Role of pyroptotic cell death in the pathogenesis of NASH

Nonalcoholic fatty liver disease(NAFLD)represents a huge threat to public health of the whole world.Around 25%of NAFLD patients will progress to nonalcoholic steatohepatitis(NASH),which has been predicted to be the main reason for liver transplantation in the United States in 2020.Extensive effort has been devoted to investigating the underlying molecular mechanisms of NASH pathogenesis and developing new promising treatments.Recent studies have demonstrated that pyroptosis,an inflammatory programmed cell death mediated by inflammasome and gasdermin-D(GSDMD),is involved in the development and progression of NASH.This review aims to summarize the recent findings regarding the role of pyroptosis and related molecules in the pathogenesis of NASH.

Differentiation of gestational diabetes mellitus by nuclear magnetic resonance-based metabolic plasma analysis

This study aimed to investigate the metabolic profile of gestational diabetes mellitus(GDM)at both antepartum and postpartum periods.Seventy pregnant women were divided into three groups:the normal glucose-tolerant group(NGT,n=35),the abnormal glucose-tolerant groups without insulin therapy(A1GDM,n=24)or with insulin therapy(A2GDM,n=11).Metabolic profiles of the plasma were acquired by proton nuclear magnetic resonance(1H-NMR)spectroscopy and analyzed by multivariate statistical data analysis.The relationship between demographic parameters and the potential metabolite biomarkers was further explored.Group antepartum or postpartum showed similar metabolic trends.Compare with those of the NGT group,the levels of 2-hydroxybutyrate,lysine,acetate,glutamine,succinate,tyrosine,formate,and all three BCAAs(leucine,valine,isoleucine)in the A2GDM group were increased dramatically,and the levels of lysine,acetate,and formate in the A1GDM group were elevated significantly.The dramatically decreased levels of 3-methyl-2-oxovalerate and methanol were observed both in the A1GDM group and A2GDM group.Compare to the A1GDM group,the branched-chain amino acids(BCAAs)of leucine,valine,and isoleucine were increased dramatically in the A2GDM group.The levels of aromatic amino acids(AAAs),tyrosine and phenylalanine,were significantly increased in GDM women,consistent with the severity of GDM.Interference of amino acid metabolism and disturbance in energy metabolism occurred in women with different grades of GDM.Metabolic profiles could reflect the severity of GDM.Plasma BCAA concentrations showing strong positive correlations with weight and pre-delivery BMI.This study provides a new perspective to understand the pathogenesis and etiology of GDM,which may help the clinical management and treatment of GDM.

~1H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic changes of gastrodin intervention in rats

Objective:To explore^1H nuclear magnetic resonance-based metabolomics on sex-specific metabolic changes of gastrodin intervention in rats.Methods:In this research,~1H NMR-based metabolomics was used for the first time to investigate metabolic changes following chronic intervention with gastrodin in rats.Results:24 endogenous metabolites were identified.Body weight.daily diet and the total volume of urine in in each day of each rat were measured synchronously.Modifications in 12 metabolites were observsd following gastrodin intervention,indicating gastrodin-induced alterations in carbohydrate and energy metabolism.Interestingly,these metabolic changes were not totally identical in female and male rats.Some metabolic changes arising from gastrodin intervention showed sexual dimorphism including LDL/VLDL and lactate which were on the decrease in the female but on the increase in the male,together with arginine/ornithine,creatine,and glycerol which were on the increase in the female but on the decrease in the male.While the decrease in pyruvate,succinate and glutamate was only shown in the male and the increase in valine,α-ketoglutarate and glucose was only in the female.Conclusions:This resesrch shows the sex-specific metabolic response to GAS intervention,weather GAS is a healthy dietary supplement for the male merits further

Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats

Benign prostatic hyperplasia(BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate(TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg×kg^(-1) for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone(DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.

A wave of Foxp3^(+) regulatory T cell accumulation in the neonatal liver plays unique roles in maintaining self-tolerance

Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period.Regulatory T cells(Tregs)are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses.The features of Tregs in the neonatal liver under steady-state conditions are not well understood.The present study aimed to investigate the phenotype,functions,and significance of neonatal Tregs in the liver.We found a wave of thymus-derived Treg influx into the liver during 1–2 weeks of age.Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder.More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation,and the liver Tregs acquired stronger suppressive functions.The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγand T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses.The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.

在土壤杆菌ZX09中透明颤菌血红蛋白的表达提高索拉胶的产量(英文)

研究目的:提高胞外多糖索拉胶的产量。创新要点:透明颤菌血红蛋白基因在质粒上表达,不加抗生素发酵生产索拉胶。研究方法:将透明颤菌血红蛋白基因构建到广谱质粒pCM158上得到重组质粒pCM158-vgb,重组质粒转入土壤杆菌ZX09中,使透明颤菌血红蛋白在土壤杆菌ZX09中表达。重要结论:在土壤杆菌ZX09中颤菌血红蛋白的表达解决了发酵过程中氧受限的问题,提高了宿主菌的呼吸速率、蔗糖酶活性和黏度,将发酵产物索拉胶的产量提高了30%。