Publications by authors named "Mostafa M Elshafey"

4 Publications

  • Page 1 of 1

Ergothioneine mitigates cisplatin-evoked nephrotoxicity via targeting Nrf2, NF-κB, and apoptotic signaling and inhibiting γ-glutamyl transpeptidase.

Life Sci 2021 Aug 6;278:119572. Epub 2021 May 6.

Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751, Egypt.

Aim: Cisplatin is a potent chemotherapeutic agent whose therapeutic application is hindered by the associated nephrotoxicity. Cisplatin-evoked nephrotoxicity has been largely attributed to the induction of oxidative stress and inflammatory responses. The current study aimed at investigating the ability of ergothioneine to mitigate cisplatin-evoked nephrotoxicity and to elucidate the underlining molecular mechanisms.

Main Methods: Wistar rats were treated with a daily dose of ergothioneine (70 mg/kg, po) for fourteen days and a single dose of cisplatin (5 mg/kg, ip) on day ten. On day fifteen, kidneys and blood specimens were collected and subjected to Western blotting, ELISA, histopathological, and spectrophotometric analysis.

Key Findings: Ergothioneine significantly enhanced renal function in cisplatin-treated rats as manifested by increased GFR and decreased serum creatinine and blood urea nitrogen. Ergothioneine effectively reduced the cisplatin-induced oxidative stress and mitigated apoptosis and the histopathological changes. Mechanistically, ergothioneine induced the expression of the antioxidant transcription factor Nrf2 and up-regulated its downstream targets NQO1 and HO-1. Equally important, ergothioneine inhibited γ-glutamyl transpeptidase that plays crucial roles in biotransformation of cisplatin into a toxic metabolite. Additionally, it reduced the pro-apoptotic protein p53 and the inflammatory transcription factor NF-κB along with its downstream pro-inflammatory cytokines TNF-α and IL-1β.

Significance: The results of the current work shed the light on the ameliorating effect of ergothioneine on cisplatin-evoked nephrotoxicity that is potentially mediated through modulation of Nrf2, p53, and NF-κB signaling and inhibition of γ-glutamyl transpeptidase. This findings support the potential application of ergothioneine in controlling cisplatin-associated nephrotoxicity although clinical investigations are warranted.
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http://dx.doi.org/10.1016/j.lfs.2021.119572DOI Listing
August 2021

MicroRNA-567 inhibits cell proliferation and induces cell apoptosis in A549 NSCLC cells by regulating cyclin-dependent kinase 8.

Saudi J Biol Sci 2021 Apr 14;28(4):2581-2590. Epub 2021 Feb 14.

Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11651, Egypt.

MicroRNA-567 (miR-567) plays a decisive role in cancers whereas its role in non-small cell lung cancer (NSCLC) is still unexplored. This study was therefore planned to explore the regulatory function of miR-567 in A549 NSCLC cells and investigate its possible molecular mechanism that may help in NSCLC treatment. In the current study, miR-567 expression was examined by quantitative real time-polymerase chain reaction (qRT-PCR) in different NSCLC cell lines in addition to normal cell line. A549 NSCLC cells were transfected by miR-567 mimic, miR-567 inhibitor, and negative control siRNA. Cell proliferation was evaluated by MTT and 5-bromo-2'deoxyuridine assays. Cell cycle distribution and apoptosis were studied by flow cytometry. Bioinformatics analysis programs were used to expect the putative target of miR-567. The expression of cyclin-dependent kinase 8 (CDK8) gene at mRNA and protein levels were evaluated by using qRT-PCR and western blotting. Our results found that miR-567 expressions decreased in all the studied NSCLC cells as compared to the normal cell line. A549 cell proliferation was suppressed by miR-567 upregulation while cell apoptosis was promoted. Also, miR-567 upregulation induced cell cycle arrest at sub-G1 and S phases. CDK8 was expected as a target gene of miR-567. MiR-567 upregulation decreased CDK8 mRNA and protein expression while the downregulation of miR-567 increased CDK8 gene expression. These findings revealed that miR-567 may be a tumor suppressor in A549 NSCLC cells through regulating CDK8 gene expression and may serve as a novel therapeutic target for NSCLC treatment.
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http://dx.doi.org/10.1016/j.sjbs.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071907PMC
April 2021

Effect of scopoletin on phagocytic activity of U937-derived human macrophages: Insights from transcriptomic analysis.

Genomics 2020 09 31;112(5):3518-3524. Epub 2020 Mar 31.

Department of Microbiology and Immunology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization St., Abbassia, Cairo 11566, Egypt. Electronic address:

Scopoletin is a botanical coumarin. Notably, scopoletin effect on phagocytic activity has not been addressed on transcriptomic level. Accordingly, this study investigated the effect of scopoletin on phagocytosis-linked gene transcription. Whole phagocytosis transcriptional profiling of stimulated U937-derived macrophages (SUDMs) in response to scopoletin as compared to non-treated SUDMs was studied. Regarding scopoletin effect on 92 phagocytosis-linked genes, 12 of them were significantly affected (p-value < .05). Seven genes were downregulated (CDC42, FCGR1A/FCGR1C, ITGA9, ITGB3, PLCE1, RHOD & RND3) and five were upregulated (DIRAS3, ITGA1, PIK3CA, PIK3R3 & PLCD1). Moreover, scopoletin enhanced phagocytic activity of SUDMs. The current results highlighted the potential use of scopoletin as immunity booster and as an adjuvant remedy in management of some autoimmune reactions. To the best of our knowledge, this is the first report that unravels the effect of scopoletin on phagocytosis via transcriptomic analysis.
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http://dx.doi.org/10.1016/j.ygeno.2020.03.022DOI Listing
September 2020

Photothermal therapeutic effect of PEGylated gold nano-semicubes in chemically-induced skin cancer in mice.

J Photochem Photobiol B 2016 Nov 13;164:21-29. Epub 2016 Sep 13.

Advanced Material Sciences and Nanotechnology Laboratory, Center of Excellence for Advanced Sciences, National Research Centre, Dokki 12622, Cairo, Egypt.

Background: The photothermal properties of gold nanoparticles (GNPs) are promising therapeutic modality for cancer. The study objective is to evaluate the therapeutic effect of the prepared PEGylated gold nano-semicubes (PEG-GNSCs) in skin cancer. The synthesized PEG-GNSCs were intermediate between cubic and rod shapes (low aspect ratio- rods).

Methods: In vitro toxicity was investigated in human skin melanoma Sk-Mel-28 cells, and skin squamous cell carcinoma was induced in CD1 mice by dimethylbenzanthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA).

Results: The calculated IC in Sk-Mel-28 cells was 3.41μg/ml of PEG-GNSCs, in presence of laser exposure. Photothermal therapy using laser-stimulated PEG-GNSCs resulted in inhibited volume of skin tumors. Our findings indicated that the inflammatory mediators, nitric oxide and cycloxygenase-2, were inhibited in mice after being treated with low and high doses of PEG-GNSCs, accompanied with laser exposure. However, the tumor necrosis factor -α was markedly elevated, while there was no change in 5-lipoxygenase. The pro-angiogenic factor vascular endothelial growth factor was inhibited, while histone acetylation and apoptosis were induced in tumor-bearing groups, after being treated with laser-stimulated PEG-GNSCs.

Conclusion: The present study indicated the promising photothermal therapeutic effect of laser-stimulated PEG-GNSCs as an effective modality to inhibit the tumor growth, the angiogenesis and partially the inflammation.
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http://dx.doi.org/10.1016/j.jphotobiol.2016.09.012DOI Listing
November 2016