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  1. Article ; Online: Jian-Gan-Xiao-Zhi decoction ameliorates high-fat high-carbohydrate diet-induced non-alcoholic fatty liver disease and insulin resistance by regulating the AMPK/JNK pathway

    Xue-Hua Xie / Jia-Bao Liao / Fang Fang / Jie Zhao / Yong-Jun Cao / Huan-Tian Cui / Hong-Wu Wang / Zhai-Yi Zhang / Zhao-Hui Sun / Yuan Yin / Wei-Bo Wen

    Traditional Medicine Research, Vol 6, Iss 1, Pp 4-

    2021  Volume 4

    Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) can cause insulin resistance (IR) and diabetes. Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction (JGXZ) could be effective for the treatment of NAFLD and IR. However, the ... ...

    Abstract Background: Non-alcoholic fatty liver disease (NAFLD) can cause insulin resistance (IR) and diabetes. Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction (JGXZ) could be effective for the treatment of NAFLD and IR. However, the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown. Methods: Fifty rats received a high-fat high-carbohydrate (HFHC) diet for 12 weeks to induce NAFLD. After 4 weeks of HFHC treatment, rats were orally treated with JGXZ (8, 16, and 32 g/kg weight) for 8 weeks. Ten rats in the control group received standard chow. In the positive control group, rats were orally treated with metformin (90 mg/kg weight) for 8 weeks. After JGXZ and metformin treatment, H&E staining was conducted on rat livers and serum biochemical markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC), were measured using test kits. Moreover, a fasting blood glucose test and an oral glucose tolerance test (OGTT) were conducted. Serum levels of insulin were determined using ELISA kit, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. The levels of total insulin receptor substrate-1 (IRS1), AMP-activated protein kinase-α (AMPKα) and c-Jun N-terminal kinase (JNK) as well as the levels of phosphorylation of IRS1 (p-IRS1), phosphorylation of AMPK (p-AMPK) and phosphorylation of JNK (p-JNK) were measured using western blotting. Results: The body weights in JGXZ low-, middle-, and high-dose groups were lower than those in the model group (P < 0.05, P < 0.01, P < 0.01, respectively). The serum levels of AST (P < 0.05 in JGXZ middle- and high-dose groups), ALT (P < 0.01 in JGXZ middle-dose group and P < 0.05 in JGXZ high-dose group), TG (P < 0.01 in JGXZ middle- and high-dose groups), and TC (P < 0.01) upon JGXZ treatment were lower those than in NAFLD model rats. H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats. JGXZ decreased the levels of fasting blood glucose (P < 0.01), HOMA-IR (P < 0.01), AUC (area under the curve) of the OGTT (P < 0.05) and p-IRS1 (P < 0.01 in JGXZ middle- and high-dose groups, P < 0.05 in JGXZ low-dose groups). Moreover, JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats, which reflected the induction of p-AMPKα and inhibition of p-JNK. Conclusion: This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats. Moreover, JGXZ improved IR in NAFLD model rats. The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.
    Keywords jian-gan-xiao-zhi decoction ; non-alcoholic fatty liver disease ; insulin resistance ; ampk/jnk pathway ; Medicine ; R ; Miscellaneous systems and treatments ; RZ409.7-999
    Subject code 630
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Hong Kong Gold Orchid Science and Technology Co., Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Imaging Features of Symptomatic Radiation-induced Cervical Artery Stenosis

    Jia-Ping Xu / Ji-Jun Shi / Guang-Xin Duan / Yong-Jun Cao

    Chinese Medical Journal, Vol 130, Iss 15, Pp 1876-

    2017  Volume 1877

    Keywords Atherosclerosis ; Cervical Artery Stenosis ; Imaging Features ; Radiotherapy ; Medicine ; R
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Wolters Kluwer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Posterior circulation ischemia due to carotid artery dissection with hyperhomocysteinemia in a 51-year-old man

    Ruo-Jun Wang / Zhi-Liang Guo / Zhi-Chao Huang / Zhi-Jie Ou / Xia Zhang / Shou-Jiang You / Yong-Jun Cao / Xiu-Yuan Hao / Xin Chen

    Chinese Medical Journal, Vol 133, Iss 19, Pp 2381-

    2020  Volume 2382

    Keywords Medicine ; R
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Wolters Kluwer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Rapamycin Inhibits Oxidized Low Density Lipoprotein Uptake in Human Umbilical Vein Endothelial Cells via mTOR/NF-κB/LOX-1 Pathway.

    Yan-De Zhou / Xue-Qin Cao / Zhi-Hua Liu / Yong-Jun Cao / Chun-Feng Liu / Yan-Lin Zhang / Ying Xie

    PLoS ONE, Vol 11, Iss 1, p e

    2016  Volume 0146777

    Abstract: Lectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in ... ...

    Abstract Lectin-like oxidized low-density lipoprotein-1 (LOX-1) is the major receptor for oxidized low density lipoprotein (ox-LDL) uptake in human umbilical vein endothelial cells (HUVECs). Previously, we found that rapamycin inhibited ox-LDL accumulation in HUVECs, and this effect was related to its role in increasing the activity of autophagy-lysosome pathway. In this study, we determined whether rapamycin could also reduce ox-LDL uptake in HUVECs and investigated the underlying signaling mechanisms.Flow cytometry and live cell imaging showed that rapamycin reduced Dil-ox-LDL accumulation in HUVECs. Furthermore, rapamycin reduced the ox-LDL-induced increase in LOX-1 mRNA and protein levels. Western blotting showed that rapamycin inhibited mechanistic target of rapamycin (mTOR), p70s6k and IκBα phosphorylation triggered by ox-LDL. Flow cytometry implied that mTOR, NF-κB knockdown and NF-κB inhibitors significantly reduced Dil-ox-LDL uptake. Moreover, immunofluorescent staining showed that rapamycin reduced the accumulation of p65 in the nucleus after ox-LDL treatment for 30 h. mTOR knockdown decreased LOX-1 protein production and IκBα phosphorylation induced by ox-LDL. NF-κB knockdown and NF-κB inhibitors reduced LOX-1 protein production, but did not inhibit mTOR phosphorylation stimulated by ox-LDL.These findings demonstrate that rapamycin reduce mTOR phosphorylation and subsequently inhibit NF-κB activation and suppresses LOX-1, resulting in a reduction in ox-LDL uptake in HUVECs.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Endovascular Treatment of a Distal C1 Dissecting Aneurysm in a Patient with Double Aortic Arch

    Jia-Ping Xu / Ji-Jun Shi / Guo-Dong Xiao / Guang-Xin Duan / Chun-Yuan Zhang / Yong-Jun Cao

    Chinese Medical Journal, Vol 129, Iss 1, Pp 112-

    2016  Volume 113

    Keywords Medicine ; R
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Wolters Kluwer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells

    Zhu, Wa-wa / Shu-rong Wang / Zhi-hua Liu / Yong-jun Cao / Fen Wang / Jing Wang / Chun-feng Liu / Ying Xie / Yan-lin Zhang

    Biochemical and biophysical research communications. 2017 Jan. 01, v. 482

    2017  

    Abstract: Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive ...

    Abstract Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells.
    Keywords ABC transporters ; Western blotting ; atherosclerosis ; cholesterol ; cholesterol metabolism ; death ; endocytosis ; endothelial cells ; flow cytometry ; foam cells ; humans ; image analysis ; low density lipoprotein ; patients ; protective effect ; protein synthesis ; reactive oxygen species
    Language English
    Dates of publication 2017-0101
    Size p. 93-99.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2016.10.138
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: DNA methylation in cystathionine-γ-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice

    Du, Hua-Ping / Jiaojiao Li / Shou-Jiang You / Ya-Li Wang / Fen Wang / Yong-Jun Cao / Li-Fang Hu / Chun-Feng Liu

    Biochemical and biophysical research communications. 2016 Jan. 15, v. 469

    2016  

    Abstract: Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that ... ...

    Abstract Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that dysregulation of cystathionine γ-lyase (CSE) -hydrogen sulfide (H2S) pathway was involved in monocyte/macrophages-mediated inflammation and atherosclerosis. However, it remains unknown whether altered cse methylation in macrophages may play a role in linking CSE-H2S dysregulation and atherosclerosis. In the present study, we showed that plasma H2S and H2S production in the peritoneal macrophages of apolipoprotein knockout (apoE−/−) mice gradually decreased with ages, and were also lower than that in control mice at 12 weeks older. Moreover, CSE mRNA expressions decreased while DNA methyltransferase (DNMT) expressions increased in the peritoneal macrophages isolated from apoE−/− mice, compared to age-matched wildtype mice. Similar observations were obtained in an in vitro study. In oxidized low-density lipoprotein (ox-LDL)-treated raw264.7 macrophages, cse transcription was down-regulated while the expression and activity of DNMT was up-regulated, associated with enhanced DNA methylation in cse promoter. Suppression of DNMT with its inhibitor or siRNA reversed the decrease of CSE mRNA. Therefore, our data suggest that DNA hypermethylation of CpG rich region in cse promoter might contribute to the decrease of cse transcription and H2S production in macrophages, and thus contribute to atherosclerosis development.
    Keywords DNA ; DNA methylation ; atherosclerosis ; cystathionine ; cystathionine gamma-lyase ; epigenetics ; gene expression regulation ; genes ; hydrogen sulfide ; in vitro studies ; inflammation ; knockout mutants ; low density lipoprotein ; macrophages ; messenger RNA ; methyltransferases ; mice ; monocytes ; pathogenesis ; small interfering RNA ; Atherosclerosis ; Cystathionine γ-lyase ; Hydrogen sulfide ; Macrophage ; ox-LDL
    Language English
    Dates of publication 2016-0115
    Size p. 776-782.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2015.11.132
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Homocysteine Triggers Inflammatory Responses in Macrophages through Inhibiting CSE-H2S Signaling via DNA Hypermethylation of CSE Promoter

    Jiao-Jiao Li / Qian Li / Hua-Ping Du / Ya-Li Wang / Shou-Jiang You / Fen Wang / Xing-Shun Xu / Jian Cheng / Yong-Jun Cao / Chun-Feng Liu / Li-Fang Hu

    International Journal of Molecular Sciences, Vol 16, Iss 6, Pp 12560-

    2015  Volume 12577

    Abstract: Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis and other cardiovascular diseases. Unfortunately, Hcy-lowering strategies were found to have limited effects in reducing cardiovascular events. The underlying mechanisms remain ... ...

    Abstract Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis and other cardiovascular diseases. Unfortunately, Hcy-lowering strategies were found to have limited effects in reducing cardiovascular events. The underlying mechanisms remain unclear. Increasing evidence reveals a role of inflammation in the pathogenesis of HHcy. Homocysteine (Hcy) is a precursor of hydrogen sulfide (H2S), which is formed via the transsulfuration pathway catalyzed by cystathionine β-synthase and cystathionine γ-lyase (CSE) and serves as a novel modulator of inflammation. In the present study, we showed that methionine supplementation induced mild HHcy in mice, associated with the elevations of TNF-α and IL-1β in the plasma and reductions of plasma H2S level and CSE expression in the peritoneal macrophages. H2S-releasing compound GYY4137 attenuated the increases of TNF-α and IL-1β in the plasma of HHcy mice and Hcy-treated raw264.7 cells while CSE inhibitor PAG exacerbated it. Moreover, the in vitro study showed that Hcy inhibited CSE expression and H2S production in macrophages, accompanied by the increases of DNA methyltransferase (DNMT) expression and DNA hypermethylation in cse promoter region. DNMT inhibition or knockdown reversed the decrease of CSE transcription induced by Hcy in macrophages. In sum, our findings demonstrate that Hcy may trigger inflammation through inhibiting CSE-H2S signaling, associated with increased promoter DNA methylation and transcriptional repression of cse in macrophages.
    Keywords homocysteine ; cystathionine γ-lyase ; hydrogen sulfide ; macrophage ; DNA methylation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 572
    Language English
    Publishing date 2015-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: DNA methylation in cystathionine-γ-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice

    Du, Hua-Ping / Jiaojiao Li / Shou-Jiang You / Ya-Li Wang / Fen Wang / Yong-Jun Cao / Li-Fang Hu / Chun-Feng Liu

    Biochemical and biophysical research communications

    Volume v. 469

    Abstract: Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that ... ...

    Abstract Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that dysregulation of cystathionine γ-lyase (CSE) -hydrogen sulfide (H2S) pathway was involved in monocyte/macrophages-mediated inflammation and atherosclerosis. However, it remains unknown whether altered cse methylation in macrophages may play a role in linking CSE-H2S dysregulation and atherosclerosis. In the present study, we showed that plasma H2S and H2S production in the peritoneal macrophages of apolipoprotein knockout (apoE−/−) mice gradually decreased with ages, and were also lower than that in control mice at 12 weeks older. Moreover, CSE mRNA expressions decreased while DNA methyltransferase (DNMT) expressions increased in the peritoneal macrophages isolated from apoE−/− mice, compared to age-matched wildtype mice. Similar observations were obtained in an in vitro study. In oxidized low-density lipoprotein (ox-LDL)-treated raw264.7 macrophages, cse transcription was down-regulated while the expression and activity of DNMT was up-regulated, associated with enhanced DNA methylation in cse promoter. Suppression of DNMT with its inhibitor or siRNA reversed the decrease of CSE mRNA. Therefore, our data suggest that DNA hypermethylation of CpG rich region in cse promoter might contribute to the decrease of cse transcription and H2S production in macrophages, and thus contribute to atherosclerosis development.
    Language English
    Document type Article
    ISSN 0006-291X
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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