Long non-coding RNA HCG18 promotes M1 macrophage polarization through regulating the miR-146a/TRAF6 axis, facilitating the progression of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most important complications in diabetes mellitus (DM), which has been reported to be modulated by long non-coding RNAs (lncRNAs). The purpose of the current study is to explore the regulatory mechanism of lncRNA HCG18 on DPN in vitro. The expression of lncRNA HCG18, miR-146a, TRAF6, CD11c, and iNOS was detected by qRT-PCR. Through Enzyme-linked immunosorbent assay, the levels of inflammatory factors (TNF-α, IL-1ß, and IL-6) were determined. M1 macrophage polarization was measured by flow cytometry analysis. The interactions between miR-146a and HCG18/TRAF6 were predicted by Starbase/Targetscan software and verified by the dual luciferase reporter assay. Western blot assay was performed to determine the protein expression of TRAF6. LncRNA HCG18 was highly expressed in DPN model and HG-induced macrophages. The levels of inflammatory factors (TNF-α, IL-1ß, and IL-6) were elevated in DPN model. The expression of M1 markers (CD11c and iNOS) was visibly up-regulated in DPN model and was positively correlated with HCG18 expression. LncRNA HCG18 facilitated M1 macrophage polarization. In addition, miR-146a was identified as a target of lncRNA HCG18. Overexpression of miR-146a reversed the promoting effect of HCG18 on M1 macrophage polarization. Simultaneously, TRAF6 was a target gene of miR-146a TRAF6 expression was positively modulated by HCG18 and was negatively modulated by miR-146a. Down-regulation of TRAF6 reversed the promoting effect of HCG18 on M1 macrophage polarization. LncRNA HCG18 promotes M1 macrophage polarization via regulating the miR-146a/TRAF6 axis, facilitating the progression of DPN. This study provides a possible therapeutic strategy for DPN.

Effect of neuron-derived neurotrophic factor on rejuvenation of human adipose-derived stem cells for cardiac repair after myocardial infarction.

The decline of cell function caused by ageing directly impacts the therapeutic effects of autologous stem cell transplantation for heart repair. The aim of this study was to investigate whether overexpression of neuron-derived neurotrophic factor (NDNF) can rejuvenate the adipose-derived stem cells in the elderly and such rejuvenated stem cells can be used for cardiac repair. Human adipose-derived stem cells (hADSCs) were obtained from donors age ranged from 17 to 92 years old. The effects of age on the biological characteristics of hADSCs and the expression of ageing-related genes were investigated. The effects of transplantation of NDNF over-expression stem cells on heart repair after myocardial infarction (MI) in adult mice were investigated. The proliferation, migration, adipogenic and osteogenic differentiation of hADSCs inversely correlated with age. The mRNA and protein levels of NDNF were significantly decreased in old (>60 years old) compared to young hADSCs (<40 years old). Overexpression of NDNF in old hADSCs significantly improved their proliferation and migration capacity in vitro. Transplantation of NDNF-overexpressing old hADSCs preserved cardiac function through promoting angiogenesis on MI mice. NDNF rejuvenated the cellular function of aged hADSCs. Implantation of NDNF-rejuvenated hADSCs improved angiogenesis and cardiac function in infarcted mouse hearts.

Chinese clinical guidelines for continuous glucose monitoring (2018 edition).

Blood glucose monitoring is an important part of diabetes management. Continuous glucose monitoring (CGM) technology has become an effective complement to conventional blood glucose monitoring methods and has been widely applied in clinical practice. The indications for its use, the accuracy of the generated data, the interpretation of the CGM results, and the application of the results must be standardized. In December 2009, the Chinese Diabetes Society (CDS) drafted and published the first Chinese Clinical Guideline for Continuous Glucose Monitoring (2009 edition), providing a basis for the standardization of CGM in clinical application. Based on the updates of international guidelines and the increasing evidence of domestic studies, it is necessary to revise the latest CGM guidelines in China so that the recent clinical evidence can be effectively translated into clinical benefit for diabetic patients. To this end, the CDS revised the Chinese Clinical Guideline for Continuous Glucose Monitoring (2012 Edition) based on the most recent evidence from international and domestic studies.

Estrogen receptor 1 gene polymorphisms are associated with metabolic syndrome in postmenopausal women in China.

BACKGROUND: Metabolic syndrome (MetS) includes obesity, diabetes, dyslipidemia and hypertension. Its incidence is rapidly increasing worldwide, particularly in postmenopausal women. Estrogens regulate glucose homeostasis and lipid metabolism via estrogen receptors 1 (ESR1) and 2 (ESR2). The current study aimed to elucidate associations of MetS with ESR1 and ESR2 gene polymorphisms in postmenopausal Chinese women. METHODS: This case-control study included 304 postmenopausal women (154 and 150 control and MetS patients, respectively). Clinical indicators related to MetS were assessed. Two ESR1 (PvuII and XbaI) and two ESR2 (RsaI and AluI) polymorphisms were evaluated by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. RESULTS: ESR1 polymorphisms were significantly different between MetS patients and healthy controls. G allele frequency for the XbaI polymorphism was significantly higher in patients than in control patients (p = 0.004, OR = 1.610, 95%CI 1.169-2.18). The haplotypes A-T (p = 0.015) and G-C (p = 0.024) showed significant differences. The minor alleles of the XbaI and PvuII gene polymorphisms in both homozygous and heterozygous forms showed associations with elevated waist circumference, fasting serum insulin and HOMA-IR. The minor G allele in homozygous and heterozygous forms of the RsaI and AluI gene polymorphisms showed associations with elevated total cholesterol and LDL-C. CONCLUSIONS: In postmenopausal Chinese women, ESR1 polymorphism and the haplotypes A-T and G-C of XbaI-PvuII are associated with MetS, unlike ESR2 polymorphisms. Patients harboring the G allele of XbaI have elevated BMI, waist circumference, systolic and diastolic BP, FBG, HOMA-IR, total cholesterol, TG, LDL-C and NAFLD (%), and reduced HDL-C.

[Analysis of metabolic risk factors for developing nonalcoholic fatty liver in patients with type 2 diabetes mellitus].

OBJECTIVE: To compare and explore metabolic risk factors related to type 2 diabetes mellitus (T2DM) and the development of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 389 in-patients with T2DM (DM group, 204 cases) and T2DM with NAFLD (DM+NAFLD group, 185 cases) were enrolled in the study between October 2012 and July 2013. Clinical data collected for analysis included levels of blood lipids, liver function markers, uric acid (UA) and insulin, as well as results from the oral glucose tolerance test (OGTT) and C peptide releasing test. Improvements in insulin level, C peptide secretion index [HOMR-IR(CP)] and whole body insulin sensitivity index (ISIcomp) were used to estimate insulin sensitivity. Improvements in insulin level, C peptide secretion index [HOMR-islet(CP)], early insulin secretion index (delta I30/delta G30), correction of the islet beta cell function index (MBC1) and glucose disposition index (DI) were used to evaluate the function of pancreatic islet 1 beta cells. The t-test and repeated measures ANOVA were used for statistical analyses. Risk factors of T2DM with NAFLD were assessed by using logistic regression analysis. RESULTS: Compared with the DM group, the DM+NAFLD group had higher body mass index (BMI) and levels of triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamine transferase and UA (all P < 0.05), but lower age and level of high density lipoprotein cholesterol (both P < 0.05). Moreover, the DM+NAFLD group had higher postprandial blood glucose levels at 30 min (10.88 ± 2.87 mmol/L vs. 12.18 ± 2.79 mmol/L, t =-3.32), 60 min (14.65 ± 3.69 mmol/L vs. 15.99 ± 3.12 mmol/L, t =-3.46), 120 min (16.56 ± 5.11 mmol/L vs. 17.65 ± 4.29 mmol/L, t =-2.81) and 180 min (13.92 ± 5.10 mmol/L vs. 14.71 ± 4.91 mmol/L, t=-2.02) (all P < 0.05). The DM+NAFLD group had higher postprandial insulin levels at 60 min (28.62 ± 23.51 muIU/ml vs. 36.91 ± 33.47 aIU/ml, t =-3.46) and 120 min (36.36 ± 25.60 muIU/mL vs. 44.38 ± 34.95 muIU/mL, t =-3.35) (both P < 0.05). The DM+NAFLD group had higher postprandial C peptide levels at 30 min (2.74 ± 1.70 ng/mL vs. 4.30 ± 6.51 ng/ml, t =-4.97), 60 min (4.17+/-2.49 ng/ml vs. 5.19 ± 2.96 ng/ml, t =-3.29) and 120 min (6.08 ± 2.79 ng/ml vs. 6.76 ± 3.10 ng/ml, t =-2.19) (all P < 0.05). The DM+NAFLD group had higher HOMA-IR(CP) (1.505 ± 0.004 vs. 1.507 ± 0.005, t =-2.208, P less than 0.05), but lower ISIcomp (90.09+/-69.31 vs. 59.93 ± 24.52, t =5.608), MBCI (4.68 ± 4.31 vs. 3.83 ± 2.41, t =2.365) and DI (35.40 ± 71.83 vs. 15.37 ± 13.93, t =3.730) (all P < 0.05). Logistic analysis showed that BMI, ALT, postprandial level of C-peptide at 30 min, and UA were the major risk factors of T2DM with NAFLD (OR =1.208, 2.080, 1.041, and 1.005, respectively; all P < 0.05). CONCLUSION: Patients with a propensity for developing nonalcoholic fatty liver disease may experience earlier open of type 2 diabetes. T2DM patients with NAFLD have more severe glucose metabolism disorders.

Expression and Mechanism of TXNIP/NLRP3 Inflammasome in Sciatic Nerve of Type 2 Diabetic Rats.

Objective: To determine the expression profiling and mechanism of thioredoxin-interacting protein (TXNIP)/nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome pathway in sciatic nerve (SN) of type 2 diabetes mellitus (T2DM) rats. Methods: Ten out of the 35 healthy SD rats (specific pathogen free) purchased were randomized into the control group, while the others were established a T2DM model by feeding a high-fat and high-sugar diet plus laparoscopic injection of 1% streptozotocin (STZ). The successfully modeled rats were subgrouped into two arms: a DM group with 10 rats and a resveratrol- (RES-) treated DM intervention group with 11 rats. Normal saline to control and DM groups. Alterations in fasting blood glucose (FBG) and body weight (BW) at different time points after administration were observed. Sciatic nerve conduction velocity (SNCV) and mechanical pain threshold (MPT) were measured. TXNIP, NLRP3, caspase-1, and interleukin- (IL-) 1ß levels in rat SN tissue were determined. Results: DM group rats showed higher FBG and lower BW than control rats at different time points (P < 0.05). The FBG of DM intervention group at 2, 4, and 6 weeks after administration was lower, and the BW at 4 and 6 weeks after dosing was higher than DM group. Higher MPT and SNCV were determined in DM intervention group versus DM group (P < 0.05). DM group rats had disordered, swollen, and dissolved SN myelin sheath structure; TXNIP inhibition led to a small amount of nerve myelin fragments and mild pathological changes. Lower TXNIP, NLRP3, caspase-1, and IL-1ß protein levels were found in DM intervention group versus DM group (P < 0.05). Conclusion: The pathogenesis of peripheral neuropathy in T2DM rats may be linked to TXNIP/NLRP3 inflammasome pathway activation, indicating the potential of this pathway as a therapeutic target for diabetic peripheral neuropathy (DPN).