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.

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).

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.

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.

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.

Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway

BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fibrosis and how this could be targeted therapeutically.METHODS CCl4(20%)and active N-terminal peptide of AnxA1(Ac2-26)and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic fibrosis.RESULTS Compared with the control group,AnxA1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with time.CCl4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of AnxA1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type mice.After treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before treatment.Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26.AnxA1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic fibrosis.In vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of AnxA1.Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC activation.These therapeutic effects were inhibited by Boc2.CONCLUSION AnxA1 inhibited liver fibrosis in mice,and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.

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.

Trends in medication use and treatment patterns in Chinese patients with inflammatory bowel disease

BACKGROUND Medications for inflammatory bowel disease(IBD)have changed dramatically over time.However,no study on long-term medication profiles has been conducted in the Chinese population.AIM To evaluate temporal changes in medication use and treatment patterns for Chinese patients with IBD.METHODS A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn’s disease(CD)and ulcerative colitis(UC)between January 1999 and December 2019.Baseline characteristics and drug prescriptions were collected.Trends in medication use and therapeutic patterns were analyzed.RESULTS In total,3610 patients were analyzed.During follow-up,5-aminosalicylates(5-ASA)and corticosteroids(CS)prescriptions gradually decreased,accompanied by a notable increase in immunosuppressants(IMS)and infliximab(IFX)prescriptions in patients with CD.Prescription rates of 5-ASA and CS were stable,whereas IMS and IFX slightly increased since 2007 in patients with UC.Subgroup(n=957)analyses showed a switch from conventional medications to IFX in patients with CD,while 5-ASA and CS were still steadily prescribed in patients with UC.Logistic regression analyses revealed that surgical history,disease behavior,and disease location were associated with initial therapeutic strategies in patients with CD.However,medications before diagnosis,disease location,and diagnostic year might affect initial strategies in patients with UC.CONCLUSION Long-term treatment strategies analyses has provided unique insight into the switch from conventional drugs to IFX in Chinese patients with CD.

Outcome and risk factors of ulcer healing after gastric endoscopic submucosal dissection: A systematic review and meta-analysis

BACKGROUND Endoscopic submucosal dissection(ESD)is widely utilized for the treatment of large adenomas,submucosal lesions,and early gastric cancer.A significant arti-ficial ulcer typically forms after ESD.Delayed or incomplete healing of these ulcers can result in complications such as delayed bleeding and perforation.However,a comprehensive review of the outcomes and risk factors related to ulcer healing following ESD is currently lacking.AIM To assess ulcer healing outcomes and identify risk factors associated with delayed ulcer healing.RESULTS Our analysis included 12 studies,involving a total of 3430 patients.The meta-analysis revealed an overall healing rate of 65.55%for ulcers following ESD[odds ratio(OR)=2.71;95%confidence interval(CI):2.45-3.00].The healing rate within eight weeks was 48.32%(OR=0.76;95%CI:0.35-1.66),while the rate beyond eight weeks was 88.32%(OR=6.73;95%CI:3.82-11.87).Risk factors included Helicobacter pylori(H.pylori)infection(OR:=5.32;95%CI:1.90-14.87;P=0.001),ulcer size(OR=2.08;95%CI:1.19-3.61;P=0.01),lesion site(OR=2.08;95%CI:1.19-3.11),and pathological type(OR=1.64;95%CI:1.06-2.52).Diabetes(OR=0.56;95%CI:0.05-5.80;P=0.63)and duration of operation(OR=1.00;95%CI:0.99-1.01;P=0.96)were not significant factors.CONCLUSION The healing rate of ulcers following ESD is high after eight weeks.Risk factors affecting the healing process include H.pylori infection,ulcer size,lesion site,and pathological type.