Xinshou Ouyang, PhD
Research & Publications
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Research Summary
Our research interests are integrative metabolism and inflammation with a primary focus on the identification of the cellular effectors and regulators of the sterile inflammatory response in metabolic stress conditions including obesity, non-alcoholic & alcoholic steatohepatitis (NASH & ASH), fibrosis, and HCC. Metabolic signal(s) are the triggers for innate immune responses, which in turn disrupt metabolic function and lead to sustained inflammation. This is the leading cause of liver injury and failure and has important implications for clinically significant inflammation in chronic liver diseases. Manipulation of this has the potential to therapeutically break down the link between metabolic stress and inflammation and to improve the disease conditions in the liver. The major topics are as below:
- Identify molecular pathways and the key metabolic regulators integrating stress and inflammatory responses with liver steatosis and fibrosis.
- Delineate the RNA modification, specifically m6A-dependent cellular pathways by metabolic signal (s) that control liver steatosis, inflammation, and fibrosis.
- Identify the enzymatic and spatiotemporal steps in inflammasome activation and provide novel insights and a potential target for therapeutic intervention in chronic inflammation.
Extensive Research Description
Identify molecular pathways and the key metabolic regulators integrating stress and inflammatory responses with liver steatosis and fibrosis.
The development of sterile inflammation after cell death is a ubiquitous response that occurs in all organs. The amplitude of this response, however, varies widely, and the liver is notable for developing exceptionally strong sterile inflammation. This is seen in alcoholic steatohepatitis (ASH), and metabolic syndrome-associated development of non-alcoholic steatohepatitis (NASH). Such a high amplitude of sterile inflammation in the liver has major clinical consequences as NASH is by far the most common liver disease in industrialized countries.
We have demonstrated that HIF-1α pathway activation potentiates and sustains the amplitude of acute inflammatory responses, and is vital for the transition from acute self-limiting to sustained chronic inflammation. These mechanistic insights into the role of the HIF-1α pathway in sterile inflammation may have great clinical relevance due to the ability of cardiac glycosides (CGs) to inhibit HIF-1α activation. Digoxin improves oxidative stress during liver injury through maintaining cellular redox homeostasis, and the suppression of HIF-1α pathway activation and downstream signature genes in the liver. We have further identified pyruvate kinase isoform 2 (PKM2) as a digoxin-binding protein. The active nuclear PKM2 directly interacts with multiple modified chromatin proteins, and digoxin reduces the binding of histones to PKM2.
Delineate the RNA modification, specifically m6A-dependent cellular pathways by metabolic signal (s) that control liver steatosis, inflammation, and fibrosis.
The 'epitranscriptome', a collective term for chemical modifications that influence the structure, metabolism, and functions of RNA, has recently emerged as vitally important for the regulation of gene expression. To date, more than 170 types of RNA modifications have been identified, including 5' cap modification, poly(A) tail, pseudouridine (Ψ), N1-methyladenosine (m1A) and N6,2'-O-dimethyladenosine (m6Am), and N6-methyladenosine (m6A). Among these modifications, m6A is the most abundant internal RNA modification in eukaryotic cells that widely occurs in mRNA and non-coding RNAs (ncRNAs). Myeloid lineage-driven metabolic inflammation is associated with significant changes in post-transcriptional mRNA modification and mRNA pool resulting in marked changes in myeloid cell functional status. We have demonstrated that myeloid lineage-restricted deletion of the m6A "writer" protein Methyltransferase Like 3 (METTL3) prevents age-related and diet-induced development of NAFLD and obesity in mice with improved inflammatory and metabolic phenotypes. Our study indicates that m6A methylation is critical in the control of myeloid cell-directed metabolic programming through the regulation of immune transcripts in NAFLD and obesity.
Identify the enzymatic and spatiotemporal steps in inflammasome activation and provide novel insights and a potential target for therapeutic intervention in chronic inflammation.
Inflammasomes are multiprotein cytosolic complexes that serve as a platform for caspase-1-dependent production of several proinflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18, and constitute a crucial step in the initiation of innate immune responses. Excessive inflammasome activity has been involved in diverse chronic inflammatory diseases, notably including metabolic disorders such as NASH. The NLRP3 inflammasome can be activated by a variety of structurally unrelated molecules ranging from insoluble particulates, endogenous danger signals, and pathogen molecules. A common theme from recent studies supports that reorganization of the intracellular organelle network is necessary for NLRP3 inflammasome activation, including lipid directed NLRP3 localization to mitochondria, microtubule-mediated NLRP3 inflammasome assembly, and NLRP3 interaction with Golgi-localized phosphatidylinositol-4-phosphate in response to diverse stimuli. We investigated the organelle dynamics and molecular requirement for NLRP3 recruitment in live cells. We have demonstrated a comprehensive model of GSK3β signaling mediated NLRP3 activation resulting in distinct NLRP3 trafficking, organelle reorganization, and inflammasome assembly.
The current model of inflammasome activation in macrophages explains the initial steps in acute inflammation but is inadequate to explain how the activity is sustained in chronic inflammation, repair, and fibrosis. We have demonstrated that cAMP/PKA/CREB/HIF-1α pathway is required for sustained inflammasome activation.
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Selected Publications
- Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activationArumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation. Hepatology 2023, 78: 1448-1461. PMID: 37013923, PMCID: PMC10804318, DOI: 10.1097/hep.0000000000000388.
- GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activationArumugam S, Qin Y, Liang Z, Han SN, Boodapati SLT, Li J, Lu Q, Flavell RA, Mehal WZ, Ouyang X. GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation. Cell Death & Differentiation 2022, 29: 2060-2069. PMID: 35477991, PMCID: PMC9525599, DOI: 10.1038/s41418-022-00997-y.
- m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesityQin Y, Li B, Arumugam S, Lu Q, Mankash SM, Li J, Sun B, Li J, Flavell RA, Li HB, Ouyang X. m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity. Cell Reports 2021, 37: 109968. PMID: 34758326, PMCID: PMC8667589, DOI: 10.1016/j.celrep.2021.109968.
- Targeting glycogen synthase kinase-3β inhibition alleviates acute myocardial infarction through reduction of NLRP3 inflammasome activationWang S, Xu L, Chang C, Yao Y, Su X, Cha X, Komal S, Wang P, Ouyang X, ZHANG L, Han S. Targeting glycogen synthase kinase-3β inhibition alleviates acute myocardial infarction through reduction of NLRP3 inflammasome activation. Journal Of Molecular And Cellular Cardiology 2020, 140: 38-39. DOI: 10.1016/j.yjmcc.2019.11.091.
- Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivationZhao P, Han SN, Arumugam S, Yousaf MN, Qin Y, Jiang JX, Torok NJ, Chen Y, Mankash MS, Liu J, Li J, Iwakiri Y, Ouyang X. Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation. AJP Gastrointestinal And Liver Physiology 2019, 317: g387-g397. PMID: 31411894, PMCID: PMC6842989, DOI: 10.1152/ajpgi.00054.2019.
- Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in SteatohepatitisOuyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz RL, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 339-350.e3. PMID: 29414684, PMCID: PMC5806149, DOI: 10.1016/j.cmet.2018.01.007.
- Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in SteatohepatitisOuyang X, Han SN, Zhang JY, Dioletis E, Nemeth BT, Pacher P, Feng D, Bataller R, Cabezas J, Stärkel P, Caballeria J, Pongratz R, Cai SY, Schnabl B, Hoque R, Chen Y, Yang WH, Garcia-Martinez I, Wang FS, Gao B, Torok NJ, Kibbey RG, Mehal WZ. Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metabolism 2018, 27: 1156. PMID: 29719229, DOI: 10.1016/j.cmet.2018.04.007.
- The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injuryHu B, Jin C, Li HB, Tong J, Ouyang X, Cetinbas NM, Zhu S, Strowig T, Lam FC, Zhao C, Henao-Mejia J, Yilmaz O, Fitzgerald KA, Eisenbarth SC, Elinav E, Flavell RA. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 2016, 354: 765-768. PMID: 27846608, PMCID: PMC5640175, DOI: 10.1126/science.aaf7532.
- Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathwayOuyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ. Adenosine is required for sustained inflammasome activation via the A2A receptor and the HIF-1α pathway. Nature Communications 2013, 4: 2909. PMID: 24352507, PMCID: PMC3895487, DOI: 10.1038/ncomms3909.
- An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technologyJia M, Zhou L, Lou Y, Yang X, Zhao H, Ouyang X, Huang Y. An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology. Frontiers In Nutrition 2023, 10: 1227027. PMID: 37560060, PMCID: PMC10408133, DOI: 10.3389/fnut.2023.1227027.
- 666 TGF-β MEDIATED HSC TRANSDIFFERENTIATION REQUIRES RELEASE OF MITOCHONDRIAL DNA AND ACTIVATION OF THE CYTOSOLIC CGASSTING-IRF3 PATHWAYArumugam S, Li B, Boodapati S, Nathanson M, Sun B, Ouyang X, Mehal W. 666 TGF-β MEDIATED HSC TRANSDIFFERENTIATION REQUIRES RELEASE OF MITOCHONDRIAL DNA AND ACTIVATION OF THE CYTOSOLIC CGASSTING-IRF3 PATHWAY. Gastroenterology 2023, 164: s-129-s-130. DOI: 10.1016/s0016-5085(23)01273-8.
- New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disordersJamshed F, Dashti F, Ouyang X, Mehal W, Banini B. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World Journal Of Gastroenterology 2023, 29: 1824-1837. PMID: 37032732, PMCID: PMC10080697, DOI: 10.3748/wjg.v29.i12.1824.
- Digoxin as an emerging therapy in noncardiac diseasesDashti F, Jamshed F, Ouyang X, Mehal W, Banini B. Digoxin as an emerging therapy in noncardiac diseases. Trends In Pharmacological Sciences 2022, 44: 199-203. PMID: 36396496, DOI: 10.1016/j.tips.2022.10.002.
- SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surfaceZhao N, Zhang X, Ding J, Pan Q, Zheng MH, Liu WY, Luo G, Qu J, Li M, Li L, Cheng Y, Peng Y, Xie Q, Wei Q, Li Q, Zou L, Ouyang X, Cai SY, Boyer JL, Chai J. SEMA7AR148W mutation promotes lipid accumulation and NAFLD progression via increased localization on the hepatocyte surface. JCI Insight 2022, 7: e154113. PMID: 35938531, PMCID: PMC9462498, DOI: 10.1172/jci.insight.154113.
- RNA m6A demethylase ALKBH5 regulates the development of γδ T cellsDing C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, Oh J, Crawford J, Gao Y, Jackson R, Sefik E, Li S, Wei Z, Skadow M, Yin Z, Ouyang X, Wang L, Zou Q, Su B, Hu W, Flavell RA, Li HB. RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2203318119. PMID: 35939687, PMCID: PMC9388086, DOI: 10.1073/pnas.2203318119.
- Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer CellsOuyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, Leapman M, Ali A. Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutrition And Cancer 2022, 74: 3670-3678. PMID: 35603899, DOI: 10.1080/01635581.2022.2077385.
- Annexin A2: The diversity of pathological effects in tumorigenesis and immune responseHuang Y, Jia M, Yang X, Han H, Hou G, Bi L, Yang Y, Zhang R, Zhao X, Peng C, Ouyang X. Annexin A2: The diversity of pathological effects in tumorigenesis and immune response. International Journal Of Cancer 2022, 151: 497-509. PMID: 35474212, DOI: 10.1002/ijc.34048.
- Revisiting the Principles of Preservation in an Era of Pandemic ObesityLangford JT, DiRito JR, Doilicho N, Chickering GR, Stern DA, Ouyang X, Mehal W, Tietjen GT. Revisiting the Principles of Preservation in an Era of Pandemic Obesity. Frontiers In Immunology 2022, 13: 830992. PMID: 35432296, PMCID: PMC9011385, DOI: 10.3389/fimmu.2022.830992.
- A digital pathology tool for quantification of color features in histologic specimensReschke M, DiRito JR, Stern D, Day W, Plebanek N, Harris M, Hosgood SA, Nicholson ML, Haakinson DJ, Zhang X, Mehal WZ, Ouyang X, Pober JS, Saltzman WM, Tietjen GT. A digital pathology tool for quantification of color features in histologic specimens. Bioengineering & Translational Medicine 2021, 7: e10242. PMID: 35111944, PMCID: PMC8780932, DOI: 10.1002/btm2.10242.
- The fermented soy beverage Q-CAN® plus induces beneficial changes in the oral and intestinal microbiomeDioletis E, Paiva RS, Kaffe E, Secor ER, Weiss TR, Fields MR, Ouyang X, Ali A. The fermented soy beverage Q-CAN® plus induces beneficial changes in the oral and intestinal microbiome. BMC Nutrition 2021, 7: 6. PMID: 33658080, PMCID: PMC7931600, DOI: 10.1186/s40795-021-00408-4.
- Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarctionWang S, Su X, Xu L, Chang C, Yao Y, Komal S, Cha X, Zang M, Ouyang X, Zhang L, Han S. Glycogen synthase kinase-3β inhibition alleviates activation of the NLRP3 inflammasome in myocardial infarction. Journal Of Molecular And Cellular Cardiology 2020, 149: 82-94. PMID: 32991876, DOI: 10.1016/j.yjmcc.2020.09.009.
- Corrigendum to “EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells”Leng W, Lei X, Meng H, Ouyang X, Liang Z. Corrigendum to “EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells”. International Journal Of Inflammation 2020, 2020: 3503814. PMID: 33062250, PMCID: PMC7537673, DOI: 10.1155/2020/3503814.
- Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated MouseCai SY, Ge M, Mennone A, Hoque R, Ouyang X, Boyer JL. Inflammasome Is Activated in the Liver of Cholestatic Patients and Aggravates Hepatic Injury in Bile Duct–Ligated Mouse. Cellular And Molecular Gastroenterology And Hepatology 2019, 9: 679-688. PMID: 31887435, PMCID: PMC7160576, DOI: 10.1016/j.jcmgh.2019.12.008.
- The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus.Leng W, Wu M, Pan H, Lei X, Chen L, Wu Q, Ouyang X, Liang Z. The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus. Annals Of Translational Medicine 2019, 7: 429. PMID: 31700865, PMCID: PMC6803170, DOI: 10.21037/atm.2019.09.03.
- Reduction in Serum Levels of Inflammatory Cytokines in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P19-010-19)Mehal W, Suyavaran A, Dioletis E, Paiva R, Weiss T, Fields M, Ouyang X. Reduction in Serum Levels of Inflammatory Cytokines in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P19-010-19). Current Developments In Nutrition 2019, 3: nzz049.p19-010-19. PMCID: PMC6579392, DOI: 10.1093/cdn/nzz049.p19-010-19.
- Hematology Safety Data for the Fermented Soy Beverage Q-CAN® Plus (P12-033-19)Mehal W, Suyavaran A, Dioletis E, Paiva R, Secor E, Weiss T, Fields M, Ouyang X, Ali A. Hematology Safety Data for the Fermented Soy Beverage Q-CAN® Plus (P12-033-19). Current Developments In Nutrition 2019, 3: 3013529. PMCID: PMC6574472, DOI: 10.1093/cdn/nzz035.p12-033-19.
- Reduction in Serum Cholesterol in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P06-118-19)Mehal W, Dioletis E, Paiva R, Secor E, Weiss T, Fields M, Ouyang X, Ali A. Reduction in Serum Cholesterol in Subjects Consuming the Fermented Soy Beverage Q-CAN® Plus (P06-118-19). Current Developments In Nutrition 2019, 3: nzz031.p06-118-19. PMCID: PMC6576748, DOI: 10.1093/cdn/nzz031.p06-118-19.
- The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot UlcerWu M, Leng W, Pan H, Lei X, Chen L, Ouyang X, Liang Z. The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer. Mediators Of Inflammation 2019, 2019: 6705424. PMID: 31007603, PMCID: PMC6441532, DOI: 10.1155/2019/6705424.
- The multi-dimensional role of intestinal HIFs in liver pathobiologyOuyang X, Mehal WZ. The multi-dimensional role of intestinal HIFs in liver pathobiology. Journal Of Hepatology 2018, 69: 772-773. PMID: 30104025, DOI: 10.1016/j.jhep.2018.07.012.
- 894 - Digoxin Protects from Alcoholic Hepatitis and Inhibits TGF-B Induced Fibrotic ResponseOuyang X, Mehal W. 894 - Digoxin Protects from Alcoholic Hepatitis and Inhibits TGF-B Induced Fibrotic Response. Gastroenterology 2018, 154: s-1109. DOI: 10.1016/s0016-5085(18)33689-8.
- β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathwayChen Y, Ouyang X, Hoque R, Garcia-Martinez I, Yousaf MN, Tonack S, Offermanns S, Dubuquoy L, Louvet A, Mathurin P, Massey V, Schnabl B, Bataller R, Mehal WZ. β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway. Journal Of Hepatology 2018, 69: 687-696. PMID: 29705237, PMCID: PMC6098974, DOI: 10.1016/j.jhep.2018.04.004.
- An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarizationPark J, Shao M, Kim MY, Baik SK, Cho MY, Utsumi T, Satoh A, Ouyang X, Chung C, Iwakiri Y. An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization. Hepatology 2017, 65: 1720-1734. PMID: 28090670, PMCID: PMC5397326, DOI: 10.1002/hep.29051.
- Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory responseCai SY, Ouyang X, Chen Y, Soroka CJ, Wang J, Mennone A, Wang Y, Mehal WZ, Jain D, Boyer JL. Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response. JCI Insight 2017, 2: e90780. PMID: 28289714, PMCID: PMC5333973, DOI: 10.1172/jci.insight.90780.
- The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− MiceLeng W, Ouyang X, Lei X, Wu M, Chen L, Wu Q, Deng W, Liang Z. The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE−/− Mice. Mediators Of Inflammation 2016, 2016: 6305735. PMID: 28104929, PMCID: PMC5220517, DOI: 10.1155/2016/6305735.
- Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9Garcia-Martinez I, Santoro N, Chen Y, Hoque R, Ouyang X, Caprio S, Shlomchik MJ, Coffman RL, Candia A, Mehal WZ. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. Journal Of Clinical Investigation 2016, 126: 859-864. PMID: 26808498, PMCID: PMC4767345, DOI: 10.1172/jci83885.
- EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 CellsLeng W, Lei X, Meng H, Ouyang X, Liang Z. EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells. International Journal Of Inflammation 2015, 2015: 301562. PMID: 26881174, PMCID: PMC4736203, DOI: 10.1155/2015/301562.
- Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injuryLi M, Mennone A, Soroka CJ, Hagey LR, Ouyang X, Weinman EJ, Boyer JL. Na+/H+ exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury. Hepatology 2015, 62: 1227-1236. PMID: 26108984, PMCID: PMC4589453, DOI: 10.1002/hep.27956.
- Identification of a novel de novo GATA3 mutation in a patient with HDR syndromeChen L, Chen B, Leng W, Lui X, Wu Q, Ouyang X, Liang Z. Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome. Journal Of International Medical Research 2015, 43: 718-724. PMID: 26268891, DOI: 10.1177/0300060515591065.
- Mo1309 Hyperglycemia-Induced Small Intestinal Dysrhythmias Attributed to Sympathovagal Imbalance in Normal and Diabetic RatsOuyang X, Li S, Foreman R, Farber J, Lin L, Yin J, Chen J. Mo1309 Hyperglycemia-Induced Small Intestinal Dysrhythmias Attributed to Sympathovagal Imbalance in Normal and Diabetic Rats. Gastroenterology 2015, 148: s-668. DOI: 10.1016/s0016-5085(15)32253-8.
- Su1058 Low Dose Digoxin Protects From NASH and Alcoholic Hepatitis in Mice by Inhibiting Inflammasome Activity and Mitochondrial ROS ProductionOuyang X, Zhang J, Feng D, Cai S, Protiva P, Garcia-Martinez I, Wang F, Gao B, Mehal W. Su1058 Low Dose Digoxin Protects From NASH and Alcoholic Hepatitis in Mice by Inhibiting Inflammasome Activity and Mitochondrial ROS Production. Gastroenterology 2015, 148: s-1052. DOI: 10.1016/s0016-5085(15)33588-5.
- 237 Humans and Mice With NASH Have Increased Plasma Levels of TLR9 Ligand, and a TLR7/9 Bifunctional Antagonist Reduces NASH in MiceGarcia-Martinez I, Santoro N, Chen Y, Ouyang X, Caprio S, Coffman R, Candia A, Mehal W. 237 Humans and Mice With NASH Have Increased Plasma Levels of TLR9 Ligand, and a TLR7/9 Bifunctional Antagonist Reduces NASH in Mice. Gastroenterology 2015, 148: s-974. DOI: 10.1016/s0016-5085(15)33328-x.
- EOLA1 inhibits lipopolysaccharide-induced vascular cell adhesion molecule-1 expression by association with MT2A in endothelial cellsLuo M, Len W, Lei X, Meng H, Ouyang X, Liang Z. EOLA1 inhibits lipopolysaccharide-induced vascular cell adhesion molecule-1 expression by association with MT2A in endothelial cells. Integrative Molecular Medicine 2015, 2 DOI: 10.15761/imm.1000182.
- Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic miceMeng H, Wang Z, Wang W, Li W, Wu Q, Lei X, Ouyang X, Liang Z. Effect of osteopontin in regulating bone marrow mesenchymal stem cell treatment of skin wounds in diabetic mice. Diabetes/Metabolism Research And Reviews 2014, 30: 457-466. PMID: 24827928, DOI: 10.1002/dmrr.2566.
- Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathwayFarooq A, Hoque R, Ouyang X, Farooq A, Ghani A, Ahsan K, Guerra M, Mehal WZ. Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway. AJP Gastrointestinal And Liver Physiology 2014, 307: g732-g740. PMID: 25104498, PMCID: PMC4187065, DOI: 10.1152/ajpgi.00073.2014.
- Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon TumorigenesisMorales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. Immune Chaperone gp96 Drives the Contributions of Macrophages to Inflammatory Colon Tumorigenesis. Cancer Research 2014, 74: 446-459. PMID: 24322981, PMCID: PMC4002507, DOI: 10.1158/0008-5472.can-13-1677.
- Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: A randomized controlled trialLiang Z, Wu Q, Chen B, Yu P, Zhao H, Ouyang X. Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: A randomized controlled trial. Diabetes Research And Clinical Practice 2013, 101: 50-56. PMID: 23706413, DOI: 10.1016/j.diabres.2013.04.005.
- Inflammasome biology in fibrogenesisOuyang X, Ghani A, Mehal WZ. Inflammasome biology in fibrogenesis. Biochimica Et Biophysica Acta 2013, 1832: 979-988. PMID: 23562491, DOI: 10.1016/j.bbadis.2013.03.020.
- Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body responseMalik AF, Hoque R, Ouyang X, Ghani A, Hong E, Khan K, Moore LB, Ng G, Munro F, Flavell RA, Shi Y, Kyriakides TR, Mehal WZ. Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20095-20100. PMID: 22109549, PMCID: PMC3250158, DOI: 10.1073/pnas.1105152108.
- Transcription factor IRF8 directs a silencing programme for TH17 cell differentiationOuyang X, Zhang R, Yang J, Li Q, Qin L, Zhu C, Liu J, Ning H, Shin MS, Gupta M, Qi CF, He JC, Lira SA, Morse HC, Ozato K, Mayer L, Xiong H. Transcription factor IRF8 directs a silencing programme for TH17 cell differentiation. Nature Communications 2011, 2: 314. PMID: 21587231, PMCID: PMC3112536, DOI: 10.1038/ncomms1311.
- Potentiation of Th17 cytokines in aging process contributes to the development of colitisOuyang X, Yang Z, Zhang R, Arnaboldi P, Lu G, Li Q, Wang W, Zhang B, Cui M, Zhang H, Liang-Chen J, Qin L, Zheng F, Huang B, Xiong H. Potentiation of Th17 cytokines in aging process contributes to the development of colitis. Cellular Immunology 2010, 266: 208-217. PMID: 21074754, PMCID: PMC3006034, DOI: 10.1016/j.cellimm.2010.10.007.
- Reduction of Stat3 Activity Attenuates HIV-Induced Kidney InjuryFeng X, Lu TC, Chuang PY, Fang W, Ratnam K, Xiong H, Ouyang X, Shen Y, Levy DE, Hyink D, Klotman M, D'Agati V, Iyengar R, Klotman PE, He JC. Reduction of Stat3 Activity Attenuates HIV-Induced Kidney Injury. Journal Of The American Society Of Nephrology 2009, 20: 2138-2146. PMID: 19608706, PMCID: PMC2754106, DOI: 10.1681/asn.2008080879.
- AP-1 Activated by Toll-like Receptors Regulates Expression of IL-23 p19*Liu W, Ouyang X, Yang J, Liu J, Li Q, Gu Y, Fukata M, Lin T, He JC, Abreu M, Unkeless JC, Mayer L, Xiong H. AP-1 Activated by Toll-like Receptors Regulates Expression of IL-23 p19*. Journal Of Biological Chemistry 2009, 284: 24006-24016. PMID: 19592489, PMCID: PMC2781995, DOI: 10.1074/jbc.m109.025528.
- IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein ExpressionYang D, Wang S, Brooks C, Dong Z, Schoenlein PV, Kumar V, Ouyang X, Xiong H, Lahat G, Hayes-Jordan A, Lazar A, Pollock R, Lev D, Liu K. IFN Regulatory Factor 8 Sensitizes Soft Tissue Sarcoma Cells to Death Receptor–Initiated Apoptosis via Repression of FLICE-like Protein Expression. Cancer Research 2009, 69: 1080-1088. PMID: 19155307, PMCID: PMC2633427, DOI: 10.1158/0008-5472.can-08-2520.
- A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunityNegishi H, Osawa T, Ogami K, Ouyang X, Sakaguchi S, Koshiba R, Yanai H, Seko Y, Shitara H, Bishop K, Yonekawa H, Tamura T, Kaisho T, Taya C, Taniguchi T, Honda K. A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 20446-20451. PMID: 19074283, PMCID: PMC2629334, DOI: 10.1073/pnas.0810372105.
- Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cellsGu Y, Yang J, Ouyang X, Liu W, Li H, Yang J, Bromberg J, Chen S, Mayer L, Unkeless JC, Xiong H. Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. European Journal Of Immunology 2008, 38: 1807-1813. PMID: 18506885, PMCID: PMC2733944, DOI: 10.1002/eji.200838331.
- Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγtYang J, Yang M, Htut TM, Ouyang X, Hanidu A, Li X, Sellati R, Jiang H, Zhang S, Li H, Zhao J, Ting AT, Mayer L, Unkeless JC, Labadia ME, Hodge M, Li J, Xiong H. Epstein‐Barr virus‐induced gene 3 negatively regulates IL‐17, IL‐22 and RORγt. European Journal Of Immunology 2008, 38: 1204-1214. PMID: 18412165, PMCID: PMC2989250, DOI: 10.1002/eji.200838145.
- Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activationOuyang X, Negishi H, Takeda R, Fujita Y, Taniguchi T, Honda K. Cooperation between MyD88 and TRIF pathways in TLR synergy via IRF5 activation. Biochemical And Biophysical Research Communications 2007, 354: 1045-1051. PMID: 17275788, DOI: 10.1016/j.bbrc.2007.01.090.
- Evidence for licensing of IFN-γ-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction programNegishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of IFN-γ-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 15136-15141. PMID: 17018642, PMCID: PMC1586247, DOI: 10.1073/pnas.0607181103.
- SOCS‐2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cellsOuyang X, Fujimoto M, Nakagawa R, Serada S, Tanaka T, Nomura S, Kawase I, Kishimoto T, Naka T. SOCS‐2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cells. Journal Of Cellular Physiology 2006, 207: 428-436. PMID: 16419040, DOI: 10.1002/jcp.20579.
- Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases.Fujimoto M, Tsutsui H, Xinshou O, Tokumoto M, Watanabe D, Shima Y, Yoshimoto T, Hirakata H, Kawase I, Nakanishi K, Kishimoto T, Naka T. Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases. International Immunology 2004, 16: 303-14. PMID: 14734616, DOI: 10.1093/intimm/dxh030.
- A regulatory role for suppressor of cytokine signaling-1 in T(h) polarization in vivo.Fujimoto M, Tsutsui H, Yumikura-Futatsugi S, Ueda H, Xingshou O, Abe T, Kawase I, Nakanishi K, Kishimoto T, Naka T. A regulatory role for suppressor of cytokine signaling-1 in T(h) polarization in vivo. International Immunology 2002, 14: 1343-50. PMID: 12407025.
- Sodium tanshinone IIA sulfonate derived from Danshen (Salvia miltiorrhiza) attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac cellsTakahashi K, Ouyang X, Komatsu K, Nakamura N, Hattori M, Baba A, Azuma J. Sodium tanshinone IIA sulfonate derived from Danshen (Salvia miltiorrhiza) attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac cells. Biochemical Pharmacology 2002, 64: 745-750. PMID: 12167494, DOI: 10.1016/s0006-2952(02)01250-9.
- Protective Effect of Salvia miltiorrhiza on Angiotensin II-Induced Hypertrophic Responses in Neonatal Rat Cardiac CellsOuyang X, Takahashi K, Komatsu K, Nakamura N, Hattori M, Baba A, Azuma J. Protective Effect of Salvia miltiorrhiza on Angiotensin II-Induced Hypertrophic Responses in Neonatal Rat Cardiac Cells. Journal Of Pharmacological Sciences 2001, 87: 289-296. PMID: 11829148, DOI: 10.1254/jjp.87.289.
Clinical Trials
Conditions | Study Title |
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Immune System | Inhibition of Sterile Inflammation by Digoxin |