The Al-Azhar University (/ˈɑːzhɑːr/ AHZ-har; Arabic: جامعة الأزهر (الشريف), IPA: [ˈɡæmʕet elˈʔɑzhɑɾ eʃʃæˈɾiːf], "the University of (the honorable) Al-Azhar") is a public university in Cairo, Egypt. Associated with Al-Azhar Mosque in Islamic Cairo, it is Egypt's oldest degree-granting university – and the world's second oldest degree granting university – and is renowned as the most prestigious university for Islamic learning. In addition to higher education, Al-Azhar oversees a national network of schools with approximately two million students. As of 1996, over 4,000 teaching institutes in Egypt were affiliated with the university.Founded in 970 or 972 by the Fatimid Caliphate as a centre of Islamic learning, its students studied the Qur'an and Islamic law in detail, along with logic, grammar, rhetoric, and how to calculate the phases of the moon. Today it is the chief centre of Arabic literature and Islamic learning in the world. In 1961 additional non-religious subjects were added to its curriculum.Its library is considered second in importance in Egypt only to the Egyptian National Library and Archives. In May 2005, Al-Azhar in partnership with a Dubai information technology enterprise, IT Education Project (ITEP) launched the H.H. Mohammed bin Rashid Al Maktoum project to preserve Al Azhar scripts and publish them online (the "Al-Azhar Online Project") to eventually publish online access to the library's entire rare manuscripts collection, comprising about seven million pages of material.
This study evaluates the protective potential of Fondaparinux (Fond), a selective antithrombin-mediated Factor Xa inhibitor, in methotrexate-induced hepatotoxicity. The work explores its ability to correct coagulation imbalance, improve endothelial function, and attenuate oxidative and inflammatory cascades (TLR4/NLRP3, NF-κB p65/IL-1β/MCP-1). Animals were allocated into 4 groups. A control group was given distilled water via the intraperitoneal route (i.p.); an MTX group was given a single intraperitoneal injection of MTX (20 mg/kg) on the seventh experimental day; and two groups received prior prophylactic administration of Fondaparinux (at doses of 5 or 10 mg/kg, intraperitoneally) throughout seven consecutive days before as well as for an additional four-day period following MTX administration. MTX significantly elevated hepatic injury markers (AST, ALT, ALP), induced oxidative stress with depleted antioxidants (SOD, GSH), and activated TLR4/NLRP3 signaling, resulting in upregulation of inflammatory mediators (TNF-α, NF-κB p65, IL-18, IL-1β, MCP-1, caspase-1, iNOS, ICAM-1, MPO) and suppression of IL-10 (p < 0.05). Endothelial dysfunction was evidenced by reduced eNOS. MTX also triggered marked coagulation disturbances, including enhanced Factor Xa–dependent thrombin generation, increased tissue factor, fibrin deposition, and elevated PAI-1. Mitochondrial apoptotic signaling was promoted, as indicated by elevated expression of cytochrome c along with induced caspase-3 and caspase-9 activation . Histologically, MTX caused extensive hepatic damage characterized by periportal fibrosis, inflammatory infiltration, bile duct proliferation, hepatocellular necrosis, vacuolation, and vascular congestion. Fondaparinux pretreatment dose-dependently restored hemostatic balance, improved endothelial function, suppressed oxidative and inflammatory responses, attenuated apoptosis, and markedly ameliorated histopathological alterations. Fondaparinux limits methotrexate-associated liver damage through inhibition of Factor Xa–dependent coagulation pathways while providing antioxidant, anti-inflammatory, anti-apoptotic, and hepatoprotective actions.
In this study, a series of novel thiadiazole derivatives (7a, 7b, 9a, 9b, and 9c) were rationally designed as potential VEGFR-2 inhibitors using a pharmacophore-guided strategy. The compounds were synthesized and assessed for their antiangiogenic and anticancer effects. Among them, compound 9b showed the strongest VEGFR-2 inhibition (IC50 = 0.030 ± 0.001 μM), outperforming the reference drug Sorafenib. Cytotoxicity tests revealed that 9b was highly effective against MCF-7 breast cancer cells (IC50 = 8.06 ± 0.7 μM) while exhibiting minimal toxicity toward normal WI-38 cells. Flow cytometry demonstrated that 9b induced significant G2/M cell cycle arrest and increased apoptosis, supported by molecular data showing upregulation of caspase-3 and Bax and downregulation of Bcl-2, indicating activation of the intrinsic apoptotic pathway. Extensive in silico studies-including molecular docking, 200 ns molecular dynamics simulations, interaction mapping, principal component analysis of trajectories, and free energy landscape analysis-confirmed that 9b binds stably and efficiently within the VEGFR-2 active site. Overall, these results highlight compound 9b as a promising VEGFR-2-targeted antiangiogenic agent with potent enzymatic and cellular activity, favorable selectivity, and mechanistic validation through combined experimental and computational approaches.
Abstract Background Stent retriever (SR), contact aspiration (CA), and combined treatment are vital mechanical thrombectomy (MT) techniques for acute ischemic stroke (AIS) patients. Aim This study aimed to compare and rank these three MT strategies for AIS caused by large vessel occlusion using a Frequentist network meta-analysis (NMA). Methods A systematic review and Frequentist NMA following PRISMA guidelines were conducted. Relevant randomized controlled trials (RCTs) and observational studies were identified from electronic databases from inception to March 2025. Random effect models were used to estimate odds ratios (ORs) and mean differences with 95% confidence interval (CI). Results A total of 55 studies was included in the current NMA study. CA showed significantly higher modified thrombolysis in cerebral infarction (mTICI) 2c/3 scores at the end of the procedure (OR = 1.99, 95% CI [1.04, 3.81]), higher favorable modified Rankin Scale (mRS 0–2) at 3 months (OR = 1.28, 95% CI [1.03, 1.58]), and fewer adverse events (OR = 0.70, 95% CI [0.50, 0.98]) compared to combined approach. No significant differences among groups regarding National Institute of Health Stroke Scale, symptomatic intracerebral hemorrhage, and all-cause mortality. Conclusions The CA group demonstrated superior outcomes in mTICI 2c/3 scores, mRS 0–2 and adverse event rates. However, no significant differences were found between CA, SR, or combined approaches for other outcomes. These findings can guide clinicians in selecting appropriate thrombectomy strategies for AIS patients.
Neltuma juliflora (Sw.) Raf. (syn. = Prosopis juliflora (Sw.) DC.) is among the world's most aggressive woody invaders, yet its ecological impacts remain poorly quantified in hyper-arid environments, where soils are calcareous and ecosystems recover slowly from disturbance. In this study, we tested two hypotheses: (1) the presence of N. juliflora changes native plant diversity, as well as soil and key physicochemical properties in hyper-arid Qatar, and (2) agricultural farms act as primary sources of N. juliflora invasion. Using a comparative observational design across 62 sites (45 invaded and 17 non-invaded), we applied a generalised additive model (GAM) and a generalised linear mixed model (GLMM) to quantify invasion drivers and the impact of invasion on perennial species diversity, respectively. Additionally, we used the Wilcoxon rank-sum test to compare the soil properties in the invaded and non-invaded sites. Our results indicate that N. juliflora is positively associated with farms, with the probability of occurrence declining by ca. 20% for each kilometre farther away from agricultural farms. This pattern suggests substantial propagule pressure from agricultural farms. Perennial species richness declined from 7.5 species at 0% N. juliflora cover to 4.8 species at full cover (36% reduction). Invaded sites were characterised by higher amounts of coarse sand (16%); reduced silt-clay fractions (5%); and elevated salinity indicators, including electrical conductivity (0.744 dS m-1) and total dissolved solids (476 mg L-1), while major N-P-K pools remained unchanged. These findings demonstrate measurable invasion-related changes in soil conditions and native perennial diversity in hyper-arid ecosystems and highlight the role of agricultural land use as a key driver of biological invasion. From a sustainability perspective, early detection, targeted control near agricultural and grazing zones, and integration of invasive species monitoring into land-use planning frameworks are essential to prevent further ecosystem degradation, protect biodiversity, and enhance the resilience of desert landscapes under increasing climate and land-use pressures.
Despite the availability of nasal drops, sprays and oral tablets for the treatment of allergic rhinitis and other inflammatory nasal conditions, those traditional therapeutic options fail to maintain sufficient drug concentration at the nasal cavity due to systemic distribution or rapid mucociliary clearance which compromises the clinical outcomes. Mizolastine (MZL) a second-generation antihistamine has a potent H1 receptor antagonistic activity and mast cell stabilizing effect offering a great efficacy in treating different allergic conditions. However, MZL clinical efficacy is hindered by its suboptimal solubility and oral bioavailability. MZL was formulated as proliposomes (PLs) and optimized for particle size, entrapment efficiency and in vitro release rate. The optimized MZL-PLs formula (particle size 182.2 nm, 80.2
