Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD. We used in vivo and in vitro techniques to investigate the protective effects of exenatide on fatty liver via fat mass and obesity associated gene (FTO) in a high-fat (HF) diet-induced NAFLD animal model and related cell culture model. Exenatide significantly decreased body weight, serum glucose, insulin, insulin resistance, serum free fatty acid, triglyceride, total cholesterol, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in HF-induced obese rabbits. Histological analysis showed that exenatide significantly reversed HF-induced lipid accumulation and inflammatory changes accompanied by decreased FTO mRNA and protein expression, which were abrogated by PI3K inhibitor LY294002. This study indicated that pharmacological interventions with GLP-1 may represent a promising therapeutic strategy for NAFLD.

Background Elevated serum uric acid is commonly associated with high triglyceride. However, the relation of triglyceride and hyperuricemia in different gender and age groups is currently not well understood. This study aimed to evaluate age- and gender-related association of high triglyceride with hyperuricemia in a subgroup of Chinese population. Methods We retrospectively analyzed physical examination data of 24,438 subjects (12,557 men and 11,881 women) in Kaifeng, China. The alanine aminotransferase, γ-glutamyl transpeptidase, serum creatinine, blood urea nitrogen, total cholesterol, high-density lipoprotein cholesterol, triglyceride and serum uric acid were measured in all subjects. The triglyceride was categorized into < 1.21, 1.21 ~, 1.7 ~, 2.83 ~ and >  5.6 mmol/L subgroups, and odds ratio (OR) and 95% confidence interval (CI) of hyperuricemia were calculated by logistic regression analysis. Results Univariate and age-adjusted analyses showed that high triglyceride was positively associated with hyperuricemia ( p <  0.01). Further age-stratified analysis showed that the positive association was significant in the 20 ~, 30 ~, 40 ~, 50 ~, 60 ~ and 80 ~ age groups in men. In women, no statistically significant was found in 60 ~ and 70 ~ age groups. Conclusion High triglyceride is positively associated with hyperuricemia in both men and women, and this association is age-related, especially in women.

Short-and long-term exposure to particulate matter (PM) has been associated with cardiovascular disease (CVD). It is well recognized that oxidative stress is a potential major mechanism in PM-induced vascular injuries, in which the nuclear factor E2-related factor 2 (Nrf2) signaling pathway plays a critical role. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential vascular injury and the potential role of Nrf2 in the angiotensin II (Ang II)-associated vascular injury. After 6-or 11-week exposure to PM, the histopathology assay revealed that PM exposure resulted in the thickening of the walls of vascular. After 6 weeks exposure to PM, the ELISA assay revealed that PM exposure resulted in the elevated plasma concentration of Ang II. The expression levels of genes of interest were then further investigated with quantitative real-time PCR. Notably, the results showed that Angiotensinogen (AGT), Angiotensin converting enzyme (ACE) and Angiotensin type I receptor (AT1R) were involved in PM-induced pathological changes. Western blotting for ACE showed similar results. Moreover, the extent of vascular thickening and the Ang II elevation was most prominent in the Nrf2 gene knockout PM exposure group (KOE). Furthermore, the expression of Nrf2 downstream relevant genes (HO1, Nqo1, Gclc, Gsta4) were significantly enhanced in the wildtype PM exposure group (WTE), while those were remarkably suppressed in the Nrf2 gene knockout groups. The ELISA result of monocyte chemoattractant protein-1 (MCP-1) serum levels in the KOE group was significantly higher in relation to that in the Nrf2 knockout control group (KOC). In summary, PM exposure is associated with thickening of vascular wall, while Nrf2 knockout may further enhance this effect. A potential mechanistic contributor of such effects is the activation of ACE/ANGII/AT1R axis, in which Nrf2 played a regulatory role.

Background: Although lack of ERβ is an acknowledged risk factor for the development of inflammatory bowel disease (IBD) and psychiatric disorders, the underlying cellular and molecular mechanisms are not fully understood. Here, we revealed the role of gut microbiota in the development of IBD and related anxiety-like behavior in ERβ deficiency mice. Results: In this study, we showed that ERβ knockout mice upon dextran sodium sulfate (DSS) insult displayed significant shifts in fecal microbiota composition with increasing enrichment of genus Prevotellaceae_UCG_001, aggravated colitis severity and anxiety-like behaviors. In addition, DSS induced colitis also enhanced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in ERβ-deficiency mice, which linked colitis and anxiety-like behaviors. In line with these observations, RNA sequencing data further identified ErbB4 might be the target of ERβ involved in regulating HPA axis hyperactivity caused by DSS insult. Gut microbiota remodeling by co-housing showed both colitis severity and anxiety-like behaviors were aggravated in co-housed WT mice compared with single-housed WT mice, suggesting that gut microbiota plays a critical role in mediating colitis disease activity and related anxiety-like behaviors via aberrant neural processing within the gut-brain axis. Conclusions: Our findings demonstrate ERβ has the potential to inhibit colitis development and anxiety-like behaviors via remodeling of gut microbiota, which reveals ERβ as a promising therapeutic target for treating IBD and related anxiety-like behaviors.

<b><i>Introduction:</i></b> Congenital auricular deformity (CAD) is a common postpartum deformity, and nonsurgical correction of CAD has been recognized as a safe and effective approach. Three-dimensional (3D) technique has been used in surgical reconstruction of unilateral microtia; however, 3D technique used in nonsurgical correction for deformational CAD has not been reported. <b><i>Methods:</i></b> In this study, 12 CAD patients aged from 0.6 to 7 months with 16 deformational CAD were treated with 3D technique-based personalized nonsurgical correction (3D-NSC). Patients’ CAD was photographed pre- and post-correction, and clinical outcome was evaluated as poor, fair, good, and excellent by comparing pre- and post-correction pictures. Different kinds of tests were used to analyze the data. <b><i>Results:</i></b> All patients got an improved auricle shape (10 excellent, 2 good, and 4 fair). Multivariate regression analysis showed that CAD type was significantly associated with correction outcome, sex and age were significantly associated with correction outcome for the 11 constructed types of CAD, and age was significantly associated with the correction outcome when we focused on the male constructed auricles. <b><i>Conclusion:</i></b> 3D-NSC provided a significant nonsurgical clinical treatment for CAD patients, with younger patients getting better clinical outcomes with shorter correction time.