Dr Mohammed Mahmoud Youssif

Human Immuno-deficiency virus (HIV) is still spreading all over the world. There are many routes through which the virus recognizes host cells by its envelope protein. One of these routes is through binding to glucose-regulated protein 78 (GRP78) which is overexpressed in stressed cells. In this study, we investigate the association between GRP78 and HIV envelope protein at four different binding sites (R1: C130-C162), (R2: C223-C252), (R3: C301-C335), and (R4: C388-C418) using a comprehensive in silico approach. Protein-protein docking and molecular dynamics simulations are conducted to evaluate the binding. Results indicate that the R4 region (C388-C418) is the potential binding site of the envelope protein to GRP78 on the cell surface with average binding energy of -12.20 ±2.0kcal/mol. The predicted findings open the gate towards further studies that could lead to the development of effective inhibitors that can alleviate viral recognition of the host cell and eradicate the viral infection.

Recent studies have shown that ferroptosis and cellular stress are related to triple-negative breast cancer (TNBC). This study used molecular dynamics simulations (MDS) and protein-peptide docking to pinpoint the glutathione peroxidase 4 (GPX4) protein and glucose-regulated protein 78 (GRP78) interaction site. The cyclic peptide Pep42 had previously been identified as a selective target for GRP78 on cancer cell membranes. Sequence alignments reveal that the GPX4 cyclic regions: R1 (C7-C16), R2 (C16-C29), R3 (C7-C29), and R7 (C93-C102) share sequence identity of 30.00 %, 30.77 %, 38.46 %, and 42.86 % against Pep42 peptide, respectively. Moreover, these four GPX4 regions have a grand average hydrophobicity index (GRAVY) of 1.2, 1.3, 1.2, and 1.5, respectively, similar to Pep42's GRAVY of 1.1. Additionally, they show strong binding affinities for GRP78 substrate binding domain β (SBDβ) (-6.81, -7.85, -8.77, and -7.25 kcal/mol, for R1, R2, R3, and R7, respectively). This study attempts to predict the binding site which needs further extensive experimental validation aimed at exploring potential disruptors of the GRP78 -GPX4 association. This would block ferroptosis resistance and chemoresistance in TNBC.

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Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired $\beta$-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced $\beta$-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1$\alpha$, IRE-1$\alpha$, and PPAR-$\gamma$, particularly IRE-1$\alpha$, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1$\alpha$, IRE-1$\alpha$, and PPAR-$\gamma$ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.

Herein, we report the controlled formation of silica/magnetite core–shell nanostructures and their potential utilization as sensors for the real-time detection of nickel ions with different concentrations in aqueous solutions. Nickel ions were presented in this work as example of contaminants. When coupled with quartz crystal microbalance (QCM) technology, the prepared core–shell nanostructures were found to exhibit high sensitivity and a prompt response toward the presence of nickel ions in an aqueous environment. The robust structure of the silica core and the increased surface area provided by the magnetite shell enhance the adsorption of metal ions. The pH of the solution was found to have a strong impact on the sensing performance of the core–shell structure. Optimal sensor performance was observed at neutral pH, demonstrating the potential of this system for continuous environmental monitoring of nickel ions pollutants.

Herein, we report the controlled formation of silica/magnetite core–shell nanostructures and their potential utilization as sensors for the real-time detection of nickel ions with different concentrations in aqueous solutions. Nickel ions were presented in this work as example of contaminants. When coupled with quartz crystal microbalance (QCM) technology, the prepared core–shell nanostructures were found to exhibit high sensitivity and a prompt response toward the presence of nickel ions in an aqueous environment. The robust structure of the silica core and the increased surface area provided by the magnetite shell enhance the adsorption of metal ions. The pH of the solution was found to have a strong impact on the sensing performance of the core–shell structure. Optimal sensor performance was observed at neutral pH, demonstrating the potential of this system for continuous environmental monitoring of nickel ions pollutants.