Publications by authors named "Marwa M Mahmoud"

9 Publications

  • Page 1 of 1

Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production.

Sci Rep 2021 May 31;11(1):11386. Epub 2021 May 31.

Department of Biomedical Engineering, The City College of New York, 160 Convent Ave, New York, NY, 10031, USA.

This study aimed to clarify the role of glypican-1 and PECAM-1 in shear-induced nitric oxide production in endothelial cells. Atomic force microscopy pulling was used to apply force to glypican-1 and PECAM-1 on the surface of human umbilical vein endothelial cells and nitric oxide was measured using a fluorescent reporter dye. Glypican-1 pulling for 30 min stimulated nitric oxide production while PECAM-1 pulling did not. However, PECAM-1 downstream activation was necessary for the glypican-1 force-induced response. Glypican-1 knockout mice exhibited impaired flow-induced phosphorylation of eNOS without changes to PECAM-1 expression. A cooperation mechanism for the mechanotransduction of fluid shear stress to nitric oxide production was elucidated in which glypican-1 senses flow and phosphorylates PECAM-1 leading to endothelial nitric oxide synthase phosphorylation and nitric oxide production.
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http://dx.doi.org/10.1038/s41598-021-90941-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166914PMC
May 2021

MicroRNAs' role in the environment-related non-communicable diseases and link to multidrug resistance, regulation, or alteration.

Environ Sci Pollut Res Int 2021 Jul 27;28(28):36984-37000. Epub 2021 May 27.

Biochemistry Department, Faculty of Pharmacy, Ain Shams University, 11566, Abassia, Cairo, Egypt.

The discovery of microRNAs (miRNAs) 20 years ago has advocated a new era of "small molecular genetics." About 2000 miRNAs are present that regulate one third of the genome. MiRNA dysregulated expression arising as a response to our environment insult or stress or changes may contribute to several diseases, namely non-communicable diseases, including tumor growth. Their presence in body fluids, reflecting level alteration in various cancers, merit circulating miRNAs as the "next-generation biomarkers" for early-stage tumor diagnosis and/or prognosis. Herein, we performed a comprehensive literature search focusing on the origin, biosynthesis, and role of miRNAs and summarized the foremost studies centering on miR value as non-invasive biomarkers in different environment-related non-communicable diseases, including various cancer types. Moreover, during chemotherapy, many miRNAs were linked to multidrug resistance, via modulating numerous, environment triggered or not, biological processes and/or pathways that will be highlighted as well.
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http://dx.doi.org/10.1007/s11356-021-14550-wDOI Listing
July 2021

DeepSinse: deep learning based detection of single molecules.

Bioinformatics 2021 May 8. Epub 2021 May 8.

Institute of Genetics, University of Cologne, Cologne, Germany.

Motivation: Imaging single molecules has emerged as a powerful characterization tool in the biological sciences. The detection of these under various noise conditions requires the use of algorithms that are dependent on the end-user inputting several parameters, the choice of which can be challenging and subjective.

Results: In this work, we propose DeepSinse, an easily-trainable and useable deep neural network that can detect single molecules with little human input and across a wide range of signal-to-noise ratios. We validate the neural network on the detection of single bursts in simulated and experimental data and compare its performance with the best-in-class, domain-specific algorithms.

Availability: Ground truth ROI simulating code, neural network training, validation code, classification code, ROI picker, GUI for simulating, training and validating DeepSinse as well as pre-trained networks are all released under the MIT License on www.github.com/jdanial/DeepSinse.The dSTORM dataset processing code is released under the MIT License on www.github.com/jdanial/StormProcessor.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab352DOI Listing
May 2021

Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis.

Invest New Drugs 2021 Feb 28;39(1):98-110. Epub 2020 Aug 28.

Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.

Two novel chemotherapeutic chalcones were synthesized and their structures were confirmed by different spectral tools. Theoretical studies such as molecular modeling were done to detect the mechanism of action of these compounds. In vitro cytotoxicity showed a strong effect against all tested cell lines (MCF7, A459, HepG2, and HCT116), and low toxic effect against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies. Real-time PCR demonstrated that the two compounds upregulated gene expression of (BAX, p53, casp-3, casp-8, casp-9) genes and decreased the expression of anti-apoptotic genes bcl2, CDK4, and MMP1. Flow-cytometry indicated that cell cycle arrest of A459 was induced at the G2/M phase and the apoptotic percentage increased significantly compared to the control sample. Cytochrome c oxidase and VEGF enzyme activity were detected by ELISA assay. SEM tool was used to follow the morphological changes that occurred on the cell surface, cell granulation, and average roughness of the cell surface. The change in the number and morphology of mitochondria, cell shrinkage, increase in the number of cytoplasmic organelles, membrane blebbing, chromatin condensation, and apoptotic bodies were observed using TEM. The obtained data suggested that new chalcones exerted their pathways on lung carcinoma through induction of two pathways of apoptosis. Graphical abstract Novel chalcones were prepared and confirmed by different spectral tools. Docking simulations were done to detect the mechanism of action. In vitro cytotoxicity indicated a strong effect against different cancer cell lines and low toxic effects against normal human melanocytes (HFB4). The lung carcinoma cell line was chosen for further molecular studies that include Real-time PCR, Flow-cytometry, Cytochrome c oxidase, and ELISA assay. SEM and TEM tool were used to follow the morphological changes occurred on the cell surface.
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http://dx.doi.org/10.1007/s10637-020-00987-2DOI Listing
February 2021

Author Correction: Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail.

Sci Rep 2020 Feb 26;10(1):3870. Epub 2020 Feb 26.

Department of Infection, Immunity and Cardiovascular Disease, the INSIGNEO Institute for In Silico Medicine and the Bateson Centre, University of Sheffield, England, UK.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-60955-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042236PMC
February 2020

Shear stress induces endothelial-to-mesenchymal transition via the transcription factor Snail.

Sci Rep 2017 06 13;7(1):3375. Epub 2017 Jun 13.

Department of Infection, Immunity and Cardiovascular Disease, the INSIGNEO Institute for In Silico Medicine and the Bateson Centre, University of Sheffield, England, UK.

Blood flow influences atherosclerosis by generating wall shear stress, which alters endothelial cell (EC) physiology. Low shear stress induces dedifferentiation of EC through a process termed endothelial-to-mesenchymal transition (EndMT). The mechanisms underlying shear stress-regulation of EndMT are uncertain. Here we investigated the role of the transcription factor Snail in low shear stress-induced EndMT. Studies of cultured EC exposed to flow revealed that low shear stress induced Snail expression. Using gene silencing it was demonstrated that Snail positively regulated the expression of EndMT markers (Slug, N-cadherin, α-SMA) in EC exposed to low shear stress. Gene silencing also revealed that Snail enhanced the permeability of endothelial monolayers to macromolecules by promoting EC proliferation and migration. En face staining of the murine aorta or carotid arteries modified with flow-altering cuffs demonstrated that Snail was expressed preferentially at low shear stress sites that are predisposed to atherosclerosis. Snail was also expressed in EC overlying atherosclerotic plaques in coronary arteries from patients with ischemic heart disease implying a role in human arterial disease. We conclude that Snail is an essential driver of EndMT under low shear stress conditions and may promote early atherogenesis by enhancing vascular permeability.
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http://dx.doi.org/10.1038/s41598-017-03532-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469771PMC
June 2017

TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis.

Circ Res 2016 07 31;119(3):450-62. Epub 2016 May 31.

From the Department of Infection, Immunity and Cardiovascular Disease, INSIGNEO Institute for In Silico Medicine, and the Bateson Centre, University of Sheffield, Sheffield, United Kingdom (M.M.M., H.R.K., S.H., J.S.-C., S.F., N.P.B., R.M., M.A., S.E.F., T.J.A.C., V.R., P.C.E.); ERASMUS MC, Rotterdam, The Netherlands (R.X., K.v.d.H.); Vascular Biology Program, Department of Surgery (A.M.) and Department of Ophthalmology (J.C.), Boston Children's Hospital, Harvard Medical School, MA; Department of Bioengineering, Imperial College London, London, United Kingdom (P.D.W.); and Department of Cardiovascular Science, Katholieke Universiteit Leuven, Leuven, Belgium (E.A.J.).

Rationale: Blood flow-induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown.

Objective: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease.

Methods And Results: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness.

Conclusions: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development.
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http://dx.doi.org/10.1161/CIRCRESAHA.116.308870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959828PMC
July 2016

Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity.

Environ Toxicol Pharmacol 2014 Mar 19;37(2):772-81. Epub 2014 Feb 19.

Department of Histology, Faculty of Medicine, Minia University, El-Minia, Egypt.

The anticancer drug; doxorubicin (DOX), causes testicular toxicity as an adverse effect. P-glycoprotein (P-gp) is a multidrug resistance efflux transporter expressed in blood-testis barrier, which extrudes DOX from the testis. We investigated whether DOX-induced gonadal injury could be prevented by the use of antioxidant; coenzyme-Q10 (CoQ10). The involvement of P-gp expression, as a possible protective mechanism, was also investigated. CoQ10 was administered orally for 8 days, and DOX toxicity was induced via a single i.p. dose of 15 mg/kg at day 4. Concomitant administration of CoQ10 with DOX significantly restored testicular oxidative stress parameters and the distorted histopathological picture, reduced the up-regulation of caspase 3 caused by DOX, and increased P-gp expression. We show for the first time that CoQ10 up-regulates P-gp as a novel mechanism for gonadal protection. In conclusion, CoQ10 protects against DOX-induced testicular toxicity in rats via ameliorating oxidative stress, reducing apoptosis and up-regulating testicular P-gp.
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http://dx.doi.org/10.1016/j.etap.2014.02.010DOI Listing
March 2014

Effect of coenzyme-q10 on Doxorubicin-induced nephrotoxicity in rats.

Adv Pharmacol Sci 2012 17;2012:981461. Epub 2012 Dec 17.

Department of Pharmacology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt.

Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox) as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10) on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg) of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg) at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH) and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology). Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment.
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http://dx.doi.org/10.1155/2012/981461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533995PMC
January 2013
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