Browsing by Author "Assal R.A."
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Item The association of megalin and cubilin genetic variants with serum levels of 25-hydroxvitamin D and the incidence of acute coronary syndrome in Egyptians: A case control study(Elsevier B.V., 2020) Elsabbagh R.A.; Abdel Rahman M.F.; Hassanein S.I.; Hanafi R.S.; Assal R.A.; Shaban G.M.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts; 6th of October City; Egypt; Department of Pharmaceutical Chemistry; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; Department of Pharmacology and Toxicology; Faculty of Pharmacy and Biotechnology; The German University in Cairo; Egypt; National Heart Institute; Cairo; EgyptMegalin and cubilin are two receptors that mediate endocytosis of 25-hydroxyvitamin D (25(OH)D) for its final activation by hydroxylation. The aim of the present study was to evaluate the association of polymorphisms in megalin (rs2075252 and rs4668123) and cubilin (rs1801222 and rs12766939) with the circulating serum levels of 25(OH)D and with the early incidence of acute coronary syndrome (ACS) in Egyptians. The study included 328 subjects; 185 ACS patients aged between 27 and 60 years, and 143 healthy age-matched controls. Genotyping of cubilin rs12766939 Single Nucleotide Polymorphism (SNP) was performed using Real-Time Polymerase Chain Reaction (qPCR) and for megalin rs4668123 and rs2075252 and cubilin rs1801222 by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP). 25(OH)D levels were measured by Ultra Performance Liquid Chromatography- Tandem Mass Spectroscopy (UPLC-MS/MS). Results showed that vitamin D deficiency was highly linked to ACS incidence (P < 0.0001). The megalin rs4668123 CC, cubilin rs1801222 GG and cubilin rs12766939 GG + GA genotypes are associated with a higher ACS incidence and can be considered risk factors, according to Chi-squared test (P = 0.0003, 0.0442, 0.013 respectively). Conversely, the megalin rs2075252 SNP was not associated with increased ACS incidence. However, after performing multiple logistic regression analysis, only the megalin rs4668123 SNP was considered an independent ACS risk factor. Furthermore, the megalin rs4668123 CC genotype was associated with lower 25(OH)D levels (P = 0.0018). In conclusion, megalin rs4668123 (CC) was linked to lower 25(OH)D levels and can be considered an independent risk factor for incidence of ACS. � 2019Item Contribution of cyp27b1 and cyp24a1 genetic variations to the incidence of acute coronary syndrome and to vitamin d serum level(Canadian Science Publishing, 2019) Fam M.S.; Hassanein S.I.; Rahman M.F.A.; Assal R.A.; Hanafi R.S.; Gad M.Z.; Clinical Biochemistry Unit; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; Egypt; Biochemistry Department; Faculty of Pharmacy; October University for Modern Sciences and Arts; 6th of October; Giza 12566; Egypt; The Molecular Pathology Research Group; Department of Pharmacology and Toxicology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy and Biotechnology; German University in Cairo; Fifth Settlement; Cairo; 11432; EgyptCardiovascular diseases remain a major public health burden worldwide. It was reported that vitamin D protects the cardiovascular system through several mechanisms mainly by hindering atherosclerosis development. Genetic variations in vitamin D metabolic pathway were found to affect vitamin D levels. This study aimed at investigating the association between single nucleotide polymorphisms in genes involved in vitamin D metabolism, CYP27B and CYP24A1; 25-hydroxyvitamin D (25(OH)D) levels; and susceptibility to acute coronary syndrome (ACS). One hundred and eighty-five patients and 138 healthy controls were recruited. CYP24A1 rs2762939 was genotyped using fast real-time PCR, while CYP24A1 rs4809960 and CYP27B1 rs703842 were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism (PCR�RFLP). 25(OH)D3 and 25(OH)D2 levels were measured using ultra-performance liquid chromatography tandem mass spectrum. Vitamin D level was significantly lower in patients than controls (p < 0.05). The GG genotype of rs2762939 was significantly associated with the risk of ACS development, but not correlated to the vitamin D level. rs4809960 and rs703842 genetic variations were not associated with ACS nor with 25(OH)D level. The genetic variant rs2762939 of CYP24A1 is remarkably associated with ACS. Meanwhile, the variants rs4809960 and rs703842 are not associated with ACS incidence. � 2019, Canadian Science Publishing. All rights reserved.Item A methoxylated quercetin glycoside harnesses HCC tumor progression in a TP53/miR-15/miR-16 dependent manner(Taylor and Francis Ltd., 2018) Youness R.A.; Assal R.A.; Ezzat Shahira M; Gad M.Z.; Abdel Motaal A.; Department of Pharmaceutical Biology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacology and Toxiciology; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Cairo University; Giza; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Modern Sciences and Arts University; 6th of October; Egypt; Department of Biochemistry; Faculty of Pharmacy and Biotechnology; German University in Cairo; Cairo; Egypt; Department of Pharmacognosy; College of Pharmacy; King Khalid University; Abha; Saudi ArabiaThis study focused on studying the impact of flavonoids isolated from Cleome droserifolia on HCC cell lines and to further unveil their possible impact on TP53 and its downstream tumor suppressor miRNAs. Three flavonol glycosides were isolated from C. droserifolia namely, Isorhamnetin-3-O-?-D-glucoside (1), Quercetin-3`-methoxy-3-O-(4``-acetylrhamnoside)-7-O-?-rhamnoside (2), and Kaempferol-4`-methoxy-3,7-O-dirhamnoside (3). They showed a concentration and time dependent reduction in cellular viability and anchorage-independent growth of HCC cells. Moreover, they exhibited a decrease in the migrating capacity of HepG2 cells in a pattern similar to positive control cells. (2) Showed the most potent effects in halting HCC tumorigenic activity (IC50=36 � 1.70 �M) and a repression of the cellular proliferation rate of HepG2 cells. Restoration of TP53 and its downstream tumor suppressor miRNAs; miR-15a, miR-16, miR-34a by (2) was observed. Moreover, attenuation of (2) mediated actions was shown upon using anti-miR-15a and anti-miR-16. To conclude, this study crystallizes a novel role of C. droserifolia in harnessing HCC progression in-vitro with a possible contribution of TP53/miR-15a/miR-16. � 2018, � 2018 Informa UK Limited, trading as Taylor & Francis Group.