Preferred Language
Articles
/
ihdyoZIBVTCNdQwCy7tP
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)

Scopus Clarivate Crossref
View Publication
Publication Date
Mon Oct 06 2014
Journal Name
Plos One
Scopus (31)
Crossref (21)
Scopus Clarivate Crossref
View Publication
Publication Date
Sun Dec 10 2017
Journal Name
Journal Of Pharmaceutical, Chemical And Biological Sciences
BRCA1 is Overexpressed in Breast Cancer Cell Lines and is Negatively Regulated by E2F6 in Normal but not Cancerous Breast Cells

This study focused on the expression and regulation of BRCA1 in breast cancer cell lines compared to normal breast. BRCA1 transcript levels were assessed by real time quantitative polymerase chain reaction (RT-qPCR) in the cancer cell lines. Our data show overexpression of BRCA1 mRNA level in all the studied breast cancer cell lines: MCF-7, T47D, MDA-MB-231 and MDA-MB-468 along with Jurkat, leukemia T-lymphocyte, the positive control, relative to normal breast tissue. To investigate whether a positive or negative correlation exists between BRCA1 and the transcription factor E2F6, three different si-RNA specific for E2F6 were used to transfect the normal and cancerous breast cell lines. Interestingly, strong negative relationship was found b

... Show More
Preview PDF
Publication Date
Sat Jul 30 2016
Journal Name
Hepatology
Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice

Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and al

... Show More
Scopus (129)
Crossref (131)
Scopus Clarivate Crossref
View Publication
Publication Date
Sat May 15 2004
Journal Name
Journal Of Biotechnology Research Center
The Morphological and Histopathological Liver Abnormalities Caused by Carbamazepine-Induced Injury in Female Albino Mice

Background: The adverse effects of drugs can damage various organs, especially the liver, leading to a hepatic injury known as hepatotoxicity. Drug-induced liver injury (DILI) is challenging nowadays because of the large number of different drugs used, one of the offending medications that cause DILI is carbamazepine (CBZ), since the liver has an array of functions including detoxification, it will deal with several damages caused by exposure to the drugs. Objective: investigate the effect of (CBZ) 20mg/kg/day on female mice liver after 14 and 30 days of treatment on morphological and histopathological levels. Materials and Methods: 20mg/kg/day of CBZ was administered orally for (14) days to (10) female mice, another (10) mice were taking t

... Show More
Publication Date
Fri Mar 29 2024
Journal Name
Molecular Biology Reports
Scopus Clarivate Crossref
View Publication
Publication Date
Thu Dec 09 2021
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Thymoquinone Attenuates Immune Mediated Liver Injury Induced by Concanavalin A in Mice

Autoimmune hepatitis is an inflammatory disease and its incidence has been increasing. The features of hepatitis are the release of inflammatory cytokines, the elevation of AST and ALT, and hepatocyte apoptosis and necrosis. Concanavalin A considered as essential model represents the acute immune-mediated liver damage in rodents. Thymoquinone is well known herbal compound that exert hepatoprotective, anti-inflammatory, and antioxidant activity. In this study, we focus on the immunoregulatory and liver protective effect of thymoquinone in a mouse model of concanavalin A-induced liver injury.

Twenty-four male mice were randomly divided into four groups each containing six animals: Negative control group, concanavalin A model group,

... Show More
Scopus (9)
Crossref (2)
Scopus Crossref
View Publication Preview PDF
Publication Date
Wed Jul 01 2020
Journal Name
Biochemical And Cellular Archives
Scopus
Publication Date
Tue Mar 19 2024
Journal Name
Jordan Journal Of Pharmaceutical Sciences
MMP-1 and MMP-7 Expression is Influenced by Ginsenosides in Mice Exposed to Aflatoxin B1: in vivo Study

Panax ginseng (PG), one of the most widely used herbal medicines, has demonstrated various beneficial effects such as anti-inflammatory, antioxidant, and anticancer impacts. Naturally occurring ginsenosides in the ginseng plant inhibit cell proliferation and significantly reduce liver damage induced by certain chemicals. Aflatoxin B1 (AFB1) is a primary mycotoxin due to its hepatotoxic, immunotoxic, and oncogenic effects in animal models and humans. In this study, we examined the effects of assorted doses of PG aqueous crude extract on the expression of matrix metalloproteinase 1 and 7 (MMP-1 and MMP-7) in the kidney, spleen, and liver of experimental AFB1-exposed mice, using immunohistochemistry (IHC). Mice were orally administered

... Show More
Scopus (1)
Scopus Crossref
View Publication
Publication Date
Sat Dec 24 2022
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Neuroprotective Effect of Vinpocetine against Lead Acetate-Instigated Neurotoxicity in Rats by Evaluation Tumor Necrosis Factor-Alpha, Interleukin-1Beta and Interleukin-10

Lead toxicity elicits neurological damage which is a well-known disorder that has been considered to be a major cause for multiple condition such as behavioral defect; mental retardation; and nerve insufficient activity.

This research is designed to estimate potential protective effect of vinpocetine on neurotoxicity stimulated by lead acetate in rats.

Eighteen adult rats of both sexes were randomly enrolled into three groups. Each group includes 6 rats as followings: Group I- Rats were given 0.3ml normal saline solution orally; then intraperitoneal injection of 100μl of the normal saline was given 1h later; this group was considered as control. Group II- Rats were given an intraperitoneal injection of 20mg/kg lead acetate

... Show More
Scopus (3)
Crossref (2)
Scopus Crossref
View Publication Preview PDF
Publication Date
Thu Apr 28 2022
Journal Name
Iraqi Journal Of Science
Histopathological changes of mice liver induced by an Aloe vera whole leaf extract

Plants commonly used in traditional medicine are assumed to be safe. This safety is based on their long usage in the treatment of diseases according to knowledge accumulated over centuries. One such plants is Aloe vera which has been used medicinally for centuries. Recent widespread importance of commercial Aloe vera has encouraged scientists to scientifically assess these products since it contains the anthraquinones which associated with considerable risks. In present study oral administration of 20 μl of Aloe vera extract (experimental group) (G) was given for 21 days to immature male Swiss Webster mice at weaning period. While the control groups (C) were given by the same dose and rout of administration with normal saline only. Afte

... Show More
View Publication Preview PDF