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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.

Mokbel, A. N., O. S. El Tookhy, A. A. Shamaa, L. A. Rashed, D. Sabry, and A. M. Elsayed, "Homing and reparative effect of intra-articular injection of autologus mesenchymal stem cells in osteoarthritic animal model", BMC musculoskeletal disorders, vol. 12, no. 1: BioMed Central Ltd, pp. 259, 2011. Abstract
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Esmat, G. E., W. A. Akel, R. A. A. Aziz, A. Al Sayed Taha, D. Sabry, L. A. Rashed, A. Mostafa, A. Y. El Kazaz, and S. H. Ahmed, "Hepatitis C Viral Kinetic Changes in a Retrospective Cohort Study of Chronic Hepatitis C Virus Egyptian Patients on Pegylated Interferon and Ribavirin Therapy.", Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, vol. 36, issue 3, pp. 149-58, 2016 Mar. Abstract

The aim of this study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting treatment outcome. A retrospective analysis of 285 chronic hepatitis C virus (HCV) patients, encompassing genotypes 4 treated with peginterferon alpha-2a and ribavirin, was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with rapid virological response (RVR) were identified. The relative significance of RVR compared to other baseline factors for predicting sustained virological response was analyzed by multiple logistic regression analysis. Ninety-seven percent of the patients harbored HCV genotype 4a patients. The positive predictive value (PPV) of RVR for end-of-treatment response (ETR) was 88% and of early virological response (EVR) was 85%, which means that achievement of both RVR and EVR is a good positive predictive factor of response. The negative predictive value (NPV) of RVR for ETR was low and equals 26.77%, which means that approximately two-thirds of patients were able to achieve ETR despite not experiencing RVR, which means RVR is a bad negative predictive factor of response. The NPV of EVR for ETR was high and equals 90%, which means that only 10% of patients were able to achieve an ETR despite not experiencing EVR, which explains that EVR is a very good negative predictive factor of response. In univariate logistic regression analysis, which included the following: female gender, alanine aminotransferase, aspartate transaminase, α-fetoprotein, baseline HCV-RNA levels, grade of activity, stage of fibrosis, and positive HCV-RNA, by polymerase chain reaction at week 4, none of the previous factors was a significant independent factor of failure of response to treatment. The current study demonstrated that a viremia at week 4 has a good PPV, but it has a very low NPV. The NPV of EVR was more robust for ETR (90%). EVR is regarded as a robust indicator of treatment outcome, and a 12-week stopping rule for patients is strongly evident.

Abdel Aziz, M. T., T. Mostafa, H. Atta, O. Kamal, M. Kamel, H. Hosni, L. Rashed, D. Sabry, and F. Waheed, "Heme oxygenase enzyme activity in seminal plasma of oligoasthenoteratozoospermic males with varicocele", Andrologia, vol. 42, no. 4: Wiley Online Library, pp. 236–241, 2010. Abstract
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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.

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