Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients

Osteoprotegerin (OPG) gene polymorphisms (T245G, T950C and G1181C) have been associated with osteoporosis and early predictors of cardiovascular disease. The aim of this study was to evaluate whether these polymorphisms contribute to cardiovascular disease (CVD) in type 2 diabetic patients. We performed a case-control study with 178 CVD subjects with diabetes and 312 diabetic patients without CVD to assess the impact of variants of the OPG gene on the risk of CVD. The OPG gene polymorphisms were analyzed by using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There was no significant association between the T245G and G1181C polymorphisms and CVD in the additive genetic model (OR = 0.96, 95% CI 0.64-1.45, p = 0.79; OR = 1.06, 95% CI 0.81-1.39, p = 0.65, respectively). However, the C allele of the T950C polymorphism was independently associated with a risk of CVD in type 2 diabetic patients in this genetic model (OR = 1.38, 95% CI 1.07-1.80, p = 0.01). This study provides evidence that the C allele of the T950C polymorphism is associated with increased risk of CVD in diabetic patients. However, well-designed prospective studies with a larger sample size are needed to validate these results

Efficient nanoarchitectonics of solid-electrolyte-interface for high-performance all-solid-state lithium metal batteries via mild fluorination on polyethylene oxide

Polyethylene oxide (PEO) based polymer electrolytes is promising for all-solid-state lithium metal batteries (ASSLMBs). Solid-electrolyte-interface (SEI) layer formed between polymer electrolytes and lithium metal is crucial to inhibit lithium dendrites growth. Herein, mild fluorination on commercial PEO is engineered as an electrolyte for ASSLMBs, which shows an outstanding cycling stability. During this process, some C-H bonds in PEO chains are substituted with C-F bonds, resulting in the formation of fluorinated PEO (F-PEO) with a low fluorine content of 2.7 at.%. Fluorination alters the regularity of PEO chains, leading to an improved ion conductivity for F-PEO/LiTFSI. An unusual and stable SEI containing relatively high LiF content forms, which can inhibit lithium dendrites growth and boost the battery performance. Li/Li cell with F-PEO/LiTFSI delivers outstanding cycling stability over 2000 h at 0.1 mA cm-2. When matching with LiFePO4 cathode, the battery exhibits high capacity of 151.0 mAh g−1 and good cycling stability for 500 cycles (0.05% decay per cycle) at 0.5 C. Even at 1.0 C, the capacity of the battery keeps at 99.8 mAh g−1 after 900 cycles. This facile and low-cost strategy opens an avenue for ASSLMBs towards their commercial applications

S1PR2 antagonist ameliorate high glucose-induced fission and dysfunction of mitochondria in HRGECs via regulating ROCK1

Abstract Aims Sphingosine-1-phosphate receptor 2 (S1PR2) is a G-protein-coupled receptor that regulates sphingosine-1-phosphate-triggered cellular response. However, the role of S1PR2 in diabetes-induced glomerular endothelial cell dysfunction remains unclear. This study aims to investigate the effect of S1PR2 blockade on the morphology and function of mitochondria in human renal glomerular endothelial cells (HRGECs). Methods HRGECs were pretreated with a S1PR2 antagonist (JTE-013) or a Rho-associated coiled coil-containing protein kinase 1 (ROCK1) inhibitor (Y27632) for 30 min and then cultured with normal glucose (5.5 mM) or high glucose (30 mM) for 72 h. The protein expression levels of RhoA, ROCK1, and Dynmin-related protein-1(Drp1) were evaluated by immunoblotting; mitochondrial morphology was observed by electron microscopy; intracellular levels of ATP, ROS, and Ca2+ were measured by ATPlite, DCF-DA, and Rhod-2 AM assays, respectively. Additionally, the permeability, apoptosis, and migration of cells were determined to evaluate the effects of S1PR2 and ROCK1 inhibition on high glucose-induced endothelial dysfunction. Results High glucose induced mitochondrial fission and dysfunction, indicated by increased mitochondrial fragmentation, ROS generation, and calcium overload but decreased ATP production. High glucose also induced endothelial cell dysfunction, indicated by increased permeability and apoptosis but decreased migration. However, inhibition of either S1PR2 or ROCK1 almost completely blocked these high glucose-mediated cellular responses. Furthermore, inhibiting S1PR2 resulted in the deceased expression of RhoA, ROCK1, and Drp1 while inhibiting ROCK1 led to the downregulated expression of Drp1. Conclusions S1PR2 antagonist modulates the morphology and function of mitochondria in HRGECs via the positive regulation of the RhoA/ROCK1/Drp1 signaling pathway, suggesting that the S1PR2/ROCK1 pathway may play a crucial role in high glucose milieu