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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
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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
Tue Nov 19 2024
Journal Name
Review Of Clinical Pharmacology And Pharmacokinetics - International Edition
Clinical use of tumor necrosis factor-alpha inhibitors in Iraq: a review of their documented efficacy, safety, and associated genetics
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This comprehensive review examines the efficacy and safety of tumor necrosis factor-alpha (TNF-α) inhibitors in treating various autoimmune diseases, and focuses on their application in Iraqi patients. Elevated TNF-α levels are linked to autoimmune disorders, leading to the development of anti-TNF-α therapies such as infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab, which have gained FDA approval for conditions like psoriasis, in¬flammatory bowel disease, ankylosing spondylitis, and rheumatoid arthritis. While these therapies demonstrate sig¬nificant therapeutic benefits, including improved quality of life and disease management, they also carry risks, such as increased susceptibility to infections and pote

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Publication Date
Wed Jan 01 2020
Journal Name
Research Journal Of Pharmacy And Technology
<i>Insilico</i> and <i>in vitro</i> Approach for Design, Synthesis, and Anti-proliferative Activity of Novel Derivatives of 5-(4-Aminophenyl)-4-Substituted Phenyl-2, 4-Dihydro-3<i>H</i>-1, 2, 4-Triazole-3-Thione
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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
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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
Wed Jul 01 2020
Journal Name
Medico-legal Update,
Histological and enzyme histochemical changes of liver induced by the action of maxxthor insecticide in male albino rats
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The present study aimed to investigate the histological, enzyme histochemical changes and liver function effects of Maxxthor insecticide on albino rats in liver. The experiment included 20 rat which were divided into four groups, the first group 5 rats were considered the control animals and the others were divided equally into three groups with a dose of 0.01, 0.1and 1 mg / kg of body weight, respectively for a period 40 days. The animals given each 48 hours via oral route Maxxthor by tube dosage after dissolved with distilled water. Microscopic examination of liver showed inflammatory cell aggregation around vessels, congestion and dilation of sinusoids hepatocytes hypertrophy with severs inflammatory cells infiltration, kupffer cells pro

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Publication Date
Thu Jun 29 2023
Journal Name
Farmacia
CORRELATION BETWEEN INTEGRIN ALPHA-4 GENE POLYMORPHISMS AND FAILURE TO RESPOND TO NATALIZUMAB THERAPY IN IRAQI MULTIPLE SCLEROSIS PATIENTS
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Publication Date
Wed Feb 20 2019
Journal Name
Political Sciences Journal
North Korea's nuclear program is facing the International Atomic Energy Agency (IAEA)
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لخلاصة Nuclear energy is among the most important discoveries reached by the human terms contributed to the solution of many problems faced by the states. The last of these that are not only utilizing it in a peaceful area, but tended toward the military field and the nuclear weapons industry , Among these countries, we find North Korea, which has openly declared their manufacture of nuclear weapons and thus entry to the club of nuclear countries. International Atomic Energy Agency has worked to resolve the North Korea standoff but has not been able to achieve positive results, prompting the intervention of European countries in order to end the crisis. تعدُّ الطاقة النووية من بين أهم الاستكشافا

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Publication Date
Thu May 25 2023
Journal Name
Results In Chemistry
Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium
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Metal corrosion is a destructive process for many industrial operations, including oil well acidizing and acid pickling. Therefore, numerous efforts made by many researchers to control the steel corrosion. In the present work, A (E)-4-(((4-(5-mercapto-1,3,4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol (MOPM) has been synthesized and characterized as a new corrosion inhibitor for mild steel in 0.1 M hydrochloric acid. FTIR and 1 HNMR were used in the diagnosis of MOPM, while electrochemical polarization technique was employed to test the performance of inhibitor at various temperatures and inhibitor concentrations. Electrochemical studies showed that MOPM acts as a mixed-type inhibitor with a maximum inhibition efficiency of

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Publication Date
Sun Jan 01 2023
Journal Name
Results In Chemistry
Synthesis and characterization of (E)-4-(((4-(5-mercapto-1, 3, 4-oxadiazol-2-yl) phenyl) amino) methyl)-2-methoxyphenol as a novel corrosion inhibitor for mild-steel in acidic medium
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Publication Date
Fri Feb 01 2013
Journal Name
Ijbpas
THE POSSIBLE RELATIONSHIP BETWEEN SERUM TUMOR NECROSIS FACTOR ALPHA LEVEL AND THE RECOVERY OF PATIENTS WITH PULMONARY TUBERCULOSIS
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Mycobacterium tuberculosis is the cause of the major world health issue, tuberculosis (TB). The cytokine, tumor necrosis factor alpha (TNF-α) has been implicated in protection against TB in the early stages of the disease. TNF-α is an effective cytokine in the killing of intracellular M. tuberculosis. This study inducted to investigate whether there is any relationship between levels of TNF-α in sera of TB patients and their recovery, and is there any difference in the level of this cytokine in sera of female and male TB patients. This study included 29 patients with pulmonary TB (18 female and 11 male), their ages ranging from 37 to 59 years. All of them received first line TB therapy. They were consulted at Pasture Center during Septem

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Publication Date
Mon Aug 22 2022
Journal Name
Biochemical And Cellular Archives
Measurement of inflammation and oxidative stress biomarkers induced by cigarette smoke among Iraqi smokers.
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To determine the association between cigarette smoking and oxidative stress, a study was conducted in the period from January 2020 to April 2021, at College of Medicine, Al-Nahrain University, Baghdad, Iraq. The Enzyme-linked immunosorbent assay (ELISA) technique was utilized for measurement the antioxidant enzymes including: Glutathione superoxide (GPX) and catalase (CAT) and the biomarker of lipid peroxidation Malondialdehyde (MDA). Also, the gene expression of Nrf2 and HO-1were determined by using RT-PCR technique. The results indicate lower level of both GPX and CAT (p ≤ 0.001) in smokers compared with non-smokers. While the result of MDA indicate higher level in smokers (p≤0.001) compared with nonsmokers. The Nrf2 and HO-1 gene exp

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