期刊：
Oxidative Medicine and Cellular Longevity,2016年2016:6043038 ISSN：1942-0900
通讯作者：
Xie, Zhi-Zhong;Bian, Jin-Song
作者机构：
[Xie, Zhi-Zhong; Liu, Yang] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Xie, Zhi-Zhong; Liu, Yang] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Bian, Jin-Song] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore 117597, Singapore.
通讯机构：
[Xie, Zhi-Zhong] U;[Xie, Zhi-Zhong] H;[Bian, Jin-Song] N;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.
摘要：
Intracellular redox imbalance is mainly caused by overproduction of reactive oxygen species (ROS) or weakness of the natural antioxidant defense system. It is involved in the pathophysiology of a wide array of human diseases. Hydrogen sulfide (H2S) is now recognized as the third "gasotransmitters" and proved to exert a wide range of physiological and cytoprotective functions in the biological systems. Among these functions, the role of H2S in oxidative stress has been one of the main focuses over years. However, the underlying mechanisms for the antioxidant effect of H2S are still poorly comprehended. This review presents an overview of the current understanding of H2S specially focusing on the new understanding and mechanisms of the antioxidant effects of H2S based on recent reports. Both inhibition of ROS generation and stimulation of antioxidants are discussed. H2S-induced S-sulfhydration of key proteins (e.g., p66Shc and Keap1) is also one of the focuses of this review.
摘要：
Chrysin is one of flavones constituents of Orocylumineicum vent. It has been a hot spot as a potential chemopreventive agent and as a natural molecule with numerous biological activities such as antioxidant, antitumor, antiviral, anti-hypertension, anti-diabetic, antibacterial, and so on in recent years. Because of its poor solubility, small intestinal absorption, and the rapid metabolism of glycosylation, a large number of efforts had been made by domestic and foreign researchers on designing its analogs and conjugates to obtain compounds with improved efficacy and selectivity for developing more active drugs for clinic. This article reviews the current research of studying on chrysin derivatives including their properties and possible applications. Additionally, this article also presents the basic information concerning chemical reactivity of chrysin, relevant to the synthesis of its derivatives.
摘要：
A novel series of apigenin derivatives with phloroglucinol or resorcinol as raw materials were synthesized according to Baker-Venaktaraman reaction and their in vitro inhibitory activities on colorectal adenocarcinoma (HT-29) and leucocythemia (HL-60) cell lines were evaluated by the standard methyl thiazole tetrazolium (MTT) method. The results of biological test showed that some of apigenin derivatives possessed stronger anti-cancer activities than apigenin. Compound 6 showed the strongest activity against colorectal adenocarcinoma (HT-29) and leucocythemia (HL-60) cell lines with IC50 valure of 2.03±0.22 µM, 2.25±0.42 µM, it was better than 5-FU (12.92±0.61 µM, 9.56±0.16 µM), which shows a potential compound for colorectal adenocarcinoma and leucocythemia.
期刊：
Lipids in Health and Disease,2012年11(1):1-9 ISSN：1476-511X
通讯作者：
Fu, Mingde
作者机构：
[Tian, Li; Long, Shiyin; Liu, Yinghui; Fu, Mingde] Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.;[Tian, Li; Liu, Yinghui; Fu, Mingde] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China.;[Long, Shiyin] Univ S China, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;[Zeng, Zhi; Chen, Yucheng; Li, Chuanwei] Sichuan Univ, W China Hosp, Cardiovasc Dept, Chengdu 610041, Sichuan, Peoples R China.
通讯机构：
[Fu, Mingde] S;Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.
关键词：
Coronary heart disease;High density lipoprotein subclasses;Diabetic mellitus;Fasting plasma glucose
摘要：
A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes. Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection. Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+preβ2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The preβ1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+preβ2. The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.
摘要：
The role of microRNA-195 in developing acquired drug resistance in hepatocellular carcinoma cells was investigated. Expression pro fi ling of miRNAs revealed a limited set of miRNAs with altered expression in drug resistant hepatocellular carcinoma cell line BEL-7402/5-FU compared to its parental BEL-7402 cell line. Real-time PCR confirmed down-regulation of miRNA-195 in BEL-7402/5-FU cells. Overexpression of miRNA-195 sensitized BEL-7402/5-FU cells to anticancer drugs. Consistent with these findings, miR-195 antisense oligonucleotide induced drug resistance in BEL-7402/5-FU cells. Also, the basal levels of the anti-apoptotic protein Bcl-w were high in BEL-7402/5-FU cells and miR-195 overexpression repressed Bcl-w protein level and inhibited the luciferase activity of a Bcl-w 3' untranslated region-based reporter construct in both BEL-7402/5-FU and BEL-7402 cells. These results indicate that miR-195 could improve the drug sensitivity at least in part by targeting Bcl-w to increase cell apoptosis in hepatocellular carcinoma cells.
期刊：
Lipids in Health and Disease,2011年10(1):1-10 ISSN：1476-511X
通讯作者：
Fu, Mingde
作者机构：
[Tian, Li; Fu, Mingde; Liu, Yinghui] Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.;[Xu, Yanhua] Chengdu Hoist Biotechnol Co LTD, Chengdu 610075, Sichuan, Peoples R China.;[Peng, Tao] Chengdu Univ, Affiliated Hosp Tradit Chinese Med, Chengdu 610072, Sichuan, Peoples R China.;[Long, Shiyin] Univ S China, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.
通讯机构：
[Fu, Mingde] S;Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.
关键词：
High Density Lipoprotein;Cholesteryl Ester Transfer Protein;Reverse Cholesterol Transport;High Density Lipoprotein Particle;High Density Lipoprotein Cholesterol Concentration
摘要：
To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preβ1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.
摘要：
The role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD). Male Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry. Feeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney. Ibrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.
期刊：
Lipids in Health and Disease,2011年10(1):1-9 ISSN：1476-511X
通讯作者：
Fu, Mingde
作者机构：
[Tian, Li; Fu, Mingde; Jia, Lianqun] Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.;[Long, Shiyin; Liu, Yinghui] Univ S China, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;[Xu, Yanhua] Chengdu Hoist Biotechnol Co LTD, Chengdu, Sichuan, Peoples R China.
通讯机构：
[Fu, Mingde] S;Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Sichuan, Peoples R China.
关键词：
Total Cholesterol;Total Cholesterol Level;High Density Lipoprotein;Total Cholesterol Concentration;High Total Cholesterol
摘要：
To investigate alteration of high density lipoproteins (HDL) subclasses distribution in different total cholesterol (TC) levels, mainly the characteristics of HDL subclasses distribution in desirable TC levels and analyze the related mechanisms. ApoA-I contents of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection. 486 Chinese Adults subjects were assigned to different TC groups according to the third Report of NCEP (ATP- III) guidelines. The increase in contents of small preβ1-HDL, HDL3c, HDL3b, and HDL3a particles clustered and reduce in HDL2b with increased of TC. The distribution of HDL subclasses have shown abnormality characterized by the lower HDL2b (324.2 mg/L) contents and the higher preβ1-HDL (90.4 mg/L) contents for desirable TC Chinese subjects. Among 176 desirable TC subjects, 58.6% subjects with triglyceride (TG) < 2.26 mmol/L, 61.2% subjects with HDL-C ≥1.03 mmol/L and 88.6% subjects with low density lipoprotein cholesterol(LDL-C) < 3.34 mmol/L, and the profile of HDL subclasses distribution for above these subjects was reasonable. The particles size of HDL subclasses shifted towards smaller with increased TC levels. The TC was liner with HDL2b contents and those can be reduced 17 mg/L for 0.5 mmol/L increment in TC levels. The HDL subclasses distribution phenotype was not expectation for Chinese Population with desirable TC levels. Thus, from the HDL subclasses distribution point, when assessing the coronary heart disease(CHD) risk not only rely on the TC levels, but also the concentrations of TG, HDL-C and LDL-C must considered in case the potential risk for desirable TC subjects with other plasma lipids metabolism disorders.
期刊：
Lipids in Health and Disease,2010年9(1):1-10 ISSN：1476-511X
通讯作者：
Qin, Yang
作者机构：
[Qin, Yang; Tian, Li; Liu, Yinghui] Sichuan Univ, Dept Biochem & Mol Biol, W China Sch Preclin & Forens Med, Chengdu 610041, Sichuan, Peoples R China.;[Fu, Mingde] Sichuan Univ, Lab Endocrinol & Metab, W China Hosp, Chengdu 610041, Sichuan, Peoples R China.;[Long, Shiyin] Univ S China, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Xu, Yanhua] Chengdu Hoist Biotechnol Co LTD, Chengdu 610075, Peoples R China.
通讯机构：
[Qin, Yang] S;Sichuan Univ, Dept Biochem & Mol Biol, W China Sch Preclin & Forens Med, Chengdu 610041, Sichuan, Peoples R China.
关键词：
Reverse Cholesterol Transport;Cholesterol Ester Transfer Protein;Quebec Cardiovascular Study;West China Medical;Monitor Atherosclerosis Regression Study
摘要：
To evaluate the relationship between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and HDL subclass distribution and to further examine and discuss the potential impact of LDL-C and HDL-C together with TG on HDL subclass metabolism. Small-sized preβ1-HDL, HDL3b and HDL3a increased significantly while large-sized HDL2a and HDL2b decreased significantly as the LDL-C/HDL-C ratio increased. The subjects in low HDL-C level (< 1.03 mmol/L) who had an elevation of the LDL-C/HDL-C ratio and a reduction of HDL2b/preβ1-HDL regardless of an undesirable or high LDL-C level. At desirable LDL-C levels (< 3.34 mmol/L), the HDL2b/preβ1-HDL ratio was 5.4 for the subjects with a high HDL-C concentration (≥ 1.55 mmol/L); however, at high LDL-C levels (≥ 3.36 mmol/L), the ratio of LDL-C/HDL-C was 2.8 in subjects, and an extremely low HDL2b/preβ1-HDL value although with high HDL-C concentration. With increase of the LDL-C/HDL-C ratio, there was a general shift toward smaller-sized HDL particles, which implied that the maturation process of HDL was blocked. High HDL-C concentrations can regulate the HDL subclass distribution at desirable and borderline LDL-C levels but cannot counteract the influence of high LDL-C levels on HDL subclass distribution.
通讯机构：
[Yin, Weidong] U;Univ S China, Life Sci Res Ctr, Inst Cardiovasc Res, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.
摘要：
Insulin resistance and dyslipidemia are both considered to be risk factors for metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from cholesterol 7α-hydroxylase (CYP7A1). NO-1886, a chemically synthesized lipoprotein lipase activator, suppresses diet-induced insulin resistance with the improvement of HDL-C. The goal of the present study is to evaluate whether NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression through the activation of signal transducer and activator of transcription 5 (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, completely abolished NO-1886-induced IGF1 secretion and CYP7A1 expression. Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma IGF1 elicited by a single dose administration of NO-1886. Long-term supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing hepatic cholesterol accumulation through increasing CYP7A1 expression in high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin resistance and hepatic cholesterol accumulation, which may represent an alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome. Abstract Insulin resistance and dyslipidemia are both considered to be risk factors for metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from cholesterol 7α-hydroxylase (CYP7A1). NO-1886, a chemically synthesized lipoprotein lipase activator, suppresses diet-induced insulin resistance with the improvement of HDL-C. The goal of the present study is to evaluate whether NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression through the activation of signal transducer and activator of transcription 5 (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, completely abolished NO-1886-induced IGF1 secretion and CYP7A1 expression. Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma IGF1 elicited by a single dose administration of NO-1886. Long-term supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing hepatic cholesterol accumulation through increasing CYP7A1 expression in high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin resistance and hepatic cholesterol accumulation, which may represent an alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome.
摘要：
To develop a minipig model of type 2 diabetes that simulates the common manifestations of the metabolic abnormalities and resembles the kidney pathology of type 2 diabetes in the human population, male Chinese Bama minipigs were divided into 2 groups (5 in each) and fed with a control diet (CD) or high-fat/ high-sucrose/ high-cholesterol diet (HFSCD) for 5 months. The biochemical parameters of blood and urine, and the oral glucose tolerance test were monitored after the feeding program. The insulin resistance was estimated by the HOMA-IR index and the glucose elimination constant (K(G)), and beta-cell function by the HOMA-beta index and the acute insulin response (AIR). Glomerulosclerosis index (GSI) was semi-quantitated by the degree of glomerular lesions in kidney sections stained with Masson trichrome. Extracellular matrix deposition in the kidney was examined by the protein expression of type IV collagen, connective tissue growth factor (CTGF) and matrix metalloproteinases 2 (MMP-2) using immunohistochemistry. Feeding HFSCD to minipigs markedly caused hyperglycaemia, hyperinsulinaemia and dyslipidaemia. HOMA-IR was significantly increased while HOMA-beta, AIR and K(G) were obviously decreased in the HFSCD group compared with control group. Microalbuminuria, glucosuria and moderate glomerulosclerosis were exhibited in HFSCD-fed minipigs. The expression of type IV collagen and CTGF was elevated whereas that of MMP-2 was reduced in the kidneys of HFSCD group compared with the CD group. We concluded that feeding HFSCD to Chinese Bama minipigs for 5 months can induce humanoid type 2 diabetes and early-stage diabetic nephropathy, and accelerate extracellular matrix deposition and glomerulosclerosis.
摘要：
Inflammation, closely associated with obesity, is emerging as an important risk factor for the pathophysiological development of atherosclerosis and diabetes mellitus. Fat balance is critical in the aetiology of obesity. Lipoprotein lipase is an important enzyme in lipid metabolism. The aim of this study was to investigate the long-term effect of the lipoprotein lipase activator, NO-1886, on inflammation cytokines, adiposity and related diseases in miniature pigs fed a high-fat/high-sucrose/high-cholesterol diet (HFSC diet). Chinese Bama-miniature pigs were fed a control diet or HFSC diet with or without NO-1886 for 5 months. The levels of inflammation-associated cytokines were determined using the antibody arrays. Feeding of the HFSC diet to miniature pigs markedly increased the expression of inflammatory cytokines. On the other hand, supplementation of NO-1886 to HFSC diet decreased the expression of inflammatory cytokines significantly, protecting against the development of atherosclerosis and diabetes mellitus. NO-1886 may have a beneficial effect on the most inflammation-associated cytokines, and this effect may contribute to improving atherosclerosis and diabetes mellitus.
