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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
Sun Dec 01 2024
Journal Name
Russian Journal Of General Chemistry
Synthesis, Characterization, and Biological Evaluation for New Derivatives Based on 2Сhloro-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl]acetamide
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Publication Date
Sun Dec 01 2024
Journal Name
Russian Journal Of General Chemistry
Synthesis, Characterization, and Biological Evaluation for New Derivatives Based on 2Сhloro-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl]acetamide
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Publication Date
Sat Nov 01 2025
Journal Name
Russian Journal Of General Chemistry
Synthesis, Antibacterial Activity, and Molecular Docking Study of Some New Azo Derivatives Based on 2(4-Aminophenyl)-5-Substituted 1,3,4-Oxadiazole
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Publication Date
Fri Mar 26 2021
Journal Name
Chemical Papers
DFT, anticancer, antioxidant and molecular docking investigations of some ternary Ni(II) complexes with 2‑[(E)‑[4‑(dimethylamino) phenyl]methyleneamino]phenol
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The biological activities of some ternary nickel complexes with a Schiff base obtained from 4-dimethylaminobenzaldehyde and 2-aminophenol have been reported. The Schiff base ( HL1) acts as a primary ligand whereas, anthranilic acid ( HL2), 2-nitroaniline ( HL3), alanine ( HL4) and histidine ( HL5) act as secondary ligand or co-ligand. The anticancer activity of these compounds was studied against human colon carcinoma (HCT-116), human hepatocellular liver carcinoma (HEPG-2) and human breast carcinoma (MCF-7) cell lines. As per the results, the compounds were active against the cell lines. The antioxidant activity of the same compounds was evaluated using DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical scavenging and compared with ascorbic aci

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Publication Date
Sun Dec 01 2024
Journal Name
Russian Journal Of General Chemistry
Synthesis, Characterization, and Biological Evaluation for New Derivatives Based on 2Сhloro-N-[4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl]acetamide
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Publication Date
Tue Jan 01 2013
Journal Name
Al-mustansiriyah Journal Of Science
Encrypting a Text by Using Affine Cipher and Hiding it in the Colored Image by Using the Quantization stage
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ST Alawi, NA Mustafa, Al-Mustansiriyah Journal of Science, 2013

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Publication Date
Wed Mar 01 2017
Journal Name
International Communications In Heat And Mass Transfer
Optimization, modeling and accurate prediction of thermal conductivity and dynamic viscosity of stabilized ethylene glycol and water mixture Al 2 O 3 nanofluids by NSGA-II using ANN
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In this study, multi-objective optimization of nanofluid aluminum oxide in a mixture of water and ethylene glycol (40:60) is studied. In order to reduce viscosity and increase thermal conductivity of nanofluids, NSGA-II algorithm is used to alter the temperature and volume fraction of nanoparticles. Neural network modeling of experimental data is used to obtain the values of viscosity and thermal conductivity on temperature and volume fraction of nanoparticles. In order to evaluate the optimization objective functions, neural network optimization is connected to NSGA-II algorithm and at any time assessment of the fitness function, the neural network model is called. Finally, Pareto Front and the corresponding optimum points are provided and

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Publication Date
Thu Dec 09 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Carvone Attenuates Irinotecan-Induced Intestinal Mucositis and Diarrhea in Mice
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Intestinal mucositis is referring to inflammatory or ulcerative lesions of the oral or gastrointestinal tract; one of the main reasons is treatment with cancer chemotherapy. The prodrug Irinotecan is converted by carboxylesterase to the active metabolite SN-38, conjugated by UGT enzyme to SN-38G and then deconjugated by ?-glucoronidase produced by intestinal bacterial flora to produce SN-38. Irinotecan induces intestinal mucositis and diarrhea due to increased concentration of its active metabolite (SN-38).To evaluate the protective effect of carvone, I.P injection of (75mg/kg/day) of irinotecan for 4 days to induce intestinal mucositis, carvone administered to mice orally for 6 days starting from day 1. Results showed that carvone (50mg

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Publication Date
Sun Dec 05 2010
Journal Name
Baghdad Science Journal
Effect of vincristine and vinblastine on mice spermatozoa in vitro
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The aim of this project was to study the in vitro effect of antineoplastic drugs (vincristine and vinblastine) on mice spermatozoa. Eighteen adult (age 8-9 weeks) male mice were divided into three groups equally. The animals in each group were slain by cervical dislocation, the testes were removed and two tails of epididymides isolated. Spermatozoa were obtained from the two tails of epididymides by mincing in 500 µl TCM-199.The first group non-treated (unadded) as a control group, second group added 10 µg/ml of vincristine to TCM-199 and the third group added 10 µg/ml of vinblastine to TCM-199. After 10 minutes from added of vincristine and vinblastin measured the following test: spermatozoa activity, percentage dead spermatozoa and mor

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Publication Date
Fri Jun 05 2026
Journal Name
Journal Of Baghdad College Of Dentistry
BAX In situ hybridization and proliferating cell nuclear antigen immunohistochemical expressions in salivary gland tumours
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Background: Epithelial salivary gland tumours are relatively uncommon and constitute a wide spectrum of variable morphologic and biologic entities. The cell proliferation / death balance is most important in the development of salivary gland tumours. The aim of this study was to examine the expression of PCNA protein immunohistochemically and Bax mRNA gene using in situ hybridization techniques and to correlate between the clinicopathological features of salivary gland tumours with the expressions of PCNA protein and Bax mRNA. Materials and Methods: Forty nine formalin fixed paraffin embedded tissue blocks of epithelial salivary gland tumours were used in this study. Haematoxylin and Eosin stain was used for reassessment of the histopath

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