Browsing by Author "Fang, Zhigang"

Now showing 1 - 4 of 4
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    Biomarkers of Oxidative Stress and Endogenous Antioxidants for Patients with Chronic Subjective Dizziness
    (Nature Research, 2020-01-30) Fang, Zhigang; Huang, Keer; Gil, Chang-Hyun; Jeong, Jin-Woo; Yoo, Ho-Ryong; Kim, Hyeong-Geug; Biochemistry and Molecular Biology, School of Medicine
    As a neurotologic disorder of persistent non-vertiginous dizziness, chronic subjective dizziness (CSD) arises unsteadily by psychological and physiological imbalance. The CSD is hypersensitivity reaction due to exposure to complex motions visual stimuli. However, the pathophysiological features and mechanism of the CSD still remains unclearly. The present study was purposed to establish possible endogenous contributors of the CSD using serum samples from patients with the CSD. A total 199 participants were gathered and divided into two groups; healthy (n = 152, male for 61, and female for 91) and CSD (n = 47, male for 5, female for 42), respectively. Oxidative stress parameters such as, hydrogen peroxide and reactive substances were significantly elevated (p < 0.01 or p < 0.001), whereas endogenous antioxidant components including total glutathione contents, and activities of catalase and superoxide dismutase were significantly deteriorated in the CSD group (p < 0.01 or p < 0.001) as comparing to the healthy group, respectively. Serum levels of tumor necrosis factor -α and interferon-γ were significantly increased in the CSD participants (p < 0.001). Additionally, emotional stress related hormones including cortisol, adrenaline, and serotonin were abnormally observed in the serum levels of the CSD group (p < 0.01 or p < 0.001). Our results confirmed that oxidative stress and antioxidants are a critical contributor of pathophysiology of the CSD, and that is first explored to establish features of redox system in the CSD subjects compared to a healthy population.
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    Ethyl Acetate Fraction of Amomum villosum var. xanthioides Attenuates Hepatic Endoplasmic Reticulum Stress-Induced Non-Alcoholic Steatohepatitis via Improvement of Antioxidant Capacities
    (MDPI, 2021-06-23) Cho, Jung-Hyo; Lee, Jong-Suk; Kim, Hyeong-Geug; Lee, Hye Won; Fang, Zhigang; Kwon, Hyeok-Hee; Kim, Dong Woon; Lee, Chang-Min; Jeong, Jin-Woo; Biochemistry and Molecular Biology, School of Medicine
    Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.
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    Sesn3 protects against diet‐induced nonalcoholic steatohepatitis in mice via suppression of the TGFβ signal transduction
    (Wiley, 2019) Huang, Menghao; Kim, Hyeong Geug; Zhong, Xiaolin; Dong, Chuanpeng; Zhang, Brian; Fang, Zhigang; Zhang, Yang; Lu, Xiaoyu; Saxena, Romil; Liu, Yunlong; Zhang, Chi; Liangpunsakul, Suthat; Dong, X. Charlie; Medicine, School of Medicine
    Sesn3 belongs to the three‐member sestrin protein family. Sestrins have been implicated in anti‐oxidative stress, AMPK and mTOR signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied. In this work, we generated Sesn3 whole‐body knockout and liver‐specific transgenic mice to investigate the hepatic function of Sesn3 in diet‐induced NASH. With only 4 weeks of dietary treatment, Sesn3 knockout mice developed severe NASH phenotype as characterized by hepatic steatosis, inflammation, and fibrosis. Strikingly, after 8‐week feeding with a NASH‐inducing diet, Sesn3 transgenic mice were largely protected against NASH development. Transcriptomic analysis revealed that multiple extracellular matrix related processes were upregulated including TGFβ signaling and collagen production. Further biochemical and cell biological analyses have illustrated a critical control of the TGFβ‐Smad pathway by Sesn3 at the TGFβ receptor and Smad3 levels. First, Sesn3 inhibits the TGFβ receptor through an interaction with Smad7; second, Sesn3 directly inhibits the Smad3 function through protein‐protein interaction and cytosolic retention.
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    Sestrin Proteins Protect Against Lipotoxicity-Induced Oxidative Stress in the Liver via Suppression of C-Jun N-Terminal Kinases
    (Elsevier, 2021) Fang, Zhigang; Kim, Hyeong-Geug; Huang, Menghao; Chowdhury, Kushan; Li, Ming O.; Liangpunsakul, Suthat; Dong, X. Charlie; Biochemistry and Molecular Biology, School of Medicine
    Background & aims: Sestrin 1/2/3 (Sesn1/2/3) belong to a small family of proteins that have been implicated in the regulation of metabolic homeostasis and oxidative stress. However, the underlying mechanisms remain incompletely understood. The aim of this work was to illustrate the collective function of Sesn1/2/3 in the protection against hepatic lipotoxicity. Methods: We used Sesn1/2/3 triple knockout (TKO) mouse and cell models to characterize oxidative stress and signal transduction under lipotoxic conditions. Biochemical, histologic, and physiological approaches were applied to illustrate the related processes. Results: After feeding with a Western diet for 8 weeks, TKO mice developed remarkable metabolic associated fatty liver disease that was manifested by exacerbated hepatic steatosis, inflammation, and fibrosis compared with wild-type counterparts. Moreover, TKO mice exhibited higher levels of hepatic lipotoxicity and oxidative stress. Our biochemical data revealed a critical signaling node from sestrins to c-Jun N-terminal kinases (JNKs) in that sestrins interact with JNKs and mitogen-activated protein kinase kinase 7 and suppress the JNK phosphorylation and activity. In doing so, sestrins markedly reduced palmitate-induced lipotoxicity and oxidative stress in both mouse and human hepatocytes. Conclusions: The data from this study suggest that Sesn1/2/3 play an important role in the protection against lipotoxicity-associated oxidative stress and related pathology in the liver.