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.

Ebrahim, N., A. A. Dessouky, O. Mostafa, A. Hassouna, M. M. Yousef, Y. Seleem, E. A. E. A. M. El Gebaly, M. M. Allam, A. S. Farid, B. A. Saffaf, et al., "Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway.", Stem cell research & therapy, vol. 12, issue 1, pp. 392, 2021. Abstract

BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway.

METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed.

RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups.

CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.

Eldin, S. A., D. Sabry, M. Abdelgwad, and M. A. Ramadan, "Some health effects of work-related stress among nurses working in critical care units.", Toxicology and industrial health, vol. 37, issue 3, pp. 142-151, 2021. Abstract

Occupational stress is a major health problem among nurses. Critical care nurses appear to experience more stress at work compared to others. Stress is associated with multiple system disorders, hormonal, and immunological disturbances, and genetic effects. The aim of our study was the detection of health effects of work-related stress and to investigate the link between stress and immune response, alterations of hormones, and expression of micro-RNA (miRNA) among critical care nurses. An exposed 80 critical care nurses matched to 80 controls were involved in our study. Full history, psychological assessment using the General Health Questionnaire (GHQ12) and a complete clinical examination were done for both groups. Serum interleukin (IL)-6, IL-10, luteinizing hormone (LH), follicle-stimulating hormone, thyroid-stimulating hormone (TSH), free triiodothyronine, and free thyroxine (FT4) were measured by enzyme-linked immunosorbent assay, micro-RNA26, and 142 extractions. The exposed group had a mean age of 41 ± 10 years old and mean work duration of 22 ± 9.7 years, matched to 80 controls. The exposed group (32.5%) was associated with severe psychological distress (GHQ scores > 20) compared to only 5% among controls. In addition, the exposed group had a significantly higher level of miRNA 26, miRNA 142, TSH, LH, and IL-6 when compared to the control group. However, there a significantly lower level of FT4 among the exposed group compared to the control group, there were no statistically significant differences between the studied participants regarging FT3,FSH and IL-10 levels. Stress is prevalent among critical care nurses and is reflected on their psychological health with an increase in inflammatory cytokines and disturbances in endocrine functions.

Ali, M. M., S. A. Khater, A. A. Fayed, D. Sabry, and S. F. Ibrahim, "Apoptotic endocrinal toxic effects of perchlorate in human placental cells.", Toxicology reports, vol. 8, pp. 863-870, 2021. Abstract

Background: Perchlorate is a strong oxidizing agent and has many adverse health effects. This study investigated the potential oxidative, apoptotic, and endocrinal toxic effects of perchlorate in human placenta-derived mesenchymal stem cells (HP-MSCs).

Methods: HP-MSCs were treated with two doses of perchlorate (5 and 15 μg/L) for three days. The perchlorate's effects were detected by histopathological examination, aromatase/CYP19 A1 activity, reactive oxygen species production (ROS), and Caspase-3 expression.

Results: The highest perchlorate concentration (15 μg/L) caused significant placental histopathological changes. The placental cell viability was significantly affected by a significant increase in ROS generation; caspase-3 expression, and a significant reduction of CYP 19 activity. Despite the slight induction effect of the lowest perchlorate concentration (5 μg/L) on caspase 3 expression, CYP 19 activity, and ROS generation, it did not affect placental cellular viability.

Conclusion: This study suggested that perchlorate could modulate aromatase activity and placental cytotoxicity. The continuous monitoring of the actual perchlorate exposure is needed and could be cost-effective.

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.

Baki, N. A. M., Z. O. Nawito, N. M. S. Abdelsalam, D. Sabry, H. Elashmawy, N. A. Seleem, A. A. A. - A. Taha, and M. E. Ghobashy, "Does Intra-Articular Injection of Platelet-Rich Plasma Have an Effect on Cartilage Thickness in Patients with Primary Knee Osteoarthritis?", Current rheumatology reviews, 2021. Abstract

OBJECTIVES: To determine the effect of intra-articular injection of platelet-rich plasma (PRP) in patients with primary knee osteoarthritis (OA) by clinical evaluation and ultrasonographic (US) assessment of cartilage thickness.

PATIENTS AND METHODS: A total of 100 patients with mild to severe primary knee OA using the Kellgren-Lawrence (K-L) grading scale were included and divided into two groups. Group I included 50 patients who were given two intra-articular knee injections of PRP, 1 week apart; Group II included 50 patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and chondroprotective drugs. Functional assessment of all OA patients done using the basal WOMAC score, at 2 and 6 months.US assessment of femoral condylar cartilage thickness was conducted basally and at 6 months.

RESULTS: Improvement of WOMAC score was observed at 2 and 6 months in Group I following PRP injection compared to Group II (p values < 0.001), The improvement of WOMAC in Group I occurred in all severity degrees of OA (p < 0.001). Moreover, a significant increase in cartilage thickness at the intercondylar area (ICA) at 6 months relative to baseline assessment by US in Group I (p = 0.041) was found.

CONCLUSION: Treatment with PRP injections can reduce pain and improve knee function in patients with various degrees of articular degeneration. Further studies are needed to clarify the anabolic effect of PRP on the articular cartilage.

Harb, I. A., H. Ashour, D. Sabry, D. F. El-Yasergy, W. M. Hamza, and A. Mostafa, "Nicorandil prevents the nephrotoxic effect of cyclosporine-A in albino rats through modulation of HIF-1α/VEGF/eNOS signaling.", Canadian journal of physiology and pharmacology, vol. 99, issue 4, pp. 411-417, 2021. Abstract

Despite that cyclosporine-A (CsA) is a widely used immunosuppressive drug, its nephrotoxic effect limits its long-term administration. Herein we tried to investigate its renal effect on endothelial dysfunction targeting the hypoxia-inducible factor (HIF-1α) / vascular endothelial growth factor (VEGF) / endothelial nitric oxide synthase (eNOS) pathway and the possible modulation by nicorandil. Eight groups of adult male Wistar rats were included: (1) control; (2) vehicle group (received oil); (3) glibenclamide 5 mg·kg·day administered orally; (4) nicorandil 10 mg·kg·day administered orally; (5) CsA 25 mg·kg·day administered orally; (6) combined administration of CsA and nicorandil; (7) glibenclamide was added to CsA; and (8) both CsA and nicorandil were combined with glibenclamide. The treatment continued for six weeks. Combined nicorandil with CsA improved renal function deterioration initiated by CsA. CsA decreased the renal expression levels ( < 0.001) of HIF-1α, eNOS, and VEGF, inducing endothelial dysfunction and triggering inflammation, and upregulated the profibrotic marker transforming growth factor (TGF-β). Nicorandil fixed the disturbed HIF-1α/VEGF/eNOS signaling. Nicorandil corrected the renal functions, confirmed by the improved histological glomerular tuft retraction that was obvious in the CsA group, without significant influence by glibenclamide. Proper protection from CsA-induced nephrotoxicity was achieved by nicorandil. Nicorandil reversed the disturbed HIF-1α/VEGF/eNOS pathway created by CsA.

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.

Shousha, H. I., R. Fouad, T. M. Elbaz, D. Sabry, M. M. Nabeel, A. H. Abdelmaksoud, A. M. E. Sharkawy, Z. A. Soliman, G. Habib, and A. O. Abdelaziz, "Predictors of recurrence and survival of hepatocellular carcinoma: A prospective study including transient elastography and cancer stem cell markers.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 21, issue 2, pp. 95-101, 2020. Abstract

BACKGROUND AND STUDY AIMS: To investigate whether the measurement of liver stiffness (LSM) using fibroscan and the serum Cancer Stem Cells (CSC): Ep-CAM and cytokeratin-19, could predict the recurrence of hepatocellular carcinoma (HCC) and their impact on clinical outcome and overall survival.

PATIENTS AND METHODS: This is a prospective study, including 179 HCV-related HCC patients. All patients were treated following the BCLC guidelines. All HCC patients had transient elastography, measurements of Ep-CAM and cytokeratin-19 before and six months post-treatment. We looked for predictors of recurrence and performed a survival analysis using Kaplan-Meier estimates.

RESULTS: TACE was the most common procedure (77.1%), followed by microwave ablation (15.6%). Complete ablation was achieved in 97 patients; 55 of them developed HCC recurrence. After treatment, LSM increased significantly with a significant reduction in CSCs levels in complete and partial response groups. The median time to observe any recurrence was 14 months. LSM increased significantly post-treatment in patients with recurrence versus no recurrence. Higher levels of CSCs were recorded at baseline and post-treatment in patients with recurrence but without statistical significance. We used univariate analysis to predict the time of recurrence by determining baseline CK-19 and platelet levels as the key factors, while the multivariate analysis determined platelet count as a single factor. The univariate analysis for prediction of overall survival included several factors, LSM and EpCAM (baseline and post-ablation) among them, while multivariate analysis included factors such as Child score B and incomplete ablation.

CONCLUSION: Dynamic changes were observed in LSM and CSCs levels in response to HCC treatment and tumour recurrence. Child score and complete ablation are factors that significantly affect survival.

Abdelgwad, M., M. Ewaiss, D. Sabry, W. A. Khalifa, Z. M. Altaib, and M. alhelf, "Comparative study on effect of mesenchymal stem cells and endothelial progenitor cells on treatment of experimental CCL4-induced liver fibrosis.", Archives of physiology and biochemistry, pp. 1-10, 2020. Abstract

We speculated impacts of BM-MSCs and UC-EPCs on reversal of hepatic injury induced by carbon tetrachloride (CCl4). Fifty adult rats were divided into five groups: control group, CCl4A group, CCl4B group, CCl4/BM-MSCs group and CCl4/UC-EPCs group. Blood samples were driven to measure concentration of albumin and ALT. Quantitative expression of HGF, TGF-β, MMP-2, and VEGF were assessed by PCR. Histological and immunohistochemistry examination of the liver tissue were performed. There was elevating albumin ( < .05) and reducing ALT ( < .05) concentrations in groups treated with BM-MSCs and UC-EPCs compared to untreated CCL4A&B groups. UC-EPCs treated group have significantly higher MMP-2 and VEGF ( < .01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BMMSCs in increasing gene expression of HGF ( < .05) and immunohistochemistry of α-SMA and Ki-67 ( < .01). BM-MSCs have significantly lower TGF-β ( < .00) compared to UC-EPCs. This study highlighted on liver regeneration role of both UC-EPCs and BM-MSCs in liver fibrosis.

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