Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway

AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.

Analysis of TLR4 and TLR2 polymorphisms in inflammatory bowel disease in a Guangxi Zhuang population

AIM: To study the polymorphisms of toll-like receptor 4 (TLR4) gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp and susceptibility to inflammatory bowel disease (IBD) in the Zhuang population from Guangxi, China. METHODS: A case-control study was performed from February 2007 to October 2011 which included 146 Zhuang patients with IBD in the experimental group and 164 healthy Zhuang subjects who acted as the control group. All patients and healthy subjects were from the Guangxi Zhuang Autonomous Region of China. Genomic DNA was extracted from intestinal tissue by the phenol chloroform method. TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp were amplified by polymerase chain reaction (PCR), and then detected by PCR-restriction fragment length polymorphism (RFLP). RESULTS: The TLR4 gene Asp299Gly was digested using Nco Ⅰ restriction enzyme, and a single band of 249 bp was observed which showed that it was a wild type (AA). The TLR4 gene Thr399Ile was digested using Hinf Ⅰrestriction enzyme and only the wild type (CC) was detected. In addition, the TLR2 gene Arg-677Trp was digested using Aci Ⅰ restriction enzyme and only the wild type (CC) was detected. The TLR2 gene Arg753Gln was digested using Pst Ⅰ restriction enzyme. Only the wild type (GG) as a single band of 254 bp was observed during RFLP. Overall, no heterozygous or homozygous single nucleotide polymorphism mutations were found in patients with Crohn's disease and ulcerative colitis both in the TLR4 gene Asp299Gly, Thr399Ile and the TLR2 gene Arg677Trp, Arg753Gln in the Zhuang population from the Guangxi Zhuang Autonomous Region of China. CONCLUSION: The TLR4 gene Asp299Gly, Thr399Ile and TLR2 gene Arg753Gln, Arg677Trp polymorphisms may not be associated with IBD in the Zhuang population from the Guangxi Zhuang Autonomous Region of China.

Placement of prophylactic pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients: A meta-analysis

AIM:To assess the effectiveness of pancreatic stents for preventing pancreatitis in high-risk patients after endoscopic retrograde cholangiopancreatography(ERCP).METHODS:PubMed,Embase,Science Citation Index,and Cochrane Controlled Trials Register were searched to identify relevant trials published in English.Inclu-sion and exclusion criteria were used to screen for suitable studies.Two reviewers independently judged the study eligibility while screening the citations.The methodological quality of the included trials was assessed using the Jadad scoring system.All results were expressed as OR and 95%CI.Data were analyzed using Stata12.0 software.RESULTS:Ten eligible randomized controlled trials were selected,including 1176 patients.A fixed-effects model in meta-analysis supported that pancreatic duct stents significantly decreased the incidence of postERCP pancreatitis(PEP)in high-risk patients(OR=0.25;95%CI:0.17-0.38;P<0.001).Pancreatic stents also alleviated the severity of PEP(mild pancreatitis after ERCP:OR=0.33;95%CI:0.21-0.54;P<0.001;moderate pancreatitis after ERCP:OR=0.30;95%CI:0.13-0.67;P=0.004).The result of severe pancreatitis after ERCP was handled more rigorously(OR=0.24;95%CI:0.05-1.16;P=0.077).Serum amylase levels were not different between patients with pancreatic stents and control patients(OR=1.08;95%CI:0.82-1.41;P=0.586).CONCLUSION:Placement of prophylactic pancreatic stents may lower the incidence of post-ERCP pancreatitis in high-risk patients and alleviate the severity of this condition.

Association between NOD2/CARD15 gene polymorphisms and Crohn's disease in Chinese Zhuang patients

AIM:To assess the relationship between the P268S,JW1 and N852S polymorphisms and Crohn’s disease(CD)susceptibility in Zhuang patients in Guangxi,China.METHODS:Intestinal tissues from 102 Zhuang[48CD and 54 ulcerative colitis(UC)]and 100 Han(50 CD and 50 UC)unrelated patients with inflammatory bowel disease and 72 Zhuang and 78 Han unrelated healthy individuals were collected in the Guangxi Zhuang Autonomous Region from January 2009 to March 2013.Genomic DNA was extracted using the phenol chloroform method.The P268S,JW1 and N852S polymorphisms were amplified using polymerase chain reaction(PCR),detected by restriction fragment length polymorphism(RFLP),and verified by gene sequencing.RESULTS:Heterozygous mutation of P268S in the NOD2/CARD15 gene was detected in 10 CD cases(six Zhuang and four Han),two Han UC cases,and one Zhuang healthy control,and P268S was strongly associated with the Chinese Zhuang and Han CD populations(P=0.016 and 0.022,respectively).No homozygous mutant P268S was detected in any of the groups.No significant difference was found in P268S genotype and allele frequencies between UC and control groups(P>0.05).Patients with CD who carried P268S were likely to be≤40 years of age(P=0.040),but were not significantly different with regard to race,lesion site,complications,and other clinical features(P>0.05).Neither JW1 nor N852S polymorphisms of the NOD2/CARD15gene were found in any of the subjects(P>0.05).CONCLUSION:P268S polymorphism may be associated with CD susceptibility in the Zhuang population in the Guangxi Zhuang Autonomous Region,China.In contrast,JW1 and N852S polymorphisms may not be related to CD susceptibility in these patients.

Infliximab is effective in the treatment of ulcerative colitis with dermatomyositis:A case report

BACKGROUND Joint,skin,oral cavity,and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset.The cases of ulcerative colitis with dermatomyositis(DM)are rare.In this study,we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.CASE SUMMARY The patient was a 57-year-old female with a 2-year history of DM.The patient was admitted to hospital with abdominal pain,diarrhea,and blood in stool lasting for more than 2 mo.Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum.Pathological sections showed chronic inflammatory cell infiltration,especially neutrophil infiltration,in the colonic mucosa;therefore,the patient was diagnosed with ulcerative colitis.Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM,but its effect was unsatisfactory.The patient’s discomfort was relieved after infliximab treatment.CONCLUSION Infliximab can improve DM in the treatment of ulcerative colitis.Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.

Pathogenesis of autoimmune hepatitis

Autoimmune hepatitis(AIH)is a chronic progressive liver disease whose etiology and pathogenesis are not yet clear.It is currently believed that the occurrence of AIH is closely related to genetic susceptibility and immune abnormalities,and other factors such as environment,viral infection and drugs that may cause immune dysfunction.This article reviews the pathogenesis of AIH and describes the latest research results in the past 5 years.