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2019
Abdelfattah, D. S., R. Sayed, G. Mostafa-Hedeab, and H. H. M. Ali, "In Vitro Characterization and Evaluation of Silver Nanoparticles Cytotoxicity on Human “Liver and Breast” Cancer Cells Versus Normal Melanocytes ", The Egyptian journal of histology, vol. 42, issue 3, pp. 755-766, 2019.
Ebrahim, N., E. Ehsan, E. A. Ghany, D. Sabry, and A. Shamaa, "Mesenchymal stem cells transplantation attenuates experimentally induced brain injury after neonatal hypoxia by different two routes of administrations ", Biocell, vol. 43, issue 1, pp. 21-28, 2019.
Motawi, T. M. K., N. A. H. Sadik, D. Sabry, N. N. Shahin, and S. A. Fahim, "rs2267531, a promoter SNP within glypican-3 gene in the X chromosome, is associated with hepatocellular carcinoma in Egyptians.", Scientific reports, vol. 9, issue 1, pp. 6868, 2019. Abstract

Hepatocellular carcinoma (HCC) is a major health concern in Egypt owing to the high prevalence of hepatitis C virus (HCV) infection. HCC incidence is characterized by obvious male predominance, yet the molecular mechanisms behind this gender bias are still unidentified. Functional variations in X-linked genes have more impact on males than females. Glypican-3 (GPC3) gene, located in the Xq26 region, has lately emerged as being potentially implicated in hepatocellular carcinogenesis. The current study was designed to examine the association of -784 G/C single nucleotide polymorphism (SNP) in GPC3 promoter region (rs2267531) with HCC susceptibility in male and female Egyptian HCV patients. Our results revealed a significant association between GPC3 and HCC risk in both males and females, evidenced by higher C allele and CC/C genotype frequencies in HCC patients when compared to controls. However, no such association was found when comparing HCV patients to controls. Moreover, GPC3 gene and protein expression levels were significantly higher in CC/C than in GG/G genotype carriers in males and females. The CC/C genotype exhibited a significant shorter overall survival than GG/G genotype in HCC patients. In conclusion, GPC3 rs2267531 on the X chromosome is significantly associated with HCC, but not with HCV infection, in the Egyptian population.

Mostafa, T., L. A. Rashed, D. A. Sabry, I. Osman, N. Nabil, F. Kareem, and I. A. Mostafa, "Serum L-carnitine and vitamin D levels may be low among oral sildenafil citrate non-responders.", International journal of impotence research, vol. 31, issue 2, pp. 85-91, 2019. Abstract

This cross-sectional comparative study aimed to compare serum L-carnitine and 25(OH)D levels between men with ED non-responding for oral sildenafil citrate and healthy volunteers. Overall, 192 men, recruited from two University Hospitals, were allocated into two equal groups of matched age; healthy potent men and men with ED non-responders for oral sildenafil citrate. Oral sildenafil citrate non-responders self-reported inadequate erectile responses after four attempts using 100 mg with the manufacturer's guidelines relative to meals, associated medications, and sexual stimulation/arousal. Exclusion criteria were: diabetes, cardiovascular disorders, beta blockers treatment, morbid obesity, thyroid disorders, post-radical prostatectomy, and hepatic/renal failure. All participants were subjected to; history taking, clinical examination, validated IIEF-5 questionnaire, estimation of serum L-carnitine by calorimetric method and serum 25(OH)D by ELISA method. Compared with potent controls, ED men non-responders for oral sildenafil citrate showed significant decreases in the mean serum L-carnitine level (16.8 ± 3.6 uM/L versus 66.3 ± 11.9 uM/L, P = 0.001), the mean serum 25(OH)D level (21.2 ± 7.1 ng/ml versus 54.6 ± 7.9 ng/mL, P = 0.001) and IIEF-5 score (7.8 ± 2.6 versus 23.9 ± 1.3). Serum L-carnitine showed significant positive correlation with IIEF-5 scores (r = 0.873, P = 001), serum 25(OH)D (r = 0.796, P = 0.001) and significant negative correlation with the age (r = -0.515, P = 0.001). Serum 25(OH)D showed significant positive correlation with IIEF-5 scores (r = 0.855, P = 0.001) and significant negative correlation with the age (r = -0.223, P = 0.005). It is concluded that normal homeostasis of serum L-carnitine and 25(OH)D play a role in male sexual health being significantly decreased in ED non-responding for oral sildenafil citrate.

2018
Hasan, E. M., R. A. Abd Al Aziz, D. Sabry, S. K. Darweesh, H. A. Badary, A. Elsharkawy, M. M. Abouelkhair, and A. Yosry, "Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to the stage of non-alcoholic fatty liver disease diagnosed by controlled attenuation parameter (CAP)-fibroscan.", Journal of gastrointestinal and liver diseases : JGLD, vol. 27, issue 3, pp. 265-272, 2018 Sep. Abstract

BACKGROUND AND AIMS: Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens®.

METHODS: Transient elastography (FibroScan®) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for the detection and quantification of hepatic steatosis/fibrosis, respectively, was assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539 were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTS: According to BMI (kg/m2), among the patients, 17 (21%) were overweight, 56 (69.1%) obese, and 8 (9.9%) morbidly obese. CAP and FibroScan diagnosed steatosis/fibrosis correlated significantly with liver biopsy. There was a significant association between polymorphisms of rs694539-NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found in 33% NAFLD patients versus 1.2% controls (P<0.001), whereas the wild type (GG-genotype) was present in 21% versus 63.8% controls (P<0.001). Moreover, the AA-genotype significantly correlated with the steatosis degree by CAP but not the fibrosis degree by FibroScan. Multivariate regression analysis of all the independent risk factors showed non-significant correlations with the degree of steatosis on CAP. However, by using a stepwise approach, waist circumference showed significance as an independent predictor of NAFLD.

CONCLUSIONS: Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk factor for developing NAFLD and NASH (indicating susceptibility for progression and complications). Individuals with wild type (GG-genotype) are at less risk of NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and fibrosis.

Sabry, D., S. E. M. El-Deek, M. Maher, M. A. H. El-Baz, H. M. El-Bader, E. Amer, E. A. Hassan, W. Fathy, and H. E. M. El-Deek, "Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway.", Molecular and cellular biochemistry, 2018 Oct 24. Abstract

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

Alaa El-Din, Y., D. Sabry, A. H. Abdelrahman, and S. Fathy, "Potential therapeutic effects of induced pluripotent stem cells on induced salivary gland cancer in experimental rats.", Biotechnic & histochemistry : official publication of the Biological Stain Commission, pp. 1-8, 2018 Oct 19. Abstract

Salivary gland neoplasms exhibit complex histopathology in a variety of tumor types and treatment options depend largely on the stage of the cancer. Induced pluripotent stem cells (iPS) have been investigated for treating induced salivary gland cancer and for restoring salivary gland function. We investigated iPS treatment for salivary gland cancer both in vitro and in vivo. For our study in vitro, we re-programmed human skin fibroblasts to form iPS cells using a plasmid containing Oct4, Sox2, L-MYC and LIN28. For our study in vivo, we used 30 white male albino rats divided into the following groups of 10: group 1 (control): rats were injected with phosphate-buffered saline (PBS), group 2 induced squamous cell carcinoma (SCC): rat submandibular glands were injected with squamous carcinoma cells (SCC), group 3 (induced SCC/iPS): SCC treated rats treated with 5 × 106 iPS cells. Submandibular glands from rats of all groups were examined histologically and real time PCR was performed for amylase, and COX I and COX II gene expression. We confirmed that submandibular gland specimens included tumor tissue before starting treatment with iPS. iPS treated cases exhibited regeneration of salivary glands, although minor degenerative and vascularization changes remained. The acinar cells regained their proper organization, but continued to exhibit abnormal activity including hyperchromatism. iPS cells may be useful for treating salivary gland carcinomas.

Ebrahim, N., I. A. Ahmed, N. I. Hussien, A. A. Dessouky, A. S. Farid, A. M. Elshazly, O. Mostafa, W. B. E. Gazzar, S. M. Sorour, Y. Seleem, et al., "Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway.", Cells, vol. 7, issue 12, 2018 Nov 22. Abstract

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes.

RESULTS: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA.

CONCLUSION: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

Sabry, D., O. O. Abdelaleem, E. M. Hefzy, A. A. Ibrahim, T. I. Ahmed, E. A. Hassan, N. D. Abdel-Hameed, and M. A. F. Khalil, "Interplay Between Helicobacter pylori Infection, Interleukin-11, and Leukemia Inhibitory Factor in Gastric Cancer Among Egyptian Patients.", Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, vol. 38, issue 11, pp. 517-525, 2018 Nov. Abstract

Helicobacter pylori is a ubiquitous Gram-negative bacterium, that is responsible for gastric mucosal inflammation. It is the most common risk factor for gastric cancer (GC). The current study aimed to investigate the association between interleukin-11 (IL-11) and leukemia inhibitory factor (LIF) levels among H. pylori-infected Egyptian patients with gastritis and GC. One hundred forty-seven patients with gastric lesions were endoscopically biopsied and assessed using rapid urease test and immunohistochemistry. Quantitative real-time polymerase chain reaction was done for the detection of H. pylori load in gastric biopsies and detection of LIF as well as IL-11 relative gene expression. The mean values of H. pylori load, LIF, and IL-11 were significantly elevated in GC patients compared to gastritis group (P < 0.0001). A positive significant correlation was detected between mucosal levels of LIF, IL-11, and H. pylori load in both groups. Both LIF and IL-11 had the same pattern of expression in gastric tissues with different types of gastritis and different types and grades of gastric carcinoma. This report could clarify the molecular events associated with the immune response against H. pylori infection and H. pylori-associated pathology. Therefore, development of immunotherapy strategies against H. pylori-induced cytokines becomes inevitable.

Sabry, D., S. R. Kaddafy, A. A. Abdelaziz, A. K. Nassar, M. M. Rayan, S. M. Sadek, and A. A. Abou-Elalla, "Association of SIRT-1 Gene Polymorphism and Vitamin D Level in Egyptian Patients With Rheumatoid Arthritis.", Journal of clinical medicine research, vol. 10, issue 3, pp. 189-195, 2018 Mar. Abstractsirt_1_vitamin_d_polymorphism.pdf

Background: We investigated SIRT-1 genetic variant and its association with vitamin D level in Egyptian patients with rheumatoid arthritis (RA).

Methods: Seventy Egyptian subjects were enrolled in our study and divided into two groups: RA group (n = 50 patients) and healthy control group (n = 20 subjects). Five milliliter blood sample was withdrawn from each subject followed by laboratory investigation and DNA extraction for SIRT-1 gene polymorphism assessment (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and vitamin D level expression.

Results: There was statistically significant difference between rheumatoid cases and controls with regard to vitamin D level with 88% of cases showing insufficient vitamin D versus all controls showing sufficient level. SIRT-1 different SNPs rs2273773, rs7895833and rs7069102 genotype frequencies were statistically significant in RA compared to control group (P = 0.001). There was no statistically significant difference between different genotypes of rs2273773, rs7895833 and rs7069102 with regard to vitamin D level.

Conclusion: We concluded that there is a strong association between SIRT-1 polymorphism genotyping and RA. Vitamin D level was insufficient in Egyptian patients with RA.

Ebrahim, N., O. Mostafa, R. E. El Dosoky, I. A. Ahmed, A. S. Saad, A. Mostafa, D. Sabry, K. A. Ibrahim, and A. S. Farid, "Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model.", Stem cell research & therapy, vol. 9, issue 1, pp. 175, 2018 Jun 28. Abstract

BACKGROUND: Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs).

METHODS: In this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-β as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and β-actin expression.

RESULTS: The therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen.

CONCLUSIONS: We conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment.

Sherif, I. O., D. Sabry, A. Abdel-Aziz, and O. M. Sarhan, "The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity.", Stem cell research & therapy, vol. 9, issue 1, pp. 196, 2018 Jul 18. Abstract

BACKGROUND: The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action.

METHODS: Thirty male Sprague-Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined.

RESULTS: Cisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats.

CONCLUSIONS: The BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Safwat, A., D. Sabry, A. Ragiae, E. Amer, R. H. Mahmoud, and R. M. Shamardan, "Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits.", Journal of circulating biomarkers, vol. 7, pp. 1849454418807827, 2018 Jan-Dec. Abstract

This study aimed to evaluate the effect of mesenchymal stem cells (MSCs)-derived exosomes in retina regeneration of experimentally induced diabetes mellitus (DM) in a rabbit model. Exosomes are extracellular vesicles that contain many microRNAs (micRNAs), mRNAs, and proteins from their cells of origin. DM was induced by intravenous (IV) injection of streptozotocin in rabbits. MSCs were isolated from adipose tissue of rabbits. Exosomes were extracted from MSCs by ultracentrifugation. Exosomes were injected by different routes (IV, subconjunctival (SC), and intraocular (IO)). Evaluation of the treatment was carried out by histopathological examination of retinal tissues and assessment of micRNA-222 expression level in retinal tissue by real-time polymerase chain reaction. Histologically, by 12 weeks following SC exosomal treatment, the cellular components of the retina were organized in well-defined layers, while IO exosomal injection showed well-defined retinal layers which were obviously similar to layers of the normal retina. However, the retina appeared after IV exosomal injection as irregular ganglionic layer with increased thickness. MicRNA-222 expression level was significantly reduced in diabetic controls when compared to each of healthy controls and other diabetic groups with IV, SC, and IO routes of injected exosomes (0.06 ± 0.02 vs. 0.51 ± 0.07, 0.28 ± 0.08, 0.48 ± 0.06, and 0.42 ± 0.11, respectively). We detected a significant negative correlation between serum glucose and retinal tissue micRNA-222 expression level ( = -0.749, = 0.001). We can associate the increased expression of micRNA-222 with regenerative changes of retina following administration of MSCs-derived exosomes. The study demonstrates the potency of rabbit adipose tissue-derived MSCs exosomes in retinal repair. So, exosomes are considered as novel therapeutic vectors in MSCs-based therapy through its role in shuttling of many factors including micRNA-222.

Motawi, T. M. K., D. Sabry, N. W. Maurice, and S. M. Rizk, "Role of mesenchymal stem cells exosomes derived microRNAs; miR-136, miR-494 and miR-495 in pre-eclampsia diagnosis and evaluation.", Archives of biochemistry and biophysics, vol. 659, pp. 13-21, 2018 Dec 01. Abstract

BACKGROUND: Pre-eclampsia (PE) is one of the most threatening pregnancy complications. So far neither a secure, competent therapy for PE nor effective biomarkers for a premature discovery has been achieved. However, currently, the use of released microRNAs (miRNAs) as potential biomarkers and therapy targets for various diseases is the dominating area of research. The aim of our study was to identify miRNAs 136, 494 and 495 genes expression in exosomes of peripheral blood compared to umbilical cord mesenchymal stem cells (UCMSCs) conditioned media released exososomes in patients with PE, as valuable markers for PE early prediction.

METHODS: Blood samples were collected from 100 patients with PE and 100 control with normal pregnancies. Thirty fresh umbilical cord samples of women with healthy pregnancies (n = 15) and PE patients (n = 15) were retrieved during caesarean deliveries and UCMSCs were isolated from Wharton jelly. The expression of miRNAs 136, 494 and 495 in exosomes of peripheral blood and UCMSCs conditioned media was measured using quantitative real-time PCR method. Unpaired t-test, Pearson correlation test and Receiver operator characteristic (ROC) analysis were used for data analysis.

RESULTS: Our study revealed a significantly higher expression levels of miRNAs 136, 494 and 495 in exosomes of peripheral blood and matched with UCMSCs released exosomes from patients with PE compared to normal pregnancies (p = 0.000). In peripheral blood of PE, they were 6.4, 3.9 and 2.1 folds higher, respectively. ROC analysis revealed that the sensitivity and specificity values of miRNA-136 were 95% and 100%, respectively, with a cut-off value of 2.55. The sensitivity and specificity values of miRNA-494 were 86% and 95%, respectively, with a cut-off value of 0.47. The sensitivity and specificity values of miRNA-495 were 90% and 83%, respectively, with a cut-off value of 1.287.

CONCLUSION: Our findings suggest that exosomes derived miRNA-136, miRNA-494 and miRNA-495 could be promising circulating biomarkers in early detection of PE. Furthermore, UCMSCs released exosomes miRNA-136, miRNA-494 and miRNA-495 genes expression confirmed peripheral blood results analysis.

Bawazeer, S., D. Sabry, R. H. Mahmoud, H. M. Elhanbuli, N. N. Yassen, and M. N. Abdelhafez, "Association of SPARC gene polymorphisms rs3210714 and rs7719521 with VEGF expression and utility of Nottingham Prognostic Index scoring in breast cancer in a sample of Egyptian women.", Molecular biology reports, vol. 45, issue 6, pp. 2313-2324, 2018 Dec. Abstract

Breast cancer is the most common malignancy in women. To our knowledge, there is no single study conducted on the role of secreted protein acidic and rich in cysteine (SPARC) gene polymorphism in breast cancer risk or prognosis. The present study aims to investigate the probable role of SPARC genetic polymorphisms in development of breast cancer; their correlation with immunohistochemical expression of VEGF; and their association with breast cancer prognosis in the Egyptian population. The study sample included 238 Egyptian females who were divided into two groups: breast cancer group (118 patients) and healthy control group (120 subjects). SPARC gene single nucleotide polymorphisms rs3210714 and rs7719521 were genotyped. Allelic and genotypic frequencies were determined in both groups and association with ductal breast carcinoma, clinicopathological and prognostic characters were determined. For SPARC rs3210714, a significant difference was observed in the codominant model and both A and G alleles' frequencies between breast cancer patients and control group (P < 0.001). For rs7719521, a significant difference in codominant and dominant models as well as in both A and C alleles' frequencies between breast cancer and control groups (P < 0.001) was observed. A significant relation was found between SPARC rs3210714 and rs7719521, and immunohistochemical expression of VEGF (P = 0.046 and P = 0.027, respectively). SPARC rs7719521 showed a significant association with Nottingham Prognostic Index (NPI) (P = 0.032). The present study revealed that SPARC rs3210714 and rs7719521 polymorphisms are associated with breast cancer risk and its prognosis. Therefore, these SNPs may be useful in predicting the increased risk of breast cancer.

Idriss, N. K., H. G. Sayyed, A. Osama, and D. Sabry, "Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model.", Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, vol. 48, issue 5, pp. 2161-2171, 2018 Aug 16. Abstract

BACKGROUND/AIMS: The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced rat liver fibrosis.

METHODS: Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue.

RESULTS: Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group.

CONCLUSION: Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.

El-Rifaie, A. - A. A., D. Sabry, R. W. Doss, M. A. Kamal, and D. M. Abd El Hassib, "Heme oxygenase and iron status in exosomes of psoriasis patients.", Archives of dermatological research, 2018 Aug 13. Abstract

Psoriasis is an autoimmune skin disease characterized by hyperproliferation of keratinocytes due to interplay between keratinocytes and immune cells. Iron status plays an important role in modifying the function of the immune system. Heme oxygenase (HO), heme-degrading enzyme, plays important role in protective response to oxidative cellular stress. We aimed in this study to map the iron status and HO levels and declare the role HO enzyme in iron homeostasis and immune-modulation in psoriasis. Fifty-one patients with psoriasis and 50 age- and sex-matched healthy controls were enrolled in this study. 5 mL blood sample was withdrawn from each subject. Hepcidin, iron soluble transferring receptor (sTfR), and total iron binding capacity (TIBC) were estimated using ELISA technique and, HO-1 gene level was detected using RT-PCR (reverse transcription-polymerase chain reaction). Iron levels, TIBC, and hepcidin were significantly lower in cases compared to controls. On the contrary, sTfR and HO-1 were significantly over-expressed in cases compared to controls (p < 0.05 in all). HO-1 expression negatively correlated with PASI score and disease extent (%) (r = - 0.614-, p = 0.001; r = - 0.807-, p = 0.001 respectively). There were no significant associations between HO-1 expression and iron, TIBC, hepcidin, sTfR levels (p > 0.05 in all). Iron supplements for the patients with psoriasis are important to maintain haematopoiesis. The induction of HO-1 might have be a promising approach for the treatment of psoriasis through antioxidant ability, immunomodulatory role as well as its role in heme synthesis.

Aboushady, I. M., Z. A. Salem, D. Sabry, and A. Mohamed, "Comparative study of the osteogenic potential of mesenchymal stem cells derived from different sources", J Clin Exp Dent. , vol. 10, issue 1, pp. e7-13, 2018. dentists_2018.pdf
Mostafa-Hedeab, G., D. Sabry, G. M. Abdelaziz, M. Ewaiss, N. Adli, and W. Fathy, "Influence of Vitamin D Receptor Gene Polymorphisms on Response to Pegylated Interferon in Chronic Hepatitis B Egyptian Patients ", Reports of Biochemistry & Molecular Biology , vol. 6, issue 2, pp. 186-196, 2018. rbmb.pdf
Assem, M., S. Kamal, D. Sabry, N. Soliman, and R. M. Aly, "Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients", Open Access Macedonian Journal of Medical Sciences, pp. 1-6, 2018. moustafa_paper.pdf
2017
Hussien, N. I., N. Ebrahim, O. M. Mohammed, and D. Sabry, "Combination of Obestatin and Bone Marrow Mesenchymal Stem Cells Prevents Aggravation of Endocrine Pancreatic Damage in Type II Diabetic Rats.", International journal of stem cells, vol. 10, issue 2, pp. 129-143, 2017 Nov 30. Abstractdiabetes_and_obostatin.pdf

One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functionalcells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA-IR and HOMA-were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-, GLP-1 and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.

Gaafar, T., W. Attia, S. Mahmoud, D. Sabry, O. AbdElAziz, D. I. N. A. RASHEED, and H. Hamza, "Cardioprotective Effects of Wharton Jelly Derived Mesenchymal Stem Cell Transplantation in a Rodent Model of Myocardial Injury.", International journal of stem cells, vol. 10, issue 1, pp. 48-59, 2017 May 30. Abstract

Background: Whartons jelly-derived mesenchymal stem cells are a valuable alternative source that possess multipotent properties, easy to obtain and available in large scale compared to BMMSCs. We investigated the possibility of cardiac function improvement post isoproterenol induced cardiac injury in a rat model following human WJMSCs transplantation.

Materials and Methods: MSCs were extracted and cultured from cord WJ, characterized by morphology, Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO group (injected with 2 doses of isoproterenol) to induce myocardial injury and ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns, cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis of myocardial cryosections were studied.

Results and Conclusions: WJ derived MSCs were expanded for more than 14 passages while maintaining their undifferentiated state, were positive for MSC markers and were able to differentiate into adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs were capable of homing predominently in the ischemic myocardium. Cardiac markers were positively altered in stem cell treated group compared to ISO group. ECG and ECHO changes were improved with higher survival rate. WJMSCs could differentiate into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs infusion promoted cardiac protection and reduced mortality, emphasizing a promising therapeutic role for myocardial insufficiency.

Abuohashish, H. M., M. M. Ahmed, D. Sabry, M. M. Khattab, and S. S. Al-Rejaie, "Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.", Scientific reports, vol. 7, issue 1, pp. 2293, 2017 May 23. Abstract

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

Abuohashish, H. M., M. M. Ahmed, D. Sabry, M. M. Khattab, and S. S. Al-Rejaie, "ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.", Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 92, pp. 58-68, 2017 May 19. Abstract

The local role of the renin angiotensin system (RAS) was documented recently beside its conventional systemic functions. Studies showed that the effector angiotensin II (AngII) alters bone health, while inhibition of the angiotensin converting enzyme (ACE-1) preserved these effects. The newly identified Ang1-7 exerts numerous beneficial effects opposing the AngII. Thus, the current study examines the role of Ang1-7 in mediating the osteo-preservative effects of ACEI (captopril) through the G-protein coupled Mas receptor using an ovariectomized (OVX) rat model of osteoporosis. 8 weeks after the surgical procedures, captopril was administered orally (40mgkg(-1) d(-1)), while the specific Mas receptor blocker (A-779) was delivered at infusion rate of 400ngkg(-1)min(-1) for 6 weeks. Bone metabolic markers were measured in serum and urine. Minerals concentrations were quantified in serum, urine and femoral bones by inductive coupled plasma mass spectroscopy (ICP-MS). Trabecular and cortical morphometry was analyzed in the right distal femurs using micro-CT. Finally, the expressions of RAS peptides, enzymes and receptors along with the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were determined femurs heads. OVX animals markedly showed altered bone metabolism and mineralization along with disturbed bone micro-structure. Captopril significantly restored the metabolic bone bio-markers and corrected Ca(2+) and P values in urine and bones of estrogen deficient rats. Moreover, the trabecular and cortical morphometric features were repaired by captopril in OVX groups. Captopril also improved the expressions of ACE-2, Ang1-7, Mas and OPG, while abolished OVX-induced up-regulation of ACE-1, AngII, Ang type 1 receptor (AT1R) and RANKL. Inhibition of Ang1-7 cascade by A-779 significantly eradicated captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restored OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade and down-regulated OPG expression and ACE-2/Ang1-7/Mas pathway. In line with the clinical observations of the bone-preservative properties following ACE-1 inhibition, local activation of ACE-2/Ang1-7/Mas signaling and suppressed osteoclastogenesis seem responsible for the osteo-preservative effect of captopril, which could offers a potential therapeutic value in treatment of disabling bone and skeletal muscular diseases.

Sabry, D., A. E. Amir, R. H. Mahmoud, A. A. Abdelaziz, and W. Fathy, "Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C.", Journal of clinical medicine research, vol. 9, issue 5, pp. 416-425, 2017 May. Abstract

BACKGROUND: The current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients.

METHODS: Thirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR.

RESULTS: Our study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed.

CONCLUSION: LncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C.

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