Cainpruitt7233

BACKGROUND AND AIMS Ischemic hepatitis (IH) following acute variceal bleed (AVB) carries an ominous prognosis. N-Acetylcysteine (NAC), a potent anti-oxidant, may prevent IH by improving tissue oxygen delivery and improving hepatic hypoxia. METHODS Consecutive cirrhotics with AVB were prospectively randomized to receive either standard of care (SOC) plus NAC intravenously for 72 h(at 150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, followed by 6.25 mg/kg for 67 h) (Group A, n = 107) or SOC alone (Group B, n = 107). RESULTS Baseline characteristics were comparable. IH developed more frequently in Gr.B 25(23%) than A-15(14%); p = 0.08). Incidence of IH increased with severity of liver disease. Binary logistic regression analysis showed reduced incidence of IH in Gr.A than B [odds ratio (OR) 0.33, 0.11-0.93] patients after controlling for other significant factors. The incidence of acute kidney injury (AKI) was also reduced in Gr.A [OR 0.34, 0.15-0.75]. Development of IH was significantly associated with increased deaths due to liver failure at 6 weeks [subdistribution hazard ratio (SHR) 21.6, 7.4-62.8]. On multivariate competing risk analysis, significantly lower deaths due to liver failure (SHR 0.33, 0.11-0.97) were noted in Gr.A than B. CONCLUSIONS One in five patients with acute variceal bleed develops ischemic hepatitis which is associated with worse outcomes. NAC therapy averts deaths due to liver failure by preventing IH and reduces AKI and is, therefore, recommended for cirrhotics with acute variceal bleed. TRIAL REGISTRATION Clinicaltrials.gov no NCT02015403.Hutchinson-Gilford progeria syndrome (HGPS), commonly called progeria, is an extremely rare disorder that affects only one child per four million births. It is characterized by accelerated aging in affected individuals leading to premature death at an average age of 14.5 years due to cardiovascular complications. The main cause of HGPS is a sporadic autosomal dominant point mutation in LMNA gene resulting in differently spliced lamin A protein known as progerin. Accumulation of progerin under nuclear lamina and activation of its downstream effectors cause perturbation in cellular morphology and physiology which leads to a systemic disorder that mainly impairs the cardiovascular system, bones, skin, and overall growth. Till now, no cure has been found for this catastrophic disorder; however, several therapeutic strategies are under development. The current review focuses on the overall progress in the field of therapeutic approaches for the management/cure of HGPS. We have also discussed the new disease models that have been developed for the study of this rare disorder. Moreover, we have highlighted the therapeutic application of extracellular vesicles derived from stem cells against aging and aging-related disorders and, therefore, suggest the same for the treatment of HGPS.Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Ex) are a promising tool for the repair of acute kidney injury (AKI) caused by cisplatin and ischemia/reperfusion. However, the roles of hucMSC-Ex in sepsis-associated AKI repair and its mechanism are largely unknown. Hence, we constructed a sepsis model through cecal ligation and puncture (CLP), testing the benefits of hucMSC-Ex in the sepsis in terms of survival rate, serum renal markers levels, morphological changes and apoptosis. Immunohistochemistry staining and immunofluorescence assay were used to investigate the role of NF-κB activity in the repair of sepsis-associated AKI with hucMSC-Ex. HK-2 cells were transfected with microRNA-146b (miR-146b) mimics and inhibitors, respectively, and the regulatory effect of miR-146b on NF-κB activity was studied. We found that hucMSC-Ex treatment significantly decreased the serum creatinine (Cr) and blood urea nitrogen (BUN) levels, ameliorated the morphological damage and inhibited renal tubular cells apoptosis. More importantly, the survival rate at 72 h was 28% in CLP group and 45% in hucMSC-Ex group, respectively. Selleck GSK1904529A Treatment with hucMSC-Ex improved survival in mice with sepsis. These effects of hucMSC-Ex were mediated by the inhibition of NF-κB activity and the lessening of pro-inflammatory response. Furthermore, hucMSC-Ex significantly increased miR-146b expression in kidney tissues. Conversely, interleukin (IL)-1 receptor-associated kinase (IRAK1) level, which is the target gene of miR-146b, clearly decreased in hucMSC-Ex group. In brief, this study showed that treatment with hucMSC-Ex decreased IRAK1 expression through the up-regulation of miR-146b level, led to the inhibition of NF-κB activity, and eventually alleviated sepsis-associated AKI and improved survival in mice with sepsis. HucMSC-Ex may be a novel therapeutic agent for the reduction of sepsis-associated AKI.OBJECTIVE Asthma is a chronic immune disease that has become a serious public health problem. The currently available medications are not ideal because of their limitations and side effects; hence, new target proteins and signaling cascades for precise and safe therapy treatment are needed. This work established an ovalbumin-induced asthma rat model and treated it with total flavonoid extract from the Xinjiang chamomile. The proteins that were differentially expressed in the chamomile extract-treated asthmatic rats and the asthma and healthy rat groups were identified using isobaric tagging followed by LC-MS/MS. Kyoto encyclopedia of genes and genomes pathway analysis of the differentially expressed proteins was performed. RESULTS Pathways involved in purine metabolism, herpes simplex infection, and JNK phosphorylation and activation mediated by activated human TAK1 were enriched, indicating the intrinsic links between the mechanism of asthma development and treatment effects. Furthermore, we constructed a protein-protein interaction network and identified KIF3A as a potential target protein of chamomile extract that affected the Hedgehog signaling pathway. CONCLUSIONS This study may provide new insights into the pathogenesis of asthma and reveal several proteins and pathways that could be exploited to develop novel treatment approaches.