MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis.

Substance P (SP) mediates colitis. SP signaling regulates the expression of several miRNAs, including miR-31-3p, in human colonocytes. However, the role of miR-31-3p in colitis and the underlying mechanisms has not been elucidated. We performed real-time PCR analysis of miR-31-3p expression in human colonic epithelial cells overexpressing neurokinin-1 receptor (NCM460 NK-1R) in response to SP stimulation and in NCM460 cells after IL-6, IL8, tumor necrosis factor (TNF)-α, and interferon-γ exposure. Functions of miR-31-3p were tested in NCM460-NK-1R cells and the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis. Targets of miRNA-31-3p were confirmed by Western blot analysis and luciferase reporter assay. Jun N-terminal kinase inhibition decreased SP-induced miR-31-3p expression. miR-31-3p expression was increased in both TNBS- and DSS-induced colitis and human colonic biopsies from ulcerative colitis, compared with controls. Intracolonic administration of a miR-31-3p chemical inhibitor exacerbated TNBS- and DSS-induced colitis and increased colonic TNF-α, CXCL10, and chemokine (C-C motif) ligand 2 (CCL2) mRNA expression. Conversely, overexpression of miR-31-3p ameliorated the severity of DSS-induced colitis. Bioinformatic, luciferase reporter assay, and Western blot analyses identified RhoA as a target of miR-31-3p in NCM460 cells. Constitutive activation of RhoA led to increased expression of CCL2, IL6, TNF-α, and CXCL10 in NCM460-NK-1R cells on SP stimulation. Our results reveal a novel SP-miR-31-3p-RhoA pathway that protects from colitis. The use of miR-31-3p mimics may be a promising approach for colitis treatment.

Impact of Quantity and Type of Dietary Protein on Cardiovascular Disease Risk Factors Using Standard and Network Meta-analyses of Randomized Controlled Trials.

CONTEXT: Higher protein diets (HPDs) have shown favorable outcomes on weight maintenance and body-composition management; however, their protective effects against cardiovascular diseases (CVDs) remain uncertain and contentious. Furthermore, it is important to consider the influence of other macronutrients in the diet and type of dietary protein when studying HPDs, because this aspect has been overlooked in previous studies. OBJECTIVE: We assessed the impacts of quantity and type of dietary protein on CVD risk factors. DATA SOURCES: A database search was conducted in PubMed, Embase, CINAHL, Web of Science, and Cochrane Library and a total of 100 articles met the eligibility criteria. DATA EXTRACTION: Extracted data from 100 articles were analyzed using standard meta-analysis, and 41 articles were also analyzed using network meta-analysis. DATA ANALYSIS: In the standard meta-analysis, an HPD had significant favorable effects on systolic blood pressure (SBP) (mean difference [MD] = -1.51 mmHg; 95% CI: -2.77, -0.25), diastolic blood pressure (DBP) (MD = -1.08 mmHg; 95% CI: -1.81, -0.35), and flow-mediated dilation (MD = 0.78%; 95% CI: 0.09, 1.47) compared with lower protein diets. The further network meta-analysis supported that the high-protein, high-carbohydrate, low-fat diet was the most recommended diet to ensure a maximum decrease in SBP, DBP, total cholesterol (TC), and low-density-lipoprotein cholesterol (LDL-C). In comparison to animal-protein-rich diets, plant-protein-rich diets (PPRs) exhibited a significant favorable effects on improving TC (MD = -0.12 mmol/L; 95% CI: -0.19, -0.05), triglyceride (MD = -0.05 mmol/L; 95% CI: -0.09, -0.01), LDL-C (MD = -0.11 mmol/L; 95% CI: -0.18, -0.04), and high-density-lipoprotein cholesterol (MD = 0.03 mmol/L; 95% CI: 0.02, 0.04) levels. CONCLUSION: Consumption of HPDs and PPRs supports improvements in vascular health and lipid-lipoprotein profiles, respectively. Furthermore, macronutrient composition should be carefully designed in the dietary approach to maximize the effectiveness of HPDs in improving CVD risk factors. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022369931.

Effect of Antioxidant Supplementation on Macular Pigment Optical Density and Visual Functions: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Antioxidants are bioactive molecules that function to scavenge free radicals and balance oxidative stress. Although all antioxidants can act as reactive oxygen species scavengers, their efficacy on eye health may vary. Moreover, the comparative effectiveness and potential additive effect between groups of antioxidants, hitherto, have not been systematically studied. A systematic review and network meta-analysis were conducted to investigate the comparative or additive effect of dietary antioxidant supplements on eye health. Four databases (PubMed, Embase, CINAHL, and Cochrane) were searched, and relevant randomized controlled trials were identified. Out of 60 articles selected for systematic review, 38 were included in the network meta-analysis, categorized into 8 distinct antioxidant-supplemented groups and placebo. All groups significantly increased macular pigment optical density and contrast sensitivity at low spatial frequency, whereas only the antioxidant mixture + lutein (L) + fatty acid combination exhibited significant improvements in visual acuity (hazard ratio = -0.15; 95% confidence interval: -0.28, -0.02) and L + zeaxanthin combination for photostress recovery time (hazard ratio = -5.75; 95% confidence interval: -8.80, -1.70). Especially, the L + zeaxanthin + fatty acid combination was ranked best for macular pigment optical density (surface under the cumulative ranking: 99.3%) and second best for contrast sensitivity at low spatial frequency (67.7%). However, these findings should be interpreted with caution due to low quality of evidence, primarily influenced by indirectness and potential publication bias. Overall, antioxidant supplementation was estimated to improve eye health parameters, whereas different combinations of antioxidants may also have varying effects on improving visual health from multiple perspectives. This study was registered at PROSPERO as CRD42022369250.