Excessive inflammatory responses and oxidative stress are considered the main characteristics of inflammatory bowel disease (IBD). Endogenous hydrogen sulfide (H₂S) has been reported to show anti-inflammatory activity in IBD. The main aim of this study was to explore the role of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous H₂S biosynthesis, in IBD. Colonic MPST expression was evaluated in mice and patients with IBD. Various approaches were used to explore the concrete mechanism underlying MPST regulation of the progression of colitis through in vivo and in vitro models. MPST expression was markedly decreased in colonic samples from patients with ulcerative colitis (UC) or Crohn's disease (CD) and from mice treated with DSS. MPST deficiency significantly aggravated the symptoms of murine colitis, exacerbated inflammatory responses and apoptosis, and inhibited epithelium stem cell-derived organoid formation in an H₂S-independent manner. Consistently, when HT29 cells were treated with TNF-α, inhibition of MPST significantly increased the expression of proinflammatory cytokines, the amount of ROS and the prevalence of apoptosis, whereas overexpression of MPST markedly improved these effects. RNA-seq analysis showed that MPST might play a role in regulating apoptosis through AKT signaling. Mechanistically, MPST directly interacted with AKT and reduced the phosphorylation of AKT. Additionally, MPST expression was positively correlated with AKT expression in human IBD samples. In addition, overexpression of AKT rescued IEC apoptosis caused by MPST deficiency, while inhibition of AKT significantly aggravated it. MPST protects the intestines from inflammation most likely by regulating the AKT/apoptosis axis in IECs. Our results may provide a novel therapeutic strategy for the treatment of colitis.

Wenxi Jiang, Jiali Wu, Shefeng Zhu, Linying Xin, Chaohui Yu, and Zhe Shen*. J Neurogastroenterol Motil 2022;28:540-8. https://doi.org/10.5056/jnm22093

The incidence of colorectal polyps is rising. Certain types of polyps are considered to be the precursor lesions for colorectal cancers. To investigate the prevalence and related factors of colorectal polyps in Chinese subjects, we first performed a cross-sectional study. A total of 3066 subjects were documented, and the prevalence of colorectal polyps was 18.1%. Then we evaluated the incidence and risk factors of polyps via a retrospective cohort study in the same population. 561 subjects who received at least twice surveillance colonoscopies with available reports during the study period and had no polyp at the first endoscopy were included in the retrospective cohort study, of whom 19.1% developed colorectal polyps. Regular smoking was independently associated with the presence and development of colorectal polyps. Further analyses indicated that polyps were associated with smoking status, daily cigarette consumption, and drinking habit. Moreover, smoking tends to be more relavent to rectal, small and single polyp. In conclusion, colorectal polyp is a common disease in China. Exploring the epidemiology and risk factors may improve the prevention of colorectal polyps, even colorectal cancer.

Background: Noninvasive methods have been used for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). The aim was to assess the efficacy and accuracy of both magnetic resonance imaging(MRI) and transient elastography(TE) for the evaluation of hepatic steatosis.Materials and Methods: The PubMed, Cochrane Library, Embase, MEDLINE and Web of Science databases were searched to retrieve studies examining the accuracy of MRI‐proton density fat fraction(PDFF) and TE‐controlled attenuation parameter(CAP) for evaluating the grading of steatosis(S0‐S3) diagnosed by liver biopsy in NAFLD. We compared the sensitivity, specificity, hierarchical summary receiver operating characteristic curves(HSROC) and clinical utility of these methods.Results: Twenty‐four articles with a total of 2979 patients with NAFLD were included. The steatosis distribution was 8.1%/35.1%/32.2%/24.6% for S0/S1/S2/S3. For the diagnostic accuracy of MRI‐PDFF, the HSROCs were 0.97 for ≥S1, 0.91 for ≥S2 and 0.90 for ≥S3. For the diagnostic accuracy of TE‐based CAP, the HSROCs were 0.85 for ≥S1, 0.83 for ≥S2 and 0.79 for ≥S3. Following a ‘positive’ measurement (over the threshold value) for ≥S1, the corresponding post‐test probabilities of PDFF and CAP for the presence of steatosis were 82% and 61%, respectively, when the pretest probability was 24%. If the values were below these thresholds (‘negative’ results), the post‐test probabilities were 3% and 7%.Conclusion: MRI‐PDFF and TE‐CAP both provide highly accurate noninvasive approaches for quantifying and staging hepatic steatosis in NAFLD. Compared with TE‐CAP, MRI‐PDFF is significantly more accurate for evaluating dichotomized grades of steatosis.

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1^−/− mice, DJ-1^−/−p53^−/− mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1^−/− mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis.