Publications by authors named "Hossein Mostafa Elbadawy"

8 Publications

  • Page 1 of 1

Introducing of acyclonucleoside analogues tethered 1,2,4-triazole as anticancer agents with dual epidermal growth factor receptor kinase and microtubule inhibitors.

Bioorg Chem 2020 01 23;94:103446. Epub 2019 Nov 23.

Department of Chemistry, Faculty of Sciences, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia; Laboratoire de Chimie & Electrochimie des Complexes Métalliques (LCECM) USTO-MB, Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, B.p. 1505 El M nouar, Oran 31000, Algeria.

This study reports an efficient and convenient regioselective synthesis of a novel series of S- and S,N-bis(acyclonucleoside) analogues carrying 5-(2-chlorophenyl)-2,4-dihydro-1,2,4-triazole-3-thione. A facile and straightforward synthesis of thiazolotriazole and triazolothiazines has also been reported. Structures of all newly synthesized compounds were well characterized by infrared IR, H and C nuclear magnetic resonance (NMR) and mass (MS) spectra analyses. Cytotoxic screening was performed according to (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium (MTT) assay method using staurosporine as a reference drug against three different types: human liver cancer cell line (Hep G2), Michigan cancer foundation-7 (MCF-7) and human colorectal carcinoma cell line (HCT116). These data showed considerable anticancer activity for these newly synthesized compounds. Biological data for most of the S-acyclonucleoside analogues and S,N-bis(acyclonucleoside) analogues showed excellent activity with micromolar (µM) half maximal inhibitory concentration (IC) values against tumor cells. EGFR assay and tubulin inhibition assay analysis were performed for the most active compounds to get more details about their mechanism of action. In order to assess and explain their binding affinities, molecular docking simulation was studied against EGFR and tubulin binding sites. The results obtained from molecular docking study and those obtained from cytotoxic screening were correlated. Extensive structure activity relationship (SAR) analyses were also carried out.
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http://dx.doi.org/10.1016/j.bioorg.2019.103446DOI Listing
January 2020

Towards xeno-free cultures of human limbal stem cells for ocular surface reconstruction.

Cell Tissue Bank 2017 Dec 26;18(4):461-474. Epub 2017 May 26.

Fondazione Banca degli Occhi del Veneto, c/o Padiglione G. Rama - Via Paccagnella 11, 30174, Zelarino, Venice, Italy.

Isolated limbal epithelial stem cells (LESCs) were cultured with or without a 3T3 murine fibroblast feeder-layer (FL) in 4 different culture media on culture plates or on denuded human amniotic membrane (AM) support and fibrin gel support: (1) control medium supplemented with fetal bovine serum; (2) control medium supplemented with the synthetic serum "XerumFree™ XF205" (XF); (3) CnT-20 medium supplemented with "XerumFree™ XF205" (CnT-XF) and (4) CnT-20 medium supplemented with human AB serum (CnT-AB). The three xenogeneic media were compared to standard condition (control + FL) and parameters assessed included cell morphology, proliferative potential, number of passages, assessment of clonogenic and abortive colonies, life span, ∆Np63α expression and epithelial morphology on AM. During serial cultivation of LESCs, most of the tested xeno-free media supported similar numbers of cell passages, total colony number, cumulative cell doublings (CCD) rates and expression of ∆Np63α compared to control. The conditions cultivated with a FL showed a non-statistically significant higher number of cell passages and CCD rates before senescence when compared to the same conditions cultured without FL. Except for the control medium, only XF medium enabled the growth of cells on AM. The expression of ∆Np63α was comparable in all the cultures grown onto AM, when compared to the controls on fibrin gel. In conclusion, the xeno-free media enabled LESC culture both on plastic and on denuded human AM. Despite the analyses were carried out in a statistically low number of samples and need re-assessment in a larger cohort, our results suggest that the production of a completely xeno-free LESC graft could be beneficial for future clinical applications.
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http://dx.doi.org/10.1007/s10561-017-9632-7DOI Listing
December 2017

Corneal Epithelial Stem Cells Repopulate the Donor Area within 1 Year from Limbus Removal for Limbal Autograft.

Ophthalmology 2016 12 21;123(12):2481-2488. Epub 2016 Sep 21.

Research Centre, Fondazione Banca degli Occhi del Veneto, Venice, Italy; Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia.

Purpose: To determine whether limbal epithelial stem cells (LESCs) repopulate the site harvested for limbal autograft transplantation (LAT), the expression of LESCs markers was evaluated in bioptic specimens obtained from the donor area 12 months or more after surgery.

Design: Interventional case series.

Participants: Patients who underwent LAT for unilateral acquired limbal stem cell deficiency after chemical burn.

Methods: Corneal limbal explants were obtained from 2 sites, the harvested area and the untouched control area, in the donor eyes of 6 patients who previously underwent LAT for unilateral acquired limbal stem cell deficiency after chemical burn. Limbal epithelial stem cells were isolated, and cellular, immunohistochemistry, and histologic parameters were assessed to compare differences between LESCs isolated from harvested or control sites.

Main Outcome Measures: Presence of LESCs 1 year or more after LAT.

Results: Specific markers (p63, Ki67, K12), percentage of LESCs, cell doubling, and number of passages in culture did not differ significantly between harvested and control sites. However, the distinctive structure of the palisades of Vogt was found only in 2 of 6 harvested sites.

Conclusions: Limbal epithelial stem cells repopulate the donor site as early as 1 year after limbus removal for LAT. Autologous transplantation of conjunctiva and limbus are safe procedures and can be performed in cases that cannot be treated by simple grafting of LESCs cultured ex vivo.
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http://dx.doi.org/10.1016/j.ophtha.2016.08.018DOI Listing
December 2016

Effect of connexin 43 inhibition by the mimetic peptide Gap27 on corneal wound healing, inflammation and neovascularization.

Br J Pharmacol 2016 10 26;173(19):2880-93. Epub 2016 Aug 26.

International Center for Ocular Physiopathology, The Veneto Eye Bank Foundation, Venice, Italy.

Background And Purpose: The connexin 43 (Cx43) mimetic peptide Gap27 was designed to transiently block the function of this gap junction. This study was undertaken to investigate the effect of Gap27 on corneal healing, inflammation and neovascularization.

Experimental Approach: The effect of Gap27 on wound healing, inflammation and vascularization was assessed in primary human corneal epithelial cells (HCEC) in vitro and whole human corneas ex vivo, and in an in vivo rat wound healing model.

Key Results: Gap27 enhanced the wound closure of HCEC in vitro and accelerated wound closure and stratification of epithelium in human corneas ex vivo, but did not suppress the corneal release of inflammatory mediators IL-6 or TNF-α in vivo. In human corneas ex vivo, F4/80 positive macrophages were observed around the wound site. In vivo, topical Gap27 treatment enhanced the speed and density of early granulocyte infiltration into rat corneas. After 7 days, the expressions of TNF-α and TGFβ1 were elevated and correlated with inflammatory cell accumulation in the tissue. Additionally, Gap27 did not suppress VEGF release in organotypic culture, nor did it suppress early or late VEGFA expression or neovascularization in vivo.

Conclusions And Implications: Gap27 can be effective in promoting the healing of superficial epithelial wounds, but in deep stromal wounds it has the potential to promote inflammatory cell migration and accumulation in the tissue and does not suppress the subsequent neovascularization response. These results support the proposal that Gap27 acts as a healing agent in the transient, early stages of corneal epithelial wounding.
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http://dx.doi.org/10.1111/bph.13568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055138PMC
October 2016

Amniotic membranes in ophthalmology: long term data on transplantation outcomes.

Cell Tissue Bank 2016 Mar 11;17(1):51-8. Epub 2015 Jul 11.

Veneto Eye Bank Foundation, Via Paccagnella 11, 30174, Venice, Italy.

The use of amniotic membrane (AM) is a widespread clinical practice for eye surgeries and the treatment of an increasing number of ocular surface pathologies. Here we describe the AM collection methods and donor selection criteria adopted by our tissue bank to distribute 5349 amniotic membrane patches over the last 12 years for the treatment of several ocular pathologies. Specific quality control measures are described and the long term results attained using the reported procedure are presented. A case of AM utilized to treat severe ocular ulceration is also described as an example of AM transplantation. Collective data for the total amniotic membrane patches deployed to treat various ocular diseases are discussed and success rates for AM transplantations are reported. An extensive follow-up is illustrated. The results suggest that the procedures and protocols used by the Treviso Tissue Bank Foundation and Veneto Eye Bank Foundation for collection, preservation, distribution and follow-up are of an optimal standard. Accordingly, the authors conclude that the safety and efficiency of the proposed procedure for the therapeutic use of AM to treat various ocular pathologies are reproducible, with additional evidence favoring the use of AM as an alternative to conventional medical treatment for certain ocular conditions.
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http://dx.doi.org/10.1007/s10561-015-9520-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786589PMC
March 2016

A superfusion apparatus for ex vivo human eye irritation investigations.

Toxicol In Vitro 2015 Oct 20;29(7):1619-27. Epub 2015 Jun 20.

International Centre for Ocular Physiopathology, The Eye Bank Foundation of Veneto, Via Paccagnella 11, Padiglione Rama, Venice 30174, Italy.

A superfusion apparatus (SA) was developed to maintain isolated human corneas ex vivo under conditions which mimic the natural eye environment in vivo, including controlled temperature, tear flow and intraocular pressure. The SA was designed, developed and tested for use in ophthalmic pre-clinical research and to test new pharmaceutical formulations. Corneas undergo an equilibration process in the new physiological environment for one day. The test was then initiated by the application of the test substance, incubation, and temporal assessment of corneal damage using various parameters. The effects of mild and severe irritant concentrations of NaOH (2% and 8%, respectively) on corneal opacity, swelling and epithelial integrity were studied, and the inflammatory status assessed using F4/80 and MPO as macrophages and neutrophils markers, respectively. The SA was then used to test new artificial tear formulations supplemented with silver ions as an active constituent, showing different degrees of inflammatory responses as indicated by the migration of MPO and F4/80 positive cells towards the epithelium. The human cornea superfusion apparatus was proposed as a model for acute eye irritation research.
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http://dx.doi.org/10.1016/j.tiv.2015.06.022DOI Listing
October 2015

Surgical Excision of Orbital Progressive Granular Cell Tumour.

Case Rep Ophthalmol Med 2015 18;2015:420490. Epub 2015 May 18.

The Department of Maxillofacial Surgery, Ospedale dell'Angelo, Via Paccagnella 11, 30174 Venice, Italy.

Granular cell tumour (GCT) is mostly benign lesion first described by Abrikossoff and named after him. Most cases are reported in the head and neck area, where the tongue is the most common site. Here we review previous cases in the literature for GCT in the orbit and present a new case. A 49-year-old male presented with apparent exophthalmos. Examination of the patient revealed the presence of a mass in the bottom side of the orbit. A substantial progress was noted after two months from the initial examination using computed tomography (CT) scan. An orbital mass was extracted and histological analysis showed signs typical for GCT. Immunohistochemistry was positive for S-100; the biopsy showed no mitotic or necrotic areas. Proptosis was resolved after surgery and a six-year follow-up CT scan was performed. We conclude that rapid progress of the tumour does not necessarily suggest malignancy.
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http://dx.doi.org/10.1155/2015/420490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451783PMC
June 2015

Targeting herpetic keratitis by gene therapy.

J Ophthalmol 2012 26;2012:594869. Epub 2012 Dec 26.

The Veneto Eye Bank Foundation, Via Paccagnella 11, Padiglione Giovanni Rama, Zelarino, 30174 Venice, Italy.

Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1) can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.
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http://dx.doi.org/10.1155/2012/594869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541562PMC
January 2013
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