Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn’s disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.

For a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, inducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis of inflammatory bowel disease (IBD) and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.

Background: Probiotics is a prevalence therapeutic method for irritable bowel syndrome (IBS), but there is lack of comparison in different protocols. We aim to differentiate the reasonable protocols by assessing the efficacy and safety through the combined way of traditional and network meta-analysis.Method: PubMed, Medline, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched from January 2006 to April 2019. The relative risk (RR) with a 95% confidence interval (CI) was used to combine dichotomous data of responders.Result: Among 14 studies included 1695 patients were identified as suitable for inclusion. The proportion of responders was associated with the administration of multispecies probiotics (RR: 1.39; 95% CI: 1.19–1.61) and the dose of 10⁹∼10¹⁰(RR: 2.08; 95% CI: 1.59–2.71). In network meta-analysis, the protocol of DUO had a significant effect for diarrhea type of IBS compared with placebo (RR: 7.46; 95% CI: 2.00–32.23). In the rest of 4 protocols, no significant difference was found in each other except F19 which appears inferior when compared with Pro (RR: 0.16; 95% CI: 0.03–0.88). Meanwhile, Pro showed a superior effect for undifferentiated-type IBS compared with placebo (RR: 7.16; 95% CI: 1.72–29.89). No probiotics-associated severe adverse event was reported in included studies.Conclusion: Probiotics is a safety choice to improve the overall symptoms for IBS patient. The protocols with suitable dose combined ofLactobacillusandBifidobacteriumcan have prepotent effects compared with single species or over-dosage protocols. Network meta-analysis shows that DUO may be the first recommendation for diarrhea-type IBS. In the remaining 4 regimes of this study, Pro has a high rank for undifferentiated-type IBS.

Acute pancreatitis (AP) is a common acute gastrointestinal disorder affecting approximately 20% of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis. This condition often progresses to multiple organ failure, significantly increasing morbidity and mortality. Oxidative stress, characterized by an imbalance between the body’s reactive oxygen species (ROS) and antioxidants, activates the inflammatory signaling pathways. Although the pathogenesis of AP is not fully understood, ROS are increasingly recognized as critical in the disease's progression and development. Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP. Despite numerous basic studies examining this pathway, comprehensive reviews of recent research remain sparse. This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

To explore the diagnostic models of Crohn’s disease (CD), Intestinal tuberculosis (ITB) and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles. Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs) were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05). Genetic algorithm combining with support vector machine (SVM) was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO) cross validation method. There were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05) to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900) can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541) can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80.0% respectively. Among the eleven protein peaks from the diagnostic models and differential diagnostic model, two have been successfully purified and identified, Those two peaks were M/Z 2900 from the diagnostic model between CD and HCs and M/Z 1541 from the differential diagnostic model between CD and ITB. M/Z 2900 was identified as appetite peptide, M/Z 1541 was identified as Lysyl oxidase-like 2 (LOXL-2). The differently expressed protein peaks analyzed by serum proteome with weak cationic magnetic beads combined MALDI-TOF-MS technique can effectively distinguish CD patients and HCs, ITB patients and HCs, CD patients and ITB patients. The diagnostic model between CD patients and HCs consisting of four protein peaks (M/Z 4964, 3029, 2833, 2900), the diagnostic model between ITB patients and HCs comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) and the differential diagnostic model between CD patients and ITB patients comprising three protein peaks (M/Z 4267, 4223, 1541) had high specificity and sensitivity and can contribute to diagnoses of CD, ITB and the differential diagnosis between CD and ITB. Two proteins from the diagnostic model of CD and the differential diagnostic model between CD and ITB were identified. Further experiments are required using a larger cohort of samples.