18,223 results match your criteria hepatocyte nuclear

Interleukin-17 in Liver Disease Pathogenesis.

Semin Liver Dis 2021 Jun 15. Epub 2021 Jun 15.

Department of Surgery, University of California, San Diego, La Jolla, CA.

Interleukin 17A (IL-17A)-producing T helper 17 (Th17) cells were identified as a subset of T helper cells that play a critical role in host defense against bacterial and fungal pathogens. Th17 cells differentiate from Th0 naïve T-cells in response to transforming growth factor β1 (TGF-β1) and IL-6, the cytokines which also drive development of liver fibrosis, require activation of transcription factor retinoic acid receptor-related orphan nuclear receptor gamma (RORγ). IL-17A signals through the ubiquitously expressed receptor IL-17RA. Read More

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TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells.

Front Oncol 2021 28;11:618540. Epub 2021 May 28.

Department of Urology, Chinese People's Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, Beijing, China.

The prognosis for endocrine-independent prostate carcinoma is still poor due to its highly metastatic feature. In the present work, TPX2 (the targeting protein for Xklp2), which is known as a micro-tubulin interacted protein, was identified as a novel coactivator of ETS-1, a transcription factor that plays a central role in mediating the metastasis of human malignancies. TPX2 enhanced the transcription factor activation of ETS-1 and increased the expression of ETS-1's downstream metastasis-related genes, such as or , induced by HGF (hepatocyte growth factor), a typical agonist of the HGF/c-MET/ETS-1 pathway. Read More

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Ameliorative role of ascorbic acid on the oxidative stress and genotoxicity induced by acetamiprid in Nile tilapia (Oreochromis niloticus).

Environ Sci Pollut Res Int 2021 Jun 14. Epub 2021 Jun 14.

Zoology Department, Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, 32511, Egypt.

On juveniles of Oreochromis niloticus, the protective potential of ascorbic acid (Asc) against oxidative stress and genotoxicity induced by acetamiprid (Aceta) sub-lethal concentrations was investigated in this study. Fishes were divided into six groups and exposed to either Asc (50 ppm), 10 and 20 ppm Aceta, 10 ppm (Aceta)+Asc, 20 ppm (Aceta)+Asc, or the unexposed control group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and their transcripts were assessed. Read More

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Diagnostic utility of the combined use of HNF4A and GATA3 in distinction between primary and metastatic breast and gastric carcinomas.

APMIS 2021 Jun 12. Epub 2021 Jun 12.

Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Background: Sometimes distinction between gastric adenocarcinomas and breast carcinomas can be challenging. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases.

Purpose: To evaluate the role of the combined use of HNF4A and GATA3 as immunohistochemical markers in distinction between primary and metastatic breast and gastric carcinomas. Read More

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Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice.

Stem Cell Res 2021 Jun 6;54:102425. Epub 2021 Jun 6.

Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan. Electronic address:

Adipose tissue-derived stem cells (ADSCs) have been suggested as a novel treatment for non-alcoholic steatohepatitis (NASH); however, the mechanisms underlying their therapeutic effect remain poorly understood. In this study, we aimed to investigate the association of Notch signaling, which is crucial for cellular proliferation and differentiation in ADSC-mediated treatment of NASH. Flow cytometry analysis of ADSCs showed that they expressed the Notch ligands JAG1, DLL1, and DLL4. Read More

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Fatty acids activate the transcriptional coactivator YAP1 to promote liver fibrosis via p38 mitogen-activated protein kinase.

Cell Mol Gastroenterol Hepatol 2021 Jun 9. Epub 2021 Jun 9.

Liver Center, Massachusetts General Hospital, Boston, MA, USA. Electronic address:

Background & Aims: Patients with simple steatosis (SS) and nonalcoholic steatohepatitis (NASH) can develop progressive liver fibrosis, which is associated with liver-related mortality. The mechanisms contributing to liver fibrosis development in SS, however, are poorly understood. SS is characterized by hepatocellular free fatty acid (FFA) accumulation without lobular inflammation seen in NASH. Read More

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Biological activity of 2α,3β,23-trihydroxyolean-12-ene on glucose homeostasis.

Eur J Pharmacol 2021 Jun 10;907:174250. Epub 2021 Jun 10.

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address:

We studied the effect and the mechanisms of action of 2α,3β,23-trihydroxyolean-12-ene (THO), from Croton heterodoxus Baill. (Euphorbiaceae), in glucose uptake in hyperglycemic rats. The effect of in vivo pretreatment with THO in hyperglycemic rats was analyzed. Read More

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Alpha lipoic acid priming enhances the hepatoprotective effect of adipose derived stem cells in CCl4 induced hepatic injury in-vitro.

Eur J Pharmacol 2021 Jun 9;906:174201. Epub 2021 Jun 9.

National Centre of Excellence in Molecular Biology, University of Punjab, 87-West Canal Bank Road, Lahore, Pakistan; Jinnah Burn & Reconstructive Surgery Centre, Lahore, Pakistan. Electronic address:

Mesenchymal stem cells are known to support hepatic defense against liver fibrosis. However, the fibrosis induced oxidative microenvironment affects the proliferative, regenerative, and angiogenic properties of mesenchymal stem cells. Alpha lipoic acid (ALA) is a strong anti-oxidant which has been shown to ameliorate the adverse effects of fibrosis that otherwise can lead to severe liver problems like cirrhosis and liver failure. Read More

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Diminished ketone interconversion, hepatic TCA cycle flux, and glucose production in D-β-hydroxybutyrate dehydrogenase hepatocyte-deficient mice.

Mol Metab 2021 Jun 8:101269. Epub 2021 Jun 8.

Division of Molecular Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA; Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN, USA. Electronic address:

Objective: Throughout the last decade, interest has intensified in intermittent fasting, ketogenic diets, and exogenous ketone therapies as prospective health-promoting, therapeutic, and performance-enhancing agents. However, the regulatory roles of ketogenesis and ketone metabolism on liver homeostasis remain unclear. Therefore, we sought to develop a better understanding of the metabolic consequences of hepatic ketone body metabolism by focusing on the redox-dependent interconversion of acetoacetate (AcAc) and D-β-hydroxybutyrate (D-βOHB). Read More

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Lipid overload impairs hepatic VLDL secretion via oxidative stress-mediated PKCδ-HNF4α-MTP pathway in large yellow croaker (Larimichthys crocea).

Free Radic Biol Med 2021 Jun 8;172:213-225. Epub 2021 Jun 8.

Key Laboratory of Aquaculture Nutrition and Feed (Ministry of Agriculture and Rural Affairs) and Key Laboratory of Mariculture (Ministry of Education), Ocean University of China, 5 Yushan Road, 266003, Qingdao, Shandong, People's Republic of China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, 266237, Qingdao, Shandong, People's Republic of China. Electronic address:

Lipid overload-induced hepatic steatosis is a major public health problem worldwide. However, the potential molecular mechanism is not completely understood. Herein, we found that high-fat diet (HFD) or oleic acid (OA) treatment induced oxidative stress which prevented the entry of hepatocyte nuclear factor 4 alpha (HNF4α) into the nucleus by activating protein kinase C delta (PKCδ) in vivo and in vitro in large yellow croaker (Larimichthys crocea). Read More

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Evaluating causality of cellular senescence in non-alcoholic fatty liver disease.

JHEP Rep 2021 Aug 1;3(4):100301. Epub 2021 May 1.

Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands.

Cellular senescence is a state of irreversible cell cycle arrest that has important physiological functions. However, cellular senescence is also a hallmark of ageing and has been associated with several pathological conditions. A wide range of factors including genotoxic stress, mitogens and inflammatory cytokines can induce senescence. Read More

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Hippo Pathway Counter-Regulates Innate Immunity in Hepatitis B Virus Infection.

Front Immunol 2021 25;12:684424. Epub 2021 May 25.

Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Whether hepatitis B virus (HBV) activates or represses innate immunity continues to be debated. Toll-like receptor (TLR) 2 has been identified to recognize HBV particles in human hepatocytes. The Hippo pathway, known for growth control, is suggested to play a vital role in immune regulation. Read More

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4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response.

Front Pharmacol 2021 25;12:651444. Epub 2021 May 25.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The liver is an important metabolic organ, and acute liver injury (ALI) is potentially lethal. Itaconate, a metabolic intermediate from the tricarboxylic acid cycle, showed emerging anti-oxidative and anti-inflammation properties, and an accumulating protective effect in multiple diseases, but its role in ALI still needs to be further explored. Here we established an ALI model induced by carbon tetrachloride in mice. Read More

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Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury.

Sci Transl Med 2021 Jun;13(597)

Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.

Acetaminophen (-acetyl--aminophenol; APAP) toxicity is a common cause of liver damage. In the mouse model of APAP-induced liver injury (AILI), interleukin 11 (IL11) is highly up-regulated and administration of recombinant human IL11 (rhIL11) has been shown to be protective. Here, we demonstrate that the beneficial effect of rhIL11 in the mouse model of AILI is due to its inhibition of endogenous mouse IL11 activity. Read More

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Lipid accumulation-induced hepatocyte senescence regulates the activation of hepatic stellate cells through the Nrf2-antioxidant response element pathway.

Exp Cell Res 2021 Jun 6;405(2):112689. Epub 2021 Jun 6.

Department of Gastroenterology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Department of Gerontology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China; Research Center on Aging and Medicine, Fudan University, Shanghai, China. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease globally. Elderly individuals are at a higher risk of developing NAFLD with severe clinical outcomes. Although NAFLD is closely related to liver aging, the role of hepatocyte senescence in the progression of NAFLD, especially in the development of fibrosis, is still unclear. Read More

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Hepatic bile acid transport increases in the postprandial state: A functional C-CSar PET/CT study in healthy humans.

JHEP Rep 2021 Jun 15;3(3):100288. Epub 2021 Apr 15.

Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.

Background & Aims: It is not known how hepatic bile acids transport kinetics changes postprandially in the intact liver. We used positron emission tomography (PET)/computed tomography (CT) with the tracer [-methyl-C]cholylsarcosine (C-CSar), a synthetic sarcosine conjugate of cholic acid, to quantify fasting and postprandial hepatic bile acid transport kinetics in healthy human participants.

Methods: Six healthy human participants underwent dynamic liver C-CSar PET/CT (60 min) during fasting and from 15 min after ingestion of a standard liquid meal. Read More

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Mapping of m6A and Its Regulatory Targets in Prostate Cancer Reveals a METTL3-low Induction of Therapy Resistance.

Mol Cancer Res 2021 Jun 4. Epub 2021 Jun 4.

Department for BioMedical Research, University of Bern

Recent evidence has highlighted the role of N6-methyladenosine (m6A) in the regulation of mRNA expression, stability and translation, supporting a potential role for post-transcriptional regulation mediated by m6A in cancer. Here we explore prostate cancer as an exemplar and demonstrate that low levels of N6-adenosine-methyltransferase (METTL3) is associated with advanced metastatic disease. To investigate this relationship, we generated the first prostate m6A maps, and further examined how METTL3 regulates expression at the level of transcription, translation, and protein. Read More

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HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas.

Arch Pathol Lab Med 2021 Jun 4. Epub 2021 Jun 4.

From the Department of Pathology (Patil, Jain, Zhang), Yale University School of Medicine, New Haven, Connecticut.

Context.—: Intrahepatic cholangiocarcinoma (iCCA) needs to be distinguished from hepatocellular carcinoma (HCC) and metastasis, and in the absence of any specific biliary markers, is often a diagnosis of exclusion. Hepatocyte nuclear factor (HNF)-1β is a transcription factor that plays a critical role in bile duct system morphogenesis. Read More

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Additional partial hepatectomy at the time of portal vein ligation accelerates the regeneration of the future liver remnant.

Sci Rep 2021 Jun 3;11(1):11740. Epub 2021 Jun 3.

Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany.

Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Read More

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Activation of AhR-NQO1 Signaling Pathway Protects Against Alcohol-Induced Liver Injury by Improving Redox Balance.

Cell Mol Gastroenterol Hepatol 2021 May 31. Epub 2021 May 31.

Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina; Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina. Electronic address:

Background & Aims: Aryl hydrocarbon receptor (AhR) is a liver-enriched xenobiotic receptor that plays important role in detoxification response in liver. This study aimed to investigate how AhR signaling may impact the pathogenesis of alcohol-related liver disease (ALD).

Methods: Chronic alcohol feeding animal studies were conducted with mouse models of hepatocyte-specific AhR knockout (AhR) and NAD(P)H quinone dehydrogenase 1 (NQO1) overexpression, and dietary supplementation of the AhR ligand indole-3-carbinol. Read More

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Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure.

Toxicol Ind Health 2021 May;37(5):251-259

Department of Toxicology, School of Public Health, 66367Zunyi Medical University, Zunyi, People's Republic of China.

This study investigated hepatic oxidative damage in rats following long-term manganese (Mn) exposure and clarified the underlying mechanisms. Forty-eight rats (SPF, male) were randomly assigned to receive low (10 mg/kg, = 16) or high doses of Mn (50 mg/kg, = 16) or sterilized distilled water (control group, = 16). Rats were euthanized after 12 months, and liver Mn levels and histopathological changes were determined. Read More

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[MODY type diabetes: an often-misunderstood entity].

Rev Med Suisse 2021 Jun;17(741):1062-1066

Service d'endocrinologie, diabétologie, nutrition et éducation thérapeutique du patient, HUG, 1211 Genève 14.

MODY diabetes, for Maturity Onset Diabetes of the Young, is a form of monogenic diabetes characterized by a typical onset before the age of 25 years, the lack of autoimmunity against the b cells of the pancreas, a preserved β cells function and an autosomal dominant mode of inheritance. This type of diabetes constitutes 2 to 5% of all cases of diabetes but remains often undiagnosed. Nearly 15 MODY subtypes have been identified to date. Read More

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NR4A1 Ligands as Potent Inhibitors of Breast Cancer Cell and Tumor Growth.

Cancers (Basel) 2021 May 29;13(11). Epub 2021 May 29.

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.

Nuclear receptor 4A1 (NR4A1, Nur77, TR3) is more highly expressed in breast and solid tumors compared to non-tumor tissues and is a pro-oncogenic factor in solid tumor-derived cancers. NR4A1 regulates cancer cell growth, survival, migration, and invasion, and bis-indole-derived compounds (CDIMs) that bind NR4A1 act as antagonists and inhibit tumor growth. Preliminary structure-binding studies identified 1,1-bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane analogs as NR4A1 ligands with low K values; we further investigated the anticancer activity of the four most active analogs (K's ≤ 3. Read More

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Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma.

Cancers (Basel) 2021 May 23;13(11). Epub 2021 May 23.

Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). Read More

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Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses.

Cancers (Basel) 2021 May 18;13(10). Epub 2021 May 18.

College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Korea.

Pgrmc1 is a non-canonical progesterone receptor related to the lethality of various types of cancer. PGRMC1 has been reported to exist in co-precipitated protein complexes with epidermal growth factor receptor (EGFR), which is considered a useful therapeutic target in hepatocellular carcinoma (HCC). Here, we investigated whether is involved in HCC progression. Read More

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Estrogen Receptor-α Suppresses Liver Carcinogenesis and Establishes Sex-Specific Gene Expression.

Cancers (Basel) 2021 May 13;13(10). Epub 2021 May 13.

McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.

Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a significantly greater extent when females lack , which encodes Estrogen Receptor-α. Read More

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The Effect of RBP4 on microRNA Expression Profiles in Porcine Granulosa Cells.

Animals (Basel) 2021 May 13;11(5). Epub 2021 May 13.

College of Animal Sciences, Jilin University, Changchun 130062, China.

Retinol binding protein 4 (RBP4) is a transporter of vitamin A that is secreted mainly by hepatocytes and adipocytes. It affects diverse pathophysiological processes, such as obesity, insulin resistance, and cardiovascular diseases. MicroRNAs (miRNAs) have been reported to play indispensable roles in regulating various developmental processes via the post-transcriptional repression of target genes in mammals. Read More

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Acquired Evolution of Mitochondrial Metabolism Regulated by HNF1B in Ovarian Clear Cell Carcinoma.

Cancers (Basel) 2021 May 17;13(10). Epub 2021 May 17.

Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Clear cell carcinoma (CCC) of the ovary exhibits a unique morphology and clinically malignant behavior. The eosinophilic cytoplasm includes abundant glycogen. Although the growth is slow, the prognosis is poor owing to resistance to conventional chemotherapies. Read More

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Hepatocyte Small Heterodimer Partner Mediates Sex-Specific Effects on Triglyceride Metabolism via Androgen Receptor in Male Mice.

Metabolites 2021 May 20;11(5). Epub 2021 May 20.

Tennessee Valley Health System, Veterans Affairs, Nashville, TN 37212, USA.

Mechanisms of sex differences in hypertriglyceridemia remain poorly understood. Small heterodimer partner (SHP) is a nuclear receptor that regulates bile acid, glucose, and lipid metabolism. SHP also regulates transcriptional activity of sex hormone receptors and may mediate sex differences in triglyceride (TG) metabolism. Read More

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Ligustilide counteracts carcinogenesis and hepatocellular carcinoma cell-evoked macrophage M2 polarization by regulating yes-associated protein-mediated interleukin-6 secretion.

Exp Biol Med (Maywood) 2021 May 29:15353702211010420. Epub 2021 May 29.

Emergency Department, Jiaozuo Hospital of Traditional Chinese Medicine, Jiaozuo 454150, China.

Cross-communication between cancer cells and macrophages within the tumor microenvironment fulfills the critical roles in the progression of cancers, including hepatocellular carcinoma (HCC). Ligustilide exerts anti-inflammation, anti-injury, and anti-tumor pleiotropic pharmacological functions. Nevertheless, its roles in HCC cells and tumor microenvironment remain elusive. Read More

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