Thompsongomez5287

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease, representing the most aggressive breast cancer (BC) subtype with limited treatment options due to a lack of estrogen receptor alpha (ERα), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2/neu) expression. Estrogen receptor beta (ERβ) is present in a fraction of TNBC patients, where its expression correlates with improved patient outcomes, supported by the fact that it exerts oncosuppressive effects in TNBC cell models in vitro. GKT137831 ERβ is involved in microRNA-mediated regulation of gene expression in hormone-responsive BC cells and could mediate its actions through small noncoding RNAs (sncRNAs) in TNBCs also. To verify this possibility, smallRNA sequencing was performed on three ERβ-expressing cell lines from different TNBC molecular subtypes. Several sncRNAs resulted modulated by ERβ, with a subset being regulated in a tumor subtype-independent manner. Interestingly, sncRNA profiling of 12 ERβ+and 32 ERβ- primary TNBC biopsies identified 7 microRNAs, 1 PIWI-interacting RNA (piRNA), and 1 transfer RNA (tRNA) differentially expressed in ERβ+ compared to ERβ- tumors and cell lines. Among them, miR-181a-5p was found to be overexpressed in ERβ+ tumors and predicted target key components of the cholesterol biosynthesis pathway previously found to be inhibited by ERβ in TNBC cells.Scrophularia tenuipes is an Algerian-Tunisian endemic species, which has not been studied yet. Ethyl acetate (EA) and n-butanol (Bu) fractions obtained from Scrophularia tenuipes were investigated for their health benefit properties, in particular with respect to in vivo/in vitro anti-inflammatory and antioxidant activities, as well as their potential to inhibit key enzymes with impact in diabetes (α-glucosidase and α-amylase). The fractions had a distinct phytochemical composition, of which EA was richer in total phenolic compounds (225 mg GAE/g) and mostly composed of the phenylethanoid acetyl martynoside. Compared to EA, Bu had higher amounts of total flavonoids, and according to the result obtained from UHPLC-DAD-ESI-MSn analysis, harpagoside (iridoid) was its major phytochemical. EA fraction was quite promising with regard to the in vivo (at 200 mg/kg, po) anti-inflammatory effect (62% and 52% for carrageenan-induced rat paw edema and xylene-induced ear edema tests, respectively), while Bu fraction exhibited a stronger antioxidant capacity in all tests (IC50 = 68 µg/mL, IC50 = 18 µg/mL, IC50 = 18 µg/mL and A0.50 = 43 µg/mL for DPPH●, ABTS•+, O2•- scavenging assays and cupric-reducing antioxidant capacity method, respectively). Both fractions also showed a strong effect against α-amylase enzyme (IC50 = 8 µg/mL and 10 µg/mL for EA and Bu fraction, respectively).Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.Schistosomiasis is a neglected tropical disease caused by parasitic blood flukes of the genus Schistosoma, which kills 300,000 people every year in developing countries, and there is no vaccine. Recently, we have shown that cholinesterases (ChEs)-enzymes that regulate neurotransmission-from Schistosoma mansoni are expressed on the outer tegument surface and present in the excretory/secretory products of larval schistosomula and adult worms, and are essential for parasite survival in the definitive host, highlighting their utility as potential schistosomiasis vaccine targets. When treated in vitro with anti-schistosome cholinesterase (SmChE) IgG, both schistosomula and adult worms displayed significantly decreased ChE activity, which eventually resulted in parasite death. Vaccination with individual SmChEs, or a combination of all three SmChEs, significantly reduced worm burdens in two independent trials compared to controls. Average adult worm numbers and liver egg burdens were significantly decreased for all vaccinated mice across both trials, with values of 29-39% and 13-46%, respectively, except for those vaccinated with SmAChE1 in trial 1. Egg viability, as determined by egg hatching from liver homogenates, was significantly reduced in the groups vaccinated with the SmChE cocktail (40%) and SmAChE2 (46%). Furthermore, surviving worms from each vaccinated group were significantly stunted and depleted of glycogen stores, compared to controls. These results suggest that SmChEs could be incorporated into a vaccine against schistosomiasis to reduce the pathology and transmission of this debilitating disease.The underlying factors contributing to metatarsophalangeal joint deformity, a known precursor to skin breakdown in individuals with diabetes mellitus (DM), is likely to involve multiple body systems. The purpose of this cross-sectional study was to identify multi-system factors associated with metatarsophalangeal joint deformity in individuals with type 2 DM and peripheral neuropathy (n = 60). Metatarsophalangeal joint deformity was quantified with a computed tomography (CT) scan. System biomarkers included the musculoskeletal system (foot intrinsic muscle deterioration, tarsal/metatarsal bone mineral density, ankle dorsiflexion, metatarsophalangeal extension movement during a sit to stand task); the vascular system (ankle-brachial index); and the endocrine/immune systems (high sensitivity C-reactive protein, skin intrinsic fluorescence, and hemoglobin A1C). Muscle deterioration (r = 0.27), bone density (r = -0.35), metatarsophalangeal extension movement (r = 0.50), maximum dorsiflexion (r = -0.31), and ankle-brachial index (r = 0.