Faculty Of Pharmacy Research Paper
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Item Targeting TGF‑β/VEGF/NF‑κB infammatory pathway using the Polyphenols of Echinacea purpurea (L.) Moench to enhance wound healing in a rat model(Birkhauser Verlag Basel, 2025-03-07) Marwa I. Ezzat; Mai M. Abdelhafez; Asmaa K. Al‑Mokaddem; Shahira M. EzzatThe present study explores the metabolic profling and molecular wound-healing mechanisms of Echinacea purpurea (L.) Moench (EP) fowers aqueous (AE) and ethanol (EE) extracts in an excision wound-healing model. Metabolic profling of the extracts was investigated using UHPLC-ESI-TOF–MS and molecular networking. Antioxidant activity was carried out using the DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging method and FRAP (ferric reducing antioxidant power). Carboxy methylcellulose gels of 5 and 10% of both aqueous (AE) and ethanol (EE) extracts were prepared. The wounds were explored macroscopically, histologically, and immunohistochemically. The UHPLC-ESI-TOF–MS method enabled the identifcation of 3 organic acids, 14 phenolic acids, 3 phenylethanoid glycosides, and 11 favonoids from EP extracts. EE had signifcant antioxidant activity compared to AE. The EP treated wounds healed faster. The EE succeeded in improving healing properties and controlling the infammatory response by reducing IL-6 and increasing IL-10 expression and enhancing angiogenesis and remodeling via increased NF-κB, TGF-β, VEGF, CD31 expression and α-SMA and collagen deposition. It is worth mentioning that the EE groups also showed improvement in the histopathological examination in a dose-dependent manner. The efectiveness of EE in wound-healing may be attributed to its higher content of polyphenols which also made the antioxidant potential of the EE and its capacity to donate electrons higher than that of AE. This study scientifcally enables the understanding of the molecular mechanisms Echinacea purpurea extract in wound healing via modulating skin infammatory response and indicates the potential usefulness of EP ethanol extract for wound healing.Item Introducing a passively targeted formulation of diclofenac potassium for application in endodontics to minimize renal and gastrointestinal side effects(Elsevier B.V, 2025-02-26) Ahmed Y. Soliman; Sarah S. Abouelenien; Hebatallah M. El-Far; Mohamed H. Hasaneen; Mohamed A. Mamdouh; Amal I. Makhlouf; Nagia N. AfifiThis research aims to formulate, evaluate, and conduct a clinical investigation of mucoadhesive buccal discs of diclofenac potassium (DP) for application in endodontics to minimize side effects, mainly renal and gastrointestinal. The discs were compressed directly utilizing bioadhesive polymers like hydroxypropyl methylcellulose K4M (HPMC K4M), sodium carboxymethyl cellulose (NaCMC), Carbopol 934 (Cp934), methylcellulose (MC) and combinations of these polymers. In-vitro, release studies and ex-vivo and in-vivo determination of bioadhesion time were conducted. The selected formula was sealed on one surface with ethyl cellulose to allow unidirectional drug release. It was evaluated for permeation through the chicken pouch membrane in the absence and presence of permeation enhancers. The formula of choice (F3) containing methyl cellulose was further assessed for the swelling index, bioadhesion strength, hardness, friability, surface pH, in-vivo bioadhesion performance, and storage effect under ambient and accelerated conditions. It showed drug release of 99 % ± 1 in 2 h, permeation flux (Jss) of 3.5 ± 1.6 mg cm− 2 h− 1 , and bioadhesion time of 4 ± 0.5 h without bitterness, irritation, or fragmentation. The introduced 25 mg DP bioadhesive disc formulation F3 was then clinically compared with the marketed 50 mg oral Cataflam® tablets regarding the effect of single-dose pretreatment in endodontic procedures of subjects with symptomatic irreversible pulpitis (SIP) through a randomized clinical trial. No significant difference was detected in all evaluated clinical criteria. This proves clinical efficiency with the advantage of half-dose administration and targeted localized effect leading to minimized renal and gastrointestinal side effects.Item Sustainable pH-responsive casein/hyaluronic acid layered nanoparticles for targeted delivery of metformin to colorectal cancer(Editions de Sante, 2025-02-23) Nihal Mohamed Elmahdy Elsayyad; Mervat Shafik Ibrahim; Shereen H. NoshiColorectal cancer (CRC) is a major global health concern, ranking as the third most diagnosed and second deadliest cancer worldwide. This study aimed to develop a novel, pH-responsive, colon-targeted oral drug delivery system (OCDDS) for metformin (MET), an antidiabetic agent, which has been repurposed for treating CRC. A hyaluronic acid (HA)-chitosan (CH) polyelectrolyte complex (PEC) core for CD44 receptor targeting in CRC was coated within pH-responsive casein (CA) and pectin (PT) outer layer, forming CA/PT-MET-CH/HA PEC nanoparticles, ensuring drug release primarily in the colon. Response surface methodology (RSM) was employed to optimize the composition of the prepared inner and outer layers of the prepared OCDDS, which were characterized in terms of particle size, entrapment efficiency, zeta potential, and in vitro drug release. The optimized formulation underwent further characterization using transmission electron microscopy (TEM), cytotoxicity and cellular uptake studies on HT-29 CRC cells. The interactions between different excipients were studied via molecular modelling and confirmed by Fourier-transform infrared spectroscopy (FTIR). The optimized formulation, F8, comprised 1 % and 2 % of CH and HA, respectively. The coated CA/PT-MET-CH/HA nanoparticles, designated as CF3, contained 1.5 % CA and 0.5 % PT, and exhibited a particle size of 798.93 ± 45.38 nm, a high drug entrapment efficiency of 83.26 %, and a controlled drug release profile with maximal release at pH 7.4, simulating the colon environment. The prepared uncoated and coated OCDDS systems exhibited higher cytotoxicity and cellular uptake compared to free metformin, suggesting the successful release of the encapsulated MET-CH/HA PECs from the CA/PT layer. These results highlight the potential of CA/PT-coated OCDDS for targeted colon delivery and treatment of CRC using HA as a targeting ligand.Item Design, synthesis and molecular modeling of new Pyrazolyl-Benzimidazolone hybrids targeting breast Cancer(Academic Press Inc, 2025-02-15) Mohamed Adardour; Al-Hassan M. Mustafa; Mehdi Oubahmane; Marouane Ait Lahcen; Emad M. Seif; Manal Abdel Fattah Ezzat; Elena Zaballos-García; Joel T. Mague; Ismail Hdoufane; Driss Cherqaoui; Oliver H. Krämer; Wolfgang Sippl; Hany S. Ibrahim; Abdesselam BaouidMethyl-piperidino-pyrazole (MPP) is a pyrazole derivative acting as a lead estrogen receptor (ER) antagonist and has an anti-breast cancer effect. Since some benzimidazole derivatives were reported for their inhibitory activity against breast cancer, hybrids from these reported compounds (5a-c, 6a-c, 7a-c and 8a-c) were designed to develop anti-breast cancer agents. The synthesis involved 1,3-dipolar cycloaddition of nitrilimines on the benzimidazolone derivatives 2a-b and 3a-b which occurred with chemo- and regioselectivity depending on the dipole and was confirmed by an X-ray structure of 6b. In vitro biological testing of the newly prepared compounds against the 60-cell line panel showed that 5a-c and 6a-c with a partially unsaturated pyrazole ring possessed a high GI% in the T-47D breast cancer cell line with a selectivity margin against different cell lines. Five compounds were selected for apoptotic studies in T-47D cells, of which 6a arrested cells in G1 phase and caused more apoptosis than MPP. The MTT assay revealed that compound 6a has an IC50 = 6.77 ± 0.03 μM against T-47D cells. Furthermore, 6a reduced the estrogen receptor 1 gene expression levels 3-fold in T-47D cells. Molecular dynamics simulations indicated that the complex of the active compound 6a remained stable over the last 150 ns. An analysis of the binding mode revealed that compound 6a exhibited a similar conformation compared to MPP and the co-ligand in the active site of via a specific pose involving noncovalent interactions.Item Investigation of bacterial gut microbiome in diverse Egyptian populations “pilot study”(Taylor and Francis Inc, 2025-01-31) Kareem Talaat Mohamed; Sarah Shabayek; Nora Fahmy Mahmoud; Mahmoud Mohamed Tawfick; Amro Mohamed Said HanoraThe gut microbiota plays a huge role in human health regarding immunity, metabolism, and nutrient absorption. In this work, the gut microbiota, with its bacterial community structure, is studied using whole genome shotgun (WGS) sequencing for populations from two different geographical regions in Egypt: Cairo (urban) and Ismailia (rural). Fecal samples were obtained from six healthy individuals, three from Cairo and three from Ismailia, of ages ranging from 43 to 52 years. Alpha diversity, measured as Shannon, inverse Simpson, and OTUs, showed no significant differences between the two cities. However, beta diversity analysis by Principal Coordinate Analysis (PCoA) revealed diverse microbial compositions. Thus, only the Ismailia samples contained higher levels of butyrate-producing bacteria involved in maintaining intestinal health, such as Faecalibacterium prausnitzii and Akkermansia muciniphila. On the other hand, there was a higher prevalence in Cairo of bacteria associated with protein and fat metabolism, like Bacteroides thetaiotaomicron. Such findings explain the influence of environmental factors in shaping gut microbiota and show that to get a comprehensive understanding of regional differences, many wider-ranging studies need to be conducted.Item Pharmacovigilance in the Community: A Special‑Interest Group of the International Society of Pharmacovigilance(Adis International Ltd, 2025-01-08) Mohamed A. Elhawary; Rebecca Noss; Loubna Alj; Manal Younus; Mayada Alkhakany; Hadir Rostom; Angela Caro‑Rojas; Thamir M. AlshammariPharmacovigilance (PV) continues to evolve globally and has changed in the last few decades from depending on a reactive approach based on spontaneous reporting of adverse drug reactions (ADRs) to a more proactive and patient-centred approach [1]. To keep pace with these developments, PV stakeholders should adopt a multidisciplinary framework to release the untapped potential of their PV allies in the community [2]. Community pharmacists are often regarded as "the frst point of contact" among healthcare professionals (HCPs) due to their high accessibility to the public [3]. However, on a daily basis, patients collect their medications from the pharmacy without seeking any clarifcation. Pharmacy staf often inquire, "Do you have any questions for the pharmacist?" to which the response is frequently "no" [4]. This recurring dialogue in general does not allow the pharmacists to inform the patients of any essential information with regard to their medication. This lack of communication is a barrier to adverse event reporting, if it occurs, and undermines trust in healthcare systems. In turn, this can negatively impact on compliance with medications and increase the susceptibility to accepting misleading information. Therefore, community pharmacists and other HCPs, should be familiar with ways to communicate risk. It is important for HCPs to be aware of the integrated PV landscape, which addresses all circumstances where safety issues may occur (e.g., medication error, abuse, poor quality, misuse, and drug addiction and falsifed products) and to include not only conventional medicines but also biological products and herbal medicines.Item Ondansetron alleviates testosterone-induced BPH in rats through cross regulation of the 5-HT/AR/P-STAT3 and the non-canonical NF-κB pathways(Elsevier B.V., 2025-02-01) Reem A. Mohamed; Maha M. ShoumanBenign prostatic hyperplasia (BPH) is a widespread age-related health issue. Every year, new pathological cues are revealed in the pathogenesis of BPH, however, the role of serotonin, Janus tyrosine kinase (JAK)-2/signal transducer and activator of the transcription (STAT)-3 and non-canonical nuclear factor-kappa B (NF-κB p52) pathways and their interaction with the androgen receptor (AR) in BPH are still not fully investigated. Accordingly, the aim of the current study was to unveil the possible modulatory effect of ondansetron alone and in combination with tamsulosin on these pathways and their utilization as therapeutic targets. Five groups of rats were utilized; group 1 received corn oil to serve as normal control, while the other groups administered testosterone (3 mg/kg, subcutaneously) dissolved in corn oil for 2 weeks followed by the co-administration of either tamsulosin (0.2 mg/kg, orally), ondansetron (2 mg/kg, intraperitoneally) or their combination for another 15 days along with testosterone injections. All treatments improved kidney function (creatinine and blood urea nitrogen), decreased oxidative stress (reduced glutathione and malondialdehyde), attenuated inflammation (NF- κB, cyclooxygenase-2), decreased AR expression, NF-κB p52, P-STAT3, transforming growth factor beta-1 in addition to markers of epithelial-mesenchymal transition (alpha smooth muscle actin and vimentin) this was associated with an increase in the prostatic content of serotonin, improvement in the histopathological picture and overall shrinkage in relative prostate weight. These results show that ondansetron is a very promising treatment for BPH especially in combination with tamsulosin and unveiled NF-κB p52 and serotonin as novel therapeutic targets in the management of BPH.Item Pelargonium graveolens Attenuates Rotenone‑Induced Parkinson’s Disease in a Rat Model: Role of MAO‑B Inhibition and In Silico Study(Humana Press, 2025-02-08) Rana M. Merghany; Salma A. El‑Sawi; Asmaa F. Aboul Naser; Mohamed A. Salem; Shahira M. Ezzat; Sherifa F. A. Moustafa; Meselhy R. MeselhyParkinson’s disease (PD), the second most common neurodegenerative condition, is primarily characterized by motor dysfunctions due to dopaminergic neuronal loss in the Substantia Nigra (SN), with oxidative stress playing a signifcant role in its progression. This study investigates the neuroprotective potential of Pelargonium graveolens (Thunb.) L’Hér leaves in a rotenone-induced PD rat model. The total ethanolic extract and its fractions, obtained via Diaion HP-20 column chromatography, were evaluated for monoamine oxidase-B (MAO-B) inhibition in vitro. The 50% methanol fraction (PG50) demonstrated the highest MAO-B inhibition (IC50 5.26±0.12 µg/ml) compared to the reference drug selegiline (IC50 0.021±0.003 µg/ml). In a rotenone-induced PD rat model, PG50 (100 mg/kg, p.o.) alleviated motor defcits (assessed via the wire hanging test), and restored norepinephrine, dopamine, and serotonin levels. PG50 and l-dopa reduced α-synuclein levels by 367.60% and 377.48%, respectively. Oxidative balance was restored with increased glutathione (23.12%) and decreased malondialdehyde (164.19%) in brain tissues. PG50 signifcantly reduced serum TNF-α (572.79%) and IL-6 (70.84%) levels, and improved succinate dehydrogenase (14.47%) and lactate dehydrogenase (7.74%) activities in brain tissues. Histopathological alterations in the SN were also ceased. UPLC-MS/MS analysis identifed 61 metabolites, including 32 favonoids, 13 phenolic acids, 7 coumarins, 5 phenolic glycosides, and 4 dicarboxylic acids, with in silico docking showing strong MAO-B binding by methoxylated favonoids like methoxyluteolin dimethyl ether (docking score:−8.0625 kcal/mol), surpassing that of safnamide (−8.2615 kcal/mol). These fndings suggest that P. graveolens holds promise as a neuroprotective agent against rotenone-induced PD.Item New series of fluoroquinolone derivatives as potential anticancer Agents: Design, Synthesis, in vitro biological Evaluation, and Topoisomerase II Inhibition(Academic Press Inc., 2025-01-13) Mina E. Adly; Azza T. Taher; Fakher M. Ahmed; Ashraf M. Mahmoud; Mohamed A. Salem; Rana M. El-MasryA series of fluoroquinolone analogs (II, IIIa-g) derived from Ciprofloxacin hydrazide were designed, and synthesized. The NCI-60 Human Tumor Cell Line Screening assay indicated that compounds II, IIIb, and IIIf are the most potent among the series and were further selected for five-dose evaluation, where they exhibited potent cytotoxicity with mean GI50 values of 3.30, 2.45, and 9.06 µM, respectively, where they reduced the cell proliferation of most of the tested cell lines with IC50 values significantly lower than the reference drug Etoposide. A selectivity study demonstrated the high selective cytotoxicity of IIIf towards cancerous cells over normal mammalian Vero cells, presenting it as a potent and selective antitumor agent. Cell cycle analysis revealed that treatment with II, IIIb, or IIIf induced cell cycle arrest at the G2/M phase in MCF-7 cells. Topoisomerase II enzyme inhibition assay showed that the three tested compounds are potent topo II inhibitors where compound II (IC50 = 51.66 µM) displayed more potent inhibitory activity compared to the well-known topo II inhibitor Etoposide (IC50 = 58.96 µM), while compounds IIIb and IIIf showed comparable activity to the reference drug. Molecular modeling study suggested that the topoisomerase inhibitory activity may be attributed to the binding to the Merbarone binding site and chelation with Mg2+Item Synthesis and Characterization of 5-FU-Loaded CaCO3Nanoparticles for Targeted Cancer Therapy(Andover House, Inc., 2024-12-22) Kshidan Marim Abdullah Salem; Mohamed Ahmed Ibrahim; Kim Wei Chan; Md Zuki Abu Bakar; Noorjahan Banu Alitheen; Mohammed Alsubbi; Ahmad Faizal Abdull Razis; Norsharina IsmailChemotherapy is often limited by its systemic toxicity and lack of specificity, necessitating the development of targeted drug delivery systems that can enhance therapeutic efficacy while minimizing adverse effects. Addressing this, our study aimed to synthesize and characterize 5-Fluorouracil loaded calcium carbonate nanoparticles derived from cockle shells. The research aimed at increasing site-specific drug release and reducing cytotoxicity. The nanoparticles were prepared using a simple co-precip itation method, ensuring eco-friendliness and cost-effectiveness. The encapsulation of 5-FU was confirmed by transmission electron microscopy (TEM), which revealed an increase in nanoparticle size from 19.2 ± 2.284 nm for the unloaded ones to 34.8 ± 4.066 nm for the 5-FU-loaded CaCO3 NPs. In vitro release studies demonstrated a pH-sensitive release profile, with more rapid drug release at pH 4.8 compared to pH 7.3. Biocompatibility assays on the HS-27 human skin fibroblast cell line indicated high cell viability, with over 90% maintained even at high nanoparticle concentrations (1000 µg/mL). In addition, cytotoxicity assays on the SW480 (primary colon cancer) and SW620 (metastatic colon cancer) cell lines showed a dose-dependent decrease in cell viability and demonstrated a more controlled and sustained release compared to free 5-FU, resulting in higher cell viability at all time points and concentrations. The 5-FU-loaded CaCO3 NPs significantly reduced the immediate cytotoxic effects observed with free 5-FU while effectively targeting cancer cells. These findings suggest that the 5-FU-CaCO3 NPs offer a promising alternative to conventional chemotherapy, providing targeted drug delivery with the potential for reduced systemic toxicity and enhanced therapeutic efficacy. © 2024, Andover House, Inc.. All rights reserved.Item Pseudocitrobacter cyperus, a novel bacterial species recovered from Cyperus alternifolius in Egypt(BioMed Central Ltd, 2025-01-12) Samira M. Hamed; Mai A. AmerBackground Strain Cyp38ST was isolated as an endophyte from the plant Cyperus alternifolius, collected along the banks of the River Nile in 2019. Preliminary analysis tentatively identified Cyp38ST as belonging to the genus Pseudocitrobacter. Methods The preliminary identification of Cyp38ST was performed using the VITEK®2 identification system, MALDITOF-MS, and 16S rRNA gene sequencing. To confirm its taxonomic classification, the draft genome of Cyp38ST was generated using DNBseq, and the genome-based taxonomic evaluation was conducted by calculating the overall genome-relatedness indices (OGRIs) such as Average Nucleotide Identity (ANI), digital DNA-DNA hybridization (dDDH), and the tetra-nucleotide signatures (Tetra). Additionally, the biochemical features, antimicrobial susceptibility profiles, and fatty acid methyl ester content of Cyp38ST were characterized. Results VITEK®2 misidentified Cyp38ST as Citrobacter werkmanii, MALDI-TOF-MS identified it as Pseudocitrobacter faecalis. While the 16S rRNA gene showed more than 99.0% similarity to other Pseudocitrobacter species, the calculated OGRIs were lower than the thresholds recommended for species assignment to all currently known Pseudocitrobacter species. Furthermore, the phylogenomic analysis revealed that Cyp38ST forms a distinct species cluster within the genus Pseudocitrobacter. Cyp38ST was predicted as a potential human pathogen and carried a unique ß-lactamase-coding gene. Conclusion Here we present Cyp38ST (=CCASU-2024-73T ) as the type strain of a novel species within the genus Pseudocitrobacter to which we propose the name Pseudocitrobacter cyperus sp. nov. We provide a full description of the novel species and present its genome sequence and annotation. The discovery of this novel species highlights the potential of endophytic bacteria associated with unique plant hosts to harbor previously uncharacterized microbial diversityItem 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 Green analytical chemistry and quality by design: A combined approach towards simultaneous determination of Letrozole with its co-administered Zoledronic Acid for cancer patients(Elsevier B.V, 2024-08-01) Nourhan A. Abd El-Fatah; Heba T. Elbalkiny; Maha A. Hegazy; Manal Mohammed Fouad; Ghada M. El-SayedNowadays, breast cancer is the most affecting and globally diagnosed malignancy among women, yet Letrozole (LTZ) was considered the first-line treatment as hormonal anticancer drug. Unfortunately, LTZ develops osteoporosis as a main side effect which was overcome by using the co-administered; Zoledronic Acid (ZDA). Thus, there was a crucial need for this simultaneous quantification innovation, especially there were no any previously reported methods regarding both drugs together. In this study, an integrated framework was conducted between the experimental analytical quality-by-design (AQbD) approach and green analytical chemistry (GAC), emerging sensitive and robust RP-HPLC method. Box-Behnken Design was the developed model for optimizing an isocratic chromatographic separation on C18 Equisil® ODS (4.6 × 250 mm, 5.0 μm) column at ambient temperature, using the mobile phase of 0.1 % aqueous trifluroacetic acid (pH 2.8): acetonitrile (54.5:45.5, v/v), at 1.0 mL/min flow rate with PDA detection at 254.0 nm and 210.0 nm for LTZ and ZDA, respectively. Model statistical and residual plots analysis was significant and normally distributed. Method was fully validated as per ICH guidelines, where good linearity was 0.20–10.00 µg/mL for both drugs in presence of Tadalafil (TDF) as an internal standard, obtaining adequate correlation coefficients (r) values. Calculated LOD results were 0.058 and 0.040 µg/mL while calculated LOQ results were 0.175 and 0.122 µg/mL for LTZ and ZDA, respectively. The proposed method was effectively applied on bulk, pharmaceutical dosage forms, and spiked human plasma. Statistical comparison of the anticipated results with the reported ones was performed. Greenness assessment was evaluated using Green Analytical Procedure Index (GAPI) and Analytical Greenness (AGREE) tools; where superiority results were achieved relative to other reported methods. Finally, an EVG method evaluation tool was assessed, and the attained results were represented through its radar chart.Item Transcriptional analysis of C. elegans fmos at diferent life stages and their roles in ageing(Springer Verlag, 2024-12-05) Mohamed Said; Bill T. Ferrara; Andreea Aprodu; Filipe Cabreiro; Elinor P. Thompson; Jeremy EverettFlavin-containing monooxygenases (FMOs) are present in most organisms including plants, fungi, bacteria, invertebrates and vertebrates, where they catalyse the oxidative metabolism of a range of xenobiotics and endogenous metabolites. FMOs have been associated with ageing and longevity in the mouse and in C. elegans. As all five FMOs of C. elegans share an evolutionary root with mouse and human FMO5, it was of interest to discover if effects on ageing and longevity persisted across the whole group. We therefore investigated the impact of fmo gene knockout (KO) in C. elegans. We found that fmo-1, fmo-3 and fmo-4 KO significantly extended C. elegans lifespan relative to wild type and, as previously reported, FMO-2 over-expression did likewise. The transcription levels of C. elegans fmo genes were determined throughout the life cycle (embryo, larva and adult) in wild type and in each mutant to discover if their expression was related to stages in ageing, and expression levels were compared to those in human and mouse. In wild type worms, fmo-1 and fmo-4 were the mostly highly transcribed genes (especially at the larval stage), whereas fmo-2 and fmo-3 were the least transcribed, at all stages. Notably, the knockout of fmo-4 led to a 17- to 30-fold up-regulation of fmo-2, along with significantly increased levels of the other fmos. This parallels recent findings in the long-lived C. elegans tald-1 mutant where fmo-2 was also significantly up-regulated and reinforces its importance in lifespan extension. © The Author(s) 2024.Item Analysis of four long non-coding RNAs for hepatocellular carcinoma screening and prognosis by the aid of machine learning techniques(Nature Publishing Group, 2024-11-04) Ahmed Samir; Amira Abdeldaim; Ammar Mohammed; Asmaa Ali; Mohamed Alorabi; Mariam M. Hussein; Yasser Mabrouk Bakr; Asmaa Mohamed Ibrahim; Ahmed Samir AbdelhafizHepatocellular carcinoma (HCC) represents a significant health burden in Egypt, largely attributable to the endemic prevalence of hepatitis B and C viruses. Early identification of HCC remains a challenge due to the lack of widespread screening among at-risk populations. The objective of this study was to assess the utility of machine learning in predicting HCC by analyzing the combined expression of lncRNAs and conventional laboratory biomarkers. Plasma levels of four lncRNAs (LINC00152, LINC00853, UCA1, and GAS5) were quantified in a cohort of 52 HCC patients and 30 age-matched controls. The individual diagnostic performance of each lncRNA was assessed using ROC curve analysis. Subsequently, a machine learning model was constructed using Python’s Scikit-learn platform to integrate these lncRNAs with additional clinical laboratory parameters for HCC diagnosis. Individual lncRNAs exhibited moderate diagnostic accuracy, with sensitivity and specificity ranging from 60 to 83% and 53–67%, respectively. In contrast, the machine learning model demonstrated superior performance, achieving 100% sensitivity and 97% specificity. Notably, a higher LINC00152 to GAS5 expression ratio significantly correlated with increased mortality risk. The integration of lncRNA biomarkers with conventional laboratory data within a machine learning framework demonstrates significant potential for developing a precise and cost-effective diagnostic tool for HCC. To enhance the model’s robustness and prognostic capabilities, future studies should incorporate larger cohorts and explore a wider array of lncRNAs.Item Curcumin-loaded PEG-coated Magnetite Nanoparticles Synthesized from Theobroma cocoa: Neuronal Biocompatibility and Anti-inflammatory Properties in SH-SY5Y and RAW 264.7 Cells(Tsinghua University Press, 2024-10-07) Mohamed Abdelmonem; Norazalina Saad; Huey Fang Teh; Ahmad Kamil Mohd Jaaffar; Mohamed Ahmed Ibrahim; Maha A. Alhadad; Che Azurahanim Che AbdullahNeurodegenerative diseases (NDDs) encompass numerous disorders affecting the nervous system's structure and functions, primarily caused by protein aggregation, oxidative stress, and inflammation. These factors make a significant contribution to the progression of various NDDs. Curcumin (CUR), a natural bioactive compound known for its anti-inflammatory and antioxidant properties, has limited application because of its hydrophobicity. To address this issue, PEGylated coated magnetite nanoparticles (MNPs) were developed as efficient nanocarriers. These MNPs were synthesized using plant polyphenols from cocoa bean (Theobroma cacao) shell extract, coated with PEG, and then loaded with CUR at various concentrations. The nanomaterials were characterized using X-ray diffraction (XRD), Dynamic light scattering (DLS), zeta potential (ZP), FTIR, Transmission electron microscopy (TEM), selected-area electron diffraction (SAED), and vibrating sample magnetometer (VSM). The nanoparticles were found to be spherical, with diameters in the range of 10-19 nm. VSM analysis showed that the MNPs exhibited superparamagnetic behavior at room temperature. In vitro studies using ultraviolet (UV) spectrophotometry revealed rapid CUR drug loading within 3 h and total drug release of 57% over 48 h, indicating the potential of the MNPs as a neuroprotective agent. The cell viability associated with exposure to the nanoformulations was also assessed in human neuroblastoma cells (SH-SY5Y) using the MTT assay. In addition, the safety and anti-inflammatory properties of PEGylated MNPs-CUR were evaluated in LPS-induced murine macrophages (RAW 264.7). Cells exposed to the nanoparticles exhibited high viability, indicating their safety for human neuroblastoma cells, and the nanoparticles effectively reduced nitric oxide production in murine macrophages. These findings suggest that PEGylated MNPs-CUR possess significant potential as neuroprotective agents for brain-related diseases, given their biosafety and anti-inflammatory properties.Item A sustainable and green HPLC-PDA technique for the simultaneous estimation of Post-COVID-19 syndrome co-administered drugs with greenness and whiteness assessment(Nature Publishing Group, 2024-11-05) Passant M. Medhat; Manal Mohamed Fouad; Hany H. Monir; Nermine S.GhoniemCOVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10–15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors’ quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00–45.00 µg/mL, 0.5–50.00 µg/mL, and 0.15–20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55–99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method’s greenness. “Non-toxic” ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method’s greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.Item Smart sequential spectrophotometric analysis of Fluconazole and its two toxic official impurities having superimposed spectra; Greenness, whiteness, blueness assessment and in silico toxicity profiling(Elsevier B.V., 2024-11-11) Christine M. El-Maraghy; Mai S. Nour; Ekram H. MohamedOwing to the health hazards of impurities presence in active pharmaceutical ingredients, even in minute amount. A smart green sustainable spectrophotometric method was developed for simultaneous determination of Fluconazole (FLU) along with its official impurities B and C. The novel sequential dual amplitude difference (SDAD) technique succeeded in resolving the severe overlapping between the three compounds and restoring their respective mother spectrum. According to international Council of Harmonization (ICH) guidelines, the developed method is accurate, precise, and selective with linearity range (50–500 µg/mL) for FLU, (0.5–6 µg/mL) for impurity B and (0.05–0.6) for impurity C. The method was successfully applied to three pharmaceutical preparations without interference from excipients. In addition, the proposed method was assessed and compared with reported chromatographic methods for its green character, sustainability, and practicality, using five tools. The spectrophotometric method was found to be the greenest with the least volume of solvents used and waste produced, moreover, it is the most practical/sustainable method. Besides, the toxicity profiling of the two impurities was predicted using two computational databases: preADMET and pKcsm. After reviewing literature, no previous analytical method to determine FLU and its two official impurities using spectrophotometry was reported.Item Impact of thermal processing on phytochemical profile and cardiovascular protection of Beta vulgaris L. in hyperlipidemic rats(Nature Publishing Group, 2024-11-02) Engy Mohsen; Marwa I. Ezzat; Ibrahim E. Sallam; Dalia Zaafar; Aya Y.Gawish; Yasmine H.Ahmed; Ahmed H. Elghandour; Marwa Y. IssaBeetroot (Beta vulgaris L.) is globally recognized for its outstanding color and flavor. It has been acknowledged for its therapeutic value since the ancient Romans. It is used to treat cardiovascular disorders. The therapeutic benefits of red beetroot are due to the substantial amounts of various bioactive metabolites, such as ascorbic acid, carotenoids, nitrates, phenolics, and betalains. However, the bioavailability and shelf life of these substances are significantly affected by the considerable variations in their processing methods among different countries. The longevity of the extracts is prolonged by employing well-established preservation techniques, such as boiling and steaming, which involve the application of heat. Our study aimed to analyze and compare the phytochemical composition of raw and heat processed beetroot using UPLC-QTOF-MS/MS. In addition, the study aimed to assess the effectiveness of processed beetroot in protecting against cardiovascular complications in a rat model of obesity induced by high-fat diet (HFD). UPLC-QTOF-MS/MS phytochemical profiling revealed the presence of 51 compounds, including organic acids, flavonoids, phenolics, betanins, and saponins. All the extracts demonstrated a significant decline in MDA, TNF- α, and IL-6 levels, suppressed the TGF-β expression, and restored the serum catalase level to normal. Among all the tested extracts, the steamed extract exhibited the slightest percentage change in body weight (10.2±6.4) and effectively lowered the TNF-α level to normal levels. In contrast, the normal histological structure of heart muscle fibers was notably preserved in the cardiac sections of rats pretreated with steamed and boiled beetroot extracts. Additionally, mild caspase-3 immunoreactivity was observed in the cardiac muscles. The current study demonstrated that the steamed beetroot extract showed improved cardioprotective properties compared to the fresh and boiled extracts.Item Evaluating the risk of listeriosis through genotypic profiling of potentially hazardous strains isolated from local food market(Zagazig University, 2024-11-02) Lamiaa I. Fahmy; Heba M. AminBackground: Listeriosis is a serious food-borne disease caused by Listeria monocytogenes pathogen that causes fatal systemic infections in the elderly and immunocompromised people. Listeria monocytogenes can be transferred from contaminated ready-to-eat or frozen foods. This study aimed to investigate the most prevalent serotypes of Listeria monocytogenes isolates in frozen food in Egypt, their phenotypic and genotypic antimicrobial resistance, biofilm formation, as well as virulence encoding genes. Methods: A total of 331 frozen food product samples were randomly chosen from various marketplaces and cultured for the presence of Listeria monocytogenes. The antibiogram of the isolated Listeria monocytogenes was assessed using the Kirby– Bauer disk diffusion method. Polymerase chain reaction (PCR) was performed to detect four antimicrobial resistance encoding genes and seven virulence genes. A multiplex PCR assay was performed. Results: Listeria monocytogenes was found in 14.2% (47/331) of the examined samples, and the most predominant serotypes belonged to molecular sero-groups 1/2a-3a. Listeria monocytogenes bacteria showed high phenotypic resistance rates to ampicillin (91%), cefotaxime (87%) and clindamycin (66%). Strong and moderate biofilm producers accounted for 21.4% and 11.9% of isolates, respectively. The most commonly detected genetic markers of resistance were strB and tetA genes (70%). The virulence genes: plcB, prs-prfA, iap and hlyA genes, were detected in 90%,87%, 87% and 30% of the isolates, respectively, while plc A, prfA and flA genes were detected in 83%, 97% and 90% of the isolates, respectively. Conclusion: Listeria monocytogenes food pathogen exists with considerable rates in frozen products, which may seriously threaten public health.