Helmy Institute

Arish, Egypt

Helmy Institute

Arish, Egypt
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Soliman A.B.,Center for Materials Science | Soliman A.B.,Ain Shams University | Haikal R.R.,Center for Materials Science | Abugable A.A.,Center for Materials Science | And 2 more authors.
Journal of Materials Chemistry A | Year: 2017

A heterogeneous catalyst for the proton reduction reaction was constructed through immobilization of cobaloxime, in a microporous solid, atop unmodified graphene sheets through a one-pot reaction. This approach afforded a true heterogeneous catalyst to circumvent the known poor stability of cobaloximes in aqueous solutions. The composite demonstrated significant electrochemical activity and ability to reload the Co ions and with enhanced activity toward proton reduction (an onset of ∼−11 mV and a current density of 9 mA cm−2 at −0.88 V vs. RHE). © The Royal Society of Chemistry.

Soliman A.B.,Center for Materials Science | Soliman A.B.,Ain Shams University | Hassan M.H.,Center for Materials Science | Abugable A.A.,Center for Materials Science | And 3 more authors.
ChemCatChem | Year: 2017

A heterogeneous catalyst composite of graphene and porous-organic polymer, post-synthetically loaded with NiII ions, is reported. The microporosity of the composite was largely maintained after Ni impregnation. The composite has a very low Ni loading of 0.7 wt %, combined with an efficient electrocatalytic behavior towards water oxidation, as demonstrated by an onset potential of 1.51 V vs. RHE and a considerably low overpotential of ≈0.28 V. Moreover, a low overpotential of 0.4 V at current density of 10 mA cm−2 was attained, and the composite shows also a high 100 mA cm−2 current density for the OER at 1.8 V vs. RHE. The Tafel slope for the Ni-loaded catalyst (45 mV decade−1) indicates enhanced water oxidation characteristics as a result of the Ni ion loading. The Ni-loaded composite shows excellent durability in the water oxidation reaction, with enhanced performance upon progression of the cycles. This approach demonstrates the feasibility of fine tuning the composite's properties through post-synthetic impregnation with selected metal ions. The pyrimidine-based porous-organic polymer (PyPOP) provides a high surface area support with suitable anchoring sites for the catalytically active Ni ions, with the graphene layers providing the required electrical conductivity to the composite. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Gomez-Herreros F.,University of Sussex | Schuurs-Hoeijmakers J.H.M.,Radboud University Nijmegen | Schuurs-Hoeijmakers J.H.M.,Donders Institute for Brain | McCormack M.,Royal College of Surgeons in Ireland | And 18 more authors.
Nature Genetics | Year: 2014

Topoisomerase II (TOP2) removes torsional stress from DNA and facilitates gene transcription by introducing transient DNA double-strand breaks (DSBs). Such DSBs are normally rejoined by TOP2 but on occasion can become abortive and remain unsealed. Here we identify homozygous mutations in the TDP2 gene encoding tyrosyl DNA phosphodiesterase-2, an enzyme that repairs 'abortive' TOP2-induced DSBs, in individuals with intellectual disability, seizures and ataxia. We show that cells from affected individuals are hypersensitive to TOP2-induced DSBs and that loss of TDP2 inhibits TOP2-dependent gene transcription in cultured human cells and in mouse post-mitotic neurons following abortive TOP2 activity. Notably, TDP2 is also required for normal levels of many gene transcripts in developing mouse brain, including numerous gene transcripts associated with neurological function and/or disease, and for normal interneuron density in mouse cerebellum. Collectively, these data implicate chromosome breakage by TOP2 as an endogenous threat to gene transcription and to normal neuronal development and maintenance. © 2014 Nature America, Inc. All rights reserved.

Meisenberg C.,University of Sussex | Gilbert D.C.,Royal Sussex County Hospital | Chalmers A.,University of Glasgow | Gollins S.,University of Wales | And 4 more authors.
Molecular Cancer Therapeutics | Year: 2015

Colorectal cancer is the third most common cancer in the world. Despite surgery, up to 50% of patients relapse with incurable disease. First-line chemotherapy uses the topoisomerase 1 (TOP1) poison irinotecan, which triggers cell death by trapping TOP1 on DNA. The removal of TOP1 peptide from TOP1-DNA breaks is conducted by tyrosyl-DNA phosphodiesterase 1 (TDP1). Despite putative roles for TDP1 and TOP1 in colorectal cancer, their role in cellular and clinical responses to TOP1-targeting therapies remains unclear. Here, we show varying expression levels of TOP1 and TDP1 polypeptides in multiple colorectal cancer cell lines and in clinical colorectal cancer samples. TDP1 overexpression or TOP1 depletion is protective. Conversely, TDP1 depletion increases DNA-strand breakage and hypersensitivity to irinotecan in a TOP1-dependent manner, presenting a potential therapeutic opportunity in colorectal cancer. TDP1 protein levels correlate well with mRNA and with TDP1 catalytic activity. However, no correlation is observed between inherent TDP1 or TOP1 levels alone and irinotecan sensitivity, pointing at their limited utility as predictive biomarkers in colorectal cancer. These findings establish TDP1 as a potential therapeutic target for the treatment of colorectal cancer and question the validity of TOP1 or TDP1 on their own as predictive biomarkers for irinotecan response. ©2014 AACR.

Ismail F.M.,Center for Materials Science | Abdellah A.M.,Center for Materials Science | Ali P.A.,Center for Materials Science | Shawky S.M.,Helmy Institute | And 2 more authors.
Materials Today Communications | Year: 2017

Supported forms of the microporous metal-organic frameworks (MOFs) are of great interest targeting applications in gas separation, small molecules sensing, and in heterogeneous catalysis. In the present work we report the synthesis of a novel composite architecture displaying a sandwich-like structure of MOFs materials supported on a flexible mat of electrospun polymeric nanofibers (NFbs). The newly developed system was designed by using a low-cost and scalable multistep synthesis protocol involving a combination of electrospinning and layer by layer (LBL) synthetic growth of MOFs. In order to enhance the MOFs loading, as the active element in the composite, a double-deck construct was attempted, in contrast to alternative routes where deposition of thicker MOFs layer atop the solid support were previously reported. This highly versatile approach enables construction of multi-layer structures of the same MOFs or potentially, of different MOFs targeting specific application with particular interest in multi-component gas separation and multi-functional detection systems. © 2017 Elsevier Ltd

Alagoz M.,University of Sheffield | Alagoz M.,University of Sussex | Wells O.S.,University of Sussex | El-Khamisy S.F.,University of Sheffield | And 2 more authors.
Nucleic Acids Research | Year: 2014

Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. Despite their frequency, the overlapping mechanisms that repair these forms of DNA breakage are largely unknown. Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. The hypersensitivity to alkylation damage is partly restored by depletion of Top1, illustrating that alkylating agents can trigger cytotoxic Top1-breaks. Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. Finally, we demonstrate that cancer cells in which TDP1 is inherently deficient are hypersensitive to alkylation damage and that TDP1 depletion sensitizes glioblastoma-resistant cancer cells to the alkylating agent temozolomide. © The Author(s) 2013.

Ashour M.E.,University of Sheffield | Ashour M.E.,Helmy Institute | Atteya R.,Helmy Institute | El-Khamisy S.F.,University of Sheffield | El-Khamisy S.F.,Helmy Institute
Nature Reviews Cancer | Year: 2015

The mammalian genome is constantly challenged by exogenous and endogenous threats. Although much is known about the mechanisms that maintain DNA and RNA integrity, we know surprisingly little about the mechanisms that underpin the pathology and tissue specificity of many disorders caused by defective responses to DNA or RNA damage. Of the different types of endogenous damage, protein-linked DNA breaks (PDBs) are emerging as an important player in cancer development and therapy. PDBs can arise during the abortive activity of DNA topoisomerases, a class of enzymes that modulate DNA topology during several chromosomal transactions, such as gene transcription and DNA replication, recombination and repair. In this Review, we discuss the mechanisms underpinning topoisomerase-induced PDB formation and repair with a focus on their role during gene transcription and the development of tissue-specific cancers. © 2015 Macmillan Publishers Limited. All rights reserved.

Talaat R.M.,Sadat City University | Alrefaey S.A.,Sadat City University | Bassyouni I.H.,Cairo University | Ashour M.E.,Sadat City University | And 2 more authors.
Lupus | Year: 2016

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Cytokine gene polymorphisms play an important role in SLE. Thus, this study aimed to investigate the associations between interleukin 6 (IL-6) and interleukin 10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) and their susceptibility to SLE and the implications for plasma levels. We genotyped IL-6-174G/C (rs1800795) using mutagenically separated polymerase chain reaction (MS-PCR) and IL-10-1082G/A (rs1800896) and -819C/T (rs1800871) using sequence specific primer polymerase chain reaction (SSP-PCR) in 100 Egyptian patients and 119 controls. The plasma levels of IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). There was significant increase in the frequency of IL-6 (-174) GG genotype (P < 0.05) and G allele (P < 0.01) compared to controls. A significant increase in the distribution of IL-10 (-1082G/A) GG (P < 0.05) and AA (P < 0.05) genotypes and a significant reduction in the frequency of GA genotype (P < 0.05) was found in SLE patients. The mean serum concentration of IL-6 (P < 0.001) and IL-10 (P < 0.001) was significantly elevated in SLE patients compared to healthy controls. There was no significant association of the most common clinical findings and IL-6 and IL-10 gene polymorphisms in SLE patients. In conclusion, our preliminary study indicated that both GG genotype and G allele of IL-6 (-174G/C) could be considered as risk factors for SLE. In addition, the polymorphisms at IL-10 (-1082 G/G and AA) may play a role in SLE susceptibility in Egyptian patients. Larger prospective studies are needed to confirm our findings. © The Author(s) 2015.

PubMed | University of Sheffield, MISR University for Science and Technology, Center for Materials Science and Helmy institute
Type: | Journal: Biosensors & bioelectronics | Year: 2016

The affordable and reliable detection of Hepatitis C Virus (HCV) RNA is a cornerstone in the management and control of infection, affecting approximately 3% of the global population. However, the existing technologies are expensive, labor intensive and time consuming, posing significant limitations to their wide-scale exploitation, particularly in economically deprived populations. Here, we utilized the unique optical and physicochemical properties of gold nanoparticles (AuNPs) to develop a novel assay platform shown to be rapid and robust in sensing and quantifying unamplified HCV RNA in clinical samples. The assay is based on inducing aggregation of citrate AuNPs decorated with a specific nucleic acid probe. Two types of cationic AuNPs, cysteamine and CTAB capped, were compared to achieve maximum assay performance. The technology is simple, rapid, cost effective and quantitative with 93.3% sensitivity, high specificity and detection limit of 4.57IU/l. Finally, our data suggest that RNA folding impact the aggregation behavior of the functionalized AuNPs, with broader applications in other nucleic acid detection technologies.

Talaat R.M.,University of Sadat City | Ashour M.E.,University of Sadat City | Ashour M.E.,Helmy Institute | Bassyouni I.H.,Cairo University | Raouf A.A.,Menoufia University
Immunobiology | Year: 2014

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 -174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 -1082 G/A (rs1800896) and -819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of -1082 GG genotype (P < 0.05, OR = 2.25, 95%CI = 1.03-4.91) and significant decrease in the frequency of -1082 GA genotype (P < 0.05, OR = 0.53, 95%CI = 0.29-0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of -1082 GG (P < 0.05, OR 0.2, 95% CI = 0.04-0.99) and G allele (P < 0.05, OR = 0.28, 95%CI = 0.08-0.93), while patients with ocular manifestations had significantly higher frequency of -1082 G allele (P < 0.01, OR = 2.28, 95%CI = 1.19-4.36). BD patients had significantly higher level of IL-6 (P < 0.001) and significantly lower level of IL-10 (P < 0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P < 0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 -1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10. © 2014 Elsevier GmbH.

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