| 1. |
- El-Serafi, Ahmed Taher, 1977-, et al.
(author)
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The potentiality of histone deacetylase inhibitors for diabetes and obesity
- 2020
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In: Histone Modifications in Therapy. - San Diego, United states : Elsevier. - 9780128164228 ; , s. 361-371
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Book chapter (other academic/artistic)abstract
- Diabetes, obesity, and metabolic syndrome represent the current global epidemic. In spite of the continuous development of related pharmaceuticals, complications of these conditions lower the patient's life quality and cause a burden on the health economy. Histone deacetylase inhibitors are slowly emerging as a line of management for several medical conditions. Many studies have described their potential role in diabetes, in terms of enhancing insulin secretion and decreasing insulin resistance. In obesity, these agents showed a very interesting role in converting white fat cells to their brown counterpart, as well as shifting the metabolic pathways toward less adiposity. Although these effects are characterized at the cellular and preclinical levels, few clinical studies have been reported. This chapter includes an overview of the relation between histone deacetylation and the development of diabetes and obesity, as well as the possible future role of histone deacetylase inhibitors in the management of these conditions.
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| 2. |
- El Serafi, Ibrahim Taher, et al.
(author)
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Effect of interleukin-6 and insulin resistance on early virological response of Egyptian chronic hepatitis C patients to combined pegylated interferon plus ribavirin therapy
- 2013
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In: Egyptian Liver Journal. - Heidelberg, Germany : Wolters Kluwer. - 2090-6218. ; 3:2, s. 21-27
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Journal article (peer-reviewed)abstract
- Background and aim: Response to hepatitis C virus (HCV)-specific therapy is variable but might be influenced by host factors. We studied whether interleukin-6 (IL-6) level, IL-6–174G>C gene polymorphism, and insulin resistance affect the response to antiviral treatment in HCV-infected patients.Patients and methods: Fifty-five chronic hepatitis C patients and 13 healthy individuals as controls were included in this study. Liver function tests, HCV RNA titer, ultrasonography, and histopathological examination of liver tissues were performed for all patients. Pretreatment plasma IL-6 levels and homeostasis model assessment-insulin resistance were estimated. The IL-6–174G>C polymorphism was detected by the PCR/RFLP method. After 12 weeks of combined pegylated interferon-α and ribavirin therapy, patients were classified into responders or nonresponders according to whether they achieved an early virological response.Results: The responders had significantly high IL-6 levels (P=0.01), low mean stage of fibrosis (P=0.03), and low viral load (P=0.04) compared with nonresponders. Although not significant, patients with the IL-6–174 CC genotype reported a higher response rate (81%) compared with those with the CG genotype (50%) and GG genotype (62%). IL-6 level at a cutoff point of 2.15 pg/ml had 81.1% sensitivity and 72.7% specificity and showed significant relation with early virological response (P=0.04).Conclusion: Estimation of basal IL-6 level could be used as a predictor of response to pegylated interferon-α and ribavirin therapy in CHC patients.
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| 3. |
- Sami, Manal M., et al.
(author)
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Expression of epidermal growth factor receptor and human epidermal growth factor receptor 2 in urothelial bladder carcinoma in an Egyptian cohort: Clinical implication and prognostic significance
- 2023
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In: UROLOGIA JOURNAL. - : SAGE PUBLICATIONS LTD. - 0391-5603 .- 1724-6075. ; 90:2, s. 246-260
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Journal article (peer-reviewed)abstract
- Background: Bladder cancer (BC) has a particular importance in Egyptian patients due to aggressive behavior and absence of prognostic markers. Objective: To evaluate the expression of gene and protein expression of HER2 and epidermal growth factor (EGFR) in Egyptian patients with BC and ultimately to investigate their clinical implication and prognostic significance. Material and methods: The study was carried out on 46 patients with urothelial bladder BC. Tissue were obtained from transurethral resection (N = 22) and radical cystectomy (N = 24) specimens. The original hematoxylin and eosin slides were re-evaluated and the formalin fixed, paraffin-embedded (FFPE) tissues which had sufficient tumor tissue (>75%) and minimal or absent tumor necrosis were selected for immunohistochemistry (IHC) and RNA extraction. Furthermore, five control biopsies were obtained from patients with cystitis. Follow-up data were retrieved from the medical records which included the treatment regimen, disease recurrence and/or progression, and survival. Results: EGFR and HER2 protein were overexpressed in 35% and 46% of patients respectively. EGFR was correlated with the tumor size, grade and pathological stage, with a similar trend for HER2. The recurrence rate was higher in patients with expression of any of the markers. Gene expression was significantly higher (10.6-folds) for EGFR and (21-folds) for HER2 in patients with BC in comparison to control patients. Survival analysis showed lower median disease-free survival in association with HER2 protein overexpression. Conclusions: Our data highlighted the prognostic significance of EGFR and HER in BC and proposed their possible use as predictive markers and potential therapeutic targets.
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| 4. |
- Ahmed, Mohamed R., et al.
(author)
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Correlation between dyslipidemia and severity of allergic rhinitis
- 2018
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In: The Egyptian Journal of Otolaryngology. - London, United Kingdom : Springer. - 1012-5574 .- 2090-8539. ; 34:2, s. 111-115
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Journal article (peer-reviewed)abstract
- Background Allergic rhinitis is a common problem affecting between 20 and 25% of the population lowering the quality of life (QOL) more than any other disease. Dyslipidemia is known to impact potently the development of atopy as it promotes proatopic Th2 immunity and allergic inflammation.Objective The aim was to test the correlation between severity of allergic rhinitis and dyslipidemia.Materials and methods A comparative study carried out on 350 allergic rhinitis patients were subjected to full serum lipid assays, visual analog scale assessing their nasal symptoms, and QOL assessment using a seven-point scale.ResultsPatients were divided into two groups (according to their lipid profile): abnormal dyslipidemia group (33%) and normal lipid profile group (67%).The abnormal dyslipidemia group showed a more intense allergic rhinitis symptoms compared with the normal lipid profile with poor QOL score (1.97).ConclusionDyslipidemia might play an important role in increasing the severity of allergic rhinitis symptoms with impaired patients’ QOL; therefore, its control could achieve better treatment outcomes.
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| 5. |
- Alghfeli, Latifa, et al.
(author)
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Non-additive effect of the DNA methylation inhibitor, 5-Aza-dC, and glass as a culture surface on osteogenic differentiation
- 2022
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In: Heliyon. - : ELSEVIER SCI LTD. - 2405-8440. ; 8:12
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Journal article (peer-reviewed)abstract
- The clinical need for bone regenerative solutions is expanding with increasing life expectancy and escalating incidence of accidents. Several strategies are being investigated to enhance the osteogenic differentiation of stem cells. We previously reported two different approaches for this purpose, in monolayer and three-dimensional cell culture. The first approach was based on pretreating cells with 5-Aza-dC, a DNA methylation inhibitor, before the applying the differentiation media. The second approach was based on culturing cells on a glass surface during differentiation. In this study, we investigated the potential effect of combining both methods. Our results sug-gested that both approaches were associated with decreasing global DNA methylation levels. Cells cultured as a monolayer on glass surface showed enhancement in alkaline phosphatase activity at day 10, while 5-Aza-dC pretreatment enhanced the activity at day 5, irrespective of the culture surface. In three-dimensional pellet cul-ture, 5-Aza-dC pretreatment enhanced osteogenesis through Runx-2 and TGF-beta 1 upregulation while the glass surface induced Osterix.Furthermore, pellets cultured on glass showed upregulation of a group of miRNAs, including pro-osteogenesis miR-20a and miR-148b and anti-osteogenesis miR-125b, miR-31, miR-138, and miR-133a. Interestingly, 5-Aza-dC was not associated with a change of miRNAs in cells cultured on tissue culture plastic but reverted the upregulated miRNAs on the glass to the basal level. This study confirms the two approaches for enhancing osteogenic differentiation and contradicts their combination.
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| 6. |
- El-Serafi, Ahmed Taher, 1977-, et al.
(author)
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Dysregulation of male sex hormones in chronic hepatitis C patients
- 2016
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In: Andrologia. - Berlin, Germany : Wiley-Blackwell. - 0303-4569 .- 1439-0272. ; 48:1, s. 82-86
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Journal article (peer-reviewed)abstract
- Chronic hepatitis C (HCV) infection is a serious problem all over the world and has a special importance in Egypt, where the prevalence of infection is 14.7% of population. In males, HCV is associated with sexual dysfunction and changes in the semen parameters. This study aimed at estimation of a panel of the most important related hormones in the serum of patients and illustration of their correlation to the routine laboratory investigations. The four studied hormones showed alteration in the patients in comparison with the controls. While androstenedione, prolactin and testosterone were significantly increased in patients, dehydroepiandrosterone sulphate was decreased. These changes in the hormones were not related to the liver functions, pathological grade or even viral load. We hypothesised a model of how HCV can induce these hormonal changes and recommended to add these hormones to the follow-up panel of male patients with HCV.
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| 7. |
- El-Awady, Raafat A, et al.
(author)
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Epigenetics and miRNA as predictive markers and targets for lung cancer chemotherapy
- 2015
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In: Cancer Biology & Therapy. - Philadelphia, PA, United States : Taylor & Francis. - 1538-4047 .- 1555-8576. ; 16:7, s. 1056-1070
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Journal article (peer-reviewed)abstract
- Lung cancer cells show inherent and acquired resistance to chemotherapy. The lack of good predictive markers/novel targets and the incomplete understanding of the mechanisms of resistance limit the success of lung cancer response to chemotherapy. In the present study, we used an isogenic pair of lung adenocarcinoma cell lines; A549 (wild-type) and A549DOX11 (doxorubicin resistant) to study the role of epigenetics and miRNA in resistance/response of non-small cell lung cancer (NSCLC) cells to doxorubicin. Our results demonstrate differential expression of epigenetic markers whereby the level of HDACs 1, 2, 3 and4, DNA methyltransferase, acetylated H2B and acetylated H3 were lower in A549DOX11 compared to A549 cells. Fourteen miRNAs were dys-regulated in A549DOX11 cells compared to A549 cells, of these 14 miRNAs, 4 (has-mir-1973, 494, 4286 and 29b-3p) have shown 2.99 – 4.44 fold increase in their expression. This was associated with reduced apoptosis and higher resistance of A549DOX11cells to doxorubicin and etoposide. Sequential treatment with the epigenetic modifiers trichostatin A or 5-aza-2'-deoxycytidine followed by doxorubicin resulted in: (i) enhanced sensitivity of both cell lines to doxorubicin especially at low concentrations, (ii) enhanced doxorubicin-induced DNA damage in both cell lines, (iii) dysregulation of some miRNAs in A549 cells. In conclusion, A549DOX11 cells resistant to DNA damaging drugs have epigenetic profile and miRNA expression different from the sensitive cells. Moreover, epigenetic modifiers may reverse the resistance of certain NSCLC cells to DNA damaging agents by enhancing induction of DNA damage. This may open the door for using epigenetic profile/miRNA expression of some cancer cells as resistance markers/targets to improve response of resistant cells to doxorubicin and for the use of combination doxorubicin/epigenetic modifiers to reduce doxorubicin toxicity.
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| 8. |
- El-Huneidi, Waseem, et al.
(author)
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Micromeria fruticosa Induces Cell Cycle Arrest and Apoptosis in Breast and Colorectal Cancer Cells
- 2020
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In: Pharmaceuticals. - : MDPI. - 1424-8247. ; 13:6
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Journal article (peer-reviewed)abstract
- Micromeria fruticosa (L.) Druce subs p.serpyllifolia (Lamiaceae) has been used widely in folk medicine to alleviate various ailments such as abdominal pains, diarrhea, colds, eye infections, heart disorders and wounds. A few reports have confirmed different therapeutic potentialities of its extracts, including the anti-inflammatory, gastroprotective, analgesic, antiobesity and antidiabetic activities. This study aimed to investigate the mechanistic pathway of the antiproliferative activity of the ethanolic extract ofM. fruticosaon two different cancer cell lines, namely human breast (mammary carcinoma F7 (MCF-7)) and human colorectal (human colon tumor cells (HCT-116)) cell lines. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay, Annexin V-FITC/PI, caspases 8/9 and cell cycle analyses, qRT-PCR and Western blot were used to assess the effect of M. fruticosaon cytotoxicity, apoptosis, cell cycle, cell cycle-related genes and protein expression profiles in MCF-7 and HCT-116. The extract inhibits cell proliferation in a time- and dose-dependent manner. The half-maximal inhibitory concentration (IC50) for both cell lines was found to be 100 mu g/mL. Apoptosis induction was confirmed by Annexin V-FITC/PI, that was related to caspases 8 and 9 activities induction. Furthermore, the cell cycle analysis revealed arrest at G2/M phase. The underlying mechanism involved in the G2/M arrest was found to be associated with the downregulation of CDK1, cyclin B1 and survivin that was confirmed by qRT-PCR and Western blotting.
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| 9. |
- Ibrahim, G.H., et al.
(author)
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Impact of Interleukin-28B gene polymorphism [rs12979860] on Egyptian patients infected with hepatitis C virus genotype-4
- 2013
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In: Eastern Mediterranean Health Journal. - Alexandria, Egypt : World Health Organization Regional Office for the Eastern Mediterranean (WHO/EMRO). - 1020-3397 .- 1687-1634. ; 19:Supp. 3, s. 98-104
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Journal article (peer-reviewed)abstract
- Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon-α-ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. A similar role was investigated in a case-control study conducted on 93 Egyptian patients chronically infected with HCV-4 in comparison to 22 individuals with spontaneous HCV clearance and 70 healthy volunteers. The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). In the SVR group, the response rate was statistically significantly higher in CC genotypes (58.6%) compared with CT/TT (20.3%). There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy.
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| 10. |
- Karlsson, Matilda, 1981-, et al.
(author)
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Sprayed cultured autologous keratinocytes in the treatment of severe burns : a retrospective matched cohort study.
- 2020
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In: Annals of burns and fire disasters. - Palermo, Italy : Mediterranean Council for Burns and Fire Disasters. - 1592-9558. ; 33:2, s. 134-142
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Journal article (peer-reviewed)abstract
- The standard treatment of burns is early excision followed by autologous skin grafting. The closure of extensive deep burns poses a considerable challenge. Cultured autologous keratinocytes have been used since 1981 in an effort to improve healing. However, the time required to culture the cells and the lack of a dermal component limit the expectations of outcome. Our aim was to compare the duration of hospital stay between patients who were treated with autologous skin grafts and cultured autologous keratinocytes and those who were treated with autologous skin grafting without cultured autologous keratinocytes. In this retrospective study all patients treated with cultured autologous keratinocytes between 2012 and 2015 were matched by size and depth of burn with patients not treated with cultured autologous keratinocytes. Multivariable regression was used to analyse associations between duration of hospital stay and treatment adjusted for age, mortality, size and depth of the burn. Then, we investigated the possibility of differentiation of human bone marrow stem cell line to keratinocyte- like cells as a future direction. The regression analysis showed a coefficient of 17.36 (95% CI -17.69 to 52.40), p= 0.32, for hospital stay in the treatment group, compared with the matched group. Our results showed no difference in the duration of hospital stay between the two treatments. Autologous stem cells should be considered as a future modality of burn management, although further studies are needed.
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| 11. |
- Maher, Shymaa, et al.
(author)
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Comparison of the osteogenic differentiation potential of mesenchymal cells isolated from human bone marrow, umbilical cord blood and placenta derived stem cells
- 2015
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In: Beni-Suef University Journal of Basic and Applied Sciences. - Heidelberg, Germany : Springer. - 2314-8535. ; 4:1, s. 80-85
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Journal article (peer-reviewed)abstract
- Bone marrow has been considered for long time as the main source for mesenchymal stem cells. However, bone marrow aspiration is an invasive process that can be associated with morbidity as well as few numbers of obtained cells. Umbilical cord blood and placental tissues are other potential sources for the same type of cells. These sources are abundant, accessible and associated with no harm to the donor. This study aimed at determining the differentiation of the three cell types towards the osteogenic lineage in short term culture and in classical osteogenic conditions. The gene expression profile showed that bone marrow derived cells were the most responsive to the culture conditions while umbilical cord blood derived cells were next, as shown by the expression by the osteogenic key transcription factors ‘Runx-2’ and osterix. At the meantime, umbilical cord blood and placenta derived cells showed significant enhancement of the gene expression over the study course, which denoted potential response of the cells. Based on these results and the availability of these two sources, umbilical cord blood and placenta should still be considered as potential sources for mesenchymal stem cells in osteogenic research program. However their differentiation potential will need further enhancement.
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| 12. |
- Mansour, Mona Farouk, et al.
(author)
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Therapeutic potential of human umbilical cord derived mesenchymal stem cells on rat model of liver fibrosis
- 2019
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In: American Journal of Stem Cells. - : E-CENTURY PUBLISHING CORP. - 2160-4150. ; 8:1
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Journal article (peer-reviewed)abstract
- End-stage liver disease is a worldwide cause of morbidity and mortality, which is associated with a considerable economic burden. As the disease progresses, fibrosis will replace the hepatic architecture and compromise liver functions. The regenerative approach for the injured liver can provide a hope for these patients; however, it is still facing many challenges. In the current study, we aimed at (1) assessing hepatic regenerative capacity of mesenchymal stem cells, isolated from human umbilical cord blood (HMSCs), in a rat model of carbon-tetrachloride (CCL4) induced liver fibrosis, (2) comparing the therapeutic effects with other cell populations derived from umbilical cord blood and (3) evaluating the host response to the human-derived cells. Fifteen rats received either the whole mononuclear cell fraction (HMNCs), CD34-ve subpopulation or HMSCs. A fourth group did not receive any treatment and another group was left without induction of fibrosis as positive and negative controls. All groups that received cellular treatment showed homing of the human cells and improvement of the liver architecture and functional capacity. The groups received CD34-ve cells and HMSCs had the most efficient improvement in liver functions, microscopic regenerative markers and histological appearance while the least immune reaction was noted with HMSCs. HUCB-MSCs showed significant immunemodulatory effect on rat immune cells. This study can provide a clue about a simple and effective method for the management of fibrotic liver diseases.
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| 13. |
- Alghfeli, Latifa, et al.
(author)
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Synthesis of scaffold-free, three dimensional, osteogenic constructs following culture of skeletal osteoprogenitor cells on glass surfaces
- 2021
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In: Bone Reports. - : ELSEVIER. - 2352-1872. ; 15
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Journal article (peer-reviewed)abstract
- Background: Efficient differentiation of stem cells into three-dimensional (3D) osteogenic construct is still an unmet challenge. These constructs can be crucial for patients with bone defects due to congenital or traumatic reasons. The modulation of cell fate and function as a consequence of interaction with the physical and chemical properties of materials is well known. Methods: The current study has examined the osteogenic differentiation potential of human skeletal populations following culture on glass surfaces, as a monolayer, or in glass tubes as a pellet culture. The 3D prosperities were assessed morphometrically and the differentiation was evaluated through molecular characterization as well as matrix formation. Results: Early temporal expression of alkaline phosphatase expression of skeletal populations was observed following culture on glass surfaces. Skeletal populations seeded on glass tubes, adhered as a monolayer to the tube base and subsequently formed 3D pellets at the air-media interface. The pellets cultured on glass displayed 4.9 +/- 1.3 times the weight and 2.9 +/- 0.1 the diameter of their counterpart cultured in plastic tubes and displayed enhanced production of osteogenic matrix proteins, such a collagen I and osteonectin. The size and weight of the pellets correlated with surface area in contrast to cell numbers seeded. Global DNA methylation level was decreased in pellets cultured on glass. In contrast, gene expression analysis confirmed upregulation extracellular matrix proteins and osteogenesis-related growth factors. Conclusion: This simple approach to the culture of skeletal cells on glass tubes provides a scaffold-free, 3D construct platform for generating pellets enabling analysis and evaluation of tissue development and integration of multiple constructs with implications for tissue repair and regenerative application on scale-up.
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| 14. |
- Bajbouj, Khuloud, et al.
(author)
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Elevated Levels of Estrogen Suppress Hepcidin Synthesis and Enhance Serum Iron Availability in Premenopausal Women
- 2018
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In: Experimental and clinical endocrinology & diabetes. - : Georg Thieme Verlag KG. - 0947-7349 .- 1439-3646. ; 126:07, s. 453-459
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Journal article (peer-reviewed)abstract
- Clinical and experimental observations have long suggested that elevated levels of estrogen associate with increased serum iron availability. Additionally, recent work has shown that estrogen can downregulate hepcidin synthesis in vitro. This study aims at assessing whether the ability of estrogen to downregulate hepcidin synthesis translates into changes in serum iron status. Hepcidin synthesis was evaluated in MCF-7, Hep-G2 and SKOV-3 cells treated with increasing concentrations of estrogen and cultured for up to 24 h post treatment. The correlation between levels of serum estrogen, hepcidin and iron was assessed using serum samples collected from 153 premenopausal women at random and samples collected from 6 women at days 1, 5, 10, 16, 21 and 28 of the monthly cycle. Estrogen-treated MCF-7 cells showed a significant reduction in hepcidin synthesis, especially at 20 nM/24 h E2 treatment. Hepcidin synthesis was also significantly reduced in Hep-G2 and SKOV-3 cells at 20 nM/24 h E2 treatment. In serum samples collected at random, estrogen (P=0.022; R=-0.213) and iron (P=0.028; R=-0.316) correlated negatively with hepcidin and positively with each other (P=0.033; R=0.319). An overall similar pattern was also observed in monthly cycle-timed samples. These findings suggest that elevated levels of estrogen reduce hepcidin synthesis as means of enhancing serum iron content in menstruating women.
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| 15. |
- Bendardaf, Riyad, et al.
(author)
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The effect of vascular endothelial growth factor-1 expression on survival of advanced colorectal cancer patients
- 2017
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In: Libyan Journal of Medicine. - Abingdon, Oxfordshire, United Kingdom : Taylor & Francis. - 1993-2820 .- 1819-6357. ; 12:1
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Journal article (peer-reviewed)abstract
- Colorectal cancer is third leading cause of cancer mortality. About 60% of patients hadalready developed metastasis at the time of diagnosis. Vascular endothelial growth factor(VEGF) is crucial for the development of neovascularization and hence metastasis. This studyaimed at investigating the relation between the expression of VEGF in biopsies from surgically dissected colon cancer and the survival of those patients. Biopsies were collected from86 patients with advanced colon cancer and sections were stained by immunohistochemistryfor VEGF. Patients received chemotherapy after the operation and were followed up fordisease progression and survival. The clinical data were statistically analyzed with respectto the immunohistochemistry results. The survival of the patients was significantly longer inthe patients for whom biopsies showed negative or weak expression of VEGF in comparisonto those with moderate to high expression (p-value = 0.04). The expression of VEGF was morefrequent in the patients who died as a consequence of the disease in comparison to the 10-year survivors. In conclusion, VEGF could be related to the survival of the patients withcolorectal carcinoma and should be considered as a predictor of the prognosis.
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| 16. |
- El-Serafi, Ahmed Taher, 1977-
(author)
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Epigenetic Modifiers and Stem Cell Differentiation
- 2012. - 1
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In: Stem Cells and Cancer Stem Cells. - Dordrecht, Netherlands : Springer. - 9789400747975 - 9789400747982 ; , s. 147-154
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Book chapter (other academic/artistic)abstract
- During stem cell differentiation, genes related to their unique characters should be silenced and genes related to the target lineage must be activated. Epigenetics is well known to control gene expression and changes of the epigenetic status during differentiation were reported. Epigenetic modifiers are chemical agents that can remove the epigenetic silencing markings and consequently activate the affected genes. The role of the epigenetic modifiers is well established in cancer treatment. Reports about enhancing stem cells differentiation (both murine and human) with treatment of the modifiers are accumulating. The modifiers have no differentiation ability by themselves but they enhance the differentiation upon culturing the cells in the corresponding conditions. This effect has been shown in monolayer culture as well as three-dimensional pellets. Epigenetic modifiers could be a valuable additive to the classical differentiation protocols, although various questions have yet to be answered including the safety of the agents.
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| 17. |
- El-Serafi, Ahmed Taher, 1977-, et al.
(author)
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Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A
- 2011
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In: Differentiation. - London, United Kingdom : Elsevier. - 0301-4681 .- 1432-0436. ; 81:1, s. 35-41
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Journal article (peer-reviewed)abstract
- Clinical imperatives for new bone to replace or restore the function of traumatized or bone lost as a consequence of age or disease has led to the need for therapies or procedures to generate bone for skeletal applications. However, current in vitro methods for the differentiation of human bone marrow stromal cells (HBMSCs) do not, to date, produce homogeneous cell populations of the osteogenic or chondrogenic lineages. As epigenetic modifiers are known to influence differentiation, we investigated the effects of the DNA demethylating agent 5-aza-2′-deoxycytidine (5-aza-dC) or the histone deacetylase inhibitor trichostatin A (TSA) on osteogenic and chondrogenic differentiation. Monolayer cultures of HBMSCs were treated for 3 days with the 5-aza-dC or TSA, followed by culture in the absence of modifiers. Cells were subsequently grown in pellet culture to determine matrix production. 5-aza-dC stimulated osteogenic differentiation as evidenced by enhanced alkaline phosphatase activity, increased Runx-2 expression in monolayer, and increased osteoid formation in 3D cell pellets. In pellets cultured in chondrogenic media, TSA enhanced cartilage matrix formation and chondrogenic structure. These findings indicate the potential of epigenetic modifiers, as agents, possibly in combination with other factors, to enhance the ability of HBMSCs to form functional bone or cartilage with significant therapeutic implications therein.
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| 18. |
- Elsharkawi, Ibrahim, et al.
(author)
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Exploring the effect of epigenetic modifiers on developing insulin-secreting cells
- 2020
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In: HUMAN CELL. - : SPRINGER JAPAN KK. - 1749-0774 .- 0914-7470. ; 33, s. 1-9
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Journal article (peer-reviewed)abstract
- Diabetes is a worldwide health problem with increasing incidence. The current management modalities did not succeed to decrease comorbidities. This study aimed at enhancing the regenerative solution for diabetes by improving the differentiation of mesenchymal stromal cells (MSC) into glucose-sensitive, insulin-secreting cells through an epigenetic modification approach. A 3-day treatment protocol with the epigenetic modifiers, either decitabine (5-aza-2 -deoxycytidine; Aza); a DNA methylation inhibitor or Vorinostat (suberoylanilide hydroxamic acid; SAHA); a histone deacetylase inhibitor was added to two different human stem cell lines. The cells followed a multi-step differentiation protocol that provided the critical triggers in a temporal approach. Aza-pretreated group showed higher intracellular expression of insulin and the transcription factor PDX-1. The cells responded to the high glucose challenge by secreting insulin in the media, as shown by ELISA. Gene expression showed induction of the genes for insulin, the glucose transporter 2, glucokinase, as well as the transcription factors MafA and NKX6.1. Although SAHA showed upregulation of insulin secretion, in comparison to control, the cells could not respond to the high glucose challenge. Interestingly, Aza-treated cells showed a significant decrease in the global DNA methylation level at the end of the culture. In conclusion, this additional step with Aza could enhance the response of MSC to the classical differentiation protocol for insulin-secreting cells and may help in establishing a regenerative solution for patients with diabetes.
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| 19. |
- Elsharkawi, Ibrahim, et al.
(author)
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Investigating the role of the histone deacetylases-inhibitor suberanilohydroxamic acid in the differentiation of stem cells into insulin secreting cells
- 2019
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In: Hamdan Medical Journal. - : Medknow Publications. - 2227-2437. ; 12:1, s. 10-14
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Journal article (peer-reviewed)abstract
- Introduction: The United Arab Emirates has the second incidence of diabetes in the world. The current diabetes management plans are associated with many complications and do not provide a cure. Stem cells offer hope for permanent alleviation of this health problem through the possible differentiation into insulin-secreting cells. The current methods for the differentiation do not produce homogeneous beta-cell populations. Histone deacetylation is an epigenetic silencing mechanism that can render many genes irresponsive to the induction protocols. This study aimed at investigating the effect of the histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) on the production of functional beta cells, based on a mesenchymal stem cells model. Methods: MG63 cells were treated for three consecutive days with SAHA, followed by a three-steps of beta cells differentiation protocol, with media-contained retinoic acid, epidermal growth factor, nicotinamide and exendin-4 at different stages. Then, glucose-stimulated insulin secretion was conducted to assess the functional state of the differentiated cells.Results: Pretreating the cells with SAHA enhanced the insulin production and secretion in comparison to the control (PBS) and the vehicle dimethyl sulfoxide, as shown by the immunofluorescence detection of insulin and the transcription factor “PDX1”, as well as an increase in insulin secretion in the media. Gene expression analysis showed that SAHA pretreated cells had more induction of the studied markers when challenged with high glucose level.Conclusion: Such findings indicate a novel approach to enhance the ability of stem cells to differentiate into insulin-producing cells with potential therapeutic implications.
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| 20. |
- Guimei, Maha, et al.
(author)
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Inhibition of Yes-Associated Protein-1 (YAP1) Enhances the Response of Invasive Breast Cancer Cells to the Standard Therapy
- 2020
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In: Breast Cancer. - : DOVE MEDICAL PRESS LTD. - 1179-1314. ; 12, s. 189-199
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Journal article (peer-reviewed)abstract
- Purpose: The deregulation of the Hippo pathway results in translocation ofYes-associated protein-1 (YAP1) to the nucleus to exert an oncogenic effect. This effect has been demonstrated in several malignancies, yet, in breast cancer (BC), it remains controversial. The present study aimed to investigate the significance of YAP1 expression in BC, its relation to cancer stem cells (CSCs), and the effect of its inhibition on tumor cell survival. Patients and Methods: We evaluated the expression of YAP1 protein and gene using immunohistochemistry (IHC) and RT-qPCR in FFPE tissue from normal and breast cancer cases. We also studied its association with CSC expression (OCT4, NANOG, and SOX2) and with different clinicopathologic characteristics. Two BC cell lines (MCF7 and MDA-MB -231) were exposed to different concentrations of YAP1 inhibitor "verteporfin" and cell viability was subsequently assessed. Results: YAP1 mRNA was higher in BC compared to the normal breast tissue (p-value=0.040) and was higher in luminal tumors compared to triple-negative breast cancer (TNBC) (p-value= 0.017). Its expression in tumors was significantly associated with the expression of pluripotency markers (OCT4 and NANOG) (p-value= 0.030 and 0.035, respectively) and its inhibition resulted in a significant reduction of CSC expression in both MCF-7 and MDA-MB-231 cells. YAP1 nuclear expression by IHC, which signifies its activation, was more evident in invasive carcinomas compared to normal breast tissue and in-situ foci where the expression was limited to the cytoplasm. The pretreatment of BC cells (MCF7 and MDA-MB-231) with YAP1 inhibitor "verteporfin" resulted in their sensitization to the effect of tamoxifen and doxorubicin, respectively, and significantly decreased tumor cell proliferation and survival. Conclusion: Our results imply that YAP1 is highly expressed and activated in BC and its inhibition could represent a possible novel therapeutic strategy that should be further explored and investigated to improve the outcome of breast cancer patients.
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| 21. |
- Hussein, Mohammad H., et al.
(author)
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Beta 2 -adrenergic receptor gene haplotypes and bronchodilator response in Egyptian patients with chronic obstructive pulmonary disease
- 2017
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In: Advances in Medical Sciences. - Warsaw, Poland : Elsevier. - 1896-1126 .- 1898-4002. ; 62:1, s. 193-201
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Journal article (peer-reviewed)abstract
- Purpose: Chronic obstructive pulmonary disease (COPD) is a multi-factorial disorder caused by environmental determinants and genetic risk factors. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. Beta2-adrenergic receptor (ADRB2) gene polymorphisms have been implicated in the pathogenesis of obstructive pulmonary diseases. This study was conducted to assess the genetic association between Arg16Gly and Gln27Glu polymorphisms and COPD in the Egyptian patients, and to analyze their impact on the clinical outcome and therapeutic response.Patients/methods: The study population included 115 participants (61 COPD patients and 54 healthy controls) were genotyped for the Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms. Pulmonary function test was done and repeated in patients after salbutamol inhalation.Results: The Gly16 and Gln27 alleles represented 57% and 70% of the whole study population, and only 3 haplotypes were detected; Arg16/Gln27, Gly16/Gln27, and Gly16/Glu27. Genotypes and haplotypes homozygous for Arg16 and Gln27 were more likely to develop COPD (p<0.05). However, individuals carrying Glu27 allele conferred protection against COPD development (p=0.002). Furthermore, Arg16 genotypes and haplotypes were significantly associated with higher grades of dyspnea, more COPD symptoms and frequent exacerbations. In contrast, patients carrying Glu27 allele had better bronchial airway responsiveness to β2-agonists.Conclusions: Our findings suggested that the ADRB2 gene polymorphisms may have vital role in COPD risk, severity, and bronchodilator response among Egyptian population. Larger epidemiological studies are needed for results validation.
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| 22. |
- Khan, Amir Ali, et al.
(author)
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Significant transcriptomic changes are associated with differentiation of bone marrow-derived mesenchymal stem cells into neural progenitor-like cells in the presence of bFGF and EGF
- 2020
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In: Cell & Bioscience. - : BMC. - 2045-3701. ; 10:1
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Journal article (peer-reviewed)abstract
- IntroductionMesenchymal stem cells (MSCs) isolated from bone marrow have different developmental origins, including neural crest. MSCs can differentiate into neural progenitor-like cells (NPCs) under the influence of bFGF and EGF. NPCs can terminally differentiate into neurons that express beta-III-tubulin and elicit action potential. The main aim of the study was to identify key genetic markers involved in differentiation of MSCs into NPCs through transcriptomic analysis.MethodTotal RNA was isolated from MSCs and MSCs-derived NPCs followed by cDNA library construction for transcriptomic analysis. Sample libraries that passed the quality and quantity assessments were subjected to high throughput mRNA sequencing using NextSeq (R) 500. Differential gene expression analysis was performed using the DESeq2 R package with MSC samples being a reference group. The expression of eight differentially regulated genes was counter validated using real-time PCR.ResultsIn total, of the 3,252 differentially regulated genes between MSCs and NPCs with two or more folds, 1,771 were upregulated genes, whereas 1,481 were downregulated in NPCs. Amongst these differential genes, 104 transcription factors were upregulated, and 45 were downregulated in NPCs. Neurogenesis related genes were upregulated in NPCs and the main non-redundant gene ontology (GO) terms enriched in NPCs were the autonomic nervous system, cell surface receptor signalling pathways), extracellular structure organisation, and programmed cell death. The main non-redundant GO terms enriched in MSCs included cytoskeleton organisation cytoskeleton structural constituent, mitotic cell cycle), and the mitotic cell cycle process Gene set enrichment analysis also confirmed cell cycle regulated pathways as well as Biocarta integrin pathway were upregulated in MSCs. Transcription factors enrichment analysis by ChEA3 revealed Foxs1 and HEYL, amongst the top five transcription factors, inhibits and enhances, respectively, the NPCs differentiation of MSCs.ConclusionsThe vast differences in the transcriptomic profiles between NPCs and MSCs revealed a set of markers that can identify the differentiation stage of NPCs as well as provide new targets to enhance MSCs differentiation into NPCs.
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| 23. |
- Khan, Amir Ali, et al.
(author)
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Significant transcriptomic changes are associated with the inhibitory effects of 5-aza-2-deoxycytidine during adipogenic differentiation of MG-63 cells
- 2021
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In: SAUDI JOURNAL OF BIOLOGICAL SCIENCES. - : ELSEVIER. - 1319-562X. ; 28:12, s. 7336-7348
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Journal article (peer-reviewed)abstract
- Our previous study revealed that the treatment of 5-aza-2-deoxycytidine (5-aza) inhibited while treatment of suberoylanilide hydroxamic acid (SAHA) enhanced the adipogenic differentiation of MG-63 cells. In this study, we examined the transcriptomic profiles of the derived adipocyte-like cells from MG-63 cells in the presence of 5-aza (Treatment 1) and SAHA (Treatment 2). Genome wide expression analysis showed high within sample variability for the adipocytes derived with 5-aza versus vehicle. Additionally, the expression profile of 5-aza derived cells was separated from the other sample groups. Differential analysis on the pairwise comparison of 5-aza versus control and SAHA versus 5-aza identified 1290 and 1086 differentially expressed (DE) genes, respectively. Furthermore, some overlap was observed between the up and down-regulated DE genes of 5-aza versus control and SAHA versus control (jaccard score 0.3) as well as between the differentially regulated genes of 5-aza versus control and 5-aza versus SAHA (jaccard score 0.29). A total of 73 transcription factors (TFs) were differentially expressed across all the pair wise comparisons with some overlap between the under and over expressed TFs of 5-aza versus control and 5-aza versus SAHA (jaccard score 0.29). Unsupervised clustering of TFs showed that the samples within the group are consistent in expression and the samples cluster in accordance with the group. Several GO terms related to enhanced adipogenesis such as neutral lipid biosynthetic process, lipid metabolic processes, cellular amide metabolic processes and cellular carbohydrate metabolic processes were enriched in the down regulated genes of 5-aza derived adipocytes versus control, indicating 5aza inhibit the adipogenic differentiation of MG-63 cells. GSEA analysis on selected gene sets of MAPK and PI3K signaling pathway in MSigDB identified the pathways were up-regulated in 5-aza versus control. This study revealed that inhibition of MG-63 adipogenesis due to 5-aza treatment is associated with large transcriptomics changes and further research is needed to unravel the roles of these genes in the adipogenesis. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 24. |
- Lagerwall, Cathrine, et al.
(author)
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Xeno-free workflow exhibits comparable efficiency and quality of keratinocytes isolated from human skin biopsies
- 2021
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In: Regenerative Therapy. - : Elsevier. - 2352-3204. ; 18, s. 401-407
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Journal article (peer-reviewed)abstract
- Introduction Regenerative solutions of the skin represent a hope for burn victims with extensive skin loss and chronic wound patients. The development of xeno-free workflow is crucial for clinical application in compliance with the directives of the European Medicines Agency. This study aimed at evaluating the outcome of the xeno-free isolation workflow of keratinocytes from human skin biopsy. Methods Skin biopsies were obtained from volunteers. The epidermis was digested with TrypLEâ„¢ Select, which was deactivated by dilution or with trypsin, deactivated by media with fetal bovine serum. Freshly isolated cells were compared for total cell number, viability, activity of caspase 3, gene expression and the presence of the keratinocyte surface markers cytokeratin 14. The cells were cultured in xeno-free conditions for one week and characterized regarding the number and viability as well as the metalloproteinase secretion. Results The number of obtained cells was similar in both workflows. The cell viability was less in the TrypLE group, with slight reduction of the cell surface marker cytokeratin 14. Caspase 3 activity was comparable as well as the gene expression of the apoptotic markers BAX, BCL2 and SLUG, as well as the keratinocyte markers cytokeratin 14, stratifin and filaggrin. Upon culture, the number of keratinocytes, their viability and secretion of matrix metalloproteinases 1 and 10 were equal in both groups. Conclusion This study reports the possibility of isolating functioning and viable keratinocytes through a xeno-free workflow for clinical application.
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| 25. |
- Madkour, Mohamed I., et al.
(author)
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Ramadan diurnal intermittent fasting modulates SOD2, TFAM, Nrf2, and sirtuins (SIRT1, SIRT3) gene expressions in subjects with overweight and obesity
- 2019
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In: Diabetes Research and Clinical Practice. - Shannon, Ireland : Elsevier Ireland Ltd.. - 0168-8227 .- 1872-8227. ; 155
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Journal article (peer-reviewed)abstract
- Aim: A growing body of evidence supports the impact of intermittent fasting on normalizing body metabolism and lowering oxidative stress and inflammation. Mounting evidence confirms that oxidative stress and chronic inflammation trigger the way for the development of metabolic diseases, such as diabetes. This research was conducted to evaluate the impact of Ramadan intermittent fasting (RIF) on the expression of cellular metabolism (SIRT1 and SIRT3) and antioxidant genes (TFAM, SOD2, and Nrf2).Methods: Fifty-six (34 males and 22 females) overweight and obese subjects and six healthy body weight controls were recruited and monitored before and after Ramadan.Results: Results showed that the relative gene expressions in obese subjects in comparison to counterpart expressions of controls for the antioxidant genes (TFAM, SOD2, and Nrf2) were significantly increased at the end of Ramadan, with percent increments of 90.5%, 54.1% and 411.5% for the three genes, respectively. However, the metabolism-controlling gene (SIRT3) showed a highly significant (P < 0.001) downregulation accompanied with a trend for reduction in SIRT1 gene at the end of Ramadan month, with percent decrements of 61.8% and 10.4%, respectively. Binary regression analysis revealed significant positive correlation (P < 0.05) between high energy intake (>2000 Kcal/day vs. <2000 Kcal/day) and expressions of SOD2 and TFAM (r = 0.84 and r = 0.9, respectively).Conclusion: Results suggest that RIF ameliorates the genetic expression of antioxidant and anti-inflammatory, and metabolic regulatory genes. Thus, RIF presumably may entail a protective impact against oxidative stress and its adverse metabolic-related derangements in non-diabetic obese patients.
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| 26. |
- Saber-Ayad, Maha, et al.
(author)
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Statin-induced myopathy SLCO1B1 521T > C is associated with prediabetes, high body mass index and normal lipid profile in Emirati population
- 2018
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In: Diabetes Research and Clinical Practice. - Shannon, Ireland : Elsevier. - 0168-8227 .- 1872-8227. ; 139, s. 272-277
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Journal article (peer-reviewed)abstract
- Background: Statin-induced myopathy has been linked to the C allele of a single nucleotide polymorphism (SNP) (rs4149056) of SLCO1B1 gene. This effect is more significant, but not restricted to simvastatin. Many studies have included European, American, African and Southeast Asian ancestries, but few were carried out on Middle Eastern population.Aim: To detect the prevalence of SLCO1B1 rs4149056 (521T > C) in Emirati population.Method: We recruited 282 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained before the study starts. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for rs4149056 (521T > C) was tested in triplicates through Real Time-PCR using TaqMan® Drug Metabolism Genotyping Assay. rs2306283 (388A > G) was analyzed for comparison. In addition, presence of minor alleles of both SNPs define stronger association with statin-induced myopathy.Results: The study included 282 individuals, 52.8% were males with median age of 39.5 years. 10% had Diabetes Mellitus and 23% were hypertensive. Median of body mass index (BMI) was 27.68 kg/m2 in males and 28.38 kg/m2 in females. One-hundred ninety-seven (69.9%) showed abnormal lipid profile (either increased LDL-cholesterol or triglycerides or both). For rs4149056, C allele was present in 21.3% (2.8% homozygous C and 18.4% heterozygous CT). Although homozygous C genotype prevalence was low, compared with Caucasians (4%) and Africans (0%), C allele was associated with a trend of having higher BMI and abnormal lipid profile. C allele subjects were all pre-diabetics with mean glycated hemoglobin above 6%. Mean BMI in CC, CT, and TT genotypes was 30.91 ± 4.4, 29.48 ± 4.2, 27.96 ± 5.5 kg/m2 respectively, with lack of such a trend observed with the different genotypes of the rs2306283 (used for comparison). Abnormal lipid profile was observed in 7/8(87.5%), 38/52(73.1%) and 152/222(70%) of the CC, CT, and TT genotypes respectively.Conclusion: There is lower prevalence of statin-induced myopathy-linked C allele of rs4149056 in SLCO1B1 gene in Emirati population, compared to Caucasians and Africans. However, there is a trend of higher glycosylated hemoglobin and BMI associated with normal lipid profile in patients having this allele.
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| 27. |
- Saber-Ayad, Maha, et al.
(author)
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The FTO rs9939609 “A” allele is associated with impaired fasting glucose and insulin resistance in Emirati population
- 2019
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In: Gene. - : Elsevier. - 0378-1119 .- 1879-0038. ; 681, s. 93-98
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Journal article (peer-reviewed)abstract
- Background: Fat mass and obesity-associated protein gene variants have shown diverse influence on body weight and metabolism across different populations. Overweight, obesity and metabolic syndrome are multifactorial major health problems in the UAE and worldwide. Insulin resistance represents the link between overweight and development of metabolic syndrome and type 2 diabetes mellitus. We investigated two (FTO) variants in Emirati population, in relation to insulin resistance and different parameters of metabolic syndrome.Methods: We recruited 259 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for (FTO) rs9939609 (A>T) and rs9930506 (G>A) were performed using real time-PCR. Insulin resistance were identified using HOMA2-IR calculation; with a cut-off point of 1.4 for female and 1.18 for male subjects.Results: The study included 259 Emiratis (age range 30-53 years, mean 41.76 years, 54.4% females), 24.5% are diabetic and 30.8% are hypertensive, with body mass index of 28.4 ± 5.9 and 28.7 ± 5.7 kg/m2 in female and male subjects, respectively. Homozygous A of rs9939609 showed significantly higher fasting glucose compared to other genotypes (p = 0.04) with a trend of higher insulin level and HOMA-2IR. The A/A diabetic patients (n = 13) showed significantly higher insulin levels compared to other genotypes. G allele of rs9930506 showed a trend of higher fasting glucose and HOMA-2IR, but lower insulin level and HbA1c. No association of genotypes was detected with other components of metabolic syndrome.Conclusion: There is an association of FTO rs9939609 A/A genotype and impaired fasting glucose and insulin resistance. Homozygous A genotype diabetic patients may be more vulnerable to blood glucose fluctuation. Focused genotyping can help the health care providers to identify high risk groups of both normal population and diabetic patients to intervene accordingly.
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| 28. |
- Sallam, Hatem, et al.
(author)
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The effect of circadian rhythm on pharmacokinetics and metabolism of the Cdk inhibitor, roscovitine, in tumor mice model
- 2015
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In: Chronobiology International. - Abingdon, Oxfordshire, United Kingdom : Taylor & Francis. - 0742-0528 .- 1525-6073. ; 32:5, s. 608-614
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Journal article (peer-reviewed)abstract
- Roscovitine is a selective Cdk-inhibitor that is under investigation in phase II clinical trials under several conditions, including chemotherapy. Tumor growth inhibition has been previously shown to be affected by the dosing time of roscovitine in a Glasgow osteosarcoma xenograft mouse model. In the current study, we examined the effect of dose timing on the pharmacokinetics, biodistribution and metabolism of this drug in different organs in B6D2F1 mice. The drug was orally administered at resting (ZT3) or activity time of the mice (ZT19) at a dose of 300 mg/kg. Plasma and organs were removed at serial time points (10, 20 and 30 min; 1, 2, 4, 6, 8, 12 and 24 h) after the administration. Roscovitine and its carboxylic metabolite concentrations were analyzed using HPLC-UV, and pharmacokinetic parameters were calculated in different organs. We found that systemic exposure to roscovitine was 38% higher when dosing at ZT3, and elimination half-life was double compared to when dosing at ZT19. Higher organ concentrations expressed as (organ/plasma) ratio were observed when dosing at ZT3 in the kidney (180%), adipose tissue (188%), testis (132%) and lungs (112%), while the liver exposure to roscovitine was 120% higher after dosing at ZT19. The metabolic ratio was approximately 23% higher at ZT19, while the intrinsic clearance (CLint) was approximately 67% higher at ZT19, indicating faster and more efficient metabolism. These differences may be caused by circadian differences in the absorption, distribution, metabolism and excretion processes governing roscovitine disposition in the mice. In this article, we describe for the first time the chronobiodistribution of roscovitine in the mouse and the contribution of the dosing time to the variability of its metabolism. Our results may help in designing better dosing schedules of roscovitine in clinical trials.
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| 29. |
- Shahin, Hady, et al.
(author)
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Human serum albumin as a clinically accepted cell carrier solution for skin regenerative application
- 2020
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- The rules governing Medicinal Products in the European Union necessitates the production of cell-based therapy in good manufacturing practice facilities. The produced cells may need several hours in transportation to reach the application sites. In this study, we investigated four candidate solutions for transporting human keratinocytes. The solutions are (1) normal saline, (2) saline with 2.5% human serum albumin (Saline + HSA), (3) chemically defined, xeno-free keratinocyte media and (4) keratinocyte media with pituitary bovine extract (PBE-media). One million keratinocytes from three donors were suspended in each solution and kept at 4 °C for up to 24 h. Cells kept in Saline + HSA showed higher viability after 1, 3 and 24 h. Then, equal number of viable cells were seeded on collagenous matrix and cultured for 48 h. The adhesion and colonization were higher in the cells kept in PBE-media, while the keratinocyte surface marker, cytokeratin 14, was present in all studied groups. These results confirmed the suitability of Saline + HSA as a cell transportation solution for clinical use, which will be the choice for the planned clinical trial. Keratinocyte PBE-media can be an alternative for cells transported for research purpose, if the same media type is going to be used in the following experiments.
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| 30. |
- Shahin, Hady, et al.
(author)
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Vascularization is the next challenge for skin tissue engineering as a solution for burn management
- 2020
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In: Burns & trauma. - : Oxford University Press. - 2321-3868 .- 2321-3876. ; 8
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Research review (peer-reviewed)abstract
- Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.
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| 31. |
- Steinvall, Ingrid, 1959-, et al.
(author)
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ABO blood group and effects on ventilatory time, length of stay and mortality in major burns a retrospective observational outcome study
- 2022
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In: Burns. - Oxford, United Kingdom : Elsevier. - 0305-4179 .- 1879-1409. ; 48:4, s. 785-790
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Journal article (peer-reviewed)abstract
- Blood group has been found to be important in the development of many diseases and the outcome of several disease processes, especially cardiovascular morbidity and mortality, such as caused by trauma and sepsis. The main reason is claimed to be related to glycobiology and effects mediated through the endothelium. This study investigated the possible effect of blood group (ABO) on burn care outcome. Burn outcome prediction models are extremely accurate and as such can be used to identify outcome effects even in single centre settings. In this retrospective risk adjusted observational study, we investigated the effect of ABO blood group on ventilatory time, length of hospital stay (LOS), and 90 day mortality among patients with burns. RESULTS: A total of 225 patients were included (2008-2019) with median TBSA of 26%; interquartile range (IQR) of 20-37%; median age 45 years (IQR 22-65 years); median Baux score (age + TBSA%); 76 (IQR 53- 97); 168 (75%) were male; median duration of hospital stay was 31 days (IQR 19-56); a total of 138 (61%) received treatment with mechanical ventilation; and 29 (13%) died. In a multivariable regression model, we were unable to isolate any significant effect of any blood group (O, A, B, AB) on the outcome measures studied (ventilatory time, LOS, and mortality). IN SUMMARY: contrary to many other major areas of disease in which ABO blood groups affect outcome, we were unable to find any such effect on patients with burns. Given the precision of the outcome models presented (AUC 0.93) any such an effect, if missed due to the limited study cohort, may be considered limited and to have only a minor clinical impact.
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| 32. |
- Tolba, Mai F., et al.
(author)
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Caffeic acid phenethyl ester protects against glucocorticoid-induced osteoporosis in vivo : Impact on oxidative stress and RANKL/OPG signals
- 2017
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In: Toxicology and Applied Pharmacology. - Maryland Heights, MO, United States : Elsevier. - 0041-008X .- 1096-0333. ; 324, s. 26-35
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Journal article (peer-reviewed)abstract
- Glucocorticoid-induced osteoporosis (GIO) is one of the most common causes of secondary osteoporosis. Given that glucocorticoids are considered as a main component of the treatment protocols for a variety of inflammation and immune-mediated diseases besides its use as adjuvant to several chemotherapeutic agents, it is crucial to find ways to overcome this critical adverse effect. Caffeic acid phenethyl ester (CAPE), which is a natural compound derived from honeybee propolis displayed promising antiosteoporotic effects against mechanical bone injury in various studies. The current work aimed at investigating the potential protective effect of CAPE against GIO in vivo with emphasis on the modulation of oxidative status and receptor activator of NF-kB ligand (RANKL)/osteoprotegrin (OPG) signaling. The results showed that CAPE opposed dexamethasone (DEX)-mediated alterations in bone histology and tartarate-resistant acid phosphatase (TRAP) activity. In addition, CAPE restored oxidative balance, Runt-related transcription factor 2 (RunX2) expression and reduced caspase-3 activity in femur tissues. Co-administration of CAPE with DEX normalized RANKL/OPG ratio and Akt activation indicating a reduction in DEX-osteoclastogenesis. In conclusion, concurrent treatment of CAPE with DEX exhibited promising effects in the protection against DEX-induced osteoporosis through opposing osteoclastogenesis and protecting osteoblasts. The potent antioxidant activity of CAPE is, at least in part, involved in its anti-apoptotic effects and modulation of RunX2 and RANKL/OPG signals. The use of CAPE-enriched propolis formulas is strongly recommended for patients on chronic glucocorticoid therapy to help in the attenuation of GIO.
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