microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis.

Chronic apical periodontitis (CAP) is defined as chronic inflammation of the dental pulp and root canal system. Porphyromonas endodontalis lipopolysaccharide ( P. endodontalis LPS) plays an important role in inducing an inflammatory response in CAP. microRNA-146a (miR-146a) is a key regulator of inflammation and is induced by LPS. Hairy and enhancer-of-split related with YRPW motif 2 (Hey2) has been confirmed to be induced by the Notch signaling pathway, which is involved in tooth development, pulp regeneration, and repair after injury. Our study aimed to investigate the functional role of miR-146a via the targeting of Hey2 in CAP as well as the underlying mechanism. Compared with 13 healthy controls, miR-146a and Hey2 expressions were significantly higher in 20 patients with CAP. In addition, miR-146a, Hey2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α expressions were significantly increased in MC3T3-E1 cells stimulated with different concentrations (0-20 µg/mL) of P. endodontalis LPS for different amounts of time (0-48 hours). Moreover, miR-146a, which acts as an anti-inflammatory mediator, negatively regulated the expression of IL-6, IL-1ß, and TNF-α, and Hey2 was confirmed as a target gene of miR-146a by a luciferase reporter assay. Hey2 also negatively regulated miR-146a, IL-6, IL-1ß, and TNF-α expressions, and P. endodontalis LPS strongly induced Hey2 recruitment to the IL-6 promoter (-400 ~ -200 bp). These findings suggest that miR-146a and Hey2 form a mutual negative feedback regulatory loop, demonstrating a novel mechanism that regulates inflammatory responses in CAP.

Home enteral nutrition and oral nutritional supplements in postoperative patients with upper gastrointestinal malignancy: A systematic review and meta-analysis.

BACKGROUND: The safety and potential benefits of home enteral route nutrition (HERN), referring specifically to home enteral nutrition (HEN) and oral nutritional supplements (ONS) in this article, after upper gastrointestinal (GI) resection are inconsistent. OBJECTIVE: To evaluate the impact of HERN on nutritional status, complications, and quality of life (QOL) after upper GI resection. METHODS: This systematic review was conducted in accordance with the PRISMA statement. Nine databases were searched from inception to October 2019. Randomized controlled trials (RCTs) comparing the impact of HERN after upper gastrointestinal resection were included. Relative risk/weighted mean difference/standardized mean difference (RR/WMD/SMD) and corresponding 95% confidence intervals (95% CI) were calculated using fixed- or random-effects models. RESULTS: Overall, 15 RCTs involving 1059 patients were included. Compared with normal oral diet, HERN significantly prevented weight loss (-3.95 vs -5.82 kg; SMD: 1.98 kg; 95% CI: 1.24-2.73); improved added-level of albumin (3.48 vs 2.41 g/L; SMD: 1.36 g/L; 95% CI: 0.81-1.91), hemoglobin (6.54 vs -1.29 g/L; WMD: 7.45 g/L; 95% CI: 5.05-9.86), pre-albumin (37.59 vs 7.35 mg/L; WMD: 21.6 mg/L; 95% CI: 5.96-37.24), and transferrin (63.08 vs 50.45 mg/L; WMD: 16.44 mg/L; 95% CI: 13.51-19.38); and reduced the incidence of malnutrition or latent malnutrition (RR = 0.54; P < 0.01). Subgroup analysis based on the approach of HERN showed that weight loss in the HEN subgroup was significantly lower than that of the control group (WMD = 2.69, P < 0.01), while there was no significant difference between the ONS subgroup and the control group (P = 0.1). The same results were found in albumin. Physical function (WMD: 5.29; 95% CI: 1.86-8.73) and fatigue (WMD: -8.59; 95% CI: -12.61, -4.58) dimensions in QOL were significantly better in the HERN group. No significant differences in gastrointestinal and tube-related complications. CONCLUSION: HERN improved nutritional status and some dimensions of QOL in upper GI malignancy patients after surgery, without increasing complications. Subgroup analysis showed that HEN experienced more benefits than ONS.