The proteolytic activity in inflammatory bowel disease: insight from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease caused by the destruction of the intestinal mucosal epithelium that affects a growing number of people worldwide. Although the etiology of IBD is complex and still elucidated, the role of dysbiosis and dysregulated proteolysis is well recognized. Various studies observed altered composition and diversity of gut microbiota, as well as increased proteolytic activity (PA) in serum, plasma, colonic mucosa, and fecal supernatant of IBD compared to healthy individuals. The imbalance of intestinal microecology and intestinal protein hydrolysis were gradually considered to be closely related to IBD. Notably, the pivotal role of intestinal microbiota in maintaining proteolytic balance received increasing attention. In summary, we have speculated a mesmerizing story, regarding the hidden role of PA and microbiota-derived PA hidden in IBD. Most importantly, we provided the diagnosis and therapeutic targets for IBD as well as the formulation of new treatment strategies for other digestive diseases and protease-related diseases.

Efficacy of extracellular vesicles as a cell-free therapy in colitis: a systematic review and meta-analysis of animal studies.

Background: Extracellular vesicles (EVs) mediate inflammation, immune responses, gut barrier integrity, and intestinal homeostasis. Recently, the application of EVs in the treatment of inflammatory bowel disease (IBD) has been under intensive focus. Some studies have been conducted in animal models of colitis, while systematic reviews and meta-analyses are lacking. The current study aimed to conduct a systematic review and meta-analysis of studies investigating the efficacy of EVs on IBD. Methods: A systematic retrieval of all studies in PubMed, EMBASE, MEDLINE, Web of Science, and Cochrane Library reported the effects of EVs in the colitis model up to 22 June 2023. The methodological quality was assessed based on SYRCLE's risk of bias (RoB) tool. Disease activity index (DAI), myeloperoxidase activity (MPO), histopathological score (HS), and inflammatory cytokines (TNF-α, NF-κB, IL-1ß, IL-6, and IL-10) were extracted as analysis indicators by Web Plot Digitizer 4.5. A meta-analysis was performed to calculate the standardized mean difference and 95% confidence interval using random-effect models by Review Manager 5.3 and STATA 14.0 software. Results: A total of 21 studies were included in this meta-analysis. Although the heterogeneity between studies and the potential publication bias limits confidence in the extent of the benefit, EV treatment was superior to the control in the colitis evaluation with reduced DAI, HS, MPO activity, and pro-inflammatory cytokines, including TNF-α, NF-κB, IL-1ß, and IL-6, while increasing the content of anti-inflammatory cytokine IL-10 (all p < 0.05). Conclusion: Our meta-analysis results supported the protective effect of EVs on colitis rodent models based on their potential role in IBD therapy and propelling the field toward clinical studies.

Activation of the aryl hydrocarbon receptor in inflammatory bowel disease: insights from gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects more than 3.5 million people, with rising prevalence. It deeply affects patients' daily life, increasing the burden on patients, families, and society. Presently, the etiology of IBD remains incompletely clarified, while emerging evidence has demonstrated that altered gut microbiota and decreased aryl hydrocarbon receptor (AHR) activity are closely associated with IBD. Furthermore, microbial metabolites are capable of AHR activation as AHR ligands, while the AHR, in turn, affects the microbiota through various pathways. In light of the complex connection among gut microbiota, the AHR, and IBD, it is urgent to review the latest research progress in this field. In this review, we describe the role of gut microbiota and AHR activation in IBD and discussed the crosstalk between gut microbiota and the AHR in the context of IBD. Taken as a whole, we propose new therapeutic strategies targeting the AHR-microbiota axis for IBD, even for other related diseases caused by AHR-microbiota dysbiosis.

Association of serum uric acid with 2-hour postload glucose in Chinese with impaired fasting plasma glucose and/or HbA1c.

OBJECTIVE: To examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C). RESEARCH DESIGN AND METHODS: Anthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110 ≤ fasting plasma glucose [FPG] <126 mg/dl and HbA1c <6.5%), IA1C (5.7% ≤ HbA1c <6.5% and FPG <126 mg/dl), or both. RESULTS: The present study included 1197 participants with IFG and/or IA1C (mean age 56.5 ± 10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04 ± 0.72 (P<0.001), 3.06 ± 1.08 (P = 0.001), 5.40 ± 1.26 (P<0.001), and 2.34 ± 2.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG ≥ 200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P<0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09-1.99]; P = 0.03). CONCLUSIONS: SUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C.

[Effects of temperature stress on physiological indices of Chilo suppressalis Walker (Lepidoptera: Pyralidae) diapause larvae].

To understand the physiological mechanisms of temperature stress on the diapause larvae of rice stem borer Chilo suppressalis Walker at physiological and biochemical levels, determinations were made on the contents of water, lipid, total sugar and low molecular mass carbohydrates and the activities of SOD, POD, CAT in the larvae after series temperature stress (STS) and gradient temperature stress (GTS). With the decrease of temperature, the water content in the larvae decreased, and the decrement below 0 degrees C was significantly larger in treatment GTS than in treatment STS. The lipid content in the larvae decreased gradually, but no significant difference was observed between treatments STS and GTS. The total sugar content in the larvae in treatment STS increased after an initial decrease, but that in treatment GTS continued to decline. Four species of low molecular carbohydrates, i. e. , trehalose, glucose, glycerol and fructose were detected in the larvae. In treatment STS, the contents of glycose, glycerol and fructose in the larvae decreased after an initial increase, while the trehalose content was in adverse. In treatment GTS, the trehalose content decreased first and increased then, the glucose and glycerol were in adverse, but the fructose content had little change. In the range from 14 to -14 degrees C, the SOD and POD activities in the larvae in treatment STS were significantly lower than those in treatment GTS, but the CAT activity was in adverse. The changes of these indices reflected the physiological responses of C. suppressalis diapause larvae to different temperature stress.