Dr Mohammed Mahmoud Youssif

Vaginal candidiasis is a medical condition that affects large majority of the women at least once in their lifetime. The condition manifests with itching, irritation, and discharges which is troublesome for women during mundane activities. The purpose of this research was to formulate and evaluate the physicochemical properties and drug permeation of Fenticonazole-loaded cubogel through vaginal mucosa. Concisely, the drug-loaded cubosomes were prepared via hot dispersion emulsification technique. Following, the percent drug entrapment efficiency, particle size, polydispersity index, and zeta potential of the cubosomes were determined. Optimization criteria involved maximizing entrapment efficiency (EE %) and zeta potential (ZP), while maintaining a nanoscale particle size to ensure colloidal stability. The optimized formulation exhibited a high desirability score of 0.933 with EE % of 85.32 2.34 %, PS of 169 0.85 nm, PDI of 0.29 0.02, and ZP of -24.40 1.27 mV. In addition, 86.77 3.79 % of Fenticonazole nitrate was released from the optimum cubosomal formulation after 8 h. Cubical nanovesicles were revealed via transmission electron microscope while infrared spectroscopy revealed the lack of interaction between the used components. Stability was unchanged upon storage for three months. The rheogram of the optimum formulation-loaded cubogel suggested a shear-thinning behavior. Additionally, the optimum cubogel demonstrated higher biofilm inhibitory effect compared to the drug suspension. Similarly, both, ex vivo permeation and confocal laser scanning, suggested the enhanced vaginal epithelium permeability and the deeper vaginal mucosa penetration of the optimum cubogel, compared to the drug suspension and aqueous Rhodamine B carbopol gel, respectively. Histopathological assessment concluded with the safety of the cubogel on the vaginal mucosal epithelium and underlying tissue.

The present study outlines the design and synthesis of dual-tail analogues of SLC-0111 as carbonic anhydrase inhibitors (CAIs) targeting tumor isoforms IX and XII 4a-h and 5a-h, along with pharmacokinetic studies. The synthesized compounds were evaluated for their inhibitory activity against four carbonic anhydrase isoforms (hCA I, II, IX, and XII), revealing potent activity, particularly against hCA IX and XII. Notably, compounds 4b, 5a, and 5b demonstrated strong inhibition of hCA IX with Ki values of 20.4, 12.9, and 18.2 nM, respectively, compared to acetazolamide (AAZ), which has a Ki of 25 nM. Additionally, compounds 5a, 5b, 5c, and 5d showed selective inhibition of hCA XII, with Ki values of 26.6, 8.7, 17.2, and 10.9 nM, respectively, relative to AAZ (Ki = 5.7 nM). Moreover, both series were tested for their anti-proliferative activity following the US-NCI protocol against a panel of more than fifty cancer cell lines. Compound 5h met the activity criteria and was automatically scheduled for further evaluation at five concentrations with 10-fold dilutions, revealing high toxicity toward leukemia and lower toxicity against melanoma. In addition, the MTT cytotoxicity assay was performed on 5f, 5d and acetazolamide using WI-38 cells. Furthermore, an in vivo pharmacokinetic study was conducted using UPLC-MS/MS on the most potent derivative, 5d, demonstrating a comparable pharmacokinetic profile compared to the reference drug acetazolamide. Furthermore, molecular docking prediction studies were conducted for the most active compounds, 5d and 5h, to elucidate their interactions with the active site hot spots of the CA isoform.

This study presents the design, synthesis, and evaluation of a novel series of coumarin-based compounds (9a-t) as potential anticancer agents. The compounds were strategically designed to inhibit cancer-related carbonic anhydrase (CA) isoforms IX and XII and tubulin polymerization. Two approaches were employed for CA inhibition: utilizing the coumarin motif to occlude the CA active site entrance and incorporating zinc-binding groups (sulfonamide, carboxylic acid, and thiol) to interact with the catalytic zinc ion. The target compounds were also designed to inhibit tubulin polymerization by combining the privileged coumarin and pyrazolo[1,5-a]pyrimidine scaffolds. Biological evaluation of the target compounds (9a-t) revealed that sulfonamide-containing derivatives 9h and 9r exhibited potent inhibitory activity in the low nanomolar range against CA IX (K = 23 and 14 nM, respectively) and CA XII (K = 6 and 17 nM, respectively). In NCI-60 human tumor cell line screening, compounds 9k, 9m, and 9q demonstrated broad-spectrum anti-proliferative activity in the five-dose assay with MG-MID values of 7.31 μM, 10.68 μM, and 5.92 μM, respectively. Compound 9m showed significant tubulin polymerization inhibition with an IC = 5.28 μM, surpassing the efficacy of colchicine. Cell cycle analysis in MDA-MB-231 breast cancer cells revealed G2/M phase arrest for 9m, which induced significant apoptosis and modulated apoptotic markers. Molecular docking studies provided insights into the binding modes of the compounds with CA IX, CA XII, and tubulin. ADMET and toxicity predictions were performed to assess the drug-like properties of the compounds. These findings pave the way for further optimization of the coumarin scaffold to develop dual inhibitors of carbonic anhydrase IX/XII and tubulin polymerization.

The current study had aimed to assess the long-term dietary supplementation with Melaleucae aetheroleum, tea tree essential oil (TTO). The impact on growth performance, biochemical indices, immune function, oxidant/antioxidant activity, gene expression, histopathology, and resistance against Aeromonas sobria in Nile tilapia (Oreochromis niloticus) was investigated. Four groups (with five replicates; G1 (control group, G2, G3, and G4) of Nile tilapia received diets enriched with TTO (doses of 0.0, 0.5, 1.0, and 2.0 mL/kg diet) for 60 days, then fish were challenged by A. sobria. Outcomes indicated an extensive elevation in growth metrics (final body weight, weight gain, SGR, feed intake and fish body protein). Similarly, the total blood protein, albumin, total globulin levels, Serum complement-3 levels, lysozyme activity, immunoglobulin M (IgM), nitric oxide, and phagocytic activity were significantly enhanced in all treatments, notably in the 2.0 mL TTO/kg fed groups compared to the control. Lower levels of urea, creatinine, AST, ALP, ALT, cortisol, glucose, triglycerides, cholesterol and body crude lipids were observed in the fish that were fed a 2.0 mL TTO/kg diet. Supplementing TTO at 2.0-mL /kg diet revealed the best results for elevating CAT, SOD, and GSH activities plus declining MDA value in hepatic homogenate. Additionally, dietary 2.0-mL TTO/kg showed the best outcomes for the intestinal morphometry plus maintaining the histological picture in spleen and liver. Concurrently, fish that were fed a 2.0 mL TTO/kg diet exhibited a substantial upregulation of TNF-α, IL-1β, IL-10, TFG-β, IFN-γ and BCL-2 genes in the liver, while, caspase-3, and BAX were downregulated. Furthermore, TTO-enriched diets enhanced the relative percentage survival post-A. sobria challenge plus enhanced the clinical picture in a dose-dependent manner. Taken together, the findings revealed that long-term exposure to dietary TTO fortified the physiological performance, oxidant/anti-oxidant stability, immune function, gene expression, histological picture, and resistance of Nile tilapia against A. sobria.

Urban Digital Twins (UDTs) represent a paradigm shift toward dynamic, data-driven urban planning, yet their potential for climate change mitigation remains under-synthesized and constrained by socio-technical barriers. This study conducts a systematic PRISMA review of 56 peer-reviewed articles (2018–2025) to analyze UDT frameworks, applications, and implementation constraints. Three dominant UDT archetypes—AI-driven platforms, City Information Models (CIMs), and Hazard-Responsive Digital Twins (H-RDTs)—are identified and mapped across urban heat island mitigation, building energy optimization, flood resilience, and participatory governance. Findings reveal that UDTs enable high-resolution simulation and cross-sectoral scenario testing, facilitating the optimization of nature-based solutions and decarbonization pathways. Critical bottlenecks include fragmented data ecosystems, algorithmic bias, computational scalability issues, and the lack of governance frameworks integrating equity and policy coherence. This review provides a mitigation-focused synthesis of UDTs and proposes a roadmap to advance them from experimental prototypes to equitable, policy-relevant decision-support systems for climate-resilient cities.