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Article: Characterizing CD38 Expression and Enzymatic Activity in the Brain of Spontaneously Hypertensive Stroke-Prone Rats.

Hannawi, Yousef / Ewees, Mohamed G / Moore, Jordan T / Zweier, Jay L

2022 Volume 13, Page(s) 881708

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.881708
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Article ; Online: Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk.

Abdel-Bakky, Mohamed S / Mohammed, Hamdoon A / Mahmoud, Nesreen I / Amin, Elham / Alsharidah, Mansour / Al Rugaie, Osamah / Ewees, Mohamed G

Environmental toxicology

2024

Abstract: Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda ... ...

Abstract	Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1463449-1
ISSN	1522-7278 ; 1520-4081
ISSN (online)	1522-7278
ISSN	1520-4081
DOI	10.1002/tox.24217
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Article: Involvement of PI3K/HIF-1α/c-MYC/iNOS Pathway in the Anticancer Effect of

Mohammed, Hamdoon A / Ewees, Mohamed G / Mahmoud, Nesreen I / Ali, Hussein M / Amin, Elham / Abdel-Bakky, Mohamed S

Pharmaceuticals (Basel, Switzerland)

2023 Volume 16, Issue 10

Abstract: ... Suaeda ... ...

Abstract	Suaeda vermiculata
Language	English
Publishing date	2023-10-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph16101470
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Article ; Online: Coagulation System Activation for Targeting of COVID-19: Insights into Anticoagulants, Vaccine-Loaded Nanoparticles, and Hypercoagulability in COVID-19 Vaccines.

Abdel-Bakky, Mohamed S / Amin, Elham / Ewees, Mohamed G / Mahmoud, Nesreen I / Mohammed, Hamdoon A / Altowayan, Waleed M / Abdellatif, Ahmed A H

Viruses

2022 Volume 14, Issue 2

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two crucial complications responsible for poor prognosis and mortality. In addition, coagulation system activation and inflammation overlap and produce life-threatening complications, including coagulopathy and cytokine storm, which are associated with overproduction of cytokines and activation of the immune system; they might be a lead cause of organ damage. However, patients with severe COVID-19 who received anticoagulant therapy had lower mortality, especially with elevated D-dimer or fibrin degradation products (FDP). In this regard, the discovery of natural products with anticoagulant potential may help mitigate the numerous side effects of the available synthetic drugs. This review sheds light on blood coagulation and its impact on the complication associated with COVID-19. Furthermore, the sources of natural anticoagulants, the role of nanoparticle formulation in this outbreak, and the prevalence of thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccines are also reviewed. These combined data provide many research ideas related to the possibility of using these anticoagulant agents as a treatment to relieve acute symptoms of COVID-19 infection.
MeSH term(s)	Anticoagulants/administration & dosage ; Anticoagulants/isolation & purification ; Anticoagulants/therapeutic use ; Blood Coagulation ; Blood Coagulation Disorders/classification ; Blood Coagulation Disorders/etiology ; Blood Coagulation Disorders/prevention & control ; Blood Coagulation Disorders/virology ; COVID-19/complications ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/chemistry ; Cytokine Release Syndrome/prevention & control ; Cytokine Release Syndrome/virology ; Humans ; Inflammation/etiology ; Inflammation/prevention & control ; Nanoparticles/chemistry ; Nanoparticles/therapeutic use ; SARS-CoV-2/pathogenicity ; Thrombophilia/etiology
Chemical Substances	Anticoagulants ; COVID-19 Vaccines
Language	English
Publishing date	2022-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020228
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Article ; Online: Electronic cigarette exposure causes vascular endothelial dysfunction due to NADPH oxidase activation and eNOS uncoupling.

El-Mahdy, Mohamed A / Ewees, Mohamed G / Eid, Mahmoud S / Mahgoup, Elsayed M / Khaleel, Sahar A / Zweier, Jay L

American journal of physiology. Heart and circulatory physiology

2022 Volume 322, Issue 4, Page(s) H549–H567

Abstract: We recently reported a mouse model of chronic electronic cigarette (e-cig) exposure-induced cardiovascular pathology, where long-term exposure to e-cig vape (ECV) induces cardiac abnormalities, impairment of endothelial function, and systemic ... ...

Abstract	We recently reported a mouse model of chronic electronic cigarette (e-cig) exposure-induced cardiovascular pathology, where long-term exposure to e-cig vape (ECV) induces cardiac abnormalities, impairment of endothelial function, and systemic hypertension. Here, we delineate the underlying mechanisms of ECV-induced vascular endothelial dysfunction (VED), a central trigger of cardiovascular disease. C57/BL6 male mice were exposed to ECV generated from e-cig liquid containing 0, 6, or 24 mg/mL nicotine for 16 and 60 wk. Time-dependent elevation in blood pressure and systemic vascular resistance were observed, along with an impairment of acetylcholine-induced aortic relaxation in ECV-exposed mice, compared with air-exposed control. Decreased intravascular nitric oxide (NO) levels and increased superoxide generation with elevated 3-nitrotyrosine levels in the aorta of ECV-exposed mice were observed, indicating that ECV-induced superoxide reacts with NO to generate cytotoxic peroxynitrite. Exposure increased NADPH oxidase expression, supporting its role in ECV-induced superoxide generation. Downregulation of endothelial nitric oxide synthase (eNOS) expression and Akt-dependent eNOS phosphorylation occurred in the aorta of ECV-exposed mice, indicating that exposure inhibited de novo NO synthesis. Following ECV exposure, the critical NOS cofactor tetrahydrobiopterin was decreased, with a concomitant loss of its salvage enzyme, dihydrofolate reductase. NADPH oxidase and NOS inhibitors abrogated ECV-induced superoxide generation in the aorta of ECV-exposed mice. Together, our data demonstrate that ECV exposure activates NADPH oxidase and uncouples eNOS, causing a vicious cycle of superoxide generation and vascular oxidant stress that triggers VED and hypertension with predisposition to other cardiovascular disease.
MeSH term(s)	Animals ; Cardiovascular Diseases ; Electronic Nicotine Delivery Systems ; Endothelium, Vascular/metabolism ; Female ; Hypertension ; Male ; Mice ; NADPH Oxidases/metabolism ; Nicotine ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Peroxynitrous Acid/metabolism ; Superoxides/metabolism
Chemical Substances	Superoxides (11062-77-4) ; Peroxynitrous Acid (14691-52-2) ; Nitric Oxide (31C4KY9ESH) ; Nicotine (6M3C89ZY6R) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00460.2021
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Article: Coagulation System Activation for Targeting of COVID-19: Insights into Anticoagulants, Vaccine-Loaded Nanoparticles, and Hypercoagulability in COVID-19 Vaccines

Abdel-Bakky, Mohamed S. / Amin, Elham / Ewees, Mohamed G. / Mahmoud, Nesreen I. / Mohammed, Hamdoon A. / Altowayan, Waleed M. / Abdellatif, Ahmed A. H.

Viruses. 2022 Jan. 24, v. 14, no. 2

2022

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two crucial complications responsible for poor prognosis and mortality. In addition, coagulation system activation and inflammation overlap and produce life-threatening complications, including coagulopathy and cytokine storm, which are associated with overproduction of cytokines and activation of the immune system; they might be a lead cause of organ damage. However, patients with severe COVID-19 who received anticoagulant therapy had lower mortality, especially with elevated D-dimer or fibrin degradation products (FDP). In this regard, the discovery of natural products with anticoagulant potential may help mitigate the numerous side effects of the available synthetic drugs. This review sheds light on blood coagulation and its impact on the complication associated with COVID-19. Furthermore, the sources of natural anticoagulants, the role of nanoparticle formulation in this outbreak, and the prevalence of thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccines are also reviewed. These combined data provide many research ideas related to the possibility of using these anticoagulant agents as a treatment to relieve acute symptoms of COVID-19 infection.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; anticoagulants ; blood coagulation ; coagulation ; cytokines ; fibrin ; immune system ; inflammation ; lead ; mortality ; pandemic ; prognosis ; therapeutics ; thrombocytopenia ; thrombosis
Language	English
Dates of publication	2022-0124
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14020228
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Correction to: "Enoxaparin prevents fibrin accumulation in liver tissues and attenuates methotrexate-induced liver injury in rats".

Ewees, Mohamed G / Abdelghany, Tamer M / Abdel-Aziz, Abdel-Aziz H / Abdelbakky, Mohamed S

Naunyn-Schmiedeberg's archives of pharmacology

2020 Volume 393, Issue 7, Page(s) 1329

Abstract: The authors found a mistake in Figure 2 and would like to correct the manuscript. ...

Abstract	The authors found a mistake in Figure 2 and would like to correct the manuscript.
Language	English
Publishing date	2020-04-29
Publishing country	Germany
Document type	Journal Article ; Published Erratum
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-020-01865-7
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Article: Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats.

Hannawi, Yousef / Caceres, Eder / Ewees, Mohamed G / Powell, Kimerly A / Bratasz, Anna / Schwab, Jan M / Rink, Cameron L / Zweier, Jay L

Frontiers in neurology

2021 Volume 12, Page(s) 740298

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2021-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.740298
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Article ; Online: Cytoglobin has potent superoxide dismutase function.

Zweier, Jay L / Hemann, Craig / Kundu, Tapan / Ewees, Mohamed G / Khaleel, Sahar A / Samouilov, Alexandre / Ilangovan, Govindasamy / El-Mahdy, Mohamed A

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 52

Abstract: Cytoglobin (Cygb) was discovered as a novel type of globin that is expressed in mammals; however, its functions remain uncertain. While Cygb protects against oxidant stress, the basis for this is unclear, and the effect of Cygb on superoxide metabolism ... ...

Abstract	Cytoglobin (Cygb) was discovered as a novel type of globin that is expressed in mammals; however, its functions remain uncertain. While Cygb protects against oxidant stress, the basis for this is unclear, and the effect of Cygb on superoxide metabolism is unknown. From dose-dependent studies of the effect of Cygb on superoxide catabolism, we identify that Cygb has potent superoxide dismutase (SOD) function. Initial assays using cytochrome
MeSH term(s)	Animals ; Cell Line ; Cytoglobin/chemistry ; Cytoglobin/genetics ; Cytoglobin/metabolism ; Electron Spin Resonance Spectroscopy ; Male ; Mice ; Mice, Knockout ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/chemistry ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism
Chemical Substances	CYGB protein, human ; Cygb protein, mouse ; Cytoglobin ; Reactive Oxygen Species ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1)
Language	English
Publishing date	2021-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2105053118
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Article ; Online: Long-term electronic cigarette exposure induces cardiovascular dysfunction similar to tobacco cigarettes: role of nicotine and exposure duration.

El-Mahdy, Mohamed A / Mahgoup, Elsayed M / Ewees, Mohamed G / Eid, Mahmoud S / Abdelghany, Tamer M / Zweier, Jay L

American journal of physiology. Heart and circulatory physiology

2021 Volume 320, Issue 5, Page(s) H2112–H2129

Abstract: Electronic cigarette (e-cig) vaping (ECV) has been proposed as a safer alternative to tobacco cigarette smoking (TCS); however, this remains controversial due to a lack of long-term comparative studies. Therefore, we developed a chronic mouse exposure ... ...

Abstract	Electronic cigarette (e-cig) vaping (ECV) has been proposed as a safer alternative to tobacco cigarette smoking (TCS); however, this remains controversial due to a lack of long-term comparative studies. Therefore, we developed a chronic mouse exposure model that mimics human vaping and allows comparison with TCS. Longitudinal studies were performed to evaluate alterations in cardiovascular function with TCS and ECV exposure durations of up to 60 wk. For ECV, e-cig liquid with box-mod were used and for TCS, 3R4F-cigarettes. C57/BL6 male mice were exposed 2 h/day, 5 days/wk to TCS, ECV, or air control. The role of vape nicotine levels was evaluated using e-cig-liquids with 0, 6, or 24 mg/mL nicotine. Following 16-wk exposure, increased constriction to phenylephrine and impaired endothelium-dependent and endothelium-independent vasodilation were observed in aortic segents, paralleling the onset of systemic hypertension, with elevations in systemic vascular resistance. Following 32 wk, TCS and ECV induced cardiac hypertrophy. All of these abnormalities further increased out to 60 wk of exposure, with elevated heart weight and aortic thickness along with increased superoxide production in vessels and cardiac tissues of both ECV and TCS mice. While ECV-induced abnormalities were seen in the absence of nicotine, these occurred earlier and were more severe with higher nicotine exposure. Thus, long-term vaping of e-cig can induce cardiovascular disease similar to TCS, and the severity of this toxicity increases with exposure duration and vape nicotine content.
MeSH term(s)	Adrenergic alpha-1 Receptor Agonists/pharmacology ; Animals ; Aorta/drug effects ; Aorta/physiopathology ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Cardiovascular Diseases/chemically induced ; Cardiovascular Diseases/physiopathology ; Electronic Nicotine Delivery Systems ; Male ; Mice ; Nicotine/administration & dosage ; Phenylephrine/pharmacology ; Time Factors ; Vaping/adverse effects ; Vasodilation/drug effects ; Vasodilation/physiology
Chemical Substances	Adrenergic alpha-1 Receptor Agonists ; Phenylephrine (1WS297W6MV) ; Nicotine (6M3C89ZY6R)
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603838-4
ISSN	1522-1539 ; 0363-6135
ISSN (online)	1522-1539
ISSN	0363-6135
DOI	10.1152/ajpheart.00997.2020
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