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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.

Motawi, T. M. K., S. A. EL-Maraghy, D. Sabry, and N. A. Mehana, "The expression of long non coding RNA genes is associated with expression with polymorphisms of HULC rs7763881 and MALAT1 rs619586 in hepatocellular carcinoma and HBV Egyptian patients.", Journal of cellular biochemistry, vol. 120, issue 9, pp. 14645-14656, 2019. Abstract

Long noncoding RNAs (lncRNAs), highly upregulated liver cancer (HULC), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), lncRNA-AF085935, and lncRNA-uc003wbd have been implicated in hepatocellular carcinoma (HCC). Single-nucleotide polymorphism (SNP) in HULC and MALAT1 are associated with HCC susceptibility. However, association between these SNPs and lncRNA-AF085935 and lncRNA-uc003wbd expression and their potential clinical value in differentiating HCC from both hepatitis B virus (HBV)-infected Egyptian patients and the healthy specimens have not been explored yet. In the present study, SNPs rs7763881 in HULC and rs619586 in MALAT1 were genotyped in 70 HBV-positive HCC, 70 HBV patients, and 70 healthy controls in Egyptian population and the level of serum lncRNA-AF085935 and lncRNA-uc003wbd of all the subjects was assayed by quantitative real-time polymerase chain reaction. HULC rs7763881 AC/CC genotype was significantly associated with decreased HCC risk. Similarly, AG/GG of MALAT1 rs619586 was associated with decreased HCC risk with a borderline significance. Serum lncRNA-AF085935 and lncRNA-uc003wbd levels were upregulated in HBV-positive HCC and HBV patients vs controls and discriminated these groups by receiver operating characteristic analysis. Patients carrying AC/CC genotype of rs7763881 and AG/GG of rs619586 had lower serum lncRNA-AF085935 and lncRNA-uc003wbd levels compared with AA genotype. In conclusion, genetic variants of lncRNA HULC and lncRNA MALAT1 are associated with the decreased susceptibility to HCC in HBV-persistent carriers and are correlated with serum lncRNA-AF085935 and lncRNAuc003wbd levels, two potential noninvasive diagnostic biomarkers for HCC.

Aziza, A. E. M. T., A. E. E. A. Nabia, A. E. M. Hamidc, D. Sabrya, H. M. Attaa, L. A. Raheda, A. Shamaae, and S. Mahfouzf, "Endothelial progenitor cells regenerate infracted myocardium with neovascularisation development.", Journal of Advanced Research, vol. 6, issue 2, pp. 133–144, 2015. Abstract

We achieved possibility of isolation, characterization human umbilical cord blood endothelial progenitor cells (EPCs), examination potency of EPCs to form new blood vessels and differentiation into cardiomyoctes in canines with acute myocardial infarction (AMI). EPCs were separated and cultured from umbilical cord blood. Their phenotypes were confirmed by uptake of double stains dioctadecyl tetramethylindocarbocyanine-labeled acetylated LDL and FITC-labeled Ulex europaeus agglutinin 1 (DILDL-UEA-1). EPCs of cord blood were counted. Human VEGFR-2 and eNOS from the cultured EPCs were assessed by qPCR. Human EPCs was transplanted intramyocardially in canines with AMI. ECG and cardiac enzymes (CK-MB and Troponin I) were measured to assess severity of cellular damage. Histopathology was done to assess neovascularisation. Immunostaining was done to detect EPCs transdifferentiation into cardiomyocytes in peri-infarct cardiac tissue. qPCR for human genes (hVEGFR-2, and eNOS) was done to assess homing and angiogenic function of transplanted EPCs. Cultured human cord blood exhibited an increased number of EPCs and significant high expression of hVEGFR-2 and eNOS genes in the culture cells. Histopathology showed increased neovascularization and immunostaining showed presence of EPCs newly differentiated into cardiomyocyte-like cells. Our findings suggested that hEPCs can mediate angiogenesis and differentiate into cardiomyoctes in canines with AMI.

CTO, chronic total occlusion; CAG, coronary angiography; AMI, acute myocardial infarction; DILDL-FITC labeled UEA-11, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine-labeled acetylated LDL (DiLDL,) and FITC-labeled Ulex europaeus agglutinin-1; MVD, multivessel disease; CFU, colony forming unit

Mostafa, T., L. A. Rashed, N. Nabil, H. Fouad, D. Sabry, and D. M. El-Saied, "Endothelial nitric oxide synthase gene polymorphism relationship with semen parameters and oxidative stress in infertile oligoasthenoteratozoospermic men", Urology, vol. 85, issue 5, pp. 1058-1061, 2015.
Lobna A Aly, H. E. - Menoufy, Hesham S Sadeq, A. Ragae, and D. Sabry, "Efficiency of systemic versus intralesional bone marrow-derived stem cells in regeneration of oral mucosa after induction of formocresol induced ulcers in dogs", Dental research journal, vol. 11, issue 2, pp. 212, 2014.
Abdelgawad, L. M., M. M. Abd El-Hamed, D. Sabry, and M. Abdelgwad, "Efficacy of Photobiomodulation and Metformin on Diabetic Cell Line of Human Periodontal Ligament Stem Cells through Pathway.", Reports of biochemistry & molecular biology, vol. 10, issue 1, pp. 30-40, 2021. Abstract

Background: Diabetes mellitus (DM) is a metabolic disorder resulting from hyperglycemia. Hyperglycemia contributes to oxidative stress, and the release of advanced glycation end products (AGEs) further promotes disease pathogenesis. Uncontrolled diabetes reflects great oral complications and affects human oral health. So, the present study aimed to assess the effects of photobiomodulation therapy (PBMT) and Metformin on proliferation and viability of human periodontal ligament stem cells (HPDLSCs) cultured in high glucose medium.

Methods: HPDLSCs were collected, isolated, and characterized and then divided into eight groups. Addition of extra glucose to diabetic groups 24 hours before cell irradiations. Metformin was added to half of the diabetic groups. Cells were irradiated with 808 nm diode laser 24, 48 hours. Cell viability was analyzed with MTT assay 24 hours post-irradiation to detect cell viability in each group. Real-time (PCR) was used to evaluate gene expression of and and the effect of PBMT on Pathway. ELISA reader was used to evaluating cell viability through (ROS, TNF-α, IL-10) protein levels after cell irradiation.

Results: Photobiomodulation at 1, 2, and 3 J/cm2 combined with metformin significantly promoted diabetic cell lines of HPDLSCs viability (in MTT assay and ELISA reader of ROS, TNF-α, IL-10 results) and gene expression of , and levels (p< 0.05).

Conclusion: photobiomodulation with 3 J/cm combined with metformin enhanced proliferation and viability of diabetic cell lines of HPDLSCs and thus could improve differentiation and function of diabetic cell lines of HPDLSCs with minimum side effects.

Roshdy, N. K., L. A. Rashed, D. Sabry, A. A. Hassouna, and F. M. Taha, Efficacy of mesenchymal stem cells in suppression of hepatocarcinorigenesis in rats: possible role of Wnt signaling, , 2011. Abstract
Zaahkouk, A. M. S., M. T. Abdel Aziz, A. M. Rezq, H. M. Atta, H. H. Fouad, H. H. Ahmed, D. Sabry, and M. H. Yehia, "Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function", International journal of impotence research, vol. 27, issue 1, pp. 9-15, 2015.
Aziz, M. T. A., M. F. El-Asmar, T. Mostafa, H. Atta, M. A. A. Wassef, H. H. Fouad, N. K. Roshdy, L. A. Rashed, and D. Sabry, "Effects of nitric oxide synthase and heme oxygenase inducers and inhibitors on molecular signaling of erectile function", Journal of Clinical Biochemistry and Nutrition, vol. 37, no. 3: 日本酸化ストレス学会 JCBN 事務局, pp. 103–111, 2005. Abstract
Aziz, A. E., M. Talaat, E. Asmer, M. Farid, T. Mostafa, H. Atta, S. Mahfouz, H. Fouad, L. Rashed, D. Sabry, et al., "Effects of Losartan, HO-1 Inducers or HO-1 Inhibitors on Erectile Signaling in Diabetic Rats", The journal of sexual medicine, vol. 6, no. 12: Wiley Online Library, pp. 3254–3264, 2009. Abstract
Aziz, M. T. A., M. F. El-Asmar, A. M. Rezq, M. A. A. Wassef, H. Fouad, N. K. Roshy, H. H. Ahmed, L. A. Rashed, D. Sabry, F. M. Taha, et al., "Effects of a novel curcumin derivative on insulin synthesis and secretion in streptozotocin-treated rat pancreatic islets in vitro", Chinese medicine, vol. 9, issue 1, pp. 1-12, 2014.
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., 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.

MT1, A. A., K. HM, E. H. A, R. NK, H. A. A. T. A. W. I. F. Rashed LA, Sabry D, Hassouna AA, T. F, and A. WI., "Effect of mesenchymal stem cells and a novel curcumin derivative on Notch1 signaling in hepatoma cell line.", Biomed Res Int, 2013. Abstract

This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs) and a novel curcumin derivative (NCD) on HepG2 cells (hepatoma cell line) and to investigate their effect on Notch1 signaling pathway target genes. HepG2 cells were divided into HepG2 control group, HepG2 cells treated with MSC conditioned medium (MSCs CM), HepG2 cells treated with a NCD, HepG2 cells treated with MSCs CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a NCD). Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time, reverse transcription-polymerase chain reaction (RT-PCR) in HepG2 cells. In addition, HepG2 proliferation assay was performed in all groups. Notch1 and its target genes (Hes1 and cyclin D1) were downregulated in all treated groups with more suppressive effect in the groups treated with both MSCs and NCD. Also, treated HepG2 cells showed significant decrease in cell proliferation rate. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can be considered as a therapeutic target in HCC.

Abdel Aziz, M. T., S. El-Haggar, T. Mostafa, H. Atta, H. Fouad, S. Mahfouz, L. Rashed, D. Sabry, A. Senbel, and G. A. Ali, "Effect of mesenchymal stem cell penile transplantation on erectile signaling of aged rats", Andrologia, vol. 42, no. 3: Wiley Online Library, pp. 187–192, 2010. Abstract
Mazen I Naga, M. A. Amin, Dina A Algendy, ahmed i elbadry, Mai M Fawzi, Ayman R Foda, Serag M Esmat, D. Sabry, L. A. Rashed, and M. Kamal, "Effect of Hemochromatosis gene mutation on HCV response to treatment in the Egyptian population", HEPATOLOGY, WILEY-BLACKWELL, 60, pp. 931A-932A, 2014.
Abdel, A. M. T., F. M. El-Asmar, T. Mostafa, H. Atta, H. H. Fouad, N. K. Roshdy, L. A. Rashed, E. A. Obaia, D. A. Sabry, A. A. T. Abdel, et al., "Effect of hemin and carbon monoxide releasing molecule (CORM-3) on cGMP in rat penile tissue.", The journal of sexual medicine, vol. 5, no. 2, pp. 336–343, 2008. Abstract
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.