Piezo1 suppression reduces demyelination after intracerebral hemorrhage

Piezo1 is a mechanically-gated calcium channel.Recent studies have shown that Piezo1,a mechanically-gated calcium channel,can attenuate both psychosineand lipopolysaccharide-induced demyelination.Because oligodendrocyte damage and demyelination occur in intracerebral hemorrhage,in this study,we investigated the role of Piezo1 in intracerebral hemorrhage.We established a mouse model of cerebral hemorrhage by injecting autologous blood into the right basal ganglia and found that Piezo1 was largely expressed soon(within 48 hours)after intracerebral hemorrhage,primarily in oligodendrocytes.Intraperitoneal injection of Dooku1 to inhibit Piezo1 resulted in marked alleviation of brain edema,myelin sheath loss,and degeneration in injured tissue,a substantial reduction in oligodendrocyte apoptosis,and a significant improvement in neurological function.In addition,we found that Dooku1-mediated Piezo1 suppression reduced intracellular endoplasmic reticulum stress and cell apoptosis through the PERK-ATF4-CHOP and inositol-requiring enzyme 1 signaling pathway.These findings suggest that Piezo1 is a potential therapeutic target for intracerebral hemorrhage,as its suppression reduces intracellular endoplasmic reticulum stress and cell apoptosis and protects the myelin sheath,thereby improving neuronal function after intracerebral hemorrhage.

Metabolic syndrome and gallstone disease

AIM:To investigate the association between metabolic syndrome(MetS) and the development of gallstone disease(GSD).METHODS:A cross-sectional study was conducted in 7570 subjects(4978 men aged 45.0 ± 8.8 years,and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital.The subjects included 918 patients with gallstones(653 men and 265 women) and 6652 healthy controls(4325 men and 2327 women) without gallstones.Body mass index(BMI),waist circumference,blood pressure,fasting plasma glucose(FPG) and serum lipids and lipoproteins levels were measured.Colorimetric method was used to measure cholesterol,high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C).Dextrose oxidizing enzyme method was used to measure FPG.Subjects were asked to complete a questionnaire that enquired about the information on demographic data,age,gender,histories of diabetes mellitus,hypertension,and chronic liver disease and so on.Metabolic syndrome was diagnosed according to the Adult Treatment Panel Ⅲ(ATP Ⅲ) criteria.Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.RESULTS:Among the 7570 subjects,the prevalence of the gallstone disease was 12.1%(13.1% in men and 10.2% in women).BMI,waist circumference,systolic blood pressure,diastolic blood pressure,fasting blood glucose and serum triglyceride(TG) in cases group were higher than in controls,while serum high-density lipid was lower than in controls.There were significant differences in the waist circumference,blood pressure,FPG and TG between cases and controls.In an ageadjusted logistic regression model,metabolic syndrome was associated with gallstone disease.The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95% confidence interval(CI),1.09-1.52;P = 0.0030],and 1.68(95% CI,1.26-2.25;P = 0.0004) in women;the overall age-adjusted odds ratio of MetS for GSD was 1.42(95% CI,1.23-1.64;P < 0.0001).The men with more metabolic disorders had a higher prevalence of gallstone disease,the trend had statistical significance(P < 0.0001).The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times(P < 0.0001).The prevalence of GSD in women who had 5 components of MetS was 5 times higher than in those without MetS component.The more the components of MetS,the higher the prevalence of GSD(P < 0.0001).The presence of 5 components of the MetS increased the risk of gallstone disease by 4.0 times.CONCLUSION:GSD appears to be strongly associated with MetS,and the more the components of MetS,the higher the prevalence of GSD.

XPC Polymorphism Increases Risk of Digestive System Cancers:Current Evidence from A Meta-Analysis

Objective： Xeroderma pigmentosum complementation group C （XPC） participates in the initial recognition of DNA damage during nucleotide excision repair process in global genomic repair. Our meta-analysis was performed to evaluate the association between three polymorphisms （Lys939Gln, PAT＋/- and Ala499Val） of XPC gene and risk of digestive system cancers. Methods： All the relevant case-control studies published to April 2011 were identified through searching PubMed. Digestive system cancer risk with the three polymorphisms was estimated for each study by odds ratio （OR） with its 95% confidence interval （95% CI）. Results： We found an increased overall risk for digestive system cancers in all three models of Lys939Gln AC （AC/CC vs. AA： OR, 1.20; 95% CI, 1.11-1.30; CC vs. AC/AA： OR, 1.24; 95% CI, 1.11-1.39; CC vs. AA： OR, 1.36; 95% CI, 1.21-1.53）. When strati？ed by ethnicity, results remained significant in Asian population （AC/CC vs. AA： OR, 1.18; 95% CI, 1.02-1.37; CC vs. AC/AA： OR, 1.32; 95% CI, 1.1-1.51; CC vs. AA： OR, 1.35; 95% CI, 1.08-1.70）, but not for Caucasians. However for Ala499Val CT, a significant protective effect of T allele was only observed in the dominant model. Otherwise, no significant results were observed for PAT＋/-. Conclusion： XPC Lys939Gln AC polymorphism may play an important role in digestive system cancer susceptibility.

Association of CASP9,CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population

The initiators caspase-9(CASP9) and caspase-10(CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis.This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer(CRC) susceptibility in a population-based study.A two-stage designed population-based case-control study was carried out,including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls.A total of eight tag selected single nucleotide polymorphisms(SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information(NCBI) datasets and genotyped by restriction fragment length polymorphism(RFLP) assay.Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk.In the first stage,from eight tag SNPs,three polymorphisms rs4646077(odds ratio(OR) AA+AG:0.654,95% confidence interval(CI):0.406-1.055;P=0.082),rs4233532(OR CC:1.667,95% CI:0.967-2.876;OR CT:1.435,95% CI:0.998-2.063;P=0.077),and rs2881930(OR CC:0.263,95% CI:0.095-0.728,P=0.036) showed possible association with CRC risk.However,none of the three SNPs,rs4646077(OR AA+AG:1.233,95% CI:0.903-1.683),rs4233532(OR CC:0.892,95% CI:0.640-1.243;OR CT:1.134,95% CI:0.897-1.433),and rs2881930(OR CC:1.096,95% CI:0.620-1.938;OR CT:1.009,95% CI:0.801-1.271),remained significant with CRC risk in the validation set,even after stratification for different tumor locations(colon or rectum).In addition,never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set(OR:1.755,95% CI:1.319-2.334).Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration.In addition,tea drinking was a protective factor for CRC.