Dr Mohammed Mahmoud Youssif

This study investigates a series of newly synthesized compounds, including pyridopyrimidine derivatives (9a-g), tricyclic pyridotriazolopyrimidine analogs (18a-d), and dihydropyrimidinones (22a-i), as apoptotic inducers and inhibitors of phosphatidylinositol-3-kinase α (PI3Kα), with potential anticancer activity. An initial in vitro screening of 60 cancer cell lines identified pyridopyrimidine derivatives 9a-g as promising broad-spectrum anticancer agents, with compound 9e demonstrating the strongest inhibitory activity, particularly against T-47D breast cancer cells. Notably, the antitumor potency of compound 9e surpassed that of Pictilisib, inducing G2-M phase cell cycle arrest and initiating apoptosis through the intrinsic apoptotic pathway. Molecular docking studies further indicated that compound 9e binds to PI3Kα in a similar fashion to the co-crystallized ligand. Moreover, compound 9e exhibited favorable drug-like properties, including compliance with Lipinski's rule and Veber's rule, good solubility, acceptable TPSA, and high gastrointestinal absorption reinforcing its potential as a highly effective anticancer agent.

This work aimed to prepare Terconazole loaded proniosomes (TCZ-PNS) utilizing modified coacervation technique for the management of fungal keratitis. Terconazole (TCZ) is a potent antifungal with poor aqueous solubility posing intricacies in its incorporation in ocular formulations. A 2 factorial design was adopted to probe independent formulation variables including A: Lecithin: cholesterol ratio, B: Surfactant: cholesterol ratio and C: Span® 80 contribution (% of total SAA). The formulae, generated by the design, were prepared and scrutinized regarding entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). Numerical desirability algorithms selected an optimum TCZ-PNS which boasted plausible %EE (89.51 % ± 0.94 %), nanoscale vesicles consistent with TEM measurements (247.9 ± 0.42 nm), a sufficiently high ZP (-43.42 ± 0.85 mV), and an in-vitro biphasic release profile that remained stable even after Gamma irradiation and short-term storage. The transcorneal ex-vivo permeation of TCZ-PNS was higher than that of TCZ suspension (≈ 2-fold). The formulation was further evaluated for pH, corneal hydration threshold, and histopathological safety, confirming its suitability for ocular application. Confocal laser microscopy revealed substantial corneal uptake (approximately twice as deep as of TCZ suspension). Additionally, microbiological assessments of the optimal TCZ-PNS compared to TCZ suspension demonstrated an inhibition zone nearly 50 % larger, a significantly lower MIC and MFC (64-fold reduction), and enhanced biofilm inhibition activity across most tested concentrations. These findings suggest that TCZ-PNS could be a propitious treatment choice to deeply deliver antifungal therapy for the eradication of deeply rooted and inaccessible fungal keratitis.

BACKGROUND: The number of people living with dementia and/or cognitive impairment worldwide is rising with a negative effect on quality of life for many older adults. This study aims to examine the factors associated with cognitive function among older adults in Kuwait.

METHODS: This cross-sectional study recruited 253 older adults ≥ 60 years from a Geriatric outpatient unit in Kuwait. Cognitive function (dependent variable) was assessed using the Arabic version of the Mini-Mental State Examination (MMSE) with scores < 24 indicative of cognitive impairment. Biochemical, nutritional, clinical, lifestyle, anthropometric, and sociodemographic independent variables were included.

RESULTS: A normal MMSE score was reported for 51.0% (n = 129) of the sample, with 34.7% and 14.2% of participants having mild and moderate/severe cognitive impairment, respectively. Multivariate ordinal logistic regression analysis indicated that Type 2 diabetes was associated with more than double the odds of cognitive impairment (OR = 2.15, 95% CI: 1.19-3.94; P = 0.01). Each additional level of education was associated with a lower likelihood of cognitive impairment (OR = 0.34, 95% CI: 0.26-0.43; P < 0.001).

CONCLUSION: This study identifies key risk factors associated with cognitive impairment in older Kuwaiti adults. These findings underscore the need for targeted interventions to mitigate cognitive decline in aging populations and provide context-specific data to support policy decisions.

In this study, the effects and mechanisms of water-soluble ferrous salts (WSFS) on the humification and carbon conversion during the co-composting of hoggery slurry (HG) and wheat husks (WH) were investigated. A composting mixture of HG and WH was treated with FeCl2 addition (T1) and FeSO4 addition (T2), and compared with an untreated control (CK), as a function of time (28 days). The duration of the high-temperature phase (>50 °C) for CK, T1, and T2 are 17, 15, and 15 days, respectively. Compared to the CK, T1 and T2 treatments reduced CO2 emissions by 11.4 % and 32.0 %, respectively. The calculated total global warming potential values were 293.67 (CK), 267.69 (T1) and 207.10 (T2) g CO2 eq kg−1. The humus concentrations increased in all treatments: CK by 28.10 %, T1 by 53.41 % and T2 by 49.73 % in composting. WSFS addition enhanced biotic humification by elevated the abundance and distribution of Bacillus, which promotes cellulose and hemicellulose decomposition, and Tepidimicrobium, which accelerates the production of humus, through use of sugars and proteins. Besides, WSFS addition decreased the levels of pathogenic bacteria in the final compost product. Notably, WSFS addition also benefited the abiotic humification by production of •OH during oxidation of Fe(II) in composting. This study enhances the understanding of the biotic and abiotic functions of FeSO4 and FeCl2 in promoting humification and reducing carbon emissions during composting. The detailed role of hydroxyl radical in composting and the effectiveness of WSFS-addition in composting nitrogen transformation are still need to be addressed in future.

In this study, the effects and mechanisms of water-soluble ferrous salts (WSFS) on the humification and carbon conversion during the co-composting of hoggery slurry (HG) and wheat husks (WH) were investigated. A composting mixture of HG and WH was treated with FeCl2 addition (T1) and FeSO4 addition (T2), and compared with an untreated control (CK), as a function of time (28 days). The duration of the high-temperature phase (>50 °C) for CK, T1, and T2 are 17, 15, and 15 days, respectively. Compared to the CK, T1 and T2 treatments reduced CO2 emissions by 11.4 % and 32.0 %, respectively. The calculated total global warming potential values were 293.67 (CK), 267.69 (T1) and 207.10 (T2) g CO2 eq kg−1. The humus concentrations increased in all treatments: CK by 28.10 %, T1 by 53.41 % and T2 by 49.73 % in composting. WSFS addition enhanced biotic humification by elevated the abundance and distribution of Bacillus, which promotes cellulose and hemicellulose decomposition, and Tepidimicrobium, which accelerates the production of humus, through use of sugars and proteins. Besides, WSFS addition decreased the levels of pathogenic bacteria in the final compost product. Notably, WSFS addition also benefited the abiotic humification by production of •OH during oxidation of Fe(II) in composting. This study enhances the understanding of the biotic and abiotic functions of FeSO4 and FeCl2 in promoting humification and reducing carbon emissions during composting. The detailed role of hydroxyl radical in composting and the effectiveness of WSFS-addition in composting nitrogen transformation are still need to be addressed in future.

Herein, we present the development of a novel plant-based nanotechnology strategy employing Astragalus polysaccharide nanoemulsion (APS-NE) to combat clinostomid excysted metacercariae, metacercarial parasites of major global public health concern. A survey conducted between January and August 2024 on 200 Nile tilapia (Oreochromis niloticus) from Giza, Egypt, revealed a high prevalence of encysted metacercariae infection (43.50 %; 87/200). Morphological and molecular analyses (targeting the cytochrome oxidase subunit I gene) confirmed the presence of Clinostomum phalacrocoracis and Euclinostomum heterostomum (99-100 % sequence identity). The APS-NE was characterized by transmission electron microscopy and dynamic light scattering, which demonstrated well-dispersed nanoemulsions (average size 75.6 nm; polydispersity index (PDI) 0.04; zeta potential -35 mV), indicating robust colloidal stability. In vitro assays revealed a dose- and time-dependent increase in excysted metacercariae mortality. Specifically, Clinostomum spp. mortality increased from 5 % at 0.01 % concentration after 10 min to 100 % at 1 % within 1 h, with lethal concentration 50 % (LC₅₀) values decreasing from 0.488 % to 0.013 %. Euclinostomum spp. exhibited even greater sensitivity, with LC₅₀ values ranging from 0.396 % to 0.004 %. Statistical analysis confirmed significant differences in mortality across concentrations and timepoints (Chi-square, p < 0.05). Ultrastructural damage, including tegumental rupture and sucker edema, was visualized using scanning electron microscopy. Comet assays revealed significant DNA fragmentation in the treated worms. For example, the percentage of DNA in the tail increased from merely 6 % to approximately 12 % for Clinostomum spp., and from approximately 9 % to over 25 % for Euclinostomum spp. (p ≤ 0.05), comparable to praziquantel. Molecular docking simulations revealed strong binding affinities of APS to parasite mitochondrial enzymes (e.g., Euclinostomum cytochrome c oxidase: -8.59 kcal/mol), supporting the proposed mechanism of action. These findings represent the first in vitro evaluation of APS nanoemulsions against excysted metacercariae of Clinostomum and Euclinostomum, underscoring their promising potential for targeted parasite control. However, comprehensive in vivo and ecotoxicological studies are essential to validate their therapeutic efficacy and establish their feasibility for large-scale implementation.

Herein, we present the development of a novel plant-based nanotechnology strategy employing Astragalus polysaccharide nanoemulsion (APS-NE) to combat clinostomid excysted metacercariae, metacercarial parasites of major global public health concern. A survey conducted between January and August 2024 on 200 Nile tilapia (Oreochromis niloticus) from Giza, Egypt, revealed a high prevalence of encysted metacercariae infection (43.50 %; 87/200). Morphological and molecular analyses (targeting the cytochrome oxidase subunit I gene) confirmed the presence of Clinostomum phalacrocoracis and Euclinostomum heterostomum (99-100 % sequence identity). The APS-NE was characterized by transmission electron microscopy and dynamic light scattering, which demonstrated well-dispersed nanoemulsions (average size 75.6 nm; polydispersity index (PDI) 0.04; zeta potential -35 mV), indicating robust colloidal stability. In vitro assays revealed a dose- and time-dependent increase in excysted metacercariae mortality. Specifically, Clinostomum spp. mortality increased from 5 % at 0.01 % concentration after 10 min to 100 % at 1 % within 1 h, with lethal concentration 50 % (LC₅₀) values decreasing from 0.488 % to 0.013 %. Euclinostomum spp. exhibited even greater sensitivity, with LC₅₀ values ranging from 0.396 % to 0.004 %. Statistical analysis confirmed significant differences in mortality across concentrations and timepoints (Chi-square, p < 0.05). Ultrastructural damage, including tegumental rupture and sucker edema, was visualized using scanning electron microscopy. Comet assays revealed significant DNA fragmentation in the treated worms. For example, the percentage of DNA in the tail increased from merely 6 % to approximately 12 % for Clinostomum spp., and from approximately 9 % to over 25 % for Euclinostomum spp. (p ≤ 0.05), comparable to praziquantel. Molecular docking simulations revealed strong binding affinities of APS to parasite mitochondrial enzymes (e.g., Euclinostomum cytochrome c oxidase: -8.59 kcal/mol), supporting the proposed mechanism of action. These findings represent the first in vitro evaluation of APS nanoemulsions against excysted metacercariae of Clinostomum and Euclinostomum, underscoring their promising potential for targeted parasite control. However, comprehensive in vivo and ecotoxicological studies are essential to validate their therapeutic efficacy and establish their feasibility for large-scale implementation.