Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of sever...Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese population.Methods A total of 714 Chinese participants with persistent HBV infection were studied.Patients were divided into cirrhotic(n=429)and non-cirrhotic(n=285)groups based on clinical and pathological evidence.The progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score system.Genotypes of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic subjects.The association between the risk of SNPs and the severity and progression rate of cirrhosis was further analyzed.Results Rs2679757 polymorphism of the antizyme inhibitor 1(AZIN1)gene and Rs886277 in the transient receptor potential cation channel subfamily M,member 5 gene(TRPM5)were found to be associated with cirrhosis risk in CHB.They were also correlated with the overall severity and progression rate of cirrhosis.Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups.Conclusions AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese patients.The emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups,and merit mechanistic studies to reveal their roles in fibrosis progression.展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
基金supported by Shanghai Pujiang Talent Program 2009 (09PJ1402600) to Jin-sheng GuoWang Bao-En Liver Fibrosis Research Foundation (20090001) to Ji-yao Wang
文摘Objective Genome-wide association studies(GWAS)have linked many single nucleotide polymorphisms(SNPs)to the outcomes of a variety of liver diseases.The aim of the present study was to evaluate the association of several candidate SNPs with the risk and severity of cirrhosis due to chronic hepatitis B in a Chinese population.Methods A total of 714 Chinese participants with persistent HBV infection were studied.Patients were divided into cirrhotic(n=429)and non-cirrhotic(n=285)groups based on clinical and pathological evidence.The progression rate and severity of liver cirrhosis were evaluated with an arbitrary t-score system.Genotypes of six SNPs in five candidate genes were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).The genotypic distributions of the SNPs were compared between the age-matched cirrhotic and non-cirrhotic subjects.The association between the risk of SNPs and the severity and progression rate of cirrhosis was further analyzed.Results Rs2679757 polymorphism of the antizyme inhibitor 1(AZIN1)gene and Rs886277 in the transient receptor potential cation channel subfamily M,member 5 gene(TRPM5)were found to be associated with cirrhosis risk in CHB.They were also correlated with the overall severity and progression rate of cirrhosis.Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups.Conclusions AZIN1 rs2679757 and TRPM5 rs886277 are associated with the risk and the progression rate of HBV-related liver fibrosis in Chinese patients.The emerging SNPs associated with cirrhosis prognosis warrant further clinical validation in other CHB cohorts or ethnic groups,and merit mechanistic studies to reveal their roles in fibrosis progression.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
