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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
Fri Sep 29 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Protective Effect of Cranberry Extract against Cisplatin-Induced Nephrotoxicity by Improving Oxidative Stress in Mice

   Cranberry (Vaccinium macrocarpon) is a North American natural fruit. consumed as food and used for health promotion and prevention of various diseases. Aim. The present study was designed to evaluate the protective effect of cranberry fruit extract on nephrotoxicity induced by cisplatin in mice by measuring selected oxidative stress markers. Methods. Twenty-eight male albino mice were used in this study. The animals were divided into 4 groups as follows: Group I [Negative Control]/orally-administered normal saline for 7 successive days; Group II [Orally-administered cranberry fruit extract alone (200 mg/kg) for 7 successive days; Group III/Mice IP injection with cisplatin (12mg/kg) on day 7 and; Group IV [Orally-administered cr

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Publication Date
Sun Jan 26 2020
Journal Name
Iraqi Journal Of Science
BRCA1 Gene Expression is Down Regulated in Both Familial and Sporadic Breast Cancer Cases in Baghdad- Iraq

Breast cancer is the commonest cancer and the leading cause of malignancies-related mortality in women worldwide. Understanding the underlying biology of the disease could improve patients’ stratification and may offer novel therapeutic targets and strategies. This study was set to investigate the association between BRCA1 gene expression and some of the clinical features of breast cancer patients in Baghdad-Iraq. Eighty peripheral blood samples were collected from sixty patients diagnosed with breast cancer and twenty healthy age-matched controls for BRCA1 qPCR gene expression analysis.

     The results showed a significant reduction in BRCA1 gene expression in all of the bre

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Publication Date
Wed Sep 09 2020
Journal Name
Frontiers In Plant Science
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Publication Date
Sat Oct 01 2022
Journal Name
The Egyptian Rheumatologist
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Publication Date
Sat Jun 12 2021
Journal Name
Biochemical And Cellular Archives
EFFECT OF SINGLE ORAL DOSE OF FUMONISIN B1 ON IMMUNOHISTOCHEMICAL EXPRESSION OF TLR-2 AND 4 IN MICE

Fumonisin B1 is toxic secondary metabolites compound produced by Fusarium spp. on maize and maize products causes health problems to human and animal. Therefore, this research is planned to study the effect of FB1 on the expression of TLR-2 & 4 in liver and kidney cells of mice. Four group of male mice were orally administrated with single dose of FB1 toxin as the following: 0 ppb, 800 ppb, 1200 ppb and 1600 ppb. After two weeks all animals were sacrificed, liver and kidney autopsies were taken and the level of TLR-2 & 4 detected in each four group by immunohistochemistry technique (IHC). According to the IHC examination of groups (1, 2, 3 and 4) strong expression of TLR2 in liver and kidney were (0%, 33.3%, 100%, 100%), respectively. This

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Publication Date
Fri Oct 06 2023
Journal Name
Journal Of The Pakistan Medical Association
The role of Tumour Necrosis Factor Alpha (TNF-ALPHA) serum level and genetic polymorphisms with cutaneous leishmania infections

Objective: To assess the role of tumour necrosis factor alpha level and genotyping in susceptibility to leishmaniasis.Method: The case-control study was conducted from March to July 2021 at Baqubah Teaching Hospital, Diyala, Iraq,and comprised patients of cutaneous leishmaniasis in group A and healthy controls in group B. The serum level andsingle nucleotide polymorphisms of tumour necrosis factor-alpha rs41297589 and rs1800629 were compared betweenthe groups. Data was analysed using SPSS 28.Results: Of the 150 subjects, there were 75(50%) in group A; 39(52%) males and 36(48%) females with mean age23.91±13.14 years. The remaining 75(50%) subjects were in group B; 38(50.7%) males and 37(49.3%) females withmean age 22.84±4.35 years.

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Publication Date
Sun Jul 03 2011
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Role of Salivary Tumor Necrosis Factor-alpha and Immunoglobulin- A in Recurrent Aphthous Stomatitis

Background: Until today, the etiology of recurrent aphthous stomatitis (RAS) remains unknown, although hints of its etiologic basis lay on genetic susceptibility, infectious agents and alterations in immune mechanics.
Objectives: The aim of this study was to investigate the possible alterations in salivary tumor necrosis factor-alpha (TNF-α) and Immunoglobulin-A (IgA) level in patients with RAS and its relation with clinical types of disease.
Subjects and Methods: Salivary TNF-α levels were investigated in 50 RAS patients and 25 healthy controls by enzyme-linked immunosorbent assay (ELISA). Single radial immune diffusion method was used for estimation of IgA level in two studied groups.
Results: S

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Publication Date
Mon Jan 01 2018
Journal Name
World Journal Of Dentistry
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Publication Date
Tue Jan 01 2019
Journal Name
Energy Procedia
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Publication Date
Tue Feb 01 2022
Journal Name
Baghdad Science Journal
Milk Tumor Necrosis Factor Alpha and Interleukin-1Beta Among Toxoplasma gondii-Free and Infected Women

Pro-inflammatory cytokines play an important role in intercellular communications. In the last two decades, many cytokines have been identified in human milk. These cytokines are variable according to different conditions such as pathogenic infections which strongly stimulated the immune response. The present study aims to determine of IL1β and TNF-α in Toxoplasma gondii-free and infected women in an attempt to clarify the impacts of the infections on cytokines especially in mother's milk. The serum and milk sample were collected from 96 samples (48 for seropositive and 48 for seronegative). To confirm the Toxoplasma gondii infection; enzyme linked immunofluorescence assay (ELIFA) was used to detect anti-Toxoplasma Ig

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