Faculty Of Pharmacy Research Paper
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Item Targeting TREM‑1 receptors with metformin and pravastatin modulate monosodium iodoacetate‑induced osteoarthritis(Springer Science and Business Media Deutschland GmbH, 2025-05-03) Eman R. Al Sawy; Mona M. Saber; Noha N. Nassar; Nesrine S. El SayedOsteoarthritis (OA), a degenerative joint condition, afects entire joints, including the tissues around it, causing pain, swelling and stifness. This study explored the combined therapeutic efects of metformin and pravastatin on knee OA induced by monosodium iodoacetate (MIA) in rats. The study encompassed fve animal groups (n=10 per group) which were allocated as follows: group 1 received 100 µL of sterile saline injected intra-articularly into the left knee joint (control group) while groups 2–5 were injected with 2 mg MIA in 100µL normal saline into the intraarticular space. After 2 weeks, group 3 received oral metformin (100 mg/kg) for 2 weeks, group 4 received oral pravastatin (10 mg/kg) for 2 weeks and group 5 received both metformin 100 mg/kg and pravastatin 10 mg/kg orally for 2 weeks. The combination of metformin and pravastatin showed to be the most efective in terms of improving radiologic and histologic fndings in knee OA. This combination also reduced both serum C reactive protein (CRP) and cartilage oligomeric matrix protein (COMP), while increasing serum collagen type II (COL2). Combining metformin and pravastatin also reduced AKT1, PI3K, STAT3 and IL-6 in the knee joint homogenate. TREM-1 levels showed the greatest reduction with the combination therapy. Furthermore, improvement was noted in oxidative stress markers with an increase in non-protein thiols and a decrease in malondialdehyde. In conclusion, the current study shows a therapeutic potential efect of combining metformin and pravastatin in OA, which could be partly attributed to TREM-1 signaling pathwayItem Chaperone‑mediated autophagy, heat shock protein 70, and serotonin: novel targets of beta‑hydroxybutyrate in HFFD/ LPS‑induced sporadic Alzheimer’s disease model(Inflammopharmacology, 2025-05-04) Reem A. Mohamed; Dalaal M. Abdallah; Hanan S. El‑AbharSporadic Alzheimer’s disease (AD), which accounts for the majority of cases, is sturdily infuenced by lifestyle factors such as dietary habits, obesity, and diabetes, leading to its classifcation as Type 3 diabetes. To model this pathological link, our AD-like model was developed by feeding Wistar male rats a high-fat diet with fructose in drinking water (HFFD) for 8 weeks, followed by a single dose of lipopolysaccharide (LPS). This group was compared with a normal control group fed a standard diet and a β-hydroxybutyrate (BHB)-treated group (125 mg/kg, p.o.), administered starting 3 h after LPS and continuing for 1 week. The results demonstrate that BHB treatment illuminated cognitive gains, as indicated by the Y-maze, Morris water maze, and novel object recognition tests. In addition, it preserved hippocampal cytoarchitecture, reduced neurodegeneration, and attenuated amyloid plaques and phosphorylated Tau deposition. Cellularly, BHB restored critical molecular mechanisms, including increased lysosomal-associated membrane protein 2A (LAMP2A) hippocampal content as the main marker of chaperone-mediated autophagy (CMA), along with the chaperon protein Hsp70. Moreover, BHB alleviated neuroinfammation by inhibiting the nucleotide-binding domain, leucine-rich–containing family, and pyrin domain–containing-3 (NLRP3) infammasome activation alongside the downstream targets cleaved caspase-1 and IL-1β/IL-18 cytokines. BHB also reduced pyroptotic markers, caspase-11 and gasdermin-N, and microglia-induced infammation as it shifted microglial polarization toward the neuroprotective M2 phenotype. Finally, BHB normalized hippocampal neurotransmitter levels of the inhibited acetylcholine and serotonin. These fndings support BHB as a promising, multifaceted treatment for AD, highlighting the roles of CMA, Hsp70, and 5-HT in slowing disease progression and improving cognitive function.Item Metabolite profiling of Cucurbita pepo L. in relation to its potential to combat experimental trichinosis(Elsevier B.V., 2025-04-06) Nashwa R. Mohameda; Seham S. El-Hawary; Fatema R. Saber; Ibrahim E. Sallam; Shaimaa H. El-SayedThis study aimed to evaluate Cucurbita pepo L. (C. pepo) seed extract against Trichinella spiralis (T. spiralis) through in vivo study for both intestinal and muscular phases. Additionally, an extensive metabolic profiling, for all parts of the fruit of Cucurbita pepo L. (seed, peel and flesh), was adopted using UPLC/ESI-qTOF-MS to reveal the phytoconstituents responsible for the biological activities. Regarding the anthelmintic evaluation of the extracts of C. pepo, the count of T. spiralis adult worm was significantly reduced in the group of mice treated early with C. pepo seed extract (CPSE) and albendazole (ABZ) as compared to the control infected non-treated group. Similarly, the total larval count was significantly reduced in groups treated with CPSE and ABZ with more reduction in the groups that received the treatment in the early phase of infection. Upon staining intestinal sections of the infected mice with haematoxylin and eosin, the analysis revealed the improvement of the inflammatory manifestation induced by the parasite upon treatment with CPSE in both the intestinal and muscular phases. UPLC/ESI-qTOF-MS technique enabled the identification and comprehensive profiling of 79 secondary metabolites, which belonged to various classes of compounds including flavonoids, phenolics, cucurbitacins and fatty acids, in addition to other minor classes. The current study suggests C. pepo seed extract as a promising candidate for management of the gastrointestinal parasites being enriched with bioactive phytoconstituents. © 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.Item Providencia pseudovermicola sp. nov.: redefining Providencia vermicola and unveiling multidrug-resistant strains from diabetic foot ulcers in Egypt(BioMed Central Ltd, 2025-04-23) Samira M. Hamed; Manal M. Darwish; Reham Monir; Ahmed Al Taweel; Ayat I. Ghanem; Ihab N. Hanna; Mai A. AmerBackground Providencia species are concerning due to their intrinsic resistance to colistin and tigecycline, complicating the treatment of multidrug-resistant (MDR) infections. Methods In the current study, two MDR isolates, DFU6 and DFU52T , were recovered from infected diabetic foot ulcers in Egypt in 2024. Following their initial identification as Providencia stuartii using VITEK® 2 and MALDI-TOF-MS, the isolates were subjected to whole-genome sequencing via DNBseq. Results While the 16S rRNA gene showed 100% similarity to that of Providencia vermicola, phylogenomic analysis against the type strains in the TYGS database, including P. vermicola DSM 17385T confirmed that these isolates represent a distinct species within the genus, further supported by overall genome-relatedness indices (ORGIs). This discrepancy prompted us to revise the taxonomy of all published genomes of P. vermicola strains (n=59) which revealed misidentification of at least 56 strains that are unrelated to the type strain of this species. DFU6 and DFU52T carried novel sequence types (ST29 and ST41, submitted to PubMLST) and harbored multiple resistance genes. Both strains contained the qnrD1 gene on a small, non-mobilizable plasmid. DFU52T possessed a conjugative plasmid encoding blaCMY−6, blaNDM−1, rmtC, aac(6’)-Ib10, sul1, aph(3’)-Ia, and qacEΔ1. DFU6 carried an ISEcp1-associated blaCTX−M−14, along with aadA, dfrA1, lnuF in a class 2 integron, and armA, msrE, and mphE on a resistance plasmid. Both isolates also featured a pathogenicity island (PAI) integrated into the pheV gene with fimbriae-encoding genes. Conclusion Following our reassessment of the taxonomic classification of all P. vermicola strains with published genomes, we propose reclassifying certain strains, including DFU6 and DFU52T , into distinct species for which we propose the name Providencia pseudovermicola sp. nov. We recommend DFU52T (=CCASU-2024-72) as the type strain for the novel species. We also shed light on the public health threat of this novel species as a human pathogen that harbours carbapenem and aminoglycoside resistance genes on mobile genetic elements.Item Nanoparticles Modified Solid-Contact Potentiometric Sensor for Selective Nanomolar Citicoline Determination(Institute of Physics, 2025-04-08) Passant M. Medhat; Heba-Alla H. Abd-ElSalam; Manal Mohamed Fouad; Amr M. Mahmoud; Hany H. Monir; Nermine S. GhoniemHighlights Citicoline sodium is administered by post-COVID-19 patients for the treatment of brain fog. Cobalt oxide nanoparticles, and copper nanoparticles modified glassy carbon potentiometric sensors were fabricated to detect Citicoline Sodium selectively. Cobalt oxide and copper nanoparticles were characterized using TEM, FTIR, and XRD. Determination of Citicoline sodium in its pharmaceutical dosage form and spiked human plasma. The proposed method was assessed for greenness using GAPI and AGREE greenness assessment tools and Whiteness assessment using RGB-12 proving its environmental safety. © 2025 The Electrochemical Society (“ECS”). Published on behalf of ECS by IOP Publishing Limited. All rights, including for text and data mining, AI training, and similar technologies, are reserved.Item Novel strategies for vancomycin-resistant Enterococcus faecalis bioflm control: bacteriophage (vB_EfaS_ZC1), propolis, and their combined efects in an ex vivo endodontic model(BioMed Central Ltd, 2025-04-10) Toka A. Hakim; Bishoy Maher Zaki; Dalia A. Mohamed; Bob Blasdel; Mohamed A. Gad; Mohamed S. Fayez; Ayman El‑ShibinyBackground Endodontic treatment failures are predominantly attributed to Enterococcus faecalis (E. faecalis) infection, a Gram-positive coccus. E. faecalis forms bioflms, resist multiple antibiotics, and can withstand endodontic disinfection protocols. Vancomycin-resistant strains, in particular, are challenging to treat and are associated with serious medical complications. Methods A novel phage, vB_EfaS_ZC1, was isolated and characterized. Its lytic activity against E. faecalis was assessed in vitro through time-killing and bioflm assays. The phage’s stability under various conditions was determined. Genomic analysis was conducted to characterize the phage and its virulence. The phage, propolis, and their combination were evaluated as an intracanal irrigation solution against a 4-week E. faecalis mature bioflm, using an ex vivo infected human dentin model. The antibioflm activity was analyzed using a colony-forming unit assay, feld emission scanning electron microscopy, and confocal laser scanning microscopy. Results The isolated phage, vB_EfaS_ZC1, a siphovirus with prolate capsid, exhibited strong lytic activity against Vancomycin-resistant strains. In vitro assays indicated its efectiveness in inhibiting planktonic growth and disrupting mature bioflms. The phage remained stable under wide range of temperatures (− 80 to 60 °C), tolerated pH levels from 4 to 11; however the phage viability signifcantly reduced after UV exposure. Genomic analysis strongly suggests the phage’s virulence and suitability for therapeutic applications; neither lysogeny markers nor antibiotic resistance markers were identifed. Phylogenetic analysis clustered vB_EfaS_ZC1 within the genus Saphexavirus. The phage, both alone and in combination with propolis, demonstrated potent antibioflm efects compared to conventional root canal irrigation. Conclusion Phage vB_EfaS_ZC1 demonstrates a promising therapy, either individually or in combination with propolis, for addressing challenging endodontic infections caused by E. faecalisItem Development and optimization of lyophilized dry emulsion tablet for improved oral delivery of Ivermectin(Editions de Sante, 2025-04-18) Eiman Abdalla Madawi; Hanan M. El-Laithy; Nihal Mohamed Elmahdy Elsayyad; Mutasem Rawas-Qalaji; Amjad Alhalaweh; Iman Saad AhmedIvermectin (IVM) is a widely used antiparasitic agent and has been repurposed for the treatment of COVID-19. However, its poor water solubility and low bioavailability present significant challenges, often requiring large doses for therapeutic effectiveness. This poses a burden on patients, as they need to take multiple tablets at once, which is both inconvenient and uncomfortable. This study aims to develop and optimize rapidly disintegrating lyophilized dry emulsion tablets (LDET) containing IVM using a quality by design (QbD) approach to enhance its solubility, dispersibility, wettability, and dissolution rate, thereby improving its absorption and bioavailability following oral administration. Oil-in-water (O/W) emulsions were prepared using sweet almond oil or Miglyol 840 as the oil phase, along with stabilizers. The optimal emulsion was subsequently lyophilized to produce IVMLDET. Tablets’ characteristics were assessed in vitro for their properties including solubility, disintegration, and dissolution, and in vivo in rabbits for their pharmacokinetic (PK) profile. Results indicated a remarkable 600-fold increase in IVM solubility in the optimal emulsion formulation. IVM-LDET significantly enhanced the extent and rate of dissolution compared to raw IVM and the marketed tablet, Iverzine®. Furthermore, the PK profile of IVM from LDET showed a 30 % increase in maximum plasma concentration (Cmax) and area under the curve (AUC), and reduced time to reach maximum concentration (tmax) by 4 h compared to Iverzine® tablets. In conclusion, the developed IVM-LDET formulation presents a promising therapeutic alternative to conventional oral IVM products for treating parasitic or viral infections, potentially leading to improved therapeutic outcomes and patient compliance.Item Extraction methods of cinnamon oil(Elsevier, 2025-04-17) Maha M. Salama; Mohamed A. Salem; Omnia Eid; Shahira M. EzzatCinnamomum zeylanicum Blume, Cinnamomum verum is a well-known spice worldwide. It is an evergreen tree belonging to the family Lauraceae. The genus Cinnamomum comprises approximately 250 species, which are mainly distributed in the Asian and Australian continents. The bark is the main part used by the tree due to its high content of volatile oil, followed by the leaves. Both bark and leaves are used as food condiments with evidence of vital biological activities. Moreover, cinnamon oil is highly recognized in aromatherapy. The major constituents of cinnamon oil are eugenol and cinnamaldehyde; both are aromatic, pungent compounds that are responsible for the aroma and fragrance. The percentage of the constituents of the oil is aligned with the botanical origin of the plant and its cultivars, as several species of cinnamon and cassia could be differentiated based on the oil composition. Likewise, the method of extraction of the cinnamon oil is a crucial step in obtaining the supreme concentration of the oil as well as avoiding its decomposition. The most common and well-known tool to determine the volatile constituents in oil is gas chromatography, which is usually coupled with mass spectrometry detector. In this chapter, the method of extraction and the cinnamon species and their impact on the quality and yield of the oil will be discussed. Hydro-distillation and steam distillation are the conventional methods. Other extraction methods are used via optimization for the conditions as applying an electric field and/or ultrasonication to obtain the best results. In addition, advanced methods such as supercritical CO2 extraction, supercritical fluid extraction (SCFE), and microwave-assisted extraction are also discussedItem Ezetimibe Loaded Nanostructured Lipid Carriers Tablets: Response Surface Methodology, In-vitro Characterization, and Pharmacokinetics Study in Rats(Springer New York, 2025-01-09) Dalia Elkhayat; Nevine S. Abdelmalak; Reham Amer; Heba H. AwadPurpose The present study aims to overcome the poor oral bioavailability of ezetimibe (EZ), a selective Biopharmaceutics Classification System (BCS) Class II cholesterol absorption inhibitor drug. EZ-loaded nanostructured lipid carriers (EZNLCs) were dried by lyophilization and incorporated in a convenient oral solid dosage form to enhance its dissolution, and absorption and increase patient compliance. Response surface methodology (RSM) was employed to systematically optimize formulation variables, improving the efficiency of disintegration and drug release characteristics. Methods RSM was adopted to study the effects of (A) increasing the amount of the super-disintegrant, crosscarmelose sodium, (CCS), and (B) varying the ratio between the used drying excipients Avicel and mannitol (A: M) on the disintegration time (R1), and the percentage drug released after 24 h (R2). Thirteen EZ-NLCs tablets were prepared and subjected to pre-compression and post-compression evaluation. Furthermore, a bioequivalence study was conducted by administering EZ-NLCs and ezetrol® tablets to Sprague Dawley male rats. Results The optimized EZ-NLCs tablet (prepared with the ratio of Avicel: mannitol (7.5:0) using 30 mg CCS), revealed a disintegration time of 3.85±0.03 min, and 98±3.09% of the drug were released at the end of the 24 h. EZ-NLCs tablet displayed a maximum concentration (Cmax) of 3.57±0.27 ng/mL and an area under the curve (AUC0−24) of 22.44±2.68 ng.hr/mL, while those of ezetrol® were 2.79±0.15 ng/mL and 15.36±0.86 ng.hr/mL, respectively. Conclusion The assessed relative bioavailability demonstrated the superiority of EZ-NLCs tablet over ezetrol® with 1.5 fold improvement which proves that EZ-NLCs tablet could be a good candidate to enhance the oral bioavailability of EZ.Item Analytical-Quality-by-Design Fluoroprobes for Quantitation of Entecavir and Penciclovir in Spiked Human Plasma and Content Uniformity Testing: Insights of DNA Mismatching, Three-Colors Assessment and Sustainability Profiling(John Wiley and Sons Ltd, 2025-03-03) Sarah S. Saleh; Ahmed Samir; Omnia A. El-NaemEntecavir and penciclovir are nucleoside-analog antiviral drugs structurally related to guanine that act by inhibiting the active viral replication process. Through this study, the quantitation of both drugs was carried out using two fluorescent probes, referred to as fluoroprobes. The first type was prepared by the addition of surfactants such as Tween 80 and sodium dodecyl sulfate (micelle-enhanced fluoroprobes), while the second type includes the formation of a tertiary complex of drug-terbium-DNA (Tb-DNA fluoroprobes). The preparation of the fluoroprobes was optimized using analytical quality by design (AQbD) via I-optimal design. A positive effect of the selected antiviral drugs on DNA mismatching was observed. The analytical procedures were validated according to ICH guidelines with a linearity range of 2.0–40.0 μM and 25.0–300.0 nM for micelle-enhanced and Tb-DNA fluoroprobes, respectively. The analytical procedures were evaluated in compliance with the three-color (GBW) assessments: greenness (using AGREE and ComplexGAPI metrics), blueness (using the BAGI tool), and whiteness (using the RGB algorithm). The sustainability profiles were established using the efficient-valid-green (EVG) framework. Both types of fluoroprobes were successfully applied to quantify entecavir and penciclovir in content uniformity testing and spiked human plasma as a simpler and cheaper alternative to hyphenated analytical techniques.Item Beyond erectile dysfunction: Optimization of vardenafil dihydrochloride for hepatic encephalopathy prophylaxis using hybrid lipid polymeric nanoparticles formulation(Editions de Sante, 2025-03-06) Marwa H.S. Dawoud; Heba T. Elbalkiny; Yasmeen E.M. Gharib; Sara A.A. Fakkar; Rowaa Saber; Marry E. Yanni; Mai A. ZaafanVardenafil dihydrochloride (VD), a phosphodiesterase-5 (PDE5) is widely used to treat erectile dysfunction, but recent studies suggested its potential for other diseases such as hepatic encephalopathy. However, VD suffers poor solubility and oral bioavailability, and significant first-pass metabolism. This study aims to enhance the bioavailability of VD by employing two combined approaches: formulation of VD into hybrid lipid-polymeric nanoparticles (HLPNPs), and incorporating piperine, a known bioavailability enhancer, to investigate its potential in preventing hepatic encephalopathy. HLPNPs were developed using homogenization/ultrasonication technique, with a one-factor design testing chitosan, oleic acid, or sodium alginate as the helper polymers. Oleic acid showed the best results and was used to prepare the optimized formula (O1), which had a particle size of 128 ± 2.8 nm, a polydispersity index of 0.173 ± 0.07, an entrapment efficiency of 93 ± 1.8 %, and a zeta potential of − 32 ± 1.67 mV. O1 showed a sustained drug release profile, with approximately 70 % of VD released over 72 h. O2 was then prepared with the addition of piperine, resulting in a longer residence time of 717 min compared to O1 (94 min) in the pharmacokinetics study. O1 showed a twofold increase in the bioavailability compared to the unformulated VD while O2 exhibited a ninefold increase. The improvement was confirmed by the higher Cmax from 9 ng/mL for standard VD to 13 ng/mL and 22 ng/mL for O1 and O2, respectively. In hepatic encephalopathy-induced mice model, O2 showed promising efficacy, with significant improvements in liver enzymes, ammonia levels, hippocampal BDNF levels, cGMP levels, and hippocampal GluR1 and P-CREB levels. These findings suggest that combining VD into HLPNPs with piperine is an effective strategy to overcome its bioavailability limitations and enhance its therapeutic potential.Item Functionalized novel carbon dots from bell pepper seeds for sustainable green Edoxaban quantification(BioMed Central Ltd, 2025-04-02) Rasha Th. El-Eryan; Mona S. Elshahed; Dalia Mohamed; Azza A. Ashour; Heba T. ElbalkinyGlobal warming and the developed worldwide awareness have persuaded efforts to minimize the generated hazardous wastes. As a result, “green” chemical procedures are being gradually included in science for sustainable development. This concept has been extended and inspired chemists to fabricate novel green carbon dots (CDs) from natural plants. Herein, we represent novel CDs synthesized by recycling seeds obtained from bell pepper as fluorescent probe for the determination of Edoxaban tosylate hydrate (EDO) a non-fluorescent drug; we exploit the advantage of the inner filter effect between the absorption peak of the drug and the emission peak of the CDs. This overlap resulted in quenching the fluorescence of CDs by increasing the concentration of EDO within the range 0.80–20.00 µg/mL with a limit of detection 0.23 and 0.22 µg/mL and a limit of quantitation 0.69 and 0.72 µg/mL for Microwave CDs and Plate CDs, respectively, at λex/λem 310/409 nm. Two facile preparation techniques for the CDs were used, the microwave-assisted method and the thermal decomposition method, using a single-step approach. The fabricated CDs were characterized using various techniques, including UV-vis, fluorescence and Fourier transform infrared spectroscopies, energy-dispersive X-ray, high-resolution transmission electron microscope, X-ray Diffaction, X-Ray photoelectron spectroscopy and zeta potential. The performance of the synthesized fluorescent probe for the determination of EDO was evaluated according to ICH guidelines. The accomplished results, together with the simplicity, sensitivity, and low cost of the developed probe, recommended its appropriateness for the routine quality control assay of EDO pharmaceutical formulation, as good % recovery was obtained upon the investigation of the marketed tablets with 99.77% and 98.79% recoveries for microwave CDs and plate CDs, respectively. The method’s greenness was evaluated using three integral matrices, the Blue Applicability Grade Index, the Complementary Green Analytical Procedure Index and Analytical Eco-Scale.Item Design, Sequential Synthesis, Kinase Inhibitors Comparative Docking, MD Simulations, 99mTc-Coupling and In-Vivo Studies of Novel Pyrazolopyrimidine Derivatives(National Information and Documentation Center (NIDOC), 2025-04-10) Wafaa Zaghary; Dina Adel; Basma M Essa; Tamer Nasr; Khaled El-Adl; Tamer M SakrPyrazolopyrimidine derivative was synthesized and labeled with 99mTc using sodium dithionite as reducing agents. The purity of radiochemical 99mTc(Na2 S2O4 )-compound was 93.4%, and the synthesized complex was stable in vitro for 6 hours. Furthermore, using a radiolabeling technique, a bio-distribution investigation showed that tumor-bearing mice exhibited a remarkable absorption of [99mTc]Tc-complex, with a significant concentration in tumor tissues and a T/NT of 6.58 after 60 minutes after injection. These encouraging results mean that the synthesized compound offers a potential radio-carrier that can be used as a tumor marker and, following additional preclinical research, can be used for cancer therapy. Molecular dynamic simulation confirmed the stability of this compound in the active sites of both EGFR and VEGFR-2 receptors.Item Historical Overview of Pharmacognosy and Phytochemistry(Wiley, 2025-04-10) Mona M. Marzouk; Mai M. Farid; Rana M. Merghany; Shahira M. EzzatThe term "pharmacognosy" is defined as "the study of natural products or more precisely secondary metabolites that are useful for their medicinal, ecological, gustatory, or other functional properties." The history of pharmacognosy represents the history of pharmacy and medicine. The nineteenth century noted the birth of scientific pharmacy and was a turning point in the understanding and application of therapeutic herbs. Modern pharmacognosy emerged between 1934 and 1960; this development was mostly a result of events, such as the discovery of penicillin, the isolation of reserpine, the study of Vinca rosea anticancer activity, and the preparation of semi-steroidal hormones. In our chapter, we will have an overview of the history of pharmacognosy, issues related to the quality of herbal raw materials, such as adulteration and contamination, the change phase of traditional medicine and approaches for quality estimation of herbal raw materials, products, and preparations, phytochemistry and its expanded role in drug discovery, as well as recent progress in pharmacognosy and phytochemistry. © 2025 John Wiley & Sons, Inc. All rights reserved.Item Novel anti-herpes simplex activity of Chryseobacterium indologenes: Genomic and metabolomic insights(Academic Press, 2025-04-03) Mai A. Amer; Reham Wasfi; Hossam M. Ashour; Samira M. HamedHerpes simplex virus (HSV) is a pathogenic virus responsible for various diseases, necessitating alternative antiviral strategies for HSV-1 treatment. Given the antiviral properties of lactic acid (LA), we screened rhizobacteria from the maize (Zea mays L.) rhizosphere for organic acid production. Among the isolates, SR50, SR126, and SR135 exhibited significant LA production, confirmed by High-Performance Liquid Chromatography (HPLC) analysis. Their antiviral efficacy against HSV-1 was evaluated by determining IC50 values and selectivity indices (SI = CC50/IC50), with SR50, SR126, and SR135 displaying SI values of 135.14, 10.74, and 2.17, respectively. SR50, identified via 16S rRNA sequencing as Chryseobacterium indologenes, was selected for further antiviral analysis. The cell-free supernatant (CFS) of SR50 demonstrated 73.3 % inhibition of viral adsorption, 60 % virucidal activity, and a 46.7 % reduction in viral replication. Metabolomic profiling using Gas ChromatographyMass Spectrometry (GC-MS) identified short- and long-chain organic fatty acids. Whole Genome Sequencing (WGS) revealed a 4,581,372 bp genome encoding diverse biosynthetic pathways, including siderophores, plant hormones, terpenoids, polyketides, and other bacterial secondary metabolites. Additionally, genes encoding lactaldehyde dehydrogenase and pyruvate dehydrogenase confirmed the presence of lactic and acetic acid biosynthesis pathways. This study presents the first report of C. indologenes SR50 exhibiting anti-HSV-1 activity, highlighting its potential as a novel antiviral resource.Item Optimization of Linagliptin-loaded polymersomes via response surface methodology: A repurposed therapeutic strategy for hepatic encephalopathy prevention(Editions de Sante, 2025-03-28) Nabila M. Sweed; Heba T. Elbalkiny; Eslam Magdy; Mahitab Ramadan; Shahin Mahmoud; Toka Mohamed; Islam S. Mannaa; Mai A. ZaafanThis study aims to prepare linagliptin-loaded polymersomes in order to enhance its stability, bioavailability, and to investigate its potential in the prophylaxis against hepatic encephalopathy (HE). Polymersomes were formulated using solvent injection technique and optimized using D-optimal design, where the effect of drug to polymer ratio (X1) and polymer type, whether Poly (D, L-lactic-co-glycolide) or polycaprolactone (X2) were studied. Fifteen formulae were prepared and evaluated for entrapment efficiency % (Y1), particle size (Y2), and zeta potential (Y3). The optimized formula was prepared using polycaprolactone polymer with a drug to polymer ratio of 1:8.9. The optimized formula showed an entrapment efficiency % of 73 ± 1.04 %, a particle size of 184.1 ± 1.45 nm, and a zeta potential of − 21.2 ± 0.97 mV. In-vitro drug release showed remarkable sustained release profile for linagliptin-loaded polymersomes as compared to the standard linagliptin. In-vivo pharmacokinetic studies in rats showed a 262 % increase in bioavailability of linagliptin-loaded polymersomes. Moreover, linagliptin-loaded polymersomes showed promising results in a rat model of hepatic encephalopathy, with marked improvement in markers such as alanine transaminase (ALT), aspartate aminotransferase (AST), ammonia levels, and hippocampus brain-derived neurotrophic factor levels (BDNF). Our results showed that the optimized linagliptin-loaded polymersomes formula is a promising drug delivery system for enhancing linagliptin bioavailability, offering potential therapeutic benefits for managing HE and other diseases requiring sustained release and enhanced bioavailability.Item Antiviral siRNA delivered using attenuated, anthrax toxin protects cells from the cytopathic efects of Zika virus(Springer Netherlands, 2025-03-30) Benedita K. L. Feron; Timothy Gomez; Natalie C. Youens; Nourhan A. M. Mahmoud; Hadeer K. S. Abdelrahman; Joachim J. Bugert; Simon C. W. RichardsonCurative drugs are needed for the treatment of viral infections. Small interfering (si)RNA ofer such a prospect but require the development of safe, efective and non-hepatotropic subcellular delivery systems. Here, 5 candidate siRNA molecules targeting defned sequences within the Zika Virus (ZIKV) genome were assayed for their ability to reduce ZIKV induced cytopathic efects in vitro. The protection of Huh-7 cells from ZIKV cytopathic efects was recorded after electroporation and the siRNA Feron-Zv2, resulting in 122.7±5.3% cell viability (n=3±standard error of the mean (SEM), 100 nM siRNA) after exposure to ZIKV relative to a virus treated control (35.2±7.1% cell viability (n=3±SEM)). Protection of BHK-21 cells was recorded after transfection with an attenuated anthrax toxin containing an RNA binding domain. Treatment with Feron-Zv4 resulted in 75.1±2.9% cell viability (n=3±SEM, 25 nM siRNA) after exposure to ZIKV. This protection was mirrored by a system containing octameric PA where a maximum of 86.2±4.4% cell viability was reported (n=3±SEM, 75 nM siRNA) after treatment with Feron-Zv2. Scrambled siRNA aforded no measurable protection. Here we report for the frst time that siRNA delivered by either attenuated anthrax toxin or octamer forming ATx can protect mammalian cells from ZIKV cytopathic efects.Item Plant-derived Synthesis of Iron Oxide Nanoparticles for Magnetic Hyperthermia and Magnetic Resonance Imaging Applications(Tsinghua University Press, 2025-03-12) Mohamed Abdelmonem; Romesa Soomro; Norazalina Saad; Mohamed Ahmed Ibrahim; Kim Wei Chan; Emmellie Laura Albert; Emma Ziezie Tarmizie; Che Azurahanim Che AbdullahThe biomedical applications of iron oxide nanoparticles (IONPs) synthesized using environmentally friendly processes are extremely promising. Using eco-friendly and nontoxic methods is a safer alternative to conventional chemical synthesis, which generates toxic byproducts. It allows for greater control over particle size and morphology. The resulting unique magnetic and optical properties of IONPs enable their use in biomedical applications such as magnetic hyperthermia (MH) and magnetic resonance imaging (MRI). This review aimed to summarize recent advances in the synthesis, characterization, and biosafety of IONPs for use in MH and MRI. It also aimed to highlight the significance of eco-friendly synthesis techniques for producing IONPs with the desired magnetic and physicochemical properties. Overall, this review elucidated the most efficient methods for utilizing iron oxide while considering biocompatibility.Item Metformin-loaded bioinspired mesoporous silica nanoparticles for targeted melanoma therapy: Nanotopographical design with in vitro and in vivo evaluation(Elsevier B.V., 2025-03-23) Omar A. Elkady; Mai A. Zaafan; Marian George; Nadeen Ashraf Elsayed; Verina Ghaly Mettias; Verina Sameh Edward; Dina Saeed GhatatyBioinspired nanotopographical carriers have emerged as innovative cancer therapy strategies, mimicking natural processes to enhance targeted delivery and reduce systemic toxicity. This study presents the development of virus-like mesoporous silica nanoparticles (MSN) as a delivery platform for repurposed metformin (MTF) in a topical multi-stimuli responsive system for melanoma treatment. Metformin-loaded virus-like MSN (MTF-MSN) were fabricated and incorporated into a thermo-responsive gelling system. The particles were evaluated for morphology, zeta potential (ZP), particle size (PS), entrapment efficiency (EE%), Fourier-transform infrared (FTIR) spectroscopy, MTT cytotoxicity assay, in vitro release, and in a melanoma in vivo model. The particles exhibited a spherical morphology, a zeta potential of +31.9 ± 1.45 mV, and a particle size of 197 ± 3.47 nm, ideal for skin penetration. MTF-MSN demonstrated significant antiproliferative activity against melanoma A375 cells, with lower IC50 values (192 μg/mL) compared to free MTF (>300 μg/mL). Sustained, pH-sensitive MTF release was observed over 48 h at pH 7.4 and 6 h at pH 5.5. In vivo studies showed enhanced anti-cancer efficacy of MTF-MSN, evidenced by elevated caspase-3 and Neurofibromin Type-1 (NF-1) levels, along with suppressed angiogenesis markers VEGF and NRAS. The MTF-MSN-treated group exhibited superior outcomes compared to free MTF and controls (p < 0.05). This innovative bioinspired MTF-MSN hydrogel system optimizes MTF delivery for melanoma therapy, pioneering advancements in drug repurposing and nano-oncology.Item Role of noncoding RNA as a pacemaker in cancer stem cell regulation: a review article(National Cancer Institute, 2025-03-24) Yasmin M. Attia; Samer A. Tadros; Sally A. Fahim; Doaa M. BadrAccumulated evidence supported the crucial role of a tiny population of cells within the tumor called cancer stem cells (CSCs) in cancer origination, and proliferation. Additionally, these cells are distinguished by their self-renewal, diferentiation, and therapeutic resistance capabilities. Interestingly, many studies recorded dysregulation of diferent types of noncoding RNAs, such as microRNA (miRNA) and long non-coding RNA (LncRNA), in cancer cells as well as CSCs. Moreover, several studies also supported the regulation of the transcription factors and signaling pathways required for CSC progression by these noncoding RNAs. However, the exact biological functions of all these noncoding RNAs are not well understood yet. These fndings are of great interest, implying usage of noncoding RNA as therapeutic tool to target these cells. In this review, we provide an insight into how noncoding RNAs regulate CSCs and how this correlation is manipulated to develop new therapies to eradicate cancer cells successfully