ABSTRACT
This study aims to investigate the impact of hepatocyte nuclear factor 1β (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.
Subject(s)
Mice , Animals , Polygonatum/metabolism , Sumoylation , Hepatocyte Nuclear Factor 1-beta/metabolism , Atherosclerosis/metabolism , Flavones , LipidsABSTRACT
Objective To study the causes of rehematomas after operations of traumatic hematomas of perisylvian area.Methods The causes of 50 cases of rehematoma after operation were analyzed retrospectively.Results The big hematoma in primary contusion and laceration of brain happened in 19 cases(38%),delayed epidural hematoma in opposite side in 15 cases(30%),increased intracerebral hematoma in 9 cases(18%),epidural hematoma in primary area in 3 cases(6%),subdural hematoma caused by postoperative lumbaropuncture in 3 cases(6%),hematoma in encephalonecrosis in 1 case(2%).Conclusion Insuitable operation and hemostasis are the main causes of rehemorrhage,and fracture line in the opposite side,and thrombocytopenia are high risk factors of rehematoma.
ABSTRACT
【Objective】To observe the effect of Buzhong Yiqi Wan(BYW)on thyroid hormones in rat model of spleen-asthenia.【Methods】Thirty-four SD male rats were randomized into 3 groups:normal control group(N=10),spleen-asthenia model group(N=12),BYW group(N=12).Except the normal control group,the rats in other groups were given the decoction of Radix et Rhizoma Rhei(4 g?d-1 for each rat)to induce spleen asthenia,and meanwhile,BYW group reveived BYW(3.9 g?kg-1?d-1).The treatment lasted 20 days.Radioimmunoassay was used to detect serum levels of triiodothyronine(T3),thyroxine(T4),reverse triiodothyronine(rT3)and thyroid stimulating hormone(TSH).Meanwhile,the body weight,spleen and thymus weight as well as their ratio with the body weight were also observed.【Results】Serum T3 and T4 levels,spleen and thymus weight as well as their ratio with the body weight were decreased in the model group as compared with those in the normal control group(P
ABSTRACT
In the genealogical investigation into 1210 patients with alopecia areata(AA), we found 75 cases with a positive family history of AA, the familial incidence was 6.2%. The incidence of AA in the 75 families (1093 cases) was 14.91% (163 cases). In these families, there were 142 patients in first-grade relatives of the family members, 17 in second-grade, and 4 in third-grade. We observed 70 cases in 33 families within one generation, 87 cases in 40 families within two succesive generations, and 6 cases in 2 families within three successive generations, four pairs of monozygotic twins appeared in this investigation, but just one of each pair was affected. The relationship between pathogenesis of AA and genetic factor has been discussed.