Correlation of Homocysteine, AHSG, CRP with Insulin Resistance, 25-(OH)2-VitD, Blood Lipids in Gestational Diabetes Patients.

BACKGROUND: To investigate the correlations of serum homocysteine (Hcy), α2-Heremans-Schmid glycoprotein (AHSG), and C-reactive protein (CRP) with insulin resistance (IR), 25-hydroxyvitamin D (25-OH-VD), and blood lipids in patients with gestational diabetes mellitus (GDM) by detecting their levels. METHODS: A total of 72 GDM patients (GDM group) and 72 healthy pregnant women (control group) delivered in our hospital from February 2017 to January 2019 were randomly selected. The basic data, somatological parameters [height, weight, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), blood pressure, and body fat content], and biochemical indexes (glucose metabolism indexes, lipid metabolism indexes, Hcy, AHSG, CRP, and 25-OH-VD) were compared between the two groups. Additionally, Pearson's correlation analysis was employed to analyze the correlations among indicators. RESULTS: In comparison with the control group, the GDM group had a higher average rate of family history of DM (p < 0.05), larger waist circumference and WHR, and higher body fat content (p < 0.05). Besides, the fasting plasma glucose (FPG), 1-hour plasma glucose (1hPG) and 2-hour plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment (HOMA)-IR, triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) were higher in the GDM group than those in the control group (p < 0.05), while the high density lipoprotein cholesterol (HDL-C) was lower in the GDM group than that in the control group (p < 0.05). Compared with those in the control group, the serum Hcy, AHSG, and CRP levels rose, while the serum 25-OH-VD level declined in the GDM group (p < 0.05). The results of Pearson's correlation analysis revealed that HOMA-IR had positive correlations with FPG, FINS, TC, TG, Hcy, AHSG, and CRP (r = 0.591, 0.825, 0.312, 0.234, 0.458, 0.647, 0.487, p < 0.05) and negative correlation with 25-OH-VD (r = -0.323, p < 0.05). CRP was positively correlated with HOMA-IR, TC, and AHSG (r = 0.485, 0.331, 0.226, p < 0.05), negatively associated with 25-OH-VD (r = -0.443, p < 0.05), and had no correlation to TG and Hcy (r = 0.019, 0.058, p > 0.05). AHSG displayed positive correlations with HOMA-IR, TC, TG, and CRP (r = 0.647, 0.321, 0.314, 0.226, p < 0.05) and no association with Hcy and 25-OH-VD (r = 0.058, -0.034, p > 0.05). CONCLUSIONS: GDM patients have increased serum Hcy, AHSG, and CRP levels and a decreased serum 25-OH-VD level, indicating that serum Hcy, AHSG, CRP, and 25-OH-VD are correlated with glucose and lipid metabolism disorders in GDM patients.

Interleukin-36 receptor antagonist attenuates atherosclerosis development by inhibiting NLRP3 inflammasome.

Atherosclerosis is characterized, as an inflammatory disorder in the circulatory system, with increasing tendency toward mortality and morbidity. Thus, developing novel therapeutic targeting inflammation is necessary. Here, we investigated the effects of interleukin-36 receptor antagonist (IL-36RN), a newly identified anti-inflammatory factor, on atherosclerosis. The regulation of NLRP3 inflammasome by IL-36RN was determined in vitro in macrophage cells after oxidized low-density lipoprotein (ox-LDL) stimulation. The IL-1ß and caspase-1 p10 secretion were assessed by enzyme-linked immunosorbent assay and western blot analysis. Finally, the IL-36RN/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice. IL-36RN suppressed the expression of NLRP3, the secretion of IL-1ß, and caspase-1 p10 in vitro, while IL-36 pathway stimulation activated the NLRP3 inflammasome, which was inhibited by IL-36RN. In the mouse model of atherosclerosis, IL-36RN delivered by the lentivirus vector inhibited the development of atherosclerosis, and the atheroprotective effects of IL-36RN were attenuated by IL-36 pathway stimulation. Furthermore, the regulation of NLRP3 inflammasome by IL-36RN was also confirmed in vivo. We demonstrated here that IL-36RN exerted atheroprotective functions through IL-36RN/NLRP3 inflammasome pathway.

Role of ERp46 in ß-cell lipoapoptosis through endoplasmic reticulum stress pathway as well as the protective effect of exendin-4.

Endoplasmic reticulum (ER) stress is considered as a key factor in free fatty acid (FFA)-induced apoptosis. ERp46, a new member of the thioredoxin family, is highly expressed in pancreatic ß-cells and plays an important role in glucose toxicity. In this study we examined the potential role of ERp46 in palmitic acid (PA)-induced cell apoptosis and the protective role of exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor. The glucose-sensitive mouse ß-pancreatic cell line, ßTC6, was used to investigate the mechanisms of PA-induced apoptosis. Our results showed that ERp46 expression was reduced in a dose- and time-dependent manner after PA treatment. Furthermore, inhibition of ERp46 expression by small interfering (si)RNA-mediated silencing enhanced the ER stress response via three separate pathways and increased ßTC6 cell apoptosis rates. Moreover, exendin-4 reduced the ER stress response and levels of apoptosis in NC transfected cells after PA treatment, but not in cells transfected with ERp46siRNA. In conclusion, ERp46 plays a protective role in PA-induced cell apoptosis by decreasing the ER stress response and might be a novel target for anti-diabetic drugs. Exendin-4 might protect against ßTC6 cell lipoapoptosis in part by activating ERp46 signaling pathway.

Effect of PANDER in ßTC6-cell lipoapoptosis and the protective role of exendin-4.

Chronic exposure to high concentrations of saturated fatty acids, such as palmitic acid (PA), leads to apoptosis of pancreatic ß-cells through the activation of the c-Jun N-terminal kinase (JNK) signaling pathway. This study of ß-cell lipoapoptosis was designed to investigate the roles of pancreatic-derived factor (PANDER), a pro-apoptosis cytokine-like peptide, and exendin-4, a long-acting agonist of the hormone glucagon-like peptide-1 (GLP-1) receptor and anti-apoptosis factor. The glucose-sensitive mouse ß-pancreatic cell line, ßTC6, was used to investigate the mechanisms of PA-induced apoptosis. Twenty-four hours of PA exposure led to increased PANDER expression in a dose- and time-dependent manner, and significantly increased phosphorylation of JNK. Treatment with the JNK-specific inhibitor SP600125 reduced the PA-induced PANDER expression. After the 24h of PA exposure, cells also underwent marked apoptosis and showed increased activation of the apoptosis protease, caspase-3. The small interfering (si)RNA-mediated silencing of PANDER gene expression significantly reduced both of these effects. When PA-treated ßTC6 cells were exposed to exogenous exendin-4, JNK activation was inhibited, PANDER expression was decreased, and the numbers of apoptotic cells were reduced. Collectively, these results demonstrated that the JNK-mediated signaling mechanism of PA-induced ß-cell apoptosis involves up-regulated expression of PANDER and activation of caspase-3. Exendin-4 may protect against lipoapoptosis by interfering with the JNK-PANDER pathway.

[Function of the hypothalamus-pituitary-adrenal axis in children with attention deficit hyperactivity disorder].

OBJECTIVE: To study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD). METHODS: One hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): ADHD-predominantly inattention type (ADHD-I, n=44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n=32) and ADHD-combined type (ADHD-C, n=52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone (ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence respectively at 8:00 am. The intelligence level was tested by Raven's standard progressive matrices. RESULTS: The children with ADHD had lower IQ score (84.5 + or - 11.3) than the control group (94.6 + or - 12.4) (p<0.01). There were significant differences in the IQ score among the three ADHD subgroups (p<0.01). The IQ score in the ADHD-I and the ADHD-C groups was significantly lower than that in the control group. The mean plasma cortisol level in the ADHD group (226.5 + or - 129.1 nmol/L) was significantly lower than that in the control group (384.5 + or - 141.4 nmol/L) (p<0.01). The three ADHD subgroups showed significantly decreased plasma cortisol level compared with the control group (p<0.01). The plasma level of cortisol was the lowest in the ADHD-HI group (154.4 + or - 71.6 nmol/L), followed by the ADHD I group (219.4 + or - 117.7 nmol/L) and the ADHD-C group (258.3 + or - 136.4 nmol/L). There were no significant differences in plasma concentration of ACTH between ADHD and control children. CONCLUSIONS: In the non-stress state, the HPA axis may be dysfunctional in children with ADHD, which may be attributed to the under reactivity of the HPA axis. Lower plasma cortisol has fewer impacts on the cognitive-behavior function, but it may closely be related to attention deficit, hyperactivity and impulsive behaviors.