Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum. / çŽ‰ç«¹é»„é ®é€šè¿‡ä¿ƒè¿›HNF1b蛋白的SUMO化修饰抑制sortilinä»‹å¯¼çš„è„‚è´¨ç§¯ç´¯åŠåŠ¨è„‰ç²¥æ ·ç¡¬åŒ–.

This study aims to investigate the impact of hepatocyte nuclear factor 1ß (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.

The Roles of Autophagy in the Genesis and Development of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common and frequent disease and always leads endocrine and metabolic disorder among women in reproductive age. Ovary is the main organ involved in polycystic ovary syndrome, and its function impairment will lead to reproductive dysfunction. Some recent studies have demonstrated that autophagy plays an important role in the pathogenesis of PCOS, and there are many different mechanisms that affect autophagy and the occurrence of PCOS, and they provide a new direction for us to predict the mechanism of PCOS. In this review, we discuss the role of autophagy in different ovarian cells: granulosa cells, oocytes, and theca cells, and introduce the important role that they play in the progress of PCOS. The main purpose of this review is to provide the research background and some relevant suggestions for our future work in autophagy and help us better explore the pathogenesis and autophagy mechanisms of PCOS. Furthermore, it will help us gain a new insight of the pathophysiology and treatment of PCOS.

[VEGF-transfected hBMSCs Aggravate Early Brain Edema in Cerebral Hemorrhage Rats].

OBJECTIVE: To investigate the effects of human bone marrow mesenchymal stem cells/vascular endothelial growth factor (hBMSCs/VEGF) transplantation on early brain edema in rats with cerebral hemorrhage. METHODS: Cultured the hBMSCs in vitro, transducted the cells with VEGF recombinant lentivirus vector to abtain the hBMSCs/VEGF cells. Intracerebral hemorrhage (ICH) rat model was established by injection of type Ⅰ collagenase and heparin into the caudate putamen. 2 h after the operation, the rats were evaluated with modified nerve function defect (mNSS) score to ensure whether the model was successfully established. At the third day after the injection, SD rats were randomly divided into sham group (only injected with empty needle), cerebral hemorrhage group, saline group, hBMSCs group and hBMSCs/VEGF group. Saline group, hBMSCs group and hBMSCs/VEGF group mice were injected with normal saline, hBMSCs (2×10 6 cells/kg body mass) and hBMSCs/VEGF (2×10 6 cells/kg body mass) respectively; sham group and model group did not perform intervention. On day 3 and 7 after injection, the rats were evaluated with modified neurological function score (mNSS). Then rats were sacrificed, and brain tissue specimens from the right caudate putamen area were separated. The wet and dry weighing method was used to measure the water content, and HE staining was used to evaluate pathological and functional changes. The expressions of VEGF, matrix metalloproteinase 9 (MMP-9) and aquaporin 4 (AQP-4) proteins were detected by immunofluorescence and Western blot. RESULTS: 2 h after injection, compared with rats in sham operation group, mNSS scores of rats in model group were increased, indicating that the models have successfully established. 3 d and 7 d after intervention, the mNSS score, the content of brain water, the expression level of VEGF, MMP-9 and AQP-4 proteins in model group and NS group were significantly higher than those of sham group (P<0.05), while the above values in hBMSCs group were significantly lower than those in saline group and model group (P<0.001), and the above values in hBMSCs/VEGF group were significantly higher than those of hBMSCs group (P<0.05). There were obvious hemorrhage and infarction in the brain tissue in the model group and NS group rats observed under the light microscope. Besides, the brain tissue developed loose structure and edema change. However, the bleeding and infarction in the brain tissue of hBMSCs group mice were reduced. Compared with the hBMSCs group mice, the brain tissue of hBMSCs/VEGF group mice was looser, more vacuoles occurred, and many neurons showed apoptosis changes such as nuclear deflation. CONCLUSION: hBMSCs transplantation could improve neurological function and relieve brain edema. But hBMSCs/VEGF will increase the vascular permeability and then aggravate the early cerebral edema in rats with cerebral hemorrhage.