MSA Repository "MSAR"

MSAR University's Digital Repository is a documentation and digitization of all university outcomes that are of effective value in the scientific and academic community and reflects the university's image, work, and effective contribution to society Through MSAR Digital Repository, the university managed to collect, store, archive and publish digital content - including documents, audio files, images and data sets - all in a safe place. MSAR is one of the strongest University Digital Repositories in Egypt and documented in the DSPACE community with its latest versions.

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    Expression of STAR and CYP19A1 Genes and Physiological Responses in Buffalo Granulosa Cells Under in vitro Heat Stress and Follicular Cysts Conditions
    (National Information and Documentation Centre, 2026-10-05) Arwa Adel Hozien; Gehad Tarek; Ayman A. Diab; Gehan Safwat; Nasser Ghanem; Fakhri E. El-Azzazi3
    Global warming and heat stress are major challenges affecting livestock productivity and reproductive performance. In Egypt, buffalo milk production has declined markedly in recent years due to climate change and the limited ability of buffaloes to tolerate high environmental temperatures. Heat stress impairs ovarian function by disrupting granulosa cell steroidogenesis, leading to reduced fertility. Therefore, this study aimed to evaluate the effect of heat stress on steroidogenic activity in normal buffalo granulosa cells and to compare it with granulosa cells isolated from cystic ovaries. Granulosa cells were aspirated from normal and cystic buffalo ovaries and cultured under standard conditions until reaching 80–90% confluence. Heat stress was induced in normal granulosa cells, by incubation at 42°C for 2 h, followed by a recovery period under normal culture conditions. Total RNA was extracted, quantified using a NanoDrop spectrophotometer, reverse transcribed into cDNA, and analyzed by quantitative real-time PCR (qRT-PCR). Relative gene expression was calculated using the 2−ΔΔCt method with GAPDH as the reference gene. Cell viability was assessed using a hemocytometer. Heat stress significantly reduced granulosa cell viability during both heat exposure and the recovery period. Moreover, the expression of STAR and CYP19A1 was significantly downregulated, accompanied by a significant decrease in steroid hormone concentrations. In contrast, granulosa cells isolated from cystic follicles showed significantly higher expression of steroidogenic genes and increased hormone concentrations compared with normal granulosa cells. These findings demonstrate that heat stress impairs steroidogenic activity in buffalo granulosa cells, whereas cystic follicles exhibit enhanced steroidogenic activity, highlighting the distinct effects of heat stress and cystic ovarian conditions on buffalo reproductive function.
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    Efficacy of chitosan hydrogel as an Adjunct to Scaling and Root Planning for reducing microbial count and inflammatory levels in gingival crevicular fluid of patients with chronic periodontitis: Randomized Clinical Trial
    (BioMed Central Ltd, 2026-10-06) Bassant Ashraf Badr; Ahmed Mohamed Aboulyazeed; Ahmed Mohamed Tawfik; Haidy Ehab Mousa; Tasneem Omar Yousef; Mohamed Ahmed Soliman; Moataz Elkholy
    Nonsurgical periodontal therapy presented in scaling and root planning (SRP) represents the gold standard management of chronic periodontal disease. On the other hand, inaccessible remaining subgingival biofilm and unmodulated host inflammatory response hinder the effectiveness of SRP. Thus, appropriate adjunct therapy should be considered. The natural polysaccharide chitosan has antimicrobial, anti-inflammatory, and biodegradable characteristics that nominated it as adjunct therapy to be chosen for potential efficacy. This randomized clinical trial aimed to evaluate the adjunctive chitosan hydrogel combined with SRP on subgingival microbial load and gingival crevicular fluid (GCF) inflammatory cytokine level over six weeks. A sample of 126 patients diagnosed with chronic periodontitis were equally randomly allocated to two groups; test group (SRP+ adjunct chitosan hydrogel alone, n = 63), and control group (SRP alone, n = 63). Outcomes were evaluated by collecting GCF samples from all participants at baseline and six weeks post-treatment. Colony-forming units per milliliter were used to quantify bacterial load, and ELISA assay was used to measure concentrations of interleukins 17 (IL-17) and 18 (IL-18) concentrations. At six weeks, the test group exhibited significantly greater reductions in microbial count (1.45 ± 0.4 × 10³ vs. 3.12 ± 0.6 × 10⁵ CFU/mL, p < 0.001) and in GCF concentrations of IL-17 (6.1 ± 1.2 vs. 14.2 ± 2.1 pg/µL, p < 0.001) and IL-18 (74.5 ± 12.4 vs. 105.8 ± 18.2 pg/µL, p < 0.001) when compared to SRP alone. Intra-pocket chitosan hydrogel application makedly reduced subgingival bacterial load and pro-inflammatory cytokines, indicating its potential as an effective local adjunctive therapy. The experiment was retrospectively registered with the Thai Clinical Trials Registry under the registration number TCTR20260829007 on August 29, 2026.
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    Nanoengineered Metformin Delivery System Targeting the AMPK/ PI3K/Akt/mTOR Pathway: A Potential Therapeutic Strategy Against Cisplatin-Induced Nephrotoxicity
    (Bentham Science Publishers, 2026-09-21) Shereen H. Noshi; Sherine M. Ibrahim; Omnia F. Hassan; Mervat Shafik Ibrahim
    Background: Cisplatin, an effective antitumor drug, is clinically limited by its dose-dependent nephrotoxicity. Rational nanocarrier design offers a strategy to improve drug delivery and minimize off-target effects. In this work, we developed a metformin-loaded mesoporous silica nanoparticle (MSNP) system, which was further coated with chitosan (CTS) and tailored into distinct sizes and geometries (elliptical vs. rounded) to enhance bioactivity, kidney targeting, and biocompatibility. Methods: Thirty-five rats were divided into seven groups after nephrotoxicity induction with cisplatin (2 mg/kg, intraperitoneally, once weekly for 4 weeks). Groups were treated orally with metformin, uncoated MET-MSNPs, or CTS-coated MET-MSNPs (elliptical and rounded; 40 mg/kg orally daily for 4 weeks. Biochemical markers, histology, and immunohistochemistry were performed to evaluate renal function and tissue remodeling. Results: Cisplatin exposure induced oxidative stress, elevated TGF-β1, TNF-α, IL-1β, and caspase- 3 levels, and caused renal dysfunction with marked histopathological damage. Both MET and CTS-MET-MSNPs mitigated these changes, with geometry- and coating-dependent improvements in renal biomarkers and tissue recovery. qPCR analysis showed that CTS-MET-MSNPs significantly downregulated cisplatin-induced AMPK/PI3K/Akt and restored mTOR expression. CTS-coated carriers showed superior anti-inflammatory, antioxidant, and anti-apoptotic effects compared with free MET. Discussion: In light of the available evidence, the design of our carrier system was guided by key parameters known to enhance kidney targeting. Rounded nanoparticles were selected since their geometry has been reported to promote efficient circulation, facilitate passage through the glomerular filtration barrier, and improve interaction with renal tissues. In addition, surface functionalization with chitosan was introduced to confer a positive charge, which is expected to favor electrostatic interactions with the negatively charged renal cell membranes. Accordingly, for our formulation strategy, rounded particles with a CH coating were deliberately chosen to maximize kidney selectivity. The morphological assessment of CTS-MET-MSNPs by TEM showed the successful formulation of the rounded nanoparticles with a defined mesoporous structure. Conclusion: This study demonstrated that the CTS-MET-MSNPs offer a superior strategy for mitigating cisplatin-induced acute kidney injury compared to free metformin. By optimizing the vehicle's architecture using rounded geometry to promote favorable glomerular filtration kinetics and applying a positively charged chitosan coating to exploit electrostatic binding with negatively charged renal membranes. We achieved highly site-specific kidney targeting. Morphological evaluation via TEM confirmed the successful fabrication of these rounded nanoparticles with a well- defined mesoporous framework. Biologically, the CTS-MET-MSNPs suppressed cisplatin-mediated oxidative stress, cellular damage, and histopathological degradation, outperforming free MET. Most notably, qPCR analysis revealed that this advanced nanoformulation achieved its potential anti- inflammatory, antioxidant, and anti-apoptotic properties by precisely downregulating the cisplatin- induced AMPK/PI3K/Akt pathway and restoring downstream mTOR expression. Collectively, these findings highlight CTS-MET-MSNPs as a highly potent, targeted nanomedicine capable of maximizing the clinical protective window of metformin against chemotherapeutic nephrotoxicity.
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    Development and optimisation using D-optimal design of dual-functionalized hyaluronic acid–chitosan-coated mesoporous silica nanoparticles for repurposed propranolol delivery in breast cancer: a proof-of-concept study
    (Taylor and Francis Ltd., 2026-10-02) Mervat Shafik Ibrahim; Nihal Mohamed Elmahdy Elsayyad; Shereen H. Noshi
    Drug repurposing combined with nanocarrier systems can accelerate cancer therapy development while reducing the time and cost of conventional drug discovery. We developed and optimised hyaluronic acid (HA)-chitosan (CH)-coated mesoporous silica nanoparticles (HA-CH-Prop-MSNPs) for delivery of the repurposed β-blocker propranolol. A two-stage D-optimal design optimised propranolol loading, then CH and HA coating, using particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulation (0.2% low-molecular-weight CH, 0.07% HA, 2 mg/mL propranolol, 10 mg/mL mesoporous silica nanoparticles) exhibited a particle size of 200.5 nm, PDI of 0.495, zeta potential of -25.7 mV, and EE of 91.2%. HA-CH coating provided controlled release and shifted the mechanism from near-Fickian diffusion toward an increasing contribution from polymer relaxation-controlled transport. Propranolol release was significantly higher at tumour-mimicking pH 5.5 than at physiological pH 7.4 across all formulations. Compared with free propranolol, HA-CH-Prop-MSNPs reduced the IC50 against MCF-7 breast cancer cells 2.8-fold while maintaining negligible carrier cytotoxicity. Under accelerated storage conditions (40 °C/75% RH), the formulation remained stable for six months, with less than a 2% reduction in EE. These findings provide proof of concept that HA-CH-coated mesoporous silica nanoparticles enhance the in vitro anticancer activity of repurposed propranolol through encapsulation and controlled release, laying the foundation for future investigation of HA-mediated cellular targeting.
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    Co-evolution of RcsD and RcsF shapes signal transduction in the enterobacteriaceae Rcs system
    (Public Library of Science, 2026-09-25) Abdelraouf O. Dapour; Moustafa Shehata; Rania Siam; Nahla A. Hussein
    Two-component systems (TCS) formed of sensor histidine kinases (HK) and response regulators (RR) are the primary prokaryotic signal transduction pathways. In Enterobacteriaceae, some TCS evolved architectural complexity, by integrating auxiliary proteins into the HK– RR dyad. The Regulator of Capsule Synthesis (Rcs), a conserved phosphorelay system in Enterobacteriaceae, recruits several auxiliary proteins, including an outer membrane lipoprotein, RcsF, which senses cell envelope threats and transduces the signal to downstream components. A second auxiliary protein located in the inner membrane, RcsD, transfers the phosphoryl group from the hybrid histidine kinase RcsC to the response regulator RcsB. RcsD is formed of a large periplasmic domain (Asn43-Asn308) sandwiched between two transmembrane helices and a cytosolic domain. For RcsD, the role and evolutionary benefit of maintaining a large periplasmic domain while the main phosphostransfer reaction occurs in the cytosol is not clear. Here, we show that RcsF and RcsD exhibit strong co-evolutionary coupling independent of host speciation (partial Mantel r = 0.950, p < 0.0001). Structure-guided docking and 500-ns molecular dynamics simulations predicted a stable interaction between RcsF and RcsD (MM-GBSA ΔG ≈ –95 kcal/mol), suggesting their functional coupling. Functional assays in Escherichia coli K12 MG1655 revealed that RcsD periplasmic domain represses basal Rcs activity in unstressed cells (~5-fold derepression) yet is essential for stress-induced activation (1.9–2.5-fold). Overexpression of rcsF beyond the chromosomal level induces Rcs signal activation only when the RcsD periplasmic domain is present. These findings demonstrate how co-evolution of an auxiliary protein generates novel regulatory function in the Rcs phosphorelay and provide insights into the role of RcsD periplasmic domain in stress signal transduction.