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Pyrrolidine dithiocarbamate and saxagliptin ameliorate ulcerative colitis in rats

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Asian Pacific Journal of Tropical Biomedicine 2019年第9期9卷 373-380页

作者： Berween Mahmoud Elmahmoudy Mai A.Abd El Fattah Mohamed F.Elyamany laila A.rashed Pharmacology and Toxicology Department Faculty of PharmacyCairo UniversityCairoEgypt Biochemistry and Molecular Biology Department Faculty of MedicineCairo UniversityEgypt

Objective: To evaluate the antioxidant, immunomodulatory and anti-inflammatory activities of pyrrolidine dithiocarbamate and saxagliptin in rats with thioacetamide-induced ulcerative colitis. Methods: Animals were orally administered with a vehicle, sulfasalazine(500 mg/kg), pyrrolidine dithiocarbamate(100 mg/kg), and saxagliptin(10 mg/kg) for two weeks. Ulcerative colitis was induced by a single intrarectal instillation of thioacetamide on day 8. Colon samples were collected to assess mitogen-activated protein kinase(MAPK), phosphorylated extracellular signal-regulated kinase(ERK), c AMP response element-binding protein(CREB), interleukin-12(IL-12), caspase-3, β-defensin, inducible nitric oxide synthase(i NOS) and glucagon like peptide-1(GLP-1). Moreover, histopathological examination was performed. Results: Rats treated with thioacetamide caused increases in colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin, i NOS, as well as decreases in body weight and GLP-1. In addition, distortion of colonic structure was found by histopathological examination. Pyrrolidine dithiocarbamate and saxagliptin mitigated colitis severity by improving body weight decrease and GLP-1, and reducing colonic MAPK, phosphorylated ERK, CREB, caspase-3, IL-12, β-defensin and i NOS. Conclusions: Pyrrolidine dithiocarbamate and saxagliptin are efficient against thioacetamide induced colitis through improving inflammatory and oxidative changes.

关键词： Ulcerative colitis Inflammatory mediators Oxidative stress Pyrrolidine dithiocarbamate Saxagliptin Thioacetamide

Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response

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World Journal of Gastroenterology 2015年第39期21卷 11141-11151页

作者： Mazen Naga Mona Amin Dina Algendy Ahmed Elbadry May Fawzi Ayman Foda Serag Esmat Dina Sabry laila rashed Samia Gabal Manal Kamal Division of Gastro-enterology Department of Internal Medicine Faculty of Medicine Cairo University Department of Biochemistry Faculty of Medicine Cairo University Department of Pathology Faculty of Medicine Cairo University Department of Clinical and Chemical pathology Faculty of Medicine Cairo University

AIM: To correlate a genetic polymorphism of the low-density lipoprotein(LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus(HCV) ***: Our study included 657 HCV-infected patients with genotype 4 who received interferonbased combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index(BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction(PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor(LDLR) genotype study of LDLR exon8 c.1171G>A and exon-10 c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all ***: There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10 c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8 c.1171G>A genotype between cases(AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls(AA: 3.8%, GA: 53.1% and GG: 43.1%)(P A polymorphism between responders(AA: 3.6%, GA: 15.2%, GG: 81.2%) and nonresponders(AA: 52.2%, GA: 30.6%, GG: 17.

关键词： Hepatitis C virus Genetic polymorphisms Low-densit

Assessment of Insulin Resistance and Insulin Growth Factor-1 in Egyptian Patients with Chronic Hepatitis C

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Open Journal of Endocrine and Metabolic Diseases 2011年第1期1卷 1-8页

作者： Inas Kostandi Magy Bahgat Naglaa Zayed laila rashed 不详

Introduction: Insulin resistance (IR) is documented in patients with chronic hepatitis C(CHC), plays an important factor in disease progression and predicting poor response to treatment. In chronic liver disease, levels of insulin-like growth factor-1 (IGF-1) were correlated with IR. Aim: To evaluate IR and serum levels of IGF-1 in Egyptian patients with CHC after anti-viral therapy. Patients and Methods: Forty biopsy-proven, non-diabetic, CHC patients, who received combined IFN/ribavirin therapy, in addition to 10 healthy controls were studied. Serum levels of IGF-1, growth hormone (GH) were measured and HOMA-IR(homeostasis model assessment of IR), body mass index (BMI) were calculated. Baseline data, retrieved from patients’ files before initiation of therapy, together with response to antiviral therapy were analyzed with respect to the measured variables. Results: All patients possessed a significant higher HOMA-IR score (p = 0.02), GH levels (p < 0.001) and blood glucose levels (p < 0.001) than controls while significantly lower levels of IGF-1 were found in patients (p = 0.008)with no significant difference between responders and non-responders as regards the previously mentioned variables. HOMA-IR score was significantly correlated with GH levels, p = 0.003 and with IGF-1 levels in both responders and non responders. Low IGF-1 levels were associated with increase in fibrosis stages and were significantly correlated with insulin(r = –0.499, p = 0.001). Conclusion: CHC patients exhibit an increased HOMA-IR score reflecting the existence of IR irrespective of treatment response. Low IGF-1 levels were associated with advanced stages of fibrosis and thus could contribute to the progression of hepatic fibrosis in CHC.

关键词： Hepatitis C Insulin Resistance Interferon Ribavirin IGF-1

Preparation, Characterization and in Vitro Evaluation of the Antitumor Activity of the Biologically Synthesized Silver Nanoparticles

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Advances in Nanoparticles 2016年第2期5卷 149-166页

作者： Omama E. Elshawy Eman A. Helmy laila A. rashed Health Radiation Research Department National Centre for Radiation Research and Technology (NCRRT) Atomic Energy Authority (AEA) Cairo Egypt Regional Centre of Mycology and Biotechnology (RCMB) Al-Azhar University Cairo Egypt Medical Biochemistry Department Faculty of Medicine Cairo University Cairo Egypt

This study was concentrated on the biosynthesis of silver nanoparticles from Penicillium aurantiogresium (IMI 89372) with a focus on its cytotoxicity in MCF-7 and MCT cancer cell lines as well as Vero (normal) cell line that was assessed by crystal violet assay after treatment with various concentrations (0.44 – 145 μg/ml) for 24 h. The cell morphology was examined by inverted light microscopy. Further, the radiosensitizing effect of silver nanoparticles (AgNPs) on MCF-7 was also demonstrated by assessing cell morphology, cell proliferation of MTT assay, LDH activity and induction of apoptosis through checking of some apoptotic genes that altered during carcinogenesis, including caspase-3, Bax and Bcl-2. Caspase-3 activity was also estimated. Synthesis of AgNPs was determined by UV-Visible spectrum and it was further characterized by TEM, FT-IR and X-Ray analysis (EDX, XRD). The biosynthesized AgNPs were spherical and of 12.7 nm in size as recorded by direct electron microscopy visualization. The biosynthesized AgNPs showed variation in cytotoxicity against MCF-7, MCT and Vero cell lines in a concentration dependant response with a varied degree of alteration in cell morphology. The result showed that AgNPs were highly toxic towards MCF-7 with IC50 value of 10.5 μg/ml. Treatment of MCF-7 (10.5 μg/ml) prior to irradiation improved the effect of irradiation dose (6 Gy) via increasing alteration of cell morphology, inhibition of cell proliferation, activation of the lactate dehydrogenase (LDH) and caspase-3 leading to induction of apoptosis which was further confirmed through increasing nuclear DNA damage and up regulation of caspase 3 and Bax genes and downrgulation of Bcl-2 genes. In conclusion, the present findings clearly indicated that AgNPs showed dose dependant cytotoxicity and verified that AgNPs acted as a potent radiosensitizer and could enhance gamma irradiation induced killing of MCF-7 breast cancer cells.

关键词： Penicillium aurantiogriseum Silver Nanoparticles in Vitro Cytotoxicity Radio-Sensitivity

Evaluation of the effects of estradiol on the hypothalamic-pitutary adrenal axis response during systemic and local inflammation

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Modern Research in Inflammation 2012年第1期1卷 1-10页

作者： Nivin Sharawy Mohamed. Hassan laila rashed Wael Shawky Moshira Rateb Department of biochemistry Kasr EL Eni University Cairo Egypt Department of pathology Kasr EL Eni University Cairo Egypt Department of physiology Kasr EL Eni University Cairo Egypt

The immune and nervous systems are closely interrelated through their messenger molecules: cytokines, hormones and nitric oxide. There are sex differences in the magnitude of the inflammatory response and one of the mechanism by which female sex steroids modulate the inflammatory response could be through the hypothalamo-pituitary-adrenal axe(HPA axes). In this study, we aimed to investigate the inter-relationship between the different levels of estradiol hormone and the different inflammatory stimuli on the HPA axis response, and the role of interleukin 6(IL6) and nitric oxide (NO). This was achieved by using 100 female albino rats divided in to 3 main groups: The first group was the sham group, which was used to test the effect of all sham procedures used in the study. The two other groups represented the two inflammatory states: local (induced by formaline injection) and systemic (cecal ligation and puncture: CLP). Under each inflammatory state, the effect of intact ovary, estradiol treated ovariectomy and placebo treated ovariectomy were studied. HPA responses were evaluated, 24 hours after the sham or the inflammatory procedure, through the measurement of the plasma levels of Corticotropin-releasing Hormone (CRH), adrenocorticotropes Hormone (ACTH) and cortisol. Both IL6 and nitrite were also *** found that high physiological levels of estradiol reduced the enhanced HPA response induced by different inflammatory mediators during systemic and local inflammation. With significant enhancement of the HPA response observed mainly during local inflammation. We conclude that both the levels of estradiol hormone and the type of inflammation seem to play an important determining role on HPA response. IL6 and NO play important roles that could explain the previous findings.

关键词： Formalin CLP Estradiol Ovariectomy HPA Inflammation

PNPLA3 and TNF-α G238A Genetic Polymorphisms in Egyptian Patients with Different Grades of Severity of NAFLD

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Open Journal of Gastroenterology 2016年第3期6卷 53-64页

作者： Mona A. Hegazy Rasha M. Abdel Samie Ahmed Ezzat Nagwa Ramadan laila A. rashed Abeer M. ElSayed Internal Medicine Department Cairo University Cairo Egypt Medical Biochemistry Department Cairo University Cairo Egypt Pathology Department National Cancer Institute Cairo University Cairo Egypt

Introduction: There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). We investigated the association of single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and TNF-α G238A polymorphism with the development and severity of NAFLD in an overweight and obese Egyptian population. Material and Methods: 100 overweight and obese patients with NAFLD and 30 control subjects were enrolled. All NAFLD patients underwent a confirmatory biopsy. Laboratory investigations included fasting plasma glucose, kidney and liver function tests, liver enzymes, lipid profile and hepatitis markers. Abdominal ultrasound was performed and all subjects were genotyped for (rs738409) PNPLA3 and (rs361525) TNF-α gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The homozygous GG genotype of the PNPLA3 was most frequent among patients with NASH (26%) as compared to borderline NASH (20.5%) and simple steatosis (20%). Higher serum levels of transaminases were observed in NAFLD patients and controls who were carriers of the G allele of rs738409, but this was not statistically significant. Regarding the TNF-α G238A SNP;the frequency of the A allele was significantly higher in NAFLD patients (20%) compared to controls (5%) (p value = 0.006). The highest TNF G allele frequency was observed in the NASH group (88%) and this was statistically significant (p value = 0.009). Conclusion: Our study confirmed the association of the PNPLA3 (rs738409) and TNF-α promoter region G238A polymorphisms with susceptibility to NAFLD and its progression.

关键词： NAFLD PNPLA3 TNF-α Polymorphism NASH

Assessment of heme oxygenase-1 （HO-1） activity in the cavernous tissues of sildenafil citrate-treated rats

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Asian Journal of Andrology 2007年第3期9卷 377-381页

作者： M. Talaat Abdel Aziz M. Farid Al-Asmar Taymour Mostafa Hazem Atta laila rashed Dina Sabry Shedeed Ashour Ahmed T. Abdel Aziz Molecular Biology Unit Medical Biochemistry Department Faculty of Medicine Cairo University Cairo 11553 Egypt Medical Biochemistry Department Faculty of Medicine Ain Shams University Cairo Egypt Andrology Department Faculty of Medicine Cairo University Cairo 11553 Egypt

Aim： To assess heine oxygenase-1 （HO-1） activity in the cavemous tissue of sildenafil citrate-treated rats. Methods： One hundred and ninety-two Sprague-Dawley male rats, divided into four equal groups, were investigated. Group 1, the control group, received regular animal chow; group 2 received sildenafil citrate by intragastric tube; group 3 received sildenafil and HO inhibitor （zinc protoporphyrin, ZnPP）; and group 4 received sildenafil and nitric oxide synthase （NOS） inhibitor L-nitroarginine methyl ester （L-NAME）. Twelve rats from each group were killed after 0.5 h, 1 h, 2 h and 3 h of drug administration. Then HO-1 activity, cGMP levels and NOS enzymatic activity in the cavernous tissues were estimated. Results： In cavemous tissue, HO-1 activity, NOS enzymatic activity and cGMP concentration increased significantly in sildenafil-treated rats compared to other groups throughout the experiment. Rats receiving either HO or NOS inhibitors showed a significant decrease in these parameters. HO- 1 cavemous tissue activity and NOS enzymatic activity demonstrated a positive significant correlation with cGMP levels （r = 0.646, r = 0.612 respectively; P 〈 0.001）. Conclusion： The actions of PDE5 inhibitor sildenafil citrate in the cavernous tissue are partly mediated through the interdependent relationship between both HO-1 and NOS activities.

关键词： erectile dysfunction heme oxygenase sildenafil citrate nitric oxide synthase carbon monoxide

Association between IL-37 and VEGF Gene Expression in Psoriasis Pathogenesis in Egyptian Population

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Journal of Biosciences and Medicines 2022年第5期10卷 136-149页

作者： Sherif M. El-Sherbini Ahmed Kh. S. Salama laila A. rashed Mohamed H. Nafady Samir A. M. El-Masry Genetic Engineering and Biotechnology Research Institute Al-Sadat University Al-Sadat Egypt Faculty of Applied Medical science Misr University for Science and Technology Giza Egypt Faculty of Medicine Cairo University Cairo Egypt

Background: Psoriasis is considered a common skin disease, marked by the production and elevation of inflammatory plaques that regularly shed scales resulting from extensive skin epithelial cell proliferation. T lymphocytes, neutrophils, and other leukocytes enter the irritated skin, resulting in epidermal keratinocyte hyperplasia, vascular hyperplasia, ectasia, and T lymphocyte, neutrophil other forms of leukocyte infiltration. Aim of the Work: the study aimed to investigate the role of IL-37 and VEGF gene expression in the pathogenesis of psoriasis in Egyptian patients. Methodology: Polymerase chain reaction techniques (PCR) were applied to detect VEGF in the skin homogenates of psoriasis patients. In addition, the ELIZA technique was applied to investigate IL-37 in skin homogenates. One hundred cases have been divided into two groups: 50 healthy volunteers as the group I healthy control;50 psoriasis patients as group II. PCR real-time technology was assessed through extracted DNA samples for VEGF amplification in skin homogenate. Result: Our results revealed that psoriasis patients significantly had a substantial reduction in IL-37 compared to the control group (p Conclusion: There is a significant inverse association between IL-37 and VEGF in psoriasis patients. Study findings revealed that IL-37 gene expression decreases while VEGF gene expression increases in psoriatic individuals. Such a measurement may be beneficial in determining the severity of the condition, as well as taking into consideration of the disease’s diagnosis.

关键词： IL-37 VEGF Gene Expression Psoriasis PCR