted from enhanced membrane IL-23R (mIL-23R) levels. Furthermore, ADAM17, an ectodomain sheddase of mIL-23R, was targeted and negatively regulated by miR-326. Inhibiting ADAM17 might attenuate the ectodomain shedding of mIL-23R. CONCLUSIONS Our findings suggest that the effect of miR-326 on the IL-23/IL-23R/Th17 cell axis in HT patients might be partially due to the targeting of ADAM17.Keratin-based drug carriers have attracted great interest due to their intrinsic biocompatibility and tumor micro-environmental responsiveness. In the study, keratin was first extracted from human hair with reduction method. The reduced keratin was successively conjugated with poly(ethylene glycol) (PEG) via thiol Michael addition reaction and iodoacetic acid (IAA) via substitution reaction to impart both physical stability and acidity responsiveness. Subsequently, the conjugated keratin was fabricated into micelles and loaded with doxorubicin (DOX) by self-assembly. The micelles exhibited pH, glutathione (GSH) and enzyme (trypsin) triple-responsiveness as well as charge reversibility under the simulated tumor microenvironment. These drug-loaded micelles exhibited high toxicity against A549 cells with low side effect on normal cells. Furthermore, anticancer efficacy in vivo revealed DOX-loaded micelles presented higher therapeutic efficiency than free DOX. Moreover, these micelles were stable under physiological conditions, and could be internalized through endocytosis without hemolysis. Based on the results, the drug-loaded micelles were satisfactory candidates for drug carriers.The treatment of pharmaceutical industrial wastewaters containing the antibiotic amoxicillin (218.29 mg L-1), via some advanced oxidation processes (POA), was studied. CX-5461 in vivo The H2O2 photolysis process presented the highest percentage of mineralization (97%), after the total reaction time (180 minutes). However, the photo-Fenton process showed the highest organic carbon removal rate, mineralizing 65% of the initial concentration, in 30 minutes. Because this fact, this process was studied in more detail. The initial concentration of ferrous ions (0.03 - 1.00 mmol L-1) did not affect the performance of the photo-Fenton process, being possible operating using concentrations below of 15 mg L-1 (0.27 mmol L-1), that is the iron content limit for discharging wastewaters established in the Brazilian environmental legislation. Furthermore, experiments were performed according to the com