Fayez Alsulaimani

King Abdulaziz University

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Prediction of promiscuous multiepitope-based peptide vaccine against RdRp of rotavirus using immunoinformatics studies

Revista do Instituto de Medicina Tropical de São Paulo (2024)

Hailah M. Almohaimeed Ahmed M. Abdulfattah Fayez Alsulaimani Aisha Alshammary Mohammad Osama Almohaini

Rotavirus, a dsRNA virus in the Reoviridae family, shows a segmented genome. The VP1 gene encodes the RNA-dependent RNA polymerase (RdRp). This study aims to develop a multiepitope-based vaccine targeting RdRp using immunoinformatic approaches. In this study, 100 available nucleotide sequences of VP1-Rotavirus belonging to different strains across the world were retrieved from NCBI database. The selected sequences were aligned, and a global consensus sequence was developed by using CLC work bench. The study involved immunoinformatic approaches and molecular docking studies to reveal the promiscuous epitopes that can be eventually used as active vaccine candidates for Rotavirus. In total, 27 highly immunogenic, antigenic, and non-allergenic T-cell and B-cell epitopes were predicted for the Multiepitope vaccine (MEV) against rotavirus. It was also observed that MEV can prove to be effective worldwide due to its high population coverage, demonstrating the consistency of this vaccine. Moreover, there is a high docking interaction and immunological response with a binding score of -50.2 kcal/mol, suggesting the vaccine's efficacy. Toll-like receptors (TLRs) also suggest that the vaccine is physiologically and immunologically effective. Collectively, our data point to an effective MEV against rotavirus that can effectively reduce viral infections and improve the health status worldwide.

Rotavirus vaccine

Peptide vaccine

10.1590/s1678-9946202466055

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Investigating the potential neuroprotective benefits of taurine and Dihydrotestosterone and Hydroxyprogesterone levels in SH-SY5Y cells

Frontiers in Aging Neuroscience (2024)

Hailah M. Almohaimeed Amany I. Almars Fayez Alsulaimani Ahmed M. Basri Norah A. Althobaiti

Background Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer’s disease (AD) is a commonly occurring type of dementia, which becomes more prevalent as people age. This experiment aimed to assess the neuroprotective effects of taurine on SH-SY5Y cells by examining its impact on Dihydrotestosterone (DHT), Dihydroprogesterone (DHP), as well as the expression of miRNA-21 and miRNA-181. Methods The effects of various taurine concentrations (0.25, and 0.75 mg/mL), and LPS (0.1, and 12 mg/mL) on the SH-SY5Y cell line were assessed using the MTT assay. The levels of DHT and DHP were quantified using an ELISA kit. Additionally, the expression levels of miRNA-181 and miRNA-21 genes were examined through Real-Time PCR analysis. Results The results of the MTT assay showed that treatment with taurine at concentrations of 0.25, and 0.75 mg/mL reduces the toxicity of LPS in SH-SY5Y cells. ELISA results indicated that taurine at a concentration of 0.25, and 0.75 mg/mL significantly elevated DHT and DHP hormones in the SH-SY5Y cell line compared to the untreated group ( p < 0.01). The expression levels of IL-1β and IL-6 were decreased under the influence of LPS in SH-SY5Y cells after taurine treatment (p < 0.01). Gene expression analysis revealed that increasing taurine concentration resulted in heightened expression of miRNA-181 and miRNA-21, with the most significant increase observed at a concentration of 0.75 mg/mL ( p < 0.001). Conclusion Our study findings revealed that the expression of miRNA-181 and miRNA-21 can be enhanced by taurine. Consequently, exploring the targeting of taurine, miRNA-181, and miRNA-21 or considering hormone therapy may offer potential therapeutic approaches for treating AD or alleviating severe symptoms. Nonetheless, in order to fully comprehend the precise mechanisms involved, additional research is required.

SH-SY5Y

MTT assay

Dihydrotestosterone

10.3389/fnagi.2024.1379431

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Measurement and Modeling of Zolpidem Solubility in Supercritical Carbon Dioxide: Effect of Two Cosolvents

Journal of Chemical & Engineering Data (2024)

Zamzam Alhuwaymil Khadeejah Alsolami Muath M. Almisbahi Mohammed M. Alsulami Maya M. Alsulami

Obtaining data on the solubility of zolpidem, a sedative–hypnotic drug, in supercritical CO2 (scCO2) is a crucial step in the development of an efficient supercritical process designed to formulate an effective drug delivery system for this medication. The current investigation entailed determining the solubility of this substance in scCO2 across a range of temperatures (308.0, 318.0, 328.0, 338.0, and 348.0 K) and pressure values between 17 and 41 MPa. Furthermore, the research delved into assessing the impact of two cosolvents, DMSO and ethanol, on the supercritical solubility of this drug under the given conditions. The solubility of zolpidem in scCO2 was within the mole fraction range of 1.19 × 10–4–3.23 × 10–4. However, when ethanol and DMSO were introduced, the solubilities were enhanced to the ranges of 3.09 × 10–4–22.13 × 10–4 and 1.31 × 10–4–12.44 × 10–4, respectively. It was noted that the impact of ethanol is more substantial, leading to an approximately 4–5 times improvement in the supercritical solubility of zolpidem. Utilizing validated empirical models to correlate supercritical solubility data for both the scCO2–zolpidem and scCO2–ethanol–zolpidem systems, it was observed that the empirical models developed by Nejad and Keshmiri for the zolpidem–scCO2 system (AARD% ≈ 1.50 and Radj = 0.996) and by MST–Sauceau for the zolpidem–scCO2–ethanol system (AARD% = 3.51 and Radj = 0.995) exhibited the highest levels of consistency between the predicted solubility values and the actual experimental data. Also, the supercritical solubility data of the scCO2–zolpidem binary system were evaluated by using the SRK and UNIQUAC models. It was observed that the SRK model demonstrated exceptional accuracy (AARD% = 1.53 and Radj = 0.999) in modeling zolpidem solubility in scCO2.

Zolpidem

Supercritical Carbon Dioxide

10.1021/acs.jced.3c00734

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Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation

Pharmaceuticals (2023)

Moutaz Y. Badr Pratap Basim Khaled M. Hosny Waleed Y. Rizg N. Raghavendra Naveen

Mucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug localization and target-specific actions, mucoadhesive polymers are essential. The current work aimed to use second-generation mucoadhesive polymers (i.e., thiolated polymers) to enhance mucoadhesive characteristics. An ITH-NC formulation was enhanced using response surface methodology. Concentrations of Tween 80 and Polyvinyl pyrrolidone (PVP K-30) were selected as independent variables that could optimize the formulation to obtain the desired entrapment efficacy and particle size/diameter. It was found that a formulation prepared using Tween 80 at a concentration of 2.55% and PVP K-30 at 2% could accomplish the goals for which an optimized formulation was needed. Either xanthan gum (XG) or thiolated xanthan gum (TXG) was added to the optimized formulation to determine how they affected the mucoadhesive properties of the formulation. Studies demonstrated that there was an initial burst release of ITH from the ITH/NC/XG and ITH/NC/TXG in the early hours and then a steady release for 24 h. As anticipated, the TXG formulation had a better mucin interaction, and this was needed to ensure that the drug was distributed to tissues that produce mucus. Finally, at the measured concentrations, the ITH/NC showed minimal cytotoxicity against lung cells, indicating that it may have potential for additional in vivo research. The enhanced bioavailability and mean residence time of the designed mucoadhesive NC formulations were confirmed by pharmacokinetic studies.

Mucoadhesion

Polyvinyl Alcohol

10.3390/ph16070925

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Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms

Biofilm (2022)

Jack A. Caudwell Jordan M. Tinkler Ben R.G. Johnson Kenneth J. McDowall Fayez Alsulaimani

Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor - a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 μL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.

Protein A

10.1016/j.bioflm.2022.100074

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Citations (11)