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Comparative Effectiveness and Basic safety regarding Polyethylene Glycerin Electrolyte Answer Compared to Lactulose to treat Hepatic Encephalopathy: A Systematic Evaluate as well as Meta-analysis.
BACKGROUND Factor XII (FXII) is a plasma serine protease that initiates the intrinsic pathway of blood coagulation upon contact with anionic substances, such as the sulfated glycolipid sulfatide. Annexins (ANXs) have been implicated in the regulation of the blood coagulation reaction by binding to anionic surfaces composed of phospholipids and sulfated glycoconjugates, but their physiological importance is only partially understood. OBJECTIVE To test the hypothesis that ANXs are involved in suppressing the intrinsic pathway initiated by sulfatide, we examined the effect of eight recombinant ANX proteins on the intrinsic coagulation reaction and their sulfatide binding activities. METHODS Recombinant ANXs were prepared in Escherichia coli expression systems and their anticoagulant effects on the intrinsic pathway initiated by sulfatide were examined using plasma clotting assay and chromogenic assay. ANXA4 active sites were identified by alanine scanning and fold deletion in the core domain. RESULTS AND CONCLUSIONS We found that ANXA3, ANXA4, and ANXA5 strongly inhibited sulfatide-induced plasma coagulation. Wild-type and mutated ANXA4 were used to clarify the molecular mechanism involved in inhibition. ANXA4 inhibited sulfatide-induced auto-activation of FXII to FXIIa and the conversion of its natural substrate FXI to FXIa but showed no effect on the protease activity of FXIIa or FXIa. Alanine scanning showed that substitution of the Ca2+ -binding amino acid residue in the fourth fold of the core domain of ANXA4 reduced anticoagulant activity, and deletion of the entire fourth fold of the core domain resulted in complete loss of anticoagulant activity. This article is protected by copyright. All rights reserved.Saccharum spontaneum L. is one of the most important germplasm resources for modern sugarcane breeding. AlizarinRedS Exploring the cold tolerance of S. spontaneum clones with different ploidy levels and screening for cold-tolerant materials can be helpful in parent selection for breeding cold-tolerant sugarcane. Morphological indexes, leaf ultrastructure and physiological indexes were used to evaluate the cold tolerance of 36 S. spontaneum clones with different ploidy levels (2n=40, 48, 54, 60, 64, 78, 80, 88, 92 and 96). The morphological indexes of S. spontaneum clones with different ploidy levels were positively correlated with ploidy. Under low-temperature stress, the chloroplast and mitochondrial structures of the clones with high ploidy were more severely damaged than were those of clones with low ploidy. A comprehensive evaluation of the physiological indexes showed that the 36 S. spontaneum clones could be divided into four categories strongly cold tolerant, cold tolerant, moderately cold tolerant and cold sensitive. Correlation analysis of the morphological indexes and cold tolerance revealed a significant negative correlation between cold tolerance and ploidy. On the basis of the morphological and physiological indexes, optimal stepwise regression equations that can be used for the selection of cold-tolerant S. spontaneum resources were established. It was concluded that the S. spontaneum clones with low ploidy are more cold tolerant than those with high ploidy. Clones 12-37, 13-10 and 12-23 are strongly cold-tolerant germplasm resources, which suggests these germplasms have high potential for use in breeding cold-tolerant sugarcane. This article is protected by copyright. All rights reserved.BACKGROUND NASH is one of the fastest growing liver diseases that leads to severe steatosis, inflammation and ultimately liver injury. However, the pathophysiological mechanisms of NASH remain unclear and pharmacological treatment against the disease is unavailable currently. Ferroptosis is a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Since NASH progression is accompanied by massive lipid accumulation, which generates lipotoxic species, we investigated the role of ferroptosis in NASH progression. METHOD Mice were fed on MCD-diet to mimic NASH progression and gene expression in liver was analysed by RNA-seq. The occurrence of hepatic ferroptosis was measured by lipid ROS level, electron microscopy and in vivo PI staining. The beneficial effects of ferroptosis inhibitors on NASH was evaluated by liver pathology analysis. The mechanism of lipid ROS induced lipid droplets accumulation was investigated by in vitro cell culture. RESULTS RNA-seq analysis suggested that elevated arachidonic acid metabolism promotes ferroptosis in MCD-diet fed mouse livers, which was further demonstrated by lipid ROS accumulation, morphological change of mitochondria and increased cell death. Iron accumulation was detected in the liver and the serum of MCD-fed mice. Scavenging of ferroptosis-linked lipid peroxides reduced lipid accumulation both in vivo and in vitro. Importantly, ferroptosis inhibitors alleviated MCD-diet induced inflammation, fibrogenesis and liver injury. Finally, lipid ROS promotes liver steatosis by boosting lipid droplets formation. CONCLUSION Our results demonstrate an important role of ferroptosis in the progression of MCD-diet induced NASH and suggest that ferroptosis may serve as a therapeutic target for NASH treatment. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND Using data from the SOX Trial, we recently developed a clinical prediction model for occurrence of the post-thrombotic syndrome (PTS) after proximal deep vein thrombosis (DVT), termed the SOX-PTS score. The score includes anatomical extent of DVT; body mass index; and baseline Villalta score. OBJECTIVE To externally validate the SOX-PTS score. METHODS Logistic regression analysis of data from the ATTRACT Trial which evaluated pharmacomechanical catheter directed thrombolysis in patients with proximal DVT. The primary outcome was the occurrence of PTS (defined as Villalta score ≥ 5) from 6 to 24 months after DVT. Secondary outcomes included moderate-severe PTS (Villalta scale ≥ 10) and severe PTS (Villalta scale ≥ 14). Predictive performance was assessed by discrimination and calibration. An updated score was evaluated in an exploratory analysis. RESULTS 691 ATTRACT patients were included, of whom 328 (47%) developed PTS. The c-statistic was 0.63; 95% confidence interval (CI) 0.59-0.67 for PTS. The model's performance appeared to be better for the outcomes moderate to severe PTS and severe PTS (c-statistic 0.
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