203 results match your criteria fibrogenic diet

The unique molecular targets associated antioxidant and antifibrotic activity of curcumin in in vitro model of acute lung injury: A proteomic approach.

Biofactors 2021 Apr 17. Epub 2021 Apr 17.

Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, Karnataka, India.

Bleomycin (BLM) injury is associated with the severity of acute lung injury (ALI) leading to fibrosis, a high-morbidity, and high-mortality respiratory disease of unknown etiology. BLM-induced ALI is marked by the activation of a potent fibrogenic cytokine transcription growth factor beta-1 (TGFβ-1), which is considered a critical cytokine in the progression of alveolar injury. Previously, our work demonstrated that a diet-derived compound curcumin (diferuloylmethane), represents its antioxidative and antifibrotic application in TGF-β1-mediated BLM-induced alveolar basal epithelial cells. Read More

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Elafibranor and liraglutide improve differentially liver health and metabolism in a mouse model of non-alcoholic steatohepatitis.

Liver Int 2021 Mar 31. Epub 2021 Mar 31.

Department of Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Background & Aims: This study aimed to assess and compare the effects of the GLP-1 analog liraglutide and the PPARα/δ agonist elafibranor on liver histology and their impact on hepatic lipidome, metabolome, Kupffer and hepatic stellate cell activation in a model of advanced non-alcoholic fatty liver disease (NAFLD).

Methods: Male C57BL/6JRj mice with biopsy-confirmed hepatosteatosis and fibrosis induced by 36-week Amylin liver NASH (AMLN) diet (high-fat, fructose and cholesterol) were randomized to receive for 12 weeks: (a) liraglutide (0.4 mg/kg/day s. Read More

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Liver specific deletion of mouse Tm6sf2 promotes steatosis, fibrosis and hepatocellular cancer.

Hepatology 2021 Feb 27. Epub 2021 Feb 27.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, United States.

Background And Aims: Human TM6SF2 variant rs58542926 is associated with nonalcoholic fatty liver disease (NAFLD) and hepatocellular cancer (HCC). However, conflicting reports in germline Tm6sf2 knockout mice suggest no change or decreased VLDL secretion and either unchanged or increased hepatic steatosis, with no increased fibrosis. We generated liver specific Tm6Sf2 knockout mice (Tm6 LKO) to study VLDL secretion and the impact on development and progression of NAFLD. Read More

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February 2021

Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD.

J Transl Med 2021 02 17;19(1):80. Epub 2021 Feb 17.

Pathology & Imaging, Novo Nordisk A/S, Novo Nordisk Park 1, 2760, Måløv, Denmark.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent comorbidities in patients with Type 2 diabetes. While many of these patients eventually will need treatment with insulin, little is known about the effects of insulin treatment on histopathological parameters and hepatic gene expression in diabetic patients with co-existing NAFLD and NASH. To investigate this further, we evaluated the effects of insulin treatment in NASH diet-fed hamsters with streptozotocin (STZ) -induced hyperglycemia. Read More

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February 2021

Heterogeneity of hepatic stellate cells in a mouse model of non-alcoholic steatohepatitis (NASH).

Hepatology 2021 Feb 7. Epub 2021 Feb 7.

Department of Medicine, University of California San Diego, La Jolla, CA, USA, La Jolla.

In clinical and experimental non-alcoholic steatohepatitis (NASH), the origin of the scar-forming myofibroblast is the hepatic stellate cell (HSC). We used foz/foz mice on a Western diet to characterize in detail the phenotypic changes of HSCs in a NASH model. We examined the single cell expression profiles (scRNA-Seq) of HSCs purified from the normal livers of foz/foz mice on a chow diet, in NASH with fibrosis of foz/foz mice on a Western diet, and in livers during regression of NASH after switching back to a chow diet. Read More

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February 2021

Resistin induces cardiac fibroblast-myofibroblast differentiation through JAK/STAT3 and JNK/c-Jun signaling.

Pharmacol Res 2021 May 29;167:105414. Epub 2021 Jan 29.

Cardiovascular Research Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Diabetes, Obesity and Metabolism Institute, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Graduate School of Biomedical Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. Electronic address:

Cardiac fibrosis is characterized by excessive deposition of extracellular matrix proteins and myofibroblast differentiation. Our previous findings have implicated resistin in cardiac fibrosis; however, the molecular mechanisms underlying this process are still unclear. Here we investigated the role of resistin in fibroblast-to-myofibroblast differentiation and elucidated the pathways involved in this process. Read More

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Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis.

JHEP Rep 2021 Apr 20;3(2):100217. Epub 2020 Nov 20.

Centre for Liver and Gastroenterology Research and National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.

Background & Aims: Increasing evidence highlights dietary fructose as a major driver of non-alcoholic fatty liver disease (NAFLD) pathogenesis, the majority of which is cleared on first pass through the hepatic circulation by enzymatic phosphorylation to fructose-1-phosphate via the ketohexokinase (KHK) enzyme. Without a current approved therapy, disease management emphasises lifestyle interventions, but few patients adhere to such strategies. New targeted therapies are urgently required. Read More

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Inhibition of hyaluronan synthesis by 4-methylumbelliferone ameliorates non-alcoholic steatohepatitis in choline-deficient L-amino acid-defined diet-induced murine model.

Arch Pharm Res 2021 Feb 24;44(2):230-240. Epub 2021 Jan 24.

Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

Hyaluronan (HA) as a glycosaminoglycan can bind to cell-surface receptors, such as TLR4, to regulate inflammation, tissue injury, repair, and fibrosis. 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, is a drug used for the treatment of biliary spasms. Currently, therapeutic interventions are not available for non-alcoholic steatohepatitis (NASH). Read More

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February 2021

Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding.

Int J Mol Sci 2020 Dec 30;22(1). Epub 2020 Dec 30.

Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea.

Liver fibrosis is a consequence of chronic liver injury associated with chronic viral infection, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical and animal studies indicates that transforming growth factor-β (TGF-β) signaling is associated with the development of liver fibrosis. Krüppel-like factor 10 (KLF10) is a transcription factor that plays a significant role in TGF-β-mediated cell growth, apoptosis, and differentiation. Read More

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December 2020

Escitalopram Ameliorates Cardiomyopathy in Type 2 Diabetic Rats via Modulation of Receptor for Advanced Glycation End Products and Its Downstream Signaling Cascades.

Front Pharmacol 2020 15;11:579206. Epub 2020 Dec 15.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Type 2 diabetes mellitus (T2DM) has been recognized as a known risk factor for cardiovascular diseases. Additionally, studies have shown the prevalence of depression among people with diabetes. Thus, the current study aimed to investigate the possible beneficial effects of escitalopram, a selective serotonin reuptake inhibitor, on metabolic changes and cardiac complications in type 2 diabetic rats. Read More

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December 2020

Identification of a Metabolic, Transcriptomic, and Molecular Signature of Patatin-Like Phospholipase Domain Containing 3-Mediated Acceleration of Steatohepatitis.

Hepatology 2021 Apr 19;73(4):1290-1306. Epub 2021 Mar 19.

Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA.

Background And Aims: The mechanisms by which the I148M mutant variant of the patatin-like phospholipase domain-containing 3 (PNPLA3 ) drives development of nonalcoholic steatohepatitis (NASH) are not known. The aim of this study was to obtain insights on mechanisms underlying PNPLA3 -induced acceleration of NASH.

Approach And Results: Hepatocyte-specific overexpression of empty vector (luciferase), human wild-type PNPLA3, or PNPLA3 was achieved using adeno-associated virus 8 in a diet-induced mouse model of nonalcoholic fatty liver disease followed by chow diet or high-fat Western diet with ad libitum administration of sugar in drinking water (WDSW) for 8 weeks. Read More

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Therapeutic effect of Prdx1 on NAFLD mice may be related to the activation of Nrf-2/HO-1 pathway.

Curr Pharm Des 2020 Oct 26. Epub 2020 Oct 26.

Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029. China.

Objective: To investigate the effect of peroxiredoxin1 (Prdx1) on the methionine-choline deficient (MCD)- induced mice model of non-alcoholic fatty liver disease (NAFLD).

Methods: Wild type (WT), transgenic Prdx1 over-expressing (TG) and Prdx1 knockout (KO) mice were fed with MCD diet to construct NAFLD model. General parameters was determined followed by detection with HE staining, oil red O staining, Immunofluorescence, Immunohistochemistry, qRT-PCR and Western blotting. Read More

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October 2020

Significance of MR/OPN/HMGB1 axis in NAFLD-associated hepatic fibrogenesis.

Life Sci 2021 Jan 20;264:118619. Epub 2020 Oct 20.

Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China. Electronic address:

Aims: The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis, however non-alcoholic fatty liver disease (NAFLD) associated liver fibrogenesis have been poorly understood. We aimed to determine the significance of mineralocorticoid receptor (MR)/osteopontin (OPN)/high-mobility group box-1 (HMGB1) axis in this setting.

Main Methods: Liver specimens were collected from NAFLD patients and murine NAFLD models established with 12-week high fat diet (HFD) for analysis of both upstream signals of MR and intrahepatic MR/OPN/HMGB1 axis. Read More

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January 2021

Alcoholic hepatitis and metabolic disturbance in female mice: a more tractable model than animals.

Dis Model Mech 2020 12 29;13(12). Epub 2020 Dec 29.

Centre for Liver and Gastroenterology Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK

Alcoholic hepatitis (AH) is the dramatic acute presentation of alcoholic liver disease, with a 15% mortality rate within 28 days in severe cases. Research into AH has been hampered by the lack of effective and reproducible murine models that can be operated under different regulatory frameworks internationally. The liquid Lieber-deCarli (LdC) diet has been used as a means of delivery of alcohol but without any additional insult, and is associated with relatively mild liver injury. Read More

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December 2020

Oligo-Fucoidan Improves Diabetes-Induced Renal Fibrosis via Activation of Sirt-1, GLP-1R, and Nrf2/HO-1: An In Vitro and In Vivo Study.

Nutrients 2020 Oct 8;12(10). Epub 2020 Oct 8.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan.

Fucoidan extracted from brown algae has multiple beneficial functions. In this study, we investigated the effects of low-molecular-weight fucoidan (oligo-FO) on renal fibrosis under in vitro and in vivo diabetic conditions, and its molecular mechanisms. Advanced glycation product (AGE)-stimulated rat renal proximal tubular epithelial cells (NRK-52E) and diabetic mice induced by high-fat diet and intraperitoneal injection of streptozotocin and nicotinamide were used. Read More

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October 2020

Role of CC chemokine receptor 9 in the progression of murine and human non-alcoholic steatohepatitis.

J Hepatol 2021 Mar 8;74(3):511-521. Epub 2020 Oct 8.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Background & Aims: The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH. Read More

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Therapeutic Targeting of Myeloperoxidase Attenuates NASH in Mice.

Hepatol Commun 2020 Oct 29;4(10):1441-1458. Epub 2020 Jul 29.

1st Department of Medicine University Medical Center Hamburg-Eppendorf Hamburg Germany.

Myeloperoxidase (MPO) activity has been associated with the metabolic syndrome, cardiovascular and liver disease. Here, we evaluate the therapeutic potential of MPO inhibition on nonalcoholic steatohepatitis (NASH) and NASH-induced fibrosis, the main determinant of outcomes. MPO plasma levels were elevated in patients with nonalcoholic fatty liver disease (NAFLD) compared with healthy controls. Read More

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October 2020

Retinoic acid signalling in fibro/adipogenic progenitors robustly enhances muscle regeneration.

EBioMedicine 2020 Oct 24;60:103020. Epub 2020 Sep 24.

Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, and School of Molecular Bioscience, Washington State University, Pullman, WA. Electronic address:

Background: During muscle regeneration, excessive formation of adipogenic and fibrogenic tissues, from their respective fibro/adipogenic progenitors (FAPs), impairs functional recovery. Intrinsic mechanisms controlling the proliferation and differentiation of FAPs remain largely unexplored.

Methods: Here, we investigated the role of retinoic acid (RA) signalling in regulating FAPs and the subsequent effects on muscle restoration from a cardiotoxin-induced injury. Read More

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October 2020

Novel oral plasminogen activator inhibitor‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats.

Mol Med Rep 2020 Oct 28;22(4):2948-2956. Epub 2020 Jul 28.

Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634‑8522, Japan.

An orally bioavailable small molecule inhibitor of plasminogen activator inhibitor‑1 (PAI‑1) is currently being clinically assessed as a novel antithrombotic agent. Although PAI‑1 is known to serve a key role in the pathogenesis of metabolic syndrome (MetS) including nonalcoholic steatohepatitis (NASH), the pharmacological action of an oral PAI‑1 inhibitor against the development of MetS‑related liver fibrosis remains unclear. The current study was designed to explicate the effect of TM5275, an oral PAI‑1 inhibitor, on MetS‑related hepatic fibrogenesis. Read More

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October 2020

Branched chain amino acids and carbohydrate restriction exacerbate ketogenesis and hepatic mitochondrial oxidative dysfunction during NAFLD.

FASEB J 2020 11 12;34(11):14832-14849. Epub 2020 Sep 12.

Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.

Mitochondrial adaptation during non-alcoholic fatty liver disease (NAFLD) include remodeling of ketogenic flux and sustained tricarboxylic acid (TCA) cycle activity, which are concurrent to onset of oxidative stress. Over 70% of obese humans have NAFLD and ketogenic diets are common weight loss strategies. However, the effectiveness of ketogenic diets toward alleviating NAFLD remains unclear. Read More

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November 2020

Comprehensive characterization of metabolic, inflammatory and fibrotic changes in a mouse model of diet-derived nonalcoholic steatohepatitis.

J Nutr Biochem 2020 11 10;85:108463. Epub 2020 Jul 10.

Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA. Electronic address:

The objective of this study was to develop a well-characterized mouse model of nonalcoholic steatohepatitis (NASH) with a strong manifestation of liver fibrosis. The progression of metabolic, inflammatory and fibrotic features of this mouse model was monitored by performing in vivo time-course study. Male C57BL/6J mice were fed a high-fat/high-sucrose/high-cholesterol diet (34% fat, 34% sucrose and 2. Read More

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November 2020

Hepatocyte pyroptosis and release of inflammasome particles induce stellate cell activation and liver fibrosis.

J Hepatol 2021 Jan 4;74(1):156-167. Epub 2020 Aug 4.

Department of Pediatrics, University of California San Diego, La Jolla, CA, USA. Electronic address:

Background & Aims: Increased hepatocyte death contributes to the pathology of acute and chronic liver diseases. However, the role of hepatocyte pyroptosis and extracellular inflammasome release in liver disease is unknown.

Methods: We used primary mouse and human hepatocytes, hepatocyte-specific leucine 351 to proline Nlrp3CreA mice, and Gsdmd mice to investigate pyroptotic cell death in hepatocytes and its impact on liver inflammation and damage. Read More

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January 2021

AGER1 downregulation associates with fibrosis in nonalcoholic steatohepatitis and type 2 diabetes.

J Clin Invest 2020 08;130(8):4320-4330

Gastroenterology and Hepatology, Stanford University, Stanford, and VA Palo Alto, California, USA.

Type 2 diabetes is clinically associated with progressive necroinflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Advanced glycation end-products (AGEs) accumulate during prolonged hyperglycemia, but the mechanistic pathways that lead to accelerated liver fibrosis have not been well defined. In this study, we show that the AGEs clearance receptor AGER1 was downregulated in patients with NASH and diabetes and in our NASH models, whereas the proinflammatory receptor RAGE was induced. Read More

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Bisphenol-A exposure worsens hepatic steatosis in ovariectomized mice fed on a high-fat diet: Role of endoplasmic reticulum stress and fibrogenic pathways.

Life Sci 2020 Sep 25;256:118012. Epub 2020 Jun 25.

Laboratório de Fisiopatologia, Divisão de Pesquisa Integrada em Produtos Bioativos e Biociências (DPBio), Polo Novo Cavaleiros, Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brazil; Setor de Ciências Biológicas e da Saúde (SEBISA), Departamento de Biologia Geral, Universidade Estadual de Ponta Grossa (UEPG), Ponta Grossa, PR, Brazil. Electronic address:

Aims: Bisphenol (BP)-A exposure can impair glucose and lipid metabolism. However, it is unclear whether this endocrine disruptor (ED) modulates these processes in postmenopause, a period with organic changes that increase the risk for metabolic diseases. Herein, we evaluated the effects of BPA exposure on adiposity, glucose homeostasis and hepatic steatosis in ovariectomized (OVX) mice fed on a high-fat diet (HFD). Read More

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September 2020

Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis.

Microorganisms 2020 Jun 19;8(6). Epub 2020 Jun 19.

Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan.

Despite the use of various pharmacotherapeutic strategies, fibrosis due to nonalcoholic steatohepatitis (NASH) remains an unsatisfied clinical issue. We investigated the effect of sevelamer, a hydrophilic bile acid sequestrant, on hepatic fibrosis in a murine NASH model. Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat (CDHF) diet for 12 weeks with or without orally administered sevelamer hydrochloride (2% per diet weight). Read More

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The PPAR α/γ Agonist Saroglitazar Improves Insulin Resistance and Steatohepatitis in a Diet Induced Animal Model of Nonalcoholic Fatty Liver Disease.

Sci Rep 2020 06 9;10(1):9330. Epub 2020 Jun 9.

Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA.

Insulin resistance and hepatic lipid accumulation constitute the metabolic underpinning of nonalcoholic steatohepatitis (NASH). We tested the hypothesis that saroglitazar, a PPAR α/γ agonist would improve NASH in the diet-induced animal model of NAFLD. Mice received chow diet and normal water (CDNW) or high fat western diet and ad lib sugar water (WDSW). Read More

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Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice.

Biochem Biophys Res Commun 2020 07 29;528(2):305-310. Epub 2020 May 29.

Faculty of Fisheries Sciences, Hokkaido University, 3-1-1 Minato, Hakodate, Hokkaido, 041-8611, Japan. Electronic address:

Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anti-cancer, anti-inflammatory, anti-oxidative and anti-obesity. Read More

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Loss of Hepatocyte-Specific PPAR Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet.

PPAR Res 2020 1;2020:9735083. Epub 2020 May 1.

Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Illinois at Chicago, Chicago, IL, USA.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. To date, there is not a specific and approved treatment for NAFLD yet, and therefore, it is important to understand the molecular mechanisms that lead to the progression of NAFLD. Methionine- and choline-deficient (MCD) diets are used to reproduce some features of NAFLD in mice. Read More

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The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice.

BMC Pulm Med 2020 Apr 29;20(1):112. Epub 2020 Apr 29.

IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, DE, Germany.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of which the etiology is still not fully understood. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Read More

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Dysregulation of nuclear factor erythroid 2-related factor 2 signaling and activation of fibrogenic pathways in hearts of high fat diet-fed rats.

Mol Biol Rep 2020 Apr 1;47(4):2821-2834. Epub 2020 Apr 1.

Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

High fat diet (HFD)-induced obesity adversely affects cardiac outcomes; however the effect of HFD consumption on myocardial remodeling and the underlying mechanisms are still elusive. This study aimed to examine the histological and molecular changes in cardiac tissue of HFD-fed rats. Eight-week old male Wistar rats were fed either HFD or normal chow diet for 16 weeks and then assessed for changes in metabolic and cardiac homeostasis (n = 10 each group). Read More

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