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Diallyl sulfide protects against N-nitrosodiethylamine-induced liver tumorigenesis:Role of aldose reductase

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World Journal of gastroenterology 2008年第40期14卷 6145-6153页

作者： Safinaz S Ibrahim noha N Nassar Department of Biochemistry Faculty of PharmacyCairo University Department of Pharmacology and Toxicology Faculty of PharmacyCairo University

AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver ***: Male Wistar rats received either NDEA or NDEA together with DAS as *** energy metabolism was assessed in terms of lactate,pyruvate,lactate/pyruvate,ATP levels,lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (g6PD) *** addition,membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products,measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (g6Pase),catalase (CAT) and superoxide dismutase (SOD) *** DNA level,glutathione-S-transferase (gST) and cytochrome c oxidase activities were used as DNA fragmentation *** reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different ***: NDEA significantly disturbed liver functions and most of the aforementioned *** with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical ***: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA,as well as improving cancer-cell sensitivity to *** is mediated through combating oxidative stress of free radicals,improving the energy metabolic state of the cell,and enhancing the activity of g6Pase,gST and AR enzymes.

关键词： N-nitrosodiethylamine Diallyl sulfide Liver cancer Energy metabolism Aldose reductase

Hepg2 cells support viral replication and gene expression of hepatitis C virus genotype 4 in vitro

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World Journal of gastroenterology 2006年第30期12卷 4836-4842页

作者： Mostafa K El-Awady Ashraf A Tabll Yasmine S El-Abd Mahmoud M Bahgat Hussein A Shoeb Samar S Youssef noha g bader El Din El-Rashdy M Redwan Maha El-Demellawy Moataza H Omran Wael T El-garf Said A goueli Department of Biomedical Technology National Research Center Tahrir Street PO 12622 Dokki Cairo Egypt Department of Medicinal Chemistry Na- tional Research Center Tahrir Street PO 12622 Dokki Cairo Egypt Department of Microbiology and Immunology Faculty of Pharmacy Cairo University Cairo Egypt genetic Engineering and Biotechnology Research Institute New Borg El-Arab City Alexandria Egypt Department of Pathology School of Medicine University of Wisconsin Madison WI United States

AIM： TO establish a cell culture system with longterm replication of hepatitis C virus （HCV） genome and expression of viral antigens in vitro. METHODS： Hepg2 cell line was tested for its susceptibility to HCV by incubation with a serum from a patient with chronic hepatitis C. Cells and supernatant were harvested at various time points during the culture. Culture supernatant was tested for its ability to infect na＇ive cells. The presence of minus （antisense） RNA strand, and the detection of core and E1 antigens in cells were examined by RT-PCR and immunological techniques （flow cytometry and Western blot） respectively. RESULTS： The intracellular HCV RNA was first detected on d 3 after infection and then could be consistently detected in both cells and supernatant over a period of at least three months. The fresh cells could be infected with supernatant from cultured infected cells. Flow cytometric analysis showed surface and intracellular HCV antigen expression using in house made polyclonal antibodies （anti-core, and anti-E1）. Western blot analysis showed the expression of a cluster of immunogenic peptides at molecular weights extended between 31 and 45 kDa in an one month old culture of infected cells whereas this cluster was undetectable in uninfected Hepg2 cells. CONCLUSION： Hepg2 cell line is not only susceptible to HCV infection but also supports its replication in vitro. Expression of HCV structural proteins can be detected in infected Hepg2 cells. These cells are also capable of shedding viral particles into culture media which in turn become infectious to uninfected cells.

关键词： Hepatitis C virus In vitro propagation genomic replication gene expression Hepg2 cells

Octreotide ameliorates gastric lesions in chronically mild stressed rats

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World Journal of gastroenterology 2011年第9期17卷 1135-1142页

作者： noha N Nassar Mona F Schaalan Hala F Zaki Dalaal M Abdallah Department of Pharmacology and Toxicology Faculty of PharmacyCairo University Department of Biochemistry Faculty of PharmacyMisr International University

AIM:To evaluate the effect of chronic mild stress(CMS) on the emergence of gastric ulcers and possible modulation by octreotide,a synthetic somatostatin analogue. METHODS:Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d,a multifactorial interactional animal model for *** was administered daily for 21 d at two dose levels(50 and 90μg/kg)before exposure to stress ***-and microscopical assessments were made,in addition to quantification of plasma corticosterone and gastric mucosal inflammatory,oxidative stress, and apoptotic biomarkers. RESULTS:Exposure to CMS elevated plasma corticosterone(28.3±0.6μg/dL,P=0.002),an event that was accompanied by gastric lesions(6.4±0.16 mm,P=0.01) and confirmed ***,the insult elevated gastric mucosal lipid peroxides(13±0.5 nmol/g tissue,P=0.001),tumor necrosis factor-α(3008.6±78.18 pg/g tissue,Pglandin E2(117.1 ±4.31 pg/g tissue,P=0.002),and caspase-3 activity (2.4±0.14 OD/mg protein,P=0.002).Conversely,CMS mitigated interleukin-10(627.9±12.82 pg/g tissue,P= 0.001).Furthermore,in animals exposed to CMS,octreotide restored plasma corticosterone(61%and 71%from CMS,P=0.002)at both dose *** beneficial effects were associated with a remarkable suppression of gastric lesions(38%and 9%from CMS,P=0.01)and reversal of derangements in gastric mucosa. CONCLUSION:The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant,anti-inflammatory,and anti-apoptotic actions.

关键词： gastric ulcer Chronic mild stress Octreotide Inflammation Oxidative stress Apoptosis Histopathology

Induction of sub-g0 arrest and apoptosis by seed extract of Moringa peregrina（Forssk.） Fiori in cervical and prostate cancer cell lines

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Journal of Integrative Medicine 2019年第6期17卷 410-422页

作者： Maged Mohamed Maher Abou-Hashem Dina Mohamed Abo-elmatty noha Mostafa Mesbah Ahmed Mohamed Abd EL-Mawgoud Faculty of Pharmacy Pharmacognosy DepartmentZagazig UniversityZagazig 44511Egypt Faculty of Pharmacy Biochemistry DepartmentSuez Canal UniversityIsmailia 41522Egypt Egyptian International Pharmaceuticals Industries Company Tenth of Ramadan City 44629Egypt

Objective: This study investigated cytotoxicity and induction of apoptosis in human cervical cancer cells(HELA) and prostate cancer cells(PC-3) using the most active fraction of Moringa peregrina seed ***: Dried and powdered seeds were extracted using 95% ethanol. The total ethanolic extract was further dissolved in distilled water and separated into petroleum ether, chloroform, ethyl acetate and aqueous extracts. Based on the results of in vitro anticancer studies of all extracts, the most highly active extract was selected for evaluation of apoptosis induction and cell cycle analysis on HELA and PC-3 cells at its half maximal inhibitory concentration using flow cytometry;DNA fragmentation by agarose gel electrophoresis and the expression of protein were measured by Western ***: The chloroform fraction from the ethanolic extract of M. peregrina(CFEE) was the most active antitumor fraction. The selectivity index, determined using the normal Vero cell line, indicated that CFEE had a high degree of selectivity against HELA and PC-3 cells. CFEE induced apoptosis, confirmed by cell cycle arrest at sub-g0 phase and DNA fragmentation. CFEE induced an increase in mRNA expression of caspase-3, a decrease in Bcl-2 mRNA expression, and decreased ATP levels. CFEE increased protein expression of caspase-3 and decreased protein expression of poly-ADP-ribose polymerase-1(PARP-1).Flow cytometric analysis showed an appreciable increase in the number of cells in the early apoptotic stage in CFEE-treated HELA and PC-3 cells. CFEE treatment significantly increased lipid peroxidation(malondialdehyde level) in HELA and PC-3 ***: Seed extract of M. peregrina displayed a significant antitumor effect through apoptosis induction in HELA and PC-3 cells.

关键词： Moringa peregrina Fractionation Antiproliferation Apoptosis

Positional effect of mutations in 5'UTR of hepatitis C virus 4a on patients' response to therapy

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World Journal of gastroenterology 2009年第12期15卷 1480-1486页

作者： Mostafa K El Awady Hassan M Azzazy Ahmed M Fahmy Sherif M Shawky noha g Badreldin Samar S Yossef Moataza H Omran Abdel Rahman N Zekri Said A goueli Department of Biomedical Technology National Research CenterDokkiCairo 12622Egypt Department of Chemistry and Yousef Jameel Science and Technology Research Center the American University in CairoCairo 11511Egypt Structural biology department Free University of AmsterdamDe Boelelaan 10851081 HV AmsterdamThe Netherlands National Cancer Institute Cairo 11796Egypt Department of Pathology and Laboratory Medicine University of WisconsinMadisonWI 53711United States

AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.

关键词： Hepatitis C virus Internal ribosome entrysequences Domain Ⅲ genotype 4a Ribosomal sub-unit Interferon therapy RNA folding

IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients

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World Journal of gastroenterology 2013年第2期19卷 290-298页

作者： Mostafa K El Awady noha g bader El Din Ashraf Tabll Yaser El Hosary Ashraf O Abdel Aziz Hesham El Khayat Mohsen Salama Tawfeek H Abdelhafez Department of Microbial Biotechnology National Research CenterCairoGiza 12622Egypt Department of Internal Medicin National Research CenterCairoGiza 12622Egypt Department of Tropical Medicine Cairo UniversityGiza 12622Egypt Theodor Bilharz Research Institute Giza 12622Egypt National Liver Institute Shebeen El Kom 32512Egypt

AIM:To test whether the status of positive cytomegalovirus(CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele ***:This study included 166 chronic hepatitis C(CHC) patients who received combined interferon and ribavirin therapy for 48 wk,84 spontaneous hepatitis C virus(HCV) resolvers who were positive for Igg anti-HCV antibody and negative for HCV RNA,and 100 healthy subjects who were negative for both HCV antibodies and RNA as *** DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism(SNP) and CMV DNA detection.A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed *** the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism(RFLP) *** presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain *** role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically ***:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response(SVR) while the genotypes C/T and TT were associated with lower SVR rates,50% and 48%,*** rates for the C/C allele were lower than other HCV genotypes and/or other *** CC was associated with the response to interferon(P = 0.025).genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to *** majority of spontaneously cleared subjects(86%) were C/C,confirming its protective *** C/T allele was present in 71% of CHC patients compared with 38% of controls,so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of *** reactivation occurred in 40% of CHC ***-infection with

关键词： Hepatitis C Interleukin 28B genetic polymorphisms Human cytomegalovirus Spontaneous clearance

Association between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection

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World Journal of Hepatology 2013年第3期5卷 97-103页

作者： Moataza H Omran Basma E Fotouh Samar S Youssef noha E Ibrahim Wael Nabil EL-Sayed M Mahdy Wafaa g Shosha Mostafa K El-Awady Microbial Biotechnology Department Genetic Engineering Division National Research Center Chemistry Department Faculty of Science Helwan University

AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P ghly significant if P g LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that g

关键词： Hepatitis C virus Interferon therapy Low molecular mass polypeptide Host gene Single nucleotide polymorphism

Tumor necrosis factor-α-g308A polymorphism is associated with liver pathological changes in hepatitis C virus patients

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World Journal of gastroenterology 2016年第34期22卷 7767-7777页

作者： noha g bader El Din Sally Farouk Reem El-Shenawy Marwa K Ibrahim Reham M Dawood Mostafa M Elhady Ahmed M Salem Naglaa Zayed Ahmed Khairy Mostafa K El Awady Department of Microbial Biotechnology National Research Centre Department of Biochemistry Faculty of ScienceAin Shams University Endemic Medicine Department Faculty of MedicineCairo University

AIM To investigate the association of tumor necrosis factor alpha(TNFα)-g308 A polymorphism with different liver pathological changes in treatment-na?ve Egyptian patients infected with hepatitis C virus(HCV) genotype *** This study included 180 subjects,composed of 120 treatment-na?ve chronic HCV patients with different fibrosis grades(F0-F4) and 60 healthy controls. The TNFα-g308 A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα-g308 A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk *** Current data showed that the TNFα-g308 A SNP frequency was significantly different between controls and HCV infected patients(P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients(F2-F4,n = 60) than in early fibrosis patients(F0-F1,n = 60)(P = 0.05,0.04 respectively). Moreover,the gA or AA genotypes increased the TNFα serum level greater than the gg genotype(P = 0.002). The results showed a clear association between severe liver pathological conditions(inflammation,steatosis and fibrosis) and(gA + AA) genotypes(P = 0.035,0.03,0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes(gA + AA) were significantly associated with liver inflammation(OR = 3.776,95%CI: 1.399-10.194,P = 0.009),severe steatosis(OR = 4.49,95%CI: 1.441-14.0,P = 0.010) and fibrosis progression(OR = 2.84,95%CI: 1.080-7.472,P = 0.034). Also,the A allele was an independent risk factor for liver inflammation(P = 0.003),steatosis(P = 0.003) and fibrosis(P = 0.014). CONCLUSION TNFα SNP at nucleotide-308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected

关键词： Hepatitis C virus immune response Tumor necrosis factor alpha Single nucleotide polymorphisms Cytokine expression Liver disease progression

Analysis and Assessment of Wind Energy Potential of Socotra Archipelago in Yemen

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Computers, Materials & Continua 2022年第1期70卷 1177-1193页

作者： Murad A.Almekhlafi Fahd N.Al-Wesabi Imran Khan Nadhem Nemri Khalid Mahmood Hany Mahgoub noha Negm Amin M.El-Kustaban Ammar Zahary Department of Electrical Engineering–Communication Engineering Sana’a UniversityYemen Department of Computer Science King Khalid UniversityMuhayel AseerKingdom of Saudi Arabia Faculty of Computer and IT Sana’a UniversitySana’aYemen Department of Electrical Engineering University of Engineering and TechnologyPeshawarP.O.B 814Pakistan Department of Information Systems King Khalid UniversityMayahel AseerKSA Computer Science Department King Khaled UniversityKSA&Faculty of Computers and InformationComputer Science DepartmentMenoufia UniversityEgypt Computer Science Department King Khaled UniversityKSA&Faculty of ScienceDepartment of Mathematics and Computer ScienceMenoufia UniversityEgypt Electronics Department Faculty of EngineeringUSTSana’aYemen Faculty of Computer and IT Sana’a UniversityYemen

The increasing use of fossil fuels has a significant impact on the environment and ecosystem,which increases the rate of *** the high potential of renewable energy sources inYemen and the absence of similar studies in the region,this study aims to examine the potential of wind energy in Socotra *** was done by analyzing and evaluating wind properties,determining available energy density,calculating wind energy extracted at different altitudes,and then computing the capacity factor for a number of wind turbines and determining the *** average wind speed in Socotra Island was obtained from the Civil Aviation and Meteorology Authority data,only for the five-year data currently *** results showed high wind speeds from June to September(9.85-14.88 m/s)while the wind speed decreased for the rest of the *** average wind speed in the five years was 7.95 m/*** average annual wind speed,wind energy density,and annual energy density were calculated at different altitudes(10,30,and 50 m).According to the International Wind Energy Rating criteria,the region of Socotra Island falls under Category 7 and is classified as‘Superb’for most of the *** study provides useful information for developing wind energy and an efficient wind approach.

关键词： Energy potential wind characteristics Weibull distribution wind power density Socotra island