Browsing by Author "Aref, Ahmed M"

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Anti-cancer Effect of Hyoscyamus muticus Extract via Its Activation of Fas/FasL-ASK1-p38 Pathway
(Korean Society for Biotechnology and Bioengineering, 2022-11) Abd El-Hafeez, Amer Ali; Marzouk, Hala Mohamed M; Abdelhamid, Mohamed A. A; Khalifa, Hazim O; Hasanin, Tamer H. A; Habib, Ahmed G. K; Abdelwahed, Fatma Mahmoud; Barakat, Fatma M; Bastawy, Eslam M; Abdelghani, Eman M. B; Ozawa, Toru Hosoi, Koichiro; Aref, Ahmed M; Fujimura, Takashi; Ibrahim, Ahmed R. N; Abdelmoniem, Aalaa S. O; Elghazawy, Hagar; Ghosh, Pradipta; Kawamoto, Seiji; Pil Pack, Seung
flow cytometric analysis, knockdown of ASK1, and reactive oxygen species (ROS) production were evaluated to clarify the mechanism of action. Phytochemical screening confirmed the presence of wide range of phytoconstituents. Hyoscyamus muticus methanolic extracts (HMME) showed the highest anti-cancer activities against leukemia, breast, renal, and prostate cancers as compared to ethanol and aqueous extracts. Specifically, HMME exerted cytotoxic effect against the MDA-MB-231 and MDA-MB-468 triple-negative breast cancer (TNBC) cell lines with IC50 values of 8.75 and 7.25 μg/mL, respectively. Mechanistically, DAPI staining and flow cytometric analysis revealed that HMME induces apoptosis via the death receptor, FAS, but not the mitochondrial pathway. Moreover, ASK1 and p38 were rapidly activated in response to HMME, and knockdown of ASK1 by a small interference of RNA specific to Ask1 attenuated p38 and caspase-3 activation and suppressed apoptosis, implying that HMME-induced apoptosis relies on the ASK1-p38-caspase-3 pathway. Furthermore, we confirmed that cellular ROS generation was a critical mediator in HMME-induced apoptosis because the ROS- scavenger N-acetyl cysteine significantly decreased the phosphorylation of ASK1 and HMME-induced apoptosis. Our results confirmed HMME cytotoxic effects in TNBCs via ROS-dependent activation of the Fas/FasL-ASK1-p38 axis.
Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer
(MDPI, 23/03/2022) Mohamed, Amal Ahmed; Allam, Ahmed E; Aref, Ahmed M; Mahmoud, Maha Osama; Eldesoky, Noha A; Fawazy, Naglaa; Sakr, Yasser; Sobeih, Mohamed Emam; Albogami, Sarah; Fayad, Eman; Althobaiti, Fayez; Jafri, Ibrahim; Alsharif, Ghadi; El-Sayed, Marwa; Abdelgeliel, Asmaa Sayed; Abdel Aziz, Rania S
Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non- invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR- 34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2–negative (p < 0.001), estrogen receptor–positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.
Molecular detection of pathogenic bacteria in the colonic biopsies from patients with Ulcerative Colitis
(Makerere University, Medical School, 2022-03) El A Helal, Thanaa; El Abdel Wahab, Hoda E; Saber, Sally M; Abdelaaty, Waleed H; Eltabbakh, Mohamed M; Aref, Ahmed M; Dawood, Mohamed H
Background/Aim: Ulcerative Colitis (UC) is an inflammatory bowel disease which is common in many areas of the world including Egypt. A lot of controversy regarding the pathogenesis of UC exist. The current study is an attempt to detect some pathogenic bacteria in UC patients. Materials and methods: Endoscopic colonic biopsies obtained from 40 patients with ulcerative colitis and 20 controls were analyzed by means of real-time PCR technique for the presence of Clostridium difficile, Helicobacter Pylori (H. pylori) and pathogenic Escherichia Coli (E. coli) which are positive for KPC and/or OXA-48. Results: All patients and control samples were negative for Clostridium difficile. Three of the 40 patient samples (7.5%) and none of the 20 controls were positive for H. pylori with no significant difference between the two groups. KPC-positive E. coli were detected in 11 of the 40 patients (27.5%) and in none of the controls with a significant difference between the two groups (P=0.01). All patients and control samples were negative for OXA-48 positive E. coli. Conclusion: Although this study does not support the claim that Clostridium difficile and/or H. pylori have a role in UC, it greatly suggests that pathogenic E. coli may be involved in one way or another in the course of UC.
The Potential Protective Effect of Orange Peel and Selenium against 17β-Estradiol-Induced Chronic Non-Bacterial Prostatitis in Rats
(Bentham Science Publishers, 2020-03) Almeer, Rafa S.; Muhammad, Nada A.E.; Othman, Mohamed S; Aref, Ahmed M; Elgamal, Basma; Abdel Moneim, Ahmed E
Background: Prostate Cancer (PCa) is defined as a major health problem facing the male population. Aims: We aimed to investigate the protective effects of Orange Peel Extract (OPE) and/or selenium (Se) on chronic non-bacterial prostatitis in a rat model. Methods: Fifty-six adult male Wistar albino rats were castrated; after 5 days, they were divided randomly into eight groups (n= 7). The control group received saline treatment; while 17β-estradiol (E2) (0.25mg/kg) was injected subcutaneously in rats from Groups V, VI, VII, and VIII to induce chronic non-bacterial prostatitis. They were then treated with OPE (400mg/kg body weight; Groups II, IV, VI, and VIII) and/or sodium selenite (0.5mg/kg body weight; Groups III, IV, VII, and VIII) for 30 days. Interleukin-2 (IL2) and Prostate Cancer Antigen 3 (PCA3) mRNA expressions were determined using qPCR; Prostate-Specific Antigen (PSA) protein expression was determined immunohistochemically. Prostate tissue histology was examined by hematoxylin and eosin staining, and the levels of oxidative stress markers and antioxidant enzymes were measured. Results: E2 administration significantly increased IL2 and PCA3 mRNA expressions, and PSA protein expression. It also increased the prostate wet weight and body weight, and lipid peroxidation, nitric oxide, TNF-α, and IL-1β levels, decreased the glutathione and antioxidant enzyme levels, and caused distinct histological alterations in the prostate gland. OPE and/or Se markedly improved all the studied parameters due to their antioxidant properties and anti-inflammatory effects. Conclusion: OPE and Se showed protective effects against 17β-estradiol-induced chronic nonbacterial prostatitis. These results suggest that protection of chronic non-bacterial prostatitis by OPE+Se combination involves anti-oxidation, and anti-inflammation. Moreover, their synergistic mechanism was mostly achieved via the regulation of oxidative stress and inflammation processes
Vitamin D Receptor Gene Polymorphisms and the Risk of Chronic Hepatitis C Related Hepatocellular Carcinoma in Egyptian Population
(Bentham Science Publishers, 30/06/2021) Mohamed, Amal A; Abd-Elsalam, Sherief; Mostafa, Hanan M; Abdalla, Asmaa; Farouk, Ahmed; Aref, Ahmed M; Elshmiy, Reham A.A; ElSayed, Eman; Shafik, Nevine F; Mahmoud, Maha O; Al-Daly, Moustafa; Zaghloul, Mariam S
Background: Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. Numerous variations on the vitamin D receptor gene (VDR) have been recognized in human cancers. The majority of them cause VDR to be unable to bind to 1, 25-OH-D. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients. Methods: A total of 311 Egyptian patients were enrolled for this study. They were divided into 3 groups: 103 patients with liver Cirrhosis, 107 patients with HCC and 101 normal healthy subjects as the control group. Human genomic DNA Extraction was carried out using QIAamp® DNA Blood Mini Kit (QIAGEN) Genotyping of VDR ApaI (rs7975232) single nucleotide polymorphism (SNP) was carried out using real-time PCR TaqMan allelic discrimination assay with allele-specific designed fluorescent MGB probes. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P=0.035) CI (0.031-0.038). Patients with HCC carried a higher ratio of ApaI CC genotype compared to those with liver cirrhosis (x2=5.4 and P = 0.03) or controls (x2=6.8 and P = 0.01). Univariate analysis revealed that age, lower platelet count (<150×103/μL), higher AFP (>100 ng/ml), and ApaI CC genotype were the factors significantly associated with the development of HCC. Stepwise logistic regression analysis showed that all were independent predictors. Conclusion: ApaI CC VDR gene mutation is an independent risk factor for HCC development in Egyptian Cirrhotic HCV patients. © 2021 Mohamed et al.