Faculty Of Pharmacy Research Paper

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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 Everett
Flavin-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.
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 Abdelhafiz
Hepatocellular 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.
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 Abdullah
Neurodegenerative 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.
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.Ghoniem
COVID-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.
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. Mohamed
Owing 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.
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. Issa
Beetroot (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.
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. Amin
Background: 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.
Clinical uses of cannabis and Catha edulis products
(Elsevier, 2024-01-01) Shahira M. Ezzat; Passent M. Abdel Baki; Rana M. Ibrahim; Doaa Abu Elezz; Mahmoud Abdelaziz; Mohamed A. Salem
The medicinal use of cannabis (Cannabis sativa) and khat (Catha edulis) as well as their products has been increased in the last decade. Medical cannabis and khat have been legalized in several countries. Additionally, the major cannabinoids, particularly cannabidiol and tetrahydrocannabinol, have been utilized for the development of FDA-approved pharmaceuticals. The clinical applications of cannabis and C. edulis products are complicated by legislation and regulations that are varied among countries. In this chapter, the pharmacological and the side effect profiles for the clinical uses of cannabis and C. edulis products are highlighted. Although, the clinical data for their use are continuing to evolve, the legal status needs to be authorized to keep the balance between clinical applications and limitations.
Extraction and isolation of cannabinoids
(Elsevier, 2024-01-01) Mohamed A. Salem; Rana M. Ibrahim; Passent M. Abdel Baki; Sohila M. Osman; Shahira M. Ezzat
Cannabis sativa L. is one of the most important medicinal plants that belongs to the family Cannabaceae. C. sativa is a herbaceous flowering plant that is indigenous to eastern Asia, but it is now cultivated worldwide due to the importance of its active constituents known as cannabinoids. Due to the growing interest in these compounds, various methods for their extraction and isolation were proposed. In this chapter, we will have an overview about the conventional and nonconventional methods for extraction of cannabinoids both from plant material and from biological samples for forensic purposes. Also we will review the methods for isolation of such compounds from different types of extracts as well as the modern methods for metabolomics and chemometric tools for analysis of cannabinoids.
Enhancing oral cancer treatment via photodynamic therapy: Gold nanoparticle-based delivery system for 5-aminolevulinic acid (5-ALA)
(Elsevier Ltd, 2024-09-10) Romesa Soomro; Mohamed Abdelmonem; Bachren Azra Saputra; Che Azurahanim Che Abdullah
Oral squamous cell carcinoma (OSCC) is a significant global health concern, responsible for approximately 300,000 new cases and 145,000 deaths annually, making it the sixth most common malignancy worldwide. Traditional treatments, including surgery, radiation, and chemotherapy, often lead to severe side effects such as physical disfigurement, functional loss, and systemic toxicity. These limitations have spurred the search for alternative therapies, with photodynamic therapy (PDT) gaining recognition for its reduced invasiveness, improved targeting, and better cosmetic outcomes. However, PDT faces challenges, including inadequate photosensitizer (PS) delivery, poor specificity, and degradation in physiological environments. Nanotechnology has emerged as a promising solution to enhance PDT by improving the stability, selectivity, and therapeutic efficacy of PSs. Gold nanoparticles (AuNPs) have shown the potential to enhance PDT outcomes, particularly in OSCC, by inhibiting tumor proliferation and improving diagnostic accuracy without systemic toxicity. Despite these advancements, the conventional chemical synthesis of AuNPs poses environmental concerns, high costs, and potential biocompatibility issues. This study introduces a novel biogenic synthesis approach for AuNPs, utilizing green chemistry principles to create more biocompatible and environmentally sustainable nanoparticles. The novelty of this research lies in the application of green-synthesized AuNPs to enhance PS delivery in PDT, offering a more effective and less toxic treatment option for oral cancer. This innovative approach addresses the limitations of current PDT and nanoparticle synthesis methods, contributing to the development of more sustainable and biocompatible cancer therapies. The study's findings are contextualized within the increasing scholarly and patent activity surrounding AuNPs and 5-aminolevulinic acid (5-ALA) in cancer therapies, underscoring the growing importance of this field in advancing OSCC management.
Metabolic Profiling of Millingtonia hortensis L.f. Leaves Using UHPLCMS/MS and Evaluation of its Antioxidant, Cytotoxic, Anticholinesterase Activities and Molecular Docking
(National Information and Documentation Centre (NIDOC), 2024-11-02) Sohila M. Elnaggar; Soumaya S. Zaghloul; Hanaa A. Kassem; Amira K. El Motayam
Background: Millingtonia hortensis L.f. known as Tree Jasmine or Indian Cork tree, stands as the only species within the genus Millingtonia and it is originated from South-East Asia, it belongs to family Bignoniaceae. The genus name, Millingtonia, is in honor of Sir Thomas Millington, the English botanist, while hortensis means “grown in gardens”. The phytochemical screening of M. hortensis L.f. showed the presence of different chemical classes as carbohydrates, tannins, saponins, flavonoids, cyclohexylethanoid glycosides, and volatile oil. Different pharmacological actions were reported such as antiproliferative, antimutagenic, antibacterial, antifungal, and antioxidant activities. Aim: This study aims to investigate the phytochemical constituents of M. hortensis L.f. and evaluate its biological activities. Material and Methods: The total ethanolic extract M. hortensis L.f. was assessed by LC-MS/MS profiling followed by spectrophotometric determination of total phenolics and flavonoids. For biological evaluation, the antioxidant activity was assessed using (DPPH, ABTS, FRAP, and ORAC) assays. In-vitro cytotoxic study was performed using colorectal cancer (LS-513) and hepatocellular carcinoma (HepG2) cell lines and also anticholinesterase activity was determined. Furthermore, some of the identified compounds were analyzed by molecular docking studies to determine the binding affinity between the ligands and the enzyme (acetylcholinesterase). Results: The LC-MS/MS analysis of the total ethanolic extract resulted in identification of twenty eight compounds. The level of total phenolic contents was (34.137 ± 0.509 µg Gallic acid Eq/mg) in the total ethanolic extract while the level of total flavonoid content in total ethanolic extract was (10.256 ± 0.579 µg Rutin Eq/mg). The results of ABTs, ORAC and DPPH antioxidant assays demonstrated that dichloromethane fraction of M. hortensis L.f. leaves has the highest effect for free radical scavenging, while the n-hexane extract showed the highest effect for free radical scavenging in the FRAP assay, in-vitro cytotoxic activity showed that the total ethanolic extract has the least IC50 which indicates its highest activity compared to the other fractions, anticholinesterase activity obtained by Ellman’s method indicates that dichloromethane fraction showed a significant activity against AChE causing 80.6 ± 0.007 % inhibition while ethyl acetate fraction showed least activity against AChE causing 31.8 ± 0.02 % inhibition at 0.1 mg/mL concentration. The molecular docking study revealed that apigenin was found to be more potent than hispidulin due to the strong interactions with amino acid residue SerA:200, HisA:440 and those of the peripheral region are crucial for strong inhibitory activities against AChE. Conclusions: The results of this study revealed that the plant’s identified phenolics and flavonoids, as detected in the LC-MS/MS analysis, may be correlated with the plant’s notable antioxidant, cytotoxic, and anticholinesterase activities.
Eco-friendly tea waste magnetite nanoparticles for enhanced adsorptive removal of norfloxacin and paroxetine from water
(Elsevier Inc., 2024-11-01) Lamis M. Fahmy; Dalia Mohamed; Marianne Nebsen; Ahmed H. Nadim
Traces of pharmaceuticals have been detected in water cycle raising concerns regarding the potential risks to human health and aquatic environment. Accordingly, removal of such compounds from water samples is a major concern. Herein, a facile and green NaOH modified tea waste magnetite nanoparticles have been fabricated for the adsorptive removal of a commonly used antibiotic (norfloxacin) and antidepressant (paroxetine) from water samples. The synthesized nanoparticles were characterized using TEM, FT-IR, DLS and VSM. Factors affecting the adsorption efficiency have been investigated with respect to pH (5, 7 and 9), adsorbent amount (0.125, 0.25 and 0.5 g), initial drug concentration (25, 50 and 100 µg/mL) and contact time (0.5, 1 and 2 h). The adsorption isotherms have been calculated. A percentage removal of 98 % and 99 % were obtained for simultaneous removal of 50 µg/mL norfloxacin and paroxetine, respectively in 2 h. Monitoring norfloxacin and paroxetine concentrations was performed through a validated HPLC-DAD method. The reusability of the nanoparticles has been studied for 3 adsorption–desorption cycles. No significant loss in adsorption efficiency was observed offering a sustainable water treatment. This study would offer a facile, green and economic protocol for the removal of complex organic compounds from water resources.
The efcacy of tixagevimab/cilgavimab (Evusheld) in prophylaxis and treatment of COVID-19 in immunocompromised patients: a systematic review and meta-analysis
(BioMed Central Ltd, 2024-12-01) Shaymaa Glhoom; Aya Fergany; Dina El‑Araby; Asmaa A. Abdelkhalek; Asmaa Gomaa; Eman O. Zayed; Mohamed Abd‑ElGwad
Background During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as preexposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efcacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophy‑ laxis for higher-risk individuals to reveal if there is a signifcant diference in efcacy between those two doses of the drug.
A cutting edge potentiometric determination of baricitinib in synthetic wastewater and in tablet dosage form using modified carbon paste ion-selective membrane
(Elsevier Inc., 2024-09-21) Heba T. Elbalkiny; Mona S. Elshahed; Dalia Mohamed; Azza A. Ashour; Rasha Th. El-Eryan
After the recent hit of COVID-19, many drugs were successively administered to save patients’ lives and those drugs reached aquatic sources, one of those drugs was Baricitinib. Driven by the current situation, a potentiometric technique using an ion-selective membrane (ISM) recipe drop cast on a modified carbon paste electrode was optimized for the superior determination of Baricitinib (BAR). The molecular docking was customized to optimize the proper ionophores incorporated in the ISM, revealing that beta-cyclodextrin (β-CD) is the most compatible ionophore with the studied drug. A multivariate optimization experimental design was employed to optimize the best experimental condition for the analytical method. To this end; dual nanoparticles (multi-walled carbon nanotubes and copper oxide nanoparticles) were incorporated in the carbon paste electrode, and the ISM recipe was enriched with β-CD and cation-exchanger (phosphotungstic acid) in a polyvinylchloride matrix plasticized with dibutyl phthalate. A Nernstian slope equal to 19.97 mV/decade with a linearity range of 7.99 × 10−7–1.00 × 10−3 M was obtained. The validated sensor exhibited good recovery when used to determine the studied drug in synthetic wastewater and tablet dosage form. The greenness of the method was evaluated using the Complementary Green Analytical Procedure Index and Blue Applicability Grade Index.
Optimizing nutraceutical-loaded trehalosomes in-situ gel for diabetic cataract management: Comprehensive in vitro and in vivo evaluations
(Editions de Sante, 2024-11-03) Aya Hussein; Maha El-Kayal; Rehab Nabil Shamma; Heba H. Awad; Nihal Farid Younes
This study aimed to develop Baicalin-loaded trehalosomes in situ gel (BA-THs-ISG) for the treatment of cataract, a degenerative eye condition that requires innovative approaches to enhance visual acuity and quality of life. A 33 D-optimal design was implemented for the preparation and statistical optimization of BA-THs. Various in-vitro studies were conducted to evaluate the features of the optimized formula, which was subsequently loaded into an optimum ISG to sustain the release pattern. To assess the therapeutic efficacy of BA-THs-ISG, an in-vivo study was conducted using a streptozotocin (STZ) induced diabetic cataract model. The results demonstrated that the optimized formula of desirability function of 0.878 had a particle size (PS) of 237.9 ± 2.87 nm, a polydispersity index (PDI) of 0.27 ± 0.03, a zeta potential (ZP) of −27.31 ± 1.27 mV, an entrapment efficiency (EE%) of 74.32 ± 1.08 % and sustained drug release over 6 h. After being loaded into ISG, BA-THs-ISG exhibited a gelation temperature of 35.00 ± 0.30 °C and a gelation time of 49 ± 2.63 s, meeting the intended criteria. Moreover, it effectively maintained drug release for a duration of 12 h. Compared to the BA solution in the in-vivo studies, BA-THs-ISG significantly reduced malondialdehyde content and enhanced superoxide dismutase and glutathione peroxidase activities without any irritation potential. Therefore, BA-THs-ISG is inferred to be a highly effective option for improving cataract symptoms.
Design, synthesis, and cytotoxicity screening of novel pyrazolopyrimidines over renal cell carcinoma (UO-31 cells) as p38α inhibitors, and apoptotic cells inducing activities
(Elsevier Masson s.r.l., 2025-01-05) Sara Y. Ewieda; Amr Sonousi; Aliaa M. Kamal; Mohamed K. Abdelhamid
A series of novel molecules with pyrazolopyrimidine-4-amine core were designed and synthesized as potential cytotoxic agents over Renal Cell Carcinoma cells (UO-31). Results of cytotoxic activity against UO-31 cells showed that pyrazolopyrimidines 19 and 31 were found to be more cytotoxic than sorafenib (SOR). The cytotoxic activity of these compounds appeared to correlate with their ability to inhibit p38α MAPK which are 2.53- and 2.27- folds more potent than SOR. Moreover, results of the cell cycle analysis as well as the results of annexin-V on the (UO-31) cells showed that pyrazolopyrimidines 19 and 31 had a pro-apoptotic activity higher than SOR by 1.42- and 1.20- folds, respectively. Furthermore, compounds 19 and 31 were found to be effective in arresting the cell cycle throughout the accumulation of the cells at G2/M phase. Finally, the tested compounds decreased the TNF concentration as well as increased the expression of tumor suppressor gene p53, Bax/BCL-2 ratio and caspase 3/7.
Relieving postherpetic neuralgia pain via gabapentin‑loaded bigels as an auspicious topical drug delivery system
(BioMed Central Ltd, 2024-10-08) Wessam H. Abd‑Elsalam; Abdulaziz Mohsen Al‑Mahallawi; Amal Makhlouf
Background Over the past decades, a substantial portion of the population worldwide has been infected with varicella zoster and most cases developed shingles. Unfortunately, shingles is usually accompanied by postherpetic neuralgia, which may persist for months to years after the resolution of the viral infection. Objectives Gabapentin is an orally gamma-aminobutyric acid analogue approved by the Food and Drug Administration to manage shingles postherpetic neuralgia. However, gabapentin shows nonlinear pharmacokinetics, with variable absorption and bioavailability along with its short half-life and long side efects that may include dizziness and somnolence, which calls for an appropriate topical dosage form. Bigels are unique semisolid dosage forms with boosted penetrability and satisfactory hydrophilic texture. Methods The current work pointed to formulating gabapentin-loaded bigels for the treatment of postherpetic neuralgia, where the analysis and optimization of design were performed via Design-Expert®. Results and conclusions The selected bigel (F5), incorporating 400 mg Span 60, 1000 mg Tween 80, and 1000 mg Transcutol, displayed spherical nanosized particles with acceptable viscosity and spreadability. Subsequent topical application of the selected bigel on the skin of Wistar rats, F5, demonstrated a boosted accumulation of gabapentin in the skin similar to PLO gel but superior to the drug solution. Furthermore, a histopathological study demonstrated the biosafety of the selected bigel when applied topically. Accordingly, gabapentin-loaded bigel would be considered a potentially topical dosage form for the delivery of gabapentin for the management of postherpetic neuralgia.
In silico analysis and comprehensive review of circular-RNA regulatory roles in breast diseases; a step-toward non-coding RNA precision
(Elsevier GmbH, 2024-10-19) Nadia M. Hamdy; Mona G. El-Sisi; Sherine M. Ibrahim; Heba ElNokoudy; Ahmad A. Hady; Gamal Eldein Fathy Abd-ellatef; Al-Aliaa M. Sallam; Bassant Mohamed Barakat
In the current comprehensive review, we first highlighted circRNAs, which are key ncRNAs. Next, we discussed the relationships among circRNAs and breast cancer subtypes via in silico databases analysis and extensive literature search. CircRNAs, that sponge miRNA axes or act as silencers of oncogenic mRNAs, have been extensively addressed in the context of this review. During BC pathogenesis, the circRNA/microRNA/messenger RNA (mRNA) axis plays a major role in disease growth, progression, and survival/resistance and could be targeted for improved treatment options. This review also aimed to address oncogenic and tumor suppressor mRNAs, which are regulated by various circRNAs in BC. Moreover, we mentioned the relation of different circRNAs with cancer hallmarks, patient survival together with drug resistance. Additionally, we discussed circRNAs as vaccines and biomarkers in BC. Finally, we studied exosomal circRNAs as a hot interesting area in the research.
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, 2024-10-01) Passant M. Medhat; Manal Mohamed Fouad; Hany H. Monir; Nermine S.Ghoniem
COVID-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.
Synthesis of S-alkylated oxadiazole bearing imidazo[2,1-b]thiazole derivatives targeting breast cancer: In vitro cytotoxic evaluation and in vivo radioactive tracing studies
(Academic Press Inc, 2024-11-02) Eman R. Mohammed; Manal Abdel Fattah Ezzat; Emad M. Seif; Basma M. Essa; Hatem A. Abdel-Aziz; Tamer M. Sakr; Hany S. Ibrahim
Breast cancer is the most common invasive cancer diagnosed in women, accounting for most cancer-related fatalities globally. Numerous investigations have revealed that breast cancer is characterized by abnormal expression and maintenance of EGFR levels. In terms of structural study and optimization of several EGFR inhibitors, two series of oxadiazole bearing imidazo[2,1-b]thiazole derivatives were designed and synthesized as potential EGFR inhibitors and assessed for their antitumor activity at NCI-USA. Four derivatives 3b, 3c, 3d and 3e elicited remarkable GI% against MDA-MB-468, T-47D and MCF-7 breast cancer cell lines. Thereafter, MTT assay was performed to reveal that compounds 3b (IC50 = 2.27 µM) and 3d (IC50 = 1.46 µM) showed promising cytotoxic activity against MCF-7 and MDA-MB-468 cell lines, respectively, compared to their reference drugs. Compounds 3b, 3d and 3e revealed good selectivity toward tumor cells with reasonable safety profile when tested against the normal cell line MCF-10a. In vitro EGFR inhibitory assay demonstrated that compounds 3b (IC50 = 0.099 µM) and 3d (IC50 = 0.086 µM) exhibited comparable inhibitory activity to the standard drug erlotinib (IC50 = 0.046 µM). A flow cytometric analysis demonstrated that derivatives 3b and 3d arrested the cell cycle at the S phase in MCF-7 and MDB-MB-468, respectively. Furthermore, the most active derivative 3d was subjected to in vivo radioactive studies. In-vivo biodistribution of 99mTc-3d complex showed a notable elevated accumulation in the targeted sarcoma muscle, indicating the targeting capacity of compound 3d in the tumor of sarcoma mice model. The binding mode of compounds 3b and 3d with EGFR was studied by molecular docking and was further inspected by molecular dynamic simulations. Both compounds were shown to be stable during the course of simulation and demonstrated a plausible interaction pattern with the EGFR binding pocket.

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