Cell division cycle protein 42 regulates the inflammatory response in mice bearing inflammatory bowel disease.

This study aimed to explore the effect of cell division cycle protein 42 (CDC42) on inflammatory response and immune response in mice bearing inflammatory bowel disease (IBD). Trinitrobenzene sulfonic acid was injected into the colon of mice to establish IBD model. The mice were divided into four groups (n = 4): control, model, Ad5, and Ad5-CDC42. After establishing IBD model, mice which were treated with AD5 empty vector and AD5-CDC42 expression vector served as the Ad5 group and Ad5-CDC42 group, respectively. The mRNA and protein levels of interleukin 10 (IL-10), interferon-γ (IFN-γ), IL-4, and tumor necrosis factor-α (TNF-α) in the colon tissues were evaluated by RT-PCR and western blot, respectively. Their levels in the serum and colon tissues were examined by ELISA assay and immunohistochemical analysis, respectively. Their changes in the mRNA and protein levels were consistent and similar changes in the colon tissues and the serum were found among various groups. The levels of IL-10, IFN-γ, IL-4, and TNF-α were lowest in the control group. Their levels in the model group and the Ad5 group were similar (p > .05) and significantly higher than those in the control group (p < .05). In comparison with the model group and the Ad5 group, their levels were significantly reduced in the Ad5-CDC42 group (p < .05). In conclusion, the levels of inflammatory cytokines were elevated in the colon tissues and serum of IBD mice, which could be reduced by the CDC42 treatment. CDC42 regulated the inflammatory response and the innate immune response in IBD mice.

Independent effect of alanine transaminase on the incidence of type 2 diabetes mellitus, stratified by age and gender: A secondary analysis based on a large cohort study in China.

BACKGROUND: Previous studies have revealed that alanine aminotransferase (ALT) may be one of the risk factors of developing diabetes. We aimed to demonstrate the independent effect of ALT on incident diabetes and to investigate whether the association between ALT and incident diabetes is modified by age and gender in the general Chinese population. METHODS: The present study was a retrospective cohort study, including 210,051 Chinese adult participants. The primary outcome was developing diabetes. The serum ALT activities were stratified by quintiles. We obtained data from 'DATADRYAD' website and used the data for secondary analysis. RESULTS: At a median follow-up of 3.0 y, 4144 of 210,051 (1.97%) participants developed diabetes. After adjustment for potential confounders, a significantly higher risk of the incident diabetes (HR: 1.43, 95% CI: 1.25-1.63) was found in participants in the fifth quintile (Q5, ≥31 U/L) compared to those in the first to fourth quintiles (Q1-4) for ALT activities. Among males aged 30 to 40 and 40 to 50 y with the fifth quintile of ALT activity had 2.4- and 1.5-fold increased odds of developing diabetes, respectively, in comparison with those in the lower ALT activities. Among females with age 30 to 40 and ≥ 70 y, the fifth quintile of ALT activity had 4.9- and 2.2-fold increased odds for incident diabetes. CONCLUSION: Our result indicated that the ALT activity was positively associated with the incident diabetes among Chinese persons. Moreover, 30-40 y individuals, whether male or female, with elevated ALT activities had the greatest increased risk for diabetes compared with persons with lower ALT activities in the same age group.

Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis.

Inflammatory bowel disease (IBD) is an autoimmune disease with an abnormal and persistent immune response. Iguratimod, a novel anti-rheumatic drug, exhibits anti-inflammatory effects and regulates immune response. The role of iguratimod in intestinal mucosal inflammation and immunity has not been examined. The aim of this study was to investigate whether iguratimod ameliorates dextran sulphate sodium (DSS)-induced murine colitis and its potential regulatory mechanism. Murine colitis was induced by administering 2.5% DSS for 5days. Some mice were administered iguratimod (5, 30mg/kg) by oral gavage once daily for 7days, beginning on the day 3 after colitis induction. Our study showed that iguratimod alleviates the symptoms of colitis and suppresses intestinal tissue damage, including macroscopic and histopathological manifestations. Moreover, iguratimod reduced interleukin (IL)-6, IL-17, and tumour necrosis factor-α levels, and increased the expression levels of IL-10 and TGF-ß. In addition, iguratimod downregulated the proportion of Th17 cells, the level of transcription factor retinoic acid-related orphan receptor γt (RORγt), and the phosphorylation of signal transducer and activator of transcription-3 (STAT3), and upregulated the proportion of Treg cells, the level of transcription factor forkhead box p3 (Foxp3), and the phosphorylation of STAT5 in the colonic tissues. In conclusion, iguratimod plays a protective role in mice with DSS-induced colitis via anti-inflammatory effects and regulation of Th17/Treg cells. Therefore, use of iguratimod may serve as a novel therapeutic strategy for the treatment of IBD.

Efficacy and safety of carbon dioxide insufflation versus air insufflation for endoscopic retrograde cholangiopancreatography: A meta-analysis update.

BACKGROUND AND OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for visualising the biliary tree and pancreatic ducts, and carbon dioxide (CO2) insufflation during ERCP is considered an alternative technique to air insufflation for relieving post-procedural abdominal discomfort (abdominal pain and distension). The aim of the present study was to evaluate the effect of CO2 insufflation on the remission of abdominal discomfort and the potential side effects by conducting a meta-analysis. METHODS: The method recommended by the Cochrane Collaboration was employed to conduct a meta-analysis of randomised controlled trials (RCTs) of CO2 insufflation versus air insufflation during ERCP. The PubMed, EMBASE, Cochrane Library, ISI Web of Science and China Biology Medicine disc (CBMdisc) databases were comprehensively searched. RESULTS: Nine high-quality RCTs were reviewed. The updated meta-analysis showed that the CO2 groups achieved a lower abdominal pain score [1-hour (SMD: -1.44, 95% CI: -2.76, -0.15), 3-hour (SMD: -1.17, 95% CI: -2.18, -0.16) and 6-hour (SMD: -1.39, 95% CI: -2.68, -0.10)], a lower abdominal distension score [1-hour (SMD: -1.05, 95% CI: -1.73, -0.38), 3-hour (SMD: -0.63, 95% CI: -1.10, -0.16) and 6-hour (SMD: -0.54, 95% CI: -0.99, -0.08)] and a lower overall rate of complications (OR: 0.59; 95% CI: 0.37, 0.93). There was no significant difference between the groups regarding abdominal discomfort immediately after recovery or 24-hour post-procedure. There was no evidence to indicate higher pressure of CO2 (pCO2) values in the CO2 groups during the procedure when the patients were under sedation anaesthesia. CONCLUSIONS: Compared to air insufflation, CO2 insufflation is currently the preferred method for ERCP and decreases post-procedural abdominal pain and distension without significant side effects.