Endotoxemia-induced acute kidney injury (AKI) is a common clinical condition and lacks effective treatments. Elabela (ELA) is a recently discovered kidney peptide hormone, encoded by the gene apela, and has been reported to improve cardio-renal outcomes in sepsis. However, ELA is a small peptide and is largely unsuitable for clinical use because of its short in vivo half-life. In this study, we evaluated the potential renoprotective effects of a long-acting Fc-ELA fusion protein in liposaccharide (LPS)-induced AKI in mice. LPS administration in mice for five days greatly lowered the gene expression of apela and impaired kidney function, as evidenced by elevated serum creatinine and the ratio of urine protein to creatinine. In addition, renal inflammation and macrophage infiltration were apparent in LPS-challenged mice. Treatment with the Fc-ELA fusion protein partially restored apela expression and attenuated the kidney inflammation. Moreover, LPS treatment induced ROS production and apoptosis in kidney HK-2 cells as well as in the mouse kidney, which were mitigated by ELA or Fc-ELA treatment. Finally, we found ELA promoted the survival of HK-2 cells treated with LPS, and this action was abolished by LY204002, a PI3K/Akt inhibitor. Collectively, we have demonstrated that the Fc-ELA fusion protein has significant renoprotective activities against LPS-induced AKI in mice.
Background Despite the fact that the majority of gallstones formed in the gallbladder are mainly composed of cholesterol, as they are formed from cholesterol-supersaturated bile, there is still no consensus regarding the contribution of blood serum lipids in the pathogenesis of gallbladder stone disease (GSD). Here, we aimed to investigate the relationship between hypercholesterolemia and the risk of new-onset asymptomatic GSD, and to determine the prevalence of factors associated with new-onset asymptomatic GSD in patients with hypercholesterolemia.Methods In this case-control study, we enrolled 927 Chinese patients with new-onset asymptomatic gallstone disease and 845 healthy controls starting in August 2012. Patients were matched for age, gender, race, occupation, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels (FBG). Body mass index, nonalcoholic fatty liver disease (NAFLD) and serum lipids indexes were compared and the relationships between BMI, blood lipid and gallbladder stone hazards were examined by using logistic multivariate regression models.Results The result showed a significant higher morbidity with GSD in hypercholesterolemia than non-hypercholesterolemia patients (X2=17.211, P<0.001). Of hypercholesterolemia patients, LDL-c (OR=1.493, P=0.029) and NAFLD (OR=2.723, P=0.022) were significant risk factors for GSD, while male sex (OR=0.244, P=0.033), weight (OR=0.961, P=0.022), HDL-c (OR=0.305, P<0.001), and FBG (OR=0.687, P=0.034) significantly negatively correlated with GSD in univariate analysis. Multivariate logistic regression indicated weakly positive correlations with NAFLD (OR=3.284, P=0.054), and significant negative correlations with weight (OR=0.930, P=0.018), HDL-c (OR=0.144, P<0.001), and GSD. Conclusion Hypercholesterolemia acts as an independent risk factor for new-onset asymptomatic GSD, while obesity and NAFLD are synergistic factors. Interestingly, we are the first to report that elevated weight was inversely associated with GSD in patients with hypercholesterolemia.
Background: Diabetes has become an epidemic in developing countries. The incidence of adverse cardiovascular events is high and the control rate is low in Chinese patients with type 2 diabetes mellitus (T2DM), particularly in low-income areas of China. The aim of this study was to identify the risk factors for acute coronary syndrome (ACS) in patients with T2DM in Northwest China. Methods: A total of 456 patients with T2DM admitted to The First Affiliated Hospital of Xi’an Jiaotong University from January 2018 to January 2019 were included in the study. Among these, 186 individuals newly diagnosed with ACS were categorized as the case group and 270 patients without ACS as the control group. Demographic characteristics and serum biomarkers between the two groups were compared using t-test or Chi-square test. Multivariate logistic regression was used to analyze the risk factors for ACS in T2DM. Results: The proportion of elderly patients was higher in the case group than in the control group (30.65% vs. 15.56%, p <0.001). Similarly, the case group had a higher proportion of patients with hypertension history (66.67% vs. 34.81%, p <0.001), substandard systolic blood pressure (SBP) (44.09% vs. 21.48%, p <0.001), hyperuricemia (34.41% vs. 11.11%, p <0.001), and higher body mass index (BMI) (26.64 ± 3.96 vs. 24.87 ± 3.53, p <0.001) compared to the control group. The multivariate logistic regression analysis showed that age ≥ 65 years, SBP ≥ 140 mm Hg, overweight or obesity, and hyperuricemia were all risk factors for ACS in T2DM, and their OR (95% CI) were 2.283 (1.371-3.802), 2.067 (1.322-3.233), 2.019 (1.501-2.716), and 3.108 (1.831-5.275), respectively. Conclusion: Aging, systolic hypertension, obesity and hyperuricemia increase the risk of ACS in T2DM in Northwest China. Thus, weight loss and lowering of SBP and of blood uric acid levels may reduce the risk of ACS in T2DM. Disclosure Q. Zhao: None. Funding Shaanxi Province Science Technology of China (2019KW-079)
Background: This case-control study aimed to assess associations of overweight/obesity with gallbladder stone disease (GSD).Methods: We enrolled 345 new-onset asymptomatic GSD and 690 healthy controls who had undergone annual health check-ups at the Affiliated Hospital of Xi’an Jiaotong University, in 2012-2017. Height, weight, blood pressure, serum lipid indexes and fasting blood glucose were assessed, and associations were determined by logistic multivariate regression analysis.Results: In overweight subjects, WC, BMI, WHtR, LDL-c and FBG showed significant positive correlations with GSD in univariate analysis, while HDL-c had a significant negative correlation (all P<0.05); in multivariate analysis, BMI (OR=37.738, P<0.001), WHtR (OR=1.128, P=0.042), LDL-c (OR=1.551, P=0.014) and FBG (OR=1.463, P=0.017) were significant risk factors, while HDL-c (OR=0.193, P<0.001) was a protective factor for GSD. In obese individuals, WC, BMI, WHtR, TG, LDL-c, and NAFLD showed significant positive correlations with GSD in univariate analysis, while HDL-c had a significant negative correlation (all P<0.05); BMI (OR=0.384, P=0.001) and HDL-c (OR=0.034, P<0.001) were protective factors, while WHtR (OR=2.863, P<0.001) and NAFLD (OR=4.730, P=0.037) were significant risk factors.Conclusion: BMI is an independent risk factor for new-onset asymptomatic GSD in overweight population. Meanwhile, obesity is associated with asymptomatic GSD formation with concurrent hyperlipidemia and NAFLD.
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