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BACKGROUND Gut microbiota and its metabolites may be involved in the pathogenesis of inflammatory bowel disease. Several clinical studies have recently shown that patients with ulcerative colitis (UC) have altered profiles of fecal bile acids (BAs). It was observed that BA receptors Takeda G-protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR) participate in intestinal inflammatory responses by regulating NF-ĸB signaling. We hypothesized that altered profiles of fecal BAs might be correlated with gut microbiota and inflammatory responses in patients with UC. AIM To investigate the changes in fecal BAs and analyze the relationship of BAs with gut microbiota and inflammation in patients with UC. METHODS The present study used 16S rDNA sequencing technology to detect the differences in the intestinal flora between UC patients and healthy controls (HCs). Fecal BAs were measured by targeted metabolomics approaches. Mucosal TGR5 and VDR expression was analyzed using immunohistochemistry, and serum inflammatory cytokine levels were detected by ELISA. RESULTS Thirty-two UC patients and twenty-three HCs were enrolled in this study. It was found that the diversity of gut microbiota in UC patients was reduced compared with that in HCs. Firmicutes , Clostridium IV , Butyricicoccus , Clostridium XlVa , Faecalibacterium , and Roseburia were significantly decreased in patients with UC ( P = 3.75E-05, P = 8.28E-07, P = 0.0002, P = 0.003, P = 0.0003, and P = 0.0004, respectively). Proteobacteria , Escherichia , Enterococcus , Klebsiella , and Streptococcus were significantly enriched in the UC group ( P = 2.99E-09, P = 3.63E-05, P = 8.59E-05, P = 0.003, and P = 0.016, respectively). The concentrations of fecal secondary BAs, such as lithocholic acid, deoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and taurolithocholate, in UC patients were significantly lower than those in HCs ( P = 8.1E-08, P = 1.2E-07, P = 3.5E-04, P = 1.9E-03, and P = 1.8E-02, respectively) and were positively correlated with Butyricicoccus , Roseburia , Clostridium IV , Faecalibacterium , and Clo...

Background: Several studies have shown that non-renal factors such as corticosteroids may increase plasma cystatin C levels without affecting kidney function. However, the mechanisms underlying this are unclear. We hypothesized that corticosteroids may increase cystatin C levels in the plasma by promoting its production in tissues. In the present study, we aimed to test our hypothesis in rats by investigating the effect of corticosteroids on cystatin C production in tissues and the glomerular filtration rate (GFR), as measured by the gold standard method (i.e., inulin clearance). Results: Dexamethasone treatment was associated with much higher concentrations of cystatin C in all organ tissue homogenates tested. Dexamethasone increased plasma cystatin C levels in rats, without any decrease in renal inulin clearance. The impact of dexamethasone on plasma and organ tissue cystatin C levels was abolished by RU486, indicating the effect was glucocorticoid receptor-mediated. Conclusions: Our study provides direct evidence that corticosteroids may increase cystatin C levels in the plasma by promoting its production, without any decrease in GFR.

Background Arginine vasopressin dependent antidiuresis plays a key role in water‐sodium retention in heart failure. In recent years, the role of glucocorticoids in the control of body fluid homeostasis has been extensively investigated. Glucocorticoid deficiency can activate V2R (vasopressin receptor 2), increase aquaporins expression, and result in hyponatremia, all of which can be reversed by glucocorticoid supplement. Methods and Results Heart failure was induced by coronary artery ligation for 8 weeks. A total of 32 rats were randomly assigned to 4 groups (n=8/group): sham surgery group, congestive heart failure group, dexamethasone group, and dexamethasone in combination with glucocorticoid receptor antagonist RU486 group. An acute water loading test was administered 6 hours after drug administration. Left ventricular function was measured by a pressure‐volume catheter. Protein expressions were determined by immunohistochemistry and immunoblotting. The pressure‐volume loop analysis showed that dexamethasone improves cardiac function in rats with heart failure. Western blotting confirmed that dexamethasone remarkably reduces the expressions of V2R, aquaporin 2, and aquaporin 3 in the renal‐collecting ducts. As a result of V2R downregulation, the expressions of glucocorticoid regulated kinase 1, apical epithelial sodium channels, and the furosemide‐sensitive Na‐K‐2Cl cotransporter were also downregulated. These favorable effects induced by dexamethasone were mostly abolished by the glucocorticoid receptor inhibitor RU486, indicating that the aforementioned effects are glucocorticoid receptor mediated. Conclusions Glucocorticoids can reverse diluted hyponatremia via inhibiting the vasopressin receptor pathway in rats with heart failure.

Background: Inflammatory bowel diseases (IBD), which include Crohn disease and ulcerative colitis, affect several million individuals worldwide. Curcumin as a complementary therapy has been used to cure the IBD, yet the efficacy and safety of curcumin remains to be assessed. In this study, we aim to draw up a protocol for systematic review to evaluate the efficacy and safety of curcumin for IBD. Methods: We will search the following electronic databases from inception to September 31, 2020: PubMed, Cochrane Library, EMBASE, Web of Science, Medline, the China National Knowledge Infrastructure Database, Wan Fang Database, the Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Clinical trial registrations, potential gray literatures, relevant conference abstracts and reference list of identified studies will also be searched. Relevant randomized controlled clinical trials were enrolled and analyzed. The literature selection, data extraction, and quality assessment will be completed by 2 independent authors. Either the fixed-effects or random-effects model will be used for data synthesis based on the heterogeneity test. Clinical remission will be evaluated as the primary outcome. Clinical response, endoscopic remission, inflammatory markers and adverse events will be assessed as the secondary outcomes. The RevManV.5.3.5 will be used for Meta-analysis. Subgroup analyses of doses, delivery way, frequency of treatment and the degree of IBD severity or different forms of IBD were also conducted. Results: This study will provide a synthesis of current evidence of curcumin for IBD from several aspects, such as clinical remission, clinical response, endoscopic remission, inflammatory markers, and adverse events. Conclusion: The conclusion of our study will provide updated evidence to judge whether curcumin is an effective solution to IBD patients. INPLASY registration number: INPLASY202090065.

Background Gastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer. Methods Bioinformatics analysis was employed to clarify the expression patterns of NEK1–NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo. Results Bioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest. Conclusion NEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.

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Background: Gastric cancer is one of the most common malignant tumors of alimentary canal. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanism of gastric cancer cells’ malignant behavior is of crucial importance to its therapeutic method exploitation. Mammalian NIMA-related kinases are considered to play a significant role in cell proliferation. However, NIMA family proteins have not been reported in gastric cancer yet. Methods: Bioinformatics analysis was used to clarify the expression patterns of NEK1-NEK11 and their effects on prognosis. We also analyzed the effect on immune infiltration and related pathways of NEK7. At cell level, EdU assay, cell cycle assay and CCK-8 assay were utilized to clarify the NEK7 effect on gastric cancer cell proliferation. Mice subcutaneous model revealed the regulating effect on gastric cancer cell proliferation of NEK7 in vivo. Results: Bioinformatics analysis revealed that NEK7 upregulates in gastric cancer and is related to poor prognosis. Meanwhile, NEK7 is related to T-stage, which has closely related to cell proliferation. Further analysis showed that NEK7 has correlation with multiple immune cells infiltration as well as related pathways of gastric cancer. Cell experiments indicated the promoting effect of NEK7 to cell proliferation, while lack of NEK7 could result in gastric cancer proliferation inhibition and G1/S arrest. Conclusion: NEK7 exert the regulatory effect during cell proliferation and is closely related to tumor immune infiltration