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Sabry, D., A. Mohamed, M. Monir, and H. A. Ibrahim, "The Effect of Mesenchymal Stem Cells Derived Microvesicles on the Treatment of Experimental CCL4 Induced Liver Fibrosis in Rats.", International journal of stem cells, vol. 12, issue 3, pp. 400-409, 2019. Abstract

Background and Objectives: The release of microvesicles (MVs) from mesenchymal stem cells (MSCs) has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. We investigated the effect of administration of MSC-MVs on the therapeutic potential of carbon tetrachloride (CCL) induced liver fibrosis in rats.

Methods: Our work included: isolation and further identification of bone marrow MSC-MVs by transmission electron microscopy (TEM). Liver fibrosis was induced in rats by CCl4 followed by injection of prepared MSC-MVs in injured rats. The effects of MSC-MVs were evaluated by biochemical analysis of liver functions, RNA gene expression quantitation for collagen-1, transforming growth factor (TGF-), interleukin-1 (IL-1), vascular endothelial growth factor (VEGF) by real time reverse transcription PCR (RT-PCR) techniques. Finally histopathological examination of the liver tissues was assessed for all studied groups.

Results: BM-MSC-MVs treated group showed significant increase in serum albumin levels, VEGF quantitative gene expression (p<0.05), while it showed a significant decrease in serum alanine transaminase (ALT) enzyme levels, quantitative gene expression of TGF-, collagen-1, IL-1 compared to CCL fibrotic group (p<0.05). Additionally, the histopathological assessment of the liver tissues of BM-MSC-MVs treated group showed marked decrease in the collagen deposition & improvement of histopathological picture in comparison with CCL fibrotic group.

Conclusions: Our study demonstrates that BM-MSC-MVs possess anti-fibrotic, anti-inflammatory, and pro-angiogenic properties which can promote the resolution of CCL induced liver fibrosis in rats.

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., 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.

Sabry, D., Olfat Noh, and M. Samir, "Comparative Evaluation for Potential Differentiation of Endothelial Progenitor Cells and Mesenchymal Stem Cells into Endothelial-Like Cells.", International journal of stem cells, vol. 9, issue 1, pp. 44-52, 2016 May 30. Abstract

Understanding the mechanisms of vascular remodeling could lead to more effective treatments for ischemic conditions. We aimed to compare between the abilities of both human Wharton jelly derived mesenchymal stem cells (hMSCs) and human cord blood endothelial progenitor cells (hEPCs) and CD34⁺ to induce angiogenesis in vitro. hMSCs, hEPCs, and CD34⁺ were isolated from human umbilical cord blood using microbead (MiniMacs). The cells characterization was assessed by flow cytometry following culture and real-time PCR for vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrand factor (vWF) to prove stem cells differentiation. The study revealed successful isolation of hEPCs, CD34⁺, and hMSCs. The hMSCs were identified by gaining CD29⁺ and CD44⁺ using FACS analysis. The hEPCs were identified by having CD133⁺, CD34⁺, and KDR. The potential ability of hEPCs and CD34⁺ to differentiate into endothelial-like cells was more than hMSCs. This finding was assessed morphologically in culture and by higher significant VEGFR2 and vWF genes expression (p<0.05) in differentiated hEPCs and CD34⁺ compared to differentiated hMSCs. hEPCs and CD34⁺ differentiation into endothelial-like cells were much better than that of hMSCs.

Sabry, D., S. Marzouk, R. Zakaria, H. A. Ibrahim, and M. Samir, "The effect of exosomes derived from mesenchymal stem cells in the treatment of induced type 1 diabetes mellitus in rats.", Biotechnology letters, 2020. Abstract

AIM: The aim of the current study was to evaluate the therapeutic and regenerative effects of MSCs derived exosomes in the treatment of type 1 DM and to compare its effects with MSCs themselves. The experiment was done on forty albino rats grouped as follows, group (1): Ten healthy rats, group (2): Ten induced type 1 DM rats, group (3): Ten induced type 1 DM rats received exosomes intraperitoneally, and group (4): Ten induced type 1 DM rats received MSCs intraperitoneally. Serum glucose and plasma insulin levels were assessed weekly. QRT-PCR was done to assess regeneration of pancreatic beta cells by measuring insulin, Pdx1, Smad2, Smad3 and TGFβ genes. Additionally, histopathological and immune-histochemical examinations were done to confirm pancreatic tissue regeneration.

RESULTS: Regarding the assessed genes (insulin, Pdx1, Smad2, Smad3 and Tgfβ) gene expression in MSCs treated group showed significant increase compared to diabetic group (p value < 0.001) and gene expression in exosomes treated group was increased significantly compared to diabetic and MSCs treated groups (p value < 0.001). Histopathological and immune-histochemical examination revealed regeneration of pancreatic islets in both treated groups.

CONCLUSION: MSCs Derived exosomes showed superior therapeutic and regenerative results than MSCs themselves.

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, 2019. 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.

Sabry, D., O. Nouh, S. Marzouk, and A. Hassouna, "Pilot study on molecular quantitation and sequencing of endometrial cytokines gene expression and their effect on the outcome of in vitro fertilization (IVF) cycle", Journal of Advanced Research, vol. 5, issue 5, pp. 595-600, 2014.
Sabry, D., N. Aboraia, and M. Samir, "A potential association between psoriasin to rs4819554 of IL-17RA gene polymorphism in psoriasis Egyptian patients.", Archives of dermatological research, vol. 312, issue 4, pp. 273-281, 2020. Abstract

Interleukin 17 (IL-17) is one of the pro-inflammatory cytokine. Psoriasin is a noticeably over-expressed protein found in the skin lesions of psoriatic patients. Our current study was planned to examine the association of (- 947 A/G) single nucleotide polymorphism (SNP) in IL-17RA promoter region (rs4819554) with psoriasis susceptibility in Egyptian psoriatic patients. Our study included 100 patients and 100, age as well as sex matched, control groups. IL-17RA SNP association was studied using allelic discrimination. RT-qPCR and ELISA were done to assess IL-17 expression. ELISA was performed to assess psoriasin expression. Our study showed a significant association between IL-17 rs4819554 SNP and psoriasis risk, evidenced by higher G allele and AG genotype frequencies in psoriatic patients when compared to controls (allelic: OR 2.283, 95% CI 1.321-3.946, p = 0.003, and genotype: OR 3.026, 95% CI 1.356-6.752, p = 0.007). Additionally, serum psoriasin level was significantly increased when comparing psoriatic patients to controls (p = 0.0003). Moreover, significant increase in IL 17 gene and protein level in AA, AG psoriatic genotypes compared to the corresponding genotypes in normal control (p = 0.0004). IL-17 rs4819554 is significantly associated with psoriasis, and with psoriasin level, in the Egyptian population.

Sabry, D., A. Osama, N Idriss, and M. Magdy, "Comparative study between the effects of human CD34+ and rat bone marrow mesenchymal stem cells on amelioration of CCL4 induced liver fibrosis", FEBS JOURNAL, France WILEY-BLACKWELL, 281, pp. 222-222, 2014.
Sabry, D., O. O. Abdelaleem, A. M. El Amin Ali, R. A. Mohammed, N. D. Abdel-Hameed, A. Hassouna, and W. A. Khalifa, "Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study.", Molecular biology reports, 2019 Feb 01. Abstract

The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.

Sabry, D., M. A. S. Al-Ghussein, G. Hamdy, A. Abul-Fotouh, T. Motawi, A. Y. El Kazaz, A. Eldemery, and M. Shaker, "Effect of vitamin D therapy on interleukin-6, visfatin, and hyaluronic acid levels in chronic hepatitis C Egyptian patients", Therapeutics and clinical risk management, vol. 11, pp. 279, 2015.
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.

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.

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.

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.

Salama, M. K., D. Sabry, MA Al-Ghussein, R. Ahmed, S. A. Allah, F. M. Taha, W. Fathy, M. S. Wadie, M. Nabih, A. Abul-Fotouh, et al., "Molecular detection of monocyte chemotactic protein-1 polymorphism in spontaneous bacterial peritonitis patients", World journal of gastroenterology: WJG, vol. 20, issue 33, pp. 11793-11799, 2014.
Salem, N., M. Y. Salem, M. M. Elmaghrabi, M. A. Elawady, M. A. Elawady, D. Sabry, A. Shamaa, A. - H. H. Elkasapy, N. Ibrhim, and A. E. Amir, "Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury?", Neural regeneration research, vol. 12, issue 12, pp. 2050-2058, 2017 Dec. Abstractneuralregenres.pdf

Methylprednisolone (MP) is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury (SCI). Vitamin C (VC) is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells (BMMSCs), as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups: control, SCI (SCI induction by weight-drop method), MP (SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times), VC (SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days), MP + VC (SCI induction, followed by administration of MP and VC as the former), BMMSCs (SCI induction, followed by injection of 3 × 10BMMSCs at the injury site), and BMMSCs + VC (SCI induction, followed by BMMSCs injection and VC administration as the former). Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.

Sayyed, H. G., A. Osama, N. K. Idriss, D. Sabry, A. S. Abdelrhim, and R. Bakry, "Comparison of the therapeutic effectiveness of human CD34(+) and rat bone marrow mesenchymal stem cells on improvement of experimental liver fibrosis in Wistar rats.", International journal of physiology, pathophysiology and pharmacology, vol. 8, issue 3, pp. 128-139, 2016. Abstract

BACKGROUND AND OBJECTIVE: Human umbilical cord blood (UCB) cells and bone marrow mesenchymal stem cells (BM-MSCs) have numerous advantages as grafts for cell transplantation. We hypothesized differing impacts of human UCB cells and rat BM-MSCs on reversal of hepatic injury and revival of liver function in carbon tetrachloride (CCl4)-induced liver fibrosis.

METHODS: Forty rats were divided into 4 groups; control group, CCl4 group, CCl4/CD34(+) group and CCl4/BM-MSCs group. Blood samples were driven from rats at 4, 8 and 12 weeks to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of collagen Iα, TGF-β, α-SMA, albumin, MMP-2, MMP-9 and TNF-α were assessed by polymerase chain reaction. Histopathological examination of the liver tissue was performed. GFP labeled cells were detected in groups injected with stem cells.

RESULTS: Regarding liver function, CD34(+) were more efficient than BM-MSCs in elevating albumin (P<0.05) and reducing ALT (P<0.05) concentrations. Concerning gene expression, CD34(+) were more effective than BM-MSCs in reducing gene expressions of collagen Iα (P<0.01), TGF-β1 (P<0.01) and α-SMA (P<0.01). Both CD34(+) and BM-MSCs have the same efficacy in reducing TNF-α (P<0.001 and P<0.01, respectively). Furthermore, CD34(+) were more valuable than BM-MSCs in increasing gene expression of albumin (P<0.05) and MMP-9 (P<0.01).

CONCLUSION: Taken together; human UCB CD34(+) stem cells were more efficient in improvement of experimental liver injury than BM-MSCs. This study highlighted an important role of human UCB CD34(+) stem cells in liver fibrosis therapy.

SH Ahmad, D. Sabry, Olfat Noh, and M. Samir, "Potential proliferative effect of lipopolysaccharide preconditioning on human umbilical cord blood-derived endothelial progenitor cells", African Journal of Biotechnology, vol. 14, issue 13, pp. 1167-1173, 2015.
Shaimaa M Masloub, Mohamed H Elmalahy, D. Sabry, Wael S Mohamed, and S. H. Ahmed, "Comparative evaluation of PLGA nanoparticle delivery system for 5-fluorouracil and curcumin on squamous cell carcinoma", Archives of oral biology, vol. 64, pp. 1-10, 2016.
Shehab, H., D. Sabry, M Mokhtar, M. Mabrouk, W. Elakel, M. Tawfik, Y Korriem, and G. Esmat, "P1101 THE VITAMIN D RECEPTOR FOKI GENE POLYMORPHISM IS ASSOCIATED WITH POOR RESPONSE TO TREATMENT IN CHRONIC HEPATITIS C GENOTYPE 4", HEPATOLOGY, WILEY-BLACKWELL, 60, pp. S445, 2014.
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.

Sherif, I. O., N. H. Al-Shaalan, and D. Sabry, "Extract Alleviates Methotrexate-Induced Renal Injury: New Impact on PI3K/Akt/mTOR Signaling and MALAT1 Expression.", Biomolecules, vol. 9, issue 11, 2019. Abstract

Renal injury induced by the chemotherapeutic agent methotrexate (MTX) is a serious adverse effect that has limited its use in the treatment of various clinical conditions. The antioxidant activity of extract (GB) was reported to mitigate renal injury induced by MTX. Our research was conducted to examine the nephroprotective role of GB versus MTX-induced renal injury for the first time through its impact on the regulation of phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling together with the renal level of TGF-β mRNA and long non-coding RNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) expression. A group of adult rats was intraperitoneally (ip) injected with MTX 20 mg/kg as a single dose to induce kidney injury (MTX group). The other group of rats was orally administered with GB 60 mg/kg every day for 10 days (GB+ MTX group). The MTX increased the serum creatinine and urea levels, renal TGF-β mRNA and MALAT1 expression, in addition to dysregulation of the PI3K/Akt/mTOR signaling when compared with normal control rats that received saline only (NC group). Moreover, renal damage was reported histopathologically in the MTX group. The GB ameliorated the renal injury induced by MTX and reversed the changes of these biochemical analyses. The involvement of PI3K/Akt/mTOR signaling and downregulation of TGF-β mRNA and MALAT1 renal expressions were firstly reported in the nephroprotective molecular mechanism of GB versus MTX-induced renal injury.

Sherif, I. O., N. H. Al-Shaalan, and D. Sabry, "Neuroprotective Potential of Bone Marrow-Derived Mesenchymal Stem Cells Following Chemotherapy.", Biomedicines, vol. 9, issue 7, 2021. Abstract

Cisplatin (CP) is extensively used in the medical oncology field for malignancy treatment, but its use is associated with neurological side effects that compromise the patients' quality of life. Cytotherapy is a new treatment strategy for tissue damage that has recently emerged. The use of bone marrow-derived mesenchymal stem cells (BM-MSCs) was investigated for its therapeutic potential against CP-induced chemobrain as well as various models of brain damage. This study was carried out to elucidate, for the first time, the role of the intravenous injection (IV) of BM-MSCs against CP-induced neurotoxicity in a rat model through investigation of the parameters of oxidative stress, inflammation, and apoptosis in brain tissue. A rat model of neurotoxicity was generated by intraperitoneal injection of 7.5 mg/kg CP while 2 × 10 BM-MSCs was given by IV as a therapeutic dose. Injection of CP led to a significant rise in malondialdehyde and nitric oxide levels accompanied by a marked depletion of superoxide dismutase and reduced glutathione content in brain tissue in comparison to the normal control (NC) rats. Furthermore, a remarkable rise in the brain levels of inflammatory cytokines interleukin (IL)-1β and IL-6, together with the expression of apoptotic marker caspase-3, and the downregulation of the brain expression of proliferating marker Ki-67 in brain tissue were detected in the CP group compared to the NC group. Histopathological alterations were observed in the brain tissue of the CP group. BM-MSCs mitigated the biochemical and histopathological alterations induced by CP without affecting brain cell proliferation. BM-MSCs could be used as a promising neuroprotective agent against CP-induced neurotoxicity.

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