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Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). So far, the underlying mechanism remains poorly understood. Here, we show that hepatic carboxylesterase 2 (CES2) is markedly reduced in NASH patients, diabetic db/db mice, and high‐fat diet (HFD)‐fed mice. Restoration of hepatic CES2 expression in db/db or HFD‐fed mice markedly ameliorates liver steatosis and insulin resistance. In contrast, knockdown of hepatic CES2 causes liver steatosis and damage in chow‐ or Western diet‐fed C57BL/6 mice. Mechanistically, we demonstrate that CES2 has triglyceride hydrolase activity. As a result, gain of hepatic CES2 function increases fatty acid oxidation and inhibits lipogenesis, whereas loss of hepatic CES2 stimulates lipogenesis by inducing endoplasmic reticulum stress. We further show that loss of hepatic CES2 stimulates lipogenesis in a sterol regulatory element‐binding protein 1 (SREBP‐1)‐dependent manner. Finally, we show that hepatocyte nuclear factor 4 alpha (HNF‐4α) plays a key role in controlling hepatic CES2 expression in diabetes, obesity, or NASH. Conclusion: CES2 plays a protective role in development of NAFLD. Targeting the HNF‐4α/CES2 pathway may be useful for treatment of NAFLD. (Hepatology 2016;63:1860‐1874)

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Publication Date
Sun Jan 04 2009
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Human Cytomegalovirus Up-regulates Nuclear Factor-κB in Women with Spontaneous Abortion

Background: Human cytomegalovirus (HCMV) infection during pregnancy causing serious problems through induction of viral genes that enhance the expression of different cellular factors ending in failure of pregnancy.
Patients and Methods: Paraffin embedded sections of curate samples were obtained from 34 women had spontaneous abortion, and 5 women had elective termination of pregnancy (as control), and then subjected for immunohistochemistry analysis to detect human cytomegalovirus (HCMV) early protein, and in situ hybridization technique to detect nuclear factor-κB (NF- κB) mRNA.
Results: Only nine out of 34 women with spontaneous abortion were positive for HCMV early protein, with a significantly higher expression of NF-κB in H

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Publication Date
Sat Sep 01 2018
Journal Name
J Of Baghdad College Of Dentistry
Publication Date
Sat Sep 30 2023
Journal Name
Romanian Journal Of Rheumatology
Association between genetic polymorphism in tumor necrosis factor-alpha gene and adverse effects of etanercept in rheumatoid arthritis patients

Background. Gene polymorphisms affect etanercept’s pharmacokinetics, pharmacodynamics, and side effects. This effect is evidenced by the extensive genetic variation in the drug’s targets. Objectives. This study aims to find the association between different genotypes of the promoter region of the TNF-α gene at -308G/A(rs1800629), -857C/T(rs1799724), -863 C/A(rs1800630), -1031 T/C (rs1799964), -806 C/T (rs4248158) and -376 G/A (rs1800750) and the side effects of ETN that occurred to Iraqi RA patients. Method. The trial included patients with rheumatoid arthritis who had been using ETN for at least six months. The participants were from the Baghdad Teaching Hospital Rheumatology Unit. The PCR was sequenced to determine the polymo

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Publication Date
Sun Jul 03 2011
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Induction of Microsomal Liver Enzymes by Silymarin in Experimental Animals

Background: previous researches showed that the hepatoprotective effect of silymarin was through inhibition of cytochrome p450- system (e.g. protection against Amanita toxin), in addition to protection from free radicals generated by this enzymatic system. In contrast to that, many evidences clarified that silymarin may increase first pass metabolism of e.g. cyclosporine and benzodiazepenes.
Objective: Our aim from this animal experiment was to relieve this confusion and detect that this herbal extract is absolutely hepatoprotective or induce hepatotoxicity in other conditions.
Materials and Methods: this study was performed on 15 healthy male rats randomized into two treatment groups; first group (5 rats)

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Publication Date
Sun Oct 01 2006
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Cadmium Chloride (CdCl2)-Induced Apoptosis in Liver of Mice

Background: Cadmium (Cd) is an industrial and environmental pollutant that affect adversely a number of organs in humans and other mammals.
Objectives: To study the effect of cadmium on liver of mice.
Material and Methods: Male Balb/c mice weighing 30-32 gm, 60 days old, were treated intraperitoneally (ip) with (1-10mg/kg body wt. /CdCl2). The body weight, liver weight, histological examination of liver, SEM, metal analysis along with DNA ladder for apoptosis.
Results: Cadmium induced both a time, and dose dependent increase in apoptotic, severity of necrosis. Liver weight, body weight decreased with increase of dose, while metal content was increased by increase of dose.
Conclusion: It has been concluded that cadmium caused

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Publication Date
Thu Oct 01 2009
Journal Name
Journal Of The Faculty Of Medicine Baghdad
IL-2 and IL-4 Serum Levels in Breast Cancer

Background: The role of cytokines in cancer immunity and carcinogenesis in general has been well established, which play an important role in the pathogenesis of many solid cancers.This study aimed to estimate serum levels of IL-2 and IL-4, and to shed light on the correlation of these interleukins with progression of breast cancer.
Patients and Methods: The study included 80 women, it comprised of 45 breast cancer patients, 12 patients with benign breast lesions and 23 apparently healthy controls. ELISA method has been used for estimation the level of IL-2 and IL-4 in serum of three studied groups.
Results: This study showed elevation of IL-4 level in the sera of breast cancer patients with significant dif

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Publication Date
Tue Nov 19 2024
Journal Name
Journal Of Baghdad College Of Dentistry
The effect of intracrevicular injection of fucose on serum interlukine -1beta and tumor necrosis factor alpha

Background: ?-L-Fucose is a methyl pentose sugar, had the ability to kill bacteria, controlling infection and normalize immune function. The objective of this study is to determine the effect of sulcular injection of fucose on rabbits periodontium , throughout measuring the level of some proinflammatory cytokine ; interlukine 1beta ( IL-1beta) and tumor necrosis factor ( TNF-alpha) in sera of rabbits before fucose injection and at 3 days after fucose injection. Materials and Methods: The study was carried on using ( 20 ) male rabbits of the same species weighted (1-1.5 kg ) , the blood samples were collected from hearts of 20 rabbits before fucose injection and consider as( non injected group) , and after 3 days of fucose injection and con

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Publication Date
Thu Jun 01 2017
Journal Name
Nuclear Physics A
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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Pharmacy Research
Publication Date
Fri Jul 01 2022
Journal Name
Eurasian Chemical Communications
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