In recent years,there are gradually increasing attentions on diabetic osteoporosis.Diabeticosteoporosis is characterized by insidious onset,high incidence,and risk of disability.Metabolic disorders caused bydiabetes mellitus are related to an imbalance between osteoblastic bone formation and osteoclastic resorption.Diabetesalters bone mass and increases the risk of fracture.In this review the influence of diabetes on osteoporosis isdiscussed.

OBJECTIVE To study the effects of the compatibility of Schisandra chinensis on Psoralea corylifolia -induced oxidative damage and endoplasmic reticulum stress in L 02 hepatocytes，and to provide reference for clinical use of the compatibility attenuation of P. corylifolia -S. chinensis . METHODS L02 cells were divided into blank control group ，P. corylifolia model group （1 200 μg/mL P. corylifolia ，calculated by crude drug ），P. corylifolia -S. chinensis low-dose，medium-dose and high-dose groups （1 200 μg/mL P. corylifolia combined with 600，1 200，2 400 μg/mL S. chinensis ，respectively，calculated by crude drug ）. After the cells in each group were cultured in culture medium or drug solution for 48 hours，the levels of aspartate aminotransferase（AST）and alanine aminotransferase （ALT）were detected ；the levels of glutathione （GSH），superoxide dismutase （SOD）and malondialdehyde （MDA）in cell culture medium were detected ；reactive oxygen species （ROS）level and mitochondrial membrane potential in cells were detected ；mRNA and protein expressions of glucose-regulated protein 78（GRP-78）and protein kinase R-like endoplasmic reticulum kinase （PERK）were detected. RESULTS Compared with blank control group ，the levels of AST，ALT，MDA and ROS ，mRNA and protein expressions of GRP- 78 and PERK were increased significantly in P. corylifolia model group （P＜0.05 or P＜0.01）；while GSH and SOD levels ，mitochondrial membrane potential were decreased significantly （P＜0.05 or P＜0.01）. Compared with P. corylifolia model group ，above indexes of P. corylifolia -S. chinensis low-dose， medium-dose and high-dose groups were all improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS The compatibility of P. corylifolia -S. chinensis can alleviate P. corylifolia -induced oxidative damage and endoplasmic reticulum stress of L 02 cells.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.