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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
Thu Jun 01 2023
Journal Name
Neurology Asia
Integrin alpha-4 gene polymorphism in relation to natalizumab response in multiple sclerosis patients

Objectives: The aim of this study was to assess the possible the association between +3061 (G>A, rs1143676) missense mutation in exon 24 of the integrin α-4 subunit (ITGA-4) gene and the response to natalizumab in a sample of Iraqi multiple sclerosis patients. Methods: A sample of 59 patients with multiple sclerosis (16 males and 43 females; mean age of 32 years; age range of 15 to 52 years) receiving natalizumab for at least 12 consecutive months were involved in the study between March and August/ 2022. The sample was categorized into two groups according to their response to natalizumab treatment (responders and non-responders). Polymerase chain reaction and Sanger’s sequencing for the extracted deoxyribonucleic acid was pe

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Publication Date
Sun Jan 03 2010
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Detection of Transcription Factor C-MYC in Oral Dysplasia and Squamous Cell Carcinoma by in Situ Hybridization

Background: Oral squamous cell carcinoma continues to be a major health problem in Iraq as well as in other countries. Many attempts were made to study molecular markers in oral squamous cell carcinoma and to link them to tumor grade, stage and prognosis, besides studying their role in carcinogenesis. The present study has been designed to detect mRNA of c-myc in oral squamous cell carcinoma compared to oral dysplasia and to link the marker to grade and degree of the two pathologies.
Materials and methods: Forty two cases, including 30 cases of oral squamous cell carcinoma and 12 cases of oral dysplasia were included in this study. Sections on positively charged slides were made from their paraffin blocks

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Publication Date
Sun Sep 07 2014
Journal Name
Baghdad Science Journal
Effect of Alcoholic Catechin Extract on Hyperglycemia, Hyperlipidemia and Liver Functions in Alloxan Diabetic Mice

The objective of this study is to estimate the effect of the hydro-ethanolic catechin extract toward blood glucose, lipid profile and liver functions in alloxan diabetic mice. 50 healthy mice (25-30 g) were divided into five groups of ten animals for each. Group A received normal saline as normal control group. To induce diabetes, alloxan (150 mg/kg), intraperitoneal (i.p.) single dose was injected to groups B, C, D and E. Group B represents diabetic control group. Groups C, D and E received ethanolic catechin extract (30 mg/kg and 40 mg/kg) for different periods of 1, 2 and 3 weeks as treated groups. Blood glucose, serum lipids [Total Cholesterol (TC), Triglycerides (TGs) and High Density Lipoproteins (HDL)], asparagine transaminase (AST),

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Publication Date
Mon May 14 2018
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Histopathological Effect of Zinc Oxide Nanoparticles on Kkidney and Liver Tissues in Albino Male Mice

    Objective: The present study investigated the effects of different dose levels of Zinc oxide Nanoparticles (ZnO NPs) on the liver and kidney tissues in albino male mice. Methadology: ZnO NPs was administrated as a daily oral dose of (150, 350 mg/kg body weight) gavage for 2 weeks. Eighteen male mices were used by dividing them into three groups. Result: Histopathological examination of kidney and hepatic tissues treated with ZnO NPs showed toxicity changes compared with control group. Conclusion:This study demonstrated the ability of ZnO NPs to affect on kidney and liver tissues. Recommendation: More study needed to know the effect of different doses of nanoparticles on human health.  

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Publication Date
Sun May 10 2020
Journal Name
Baghdad Science Journal
Immunohistochemical Expression of P16 Protein and TGF β1 in Mice Liver Exposed to Fumonisin B1

Fumonisin B1 (FB1) is a mycotoxin produced in some grains (mainly corn) by Fusarium species. Due to a structural similarity between FB1 and sphinganine, sphingolipids metabolism is inhibited. Such inhibition plays a critical role in cell to cell singling and structure of lipoprotein; therefore FB1 has been suggested to have a relationship with human and animal cancer. This research is planned to study the effect of FB1 on male mice at two doses (20 and 30 µg/ ml) on the expression of TGF-β1 and p16 in liver cells. Three groups of Swiss albino male mice; each group was orally administrated with FB1 toxin as the following: normal saline (control group); 20 and 30 µg/ ml. All groups were sacrificed after two weeks of oral manage

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Publication Date
Sun Mar 03 2013
Journal Name
Baghdad Science Journal
Effect of Methotrexate on the Liver Enzymes and Lipid Profile in Adult Female Albino Mice

Methotrexate (MTX) was used for treatment of malignancies and now is widely used in treatment of rheumatoid arthritis. In this research the evaluation of the effects of MTX on some liver enzymes and lipid profile was studied. Twenty four adult female mice divided into three groups (8 mice each). The first two groups were treated with MTX while the third group was used as a control. MTX was intraperitoneally given at 50 µg/ml and 75 µg/ml to the first and second groups respectively for 35 days ,whereas the control group was intraperitoneally injected with normal saline. The results showed a significant (p<0.05) increase in serum levels of glutamic oxaloacetate transaminase (GOT) , glutamic pyruric transaminase (GPT), Alkaline pho

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Formulation of Alpha Tocopherol Acetate as a Powder Dosage Form by Adsorption

Alpha-tocopherol acetate is one of the most important vitamin E derivatives,that were used  as antioxidants. Adsorbents like kaolin, magnesium carbonate, and microcrystalline cellulose were used successfully to incorporate oily alpha-tocopherol acetate into an acceptable powder dosage form. The results revealed that microcrystalline cellulose as an adsorbents gave the best results with 50% loading capacity at time, 8 minutes before and after incubation period (3 months at 30C°), while kaolin and magnesium carbonate have been shown a significant difference before and after incubation. Addition of 1% w/w magnesium carbonate to the kaolin enhanced the loading capacity by decreasing the time of adsorption from 20 to 6 minutes and 47

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Publication Date
Thu Feb 01 2018
Journal Name
Research Journal Of Pharmaceutical,biological And Chemical Sciense
Publication Date
Tue Mar 28 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Changes in Serum Levels of Tumor Necrosis Factor-Alpha and Antioxidant status in Different Stages of Malignant Prostate Cancer Patients in Iraq

Chronic inflammation can induce proliferative events and posttranslational DNA modifications in prostate tissue through oxidative stress. The present study was designed to evaluate the changes in serum levels of TNF-α, malomdialdehyde (MDA) and total antioxidant status (TAS) patients with different stages of malignant prostatic cancer (PCa) and benign prostatic hyperplasia (BPH). One hundred males (age range of 58-72 years) with different stages of malignant PCa were recruited from the Radiotherapy and Nuclear Medicine Teaching Hospital in Baghdad during the period from September 2010 to April 2011. The patients were categorized according to the 4 disease stages (I, II, III, and IV); 25 patients with benign prostatic hyperplasia (BPH)

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Publication Date
Fri Nov 24 2023
Journal Name
Iraqi Journal Of Science
Species Identification and Strain Differentiation of Dermatophyte by (GACA)4-Primer based PCR

Dermatophytes are a group of morphologically and physiologically related molds some of which cause well defined infections: dermatophytoses (tineas or ringworm). The present study aims at identification of dermatophytes species and varieties from patients in Wasit province-Iraq using molecular approach based PCR fingerprint.
The short oligonucleotide (GACA)4 is a microsatellite primer was used in this study for identification of dermatophyte isolates. The results identified different species and varieties among dermatophytes. The numbers of resulting PCR bands ranged from 1 to 4 (size range, 600bp to 1600bp) for each species. The resulting patterns were distinct for Trichophyton and Microsporum species and varieties.
Trichophyton s

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