Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

OBJECTIVE: To explore the effect of decoction (DGNTD) on cell apoptosis and TNF receptor super family 6 (Fas)/caspase-8 pathway in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). METHODS: FLS isolated from the synovial tissue of RA patients were cultured and identified using immunofluorescence staining. The cells were treated with 10% blank serum (blank control group), 10% sera containing low, moderate or high doses of DGNTD, or 20 μmol/mL KR-33493 (a Fas inhibitor) combined with 10% serum containing high-dose DGNTD. MTT assay was used to detect the proliferation of the cells after the treatments. Apoptosis of the cells was detected at 48 h in each group using Hoechst 33342 staining and flow cytometry with annexin V-FITC/PI staining. The mRNA and protein expressions of Fas, FADD, caspase-8 and caspase-3 in the cells at 48 h were detected using qPCR and Western blotting. RESULTS: Immunofluorescence staining identified the cultured cells as FLS. Treatment with DGNTD-containing sera significantly inhibited the proliferation of FLS, and the inhibitory effects were enhanced as the dose and intervention time increased ( < 0.05). Hoechst 33342 staining and flow cytometry showed that the sera containing different doses of DGNTD significantly promoted apoptosis of FLS ( < 0.05). The expression levels of Fas, FADD, caspase-8, and caspase-3 at both mRNA and protein levels were significantly increased in the cells after treatment with different doses of DGNTD-containing sera ( < 0.05). The application of KR-33493 obviously reversed the effects of DGNTD on the FLS ( < 0.05). CONCLUSIONS DGNTD can induce apoptosis of the FLS by activating Fas/caspase-8 signaling pathway.
Apoptosis ; Arthritis, Rheumatoid ; Caspase 8 ; Cell Proliferation ; Cells, Cultured ; Fibroblasts ; Synovial Membrane ; Synoviocytes

Objective To explore the efficacy of sulfasalazine for treatment for epilepsy induced by gliomas .Methods The patients with epilepsy caused by gliomas in neurosurgery department were recruited from March 2006 to December 2013 .Epilepsy was controlled with sulfasalazine .The efficacy of sulfasalazine for treatment for epilepsy induced by glioma were analyzed to calcu-late the 50% response rate ,75% response rate and seizure-free rate .Meanwhile the outcomes scores of therapy of sulfasalazine for varieties types of epilepsy were evaluated ,according to the end result of scoring criteria in epileptic seizures .Results A total of 31 patients were controlled with sulfasalazine .The average reduction rate of seizure frequency per month was 54 .32% ,61 .71% , 75 .74% after three months of treatment .The differences of average reduction rate of seizure frequency before and after the treat -ment have an evident statistic significance (P< 0 .01) .The 50% response rate ,75% response rate and seizure-free rate per month af-ter treatment with sulfasalazine have significant higher than those before treatment (F= 20 .007 ,P< 0 .01) .After 3 month of thera-py ,four different types of epilepsy was 100 .00% ,100 .00% ,84 .62% and 75 .00% in improvement rate added complete control rate .Those have no statistical difference(P> 0 .05) .Conclusion Sulfasalazine can effectively control seizures ,and both effective va-rious types of epileptic .

Objective To explore the protective effect of Mn (Ⅲl)tetrakis (4-benzoic acid) porphyrin (MnTBAP) on rats after intracerebral hemorrhage (ICH) and its mechanism.Methods Sixty-six adult SD rats were randomized into sham-operated group,control group and experimental group (n=22).Rats in the latter two groups were performed stereotactic injection of autologous tail arterial blood to induce ICH models;the rats in the experimental group were given 2 μL MnTBAP (100 μg/μL) by intracerebroventricular injection 30 min after ICH,while the rats in the control group were given normal saline of same volume.The expressions of 4-hydroxynonenonal (4-HNE,a marker of lipid peroxidation),3-nitrotyrosine (3-NT,a reliable marker of protein nitration),8-hydroxy-2'-deoxyguanosine (8-OHdG,a marker of DNA oxidative damage),Zonula occludens-1 (ZO-1,a kind of tight junction protein) and myeloperoxidase (MPO,a marker of neutrophil) in the perihematomal brain tissues 24 h after ICH were detected by immunofluorescence;protein expressions of ZO-1 and matrix metalloproteinase-9 (MMP-9) were detected by Western blotting 24 h after ICH;brain water content and modified neurological severity (mNSS) scores were measured 24 and 72 h after ICH.Results As compared with those in the control group,3-NT (264.53±83.99vs413.22±89.16),4-HNE (245.64±73.10vs 391.41±51.43),8-OHdG (221.53±68.25 vs 332.32±94.93),MPO (296.14±66.34 vs 431.59±102.68) and MMP-9 (0.75±0.07 vs 0.96±0.04) expressions in perihematomal brains of experimental group were significantly decreased,while the expressions of ZO-1 (0.74±0.05 vs 0.56±0.06) were significantly increased (P＜0.05).The mNSS scores (9.33±1.37 vs 11.33±1.51;6.17±0.98 vs 9.50±1.38) and brain water contents in the experimental group were significantly lower as compared with those in the control group 24 and 72 h after ICH (80.41％±0.69％ vs 82.48％±0.94％;79.78％±0.65％ vs 81.57％±0.82％) (P＜0.05).Conclusion MnTBAP could protect injured brain tissues by alleviating oxidative and nitrative stress,decreasing neutrophils invasion and MMP-9 activation at early stage of ICH;meanwhile,MnTBAP could relieve the blood-brain barrier disruption and neurological deficit following ICH.