Novel transition metal complexes of Ni(II), Cu(II), and Co(II) incorporating p-anisidine and cyclohexanedione hydrazone ligands were rationally designed, synthesized, and comprehensively characterized as potential breast cancer-targeting agents. Spectroscopic and physicochemical analyses (1H NMR, TGA, FT-IR, LC-MS, UV-Vis, molar conductance, and magnetic measurements) confirmed the proposed structures. Single-point analysis indicates that the Cu(II) complex adopts a square-based pyramidal geometry, whereas the Ni(II) and Co(II) complexes exhibit distorted octahedral configurations. TD-DFT theoretical calculations provided insight into optimized geometries and electronic transitions, in good agreement with experimental data. In vitro cytotoxicity studies against MCF-7 cells revealed dose-dependent activity for all complexes, with the Co(II) system exhibiting superior potency (lowest IC50). Molecular docking studies against key breast cancer protein targets (PDB IDs: 4F5S, 3HB5, and 1JNX) demonstrated favorable binding interactions, with the Co(II) complex displaying superior binding affinity and stability within the active sites. These findings identify the Co (II) complex as a promising scaffold for further development of metal-based anticancer therapeutics.
The advent of continuous glucose monitoring (CGM) has revolutionized diabetes management by enabling real-time glucose monitoring and significantly enhancing patient outcomes. This comprehensive review examines the current landscape of CGM, detailing its technological evolution, diverse applications, and future perspectives. The review discusses various technological modalities, including electrochemical CGM sensors, which utilize glucose oxidase as a receptor, as well as innovative optical, magnetic, piezoelectric, and thermo-responsive CGM sensors, with an emphasis on innovations to enhance CGM sensor sensitivity. It highlights key advancements, such as sensor miniaturization, biocompatibility enhancements, and improved wireless connectivity, which are crucial for integrating CGM sensors into wearable devices. While these technologies show great promise, significant challenges such as biocompatibility, sensor stability, and calibration accuracy remain. This review concludes that the future of CGM lies in the integration of artificial intelligence for personalized diabetes and the continued development of novel biocompatible materials and advanced sensing modalities, all of which are essential for the ongoing optimization of diabetes care.
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.
Abstract Background Adult living donor liver transplantation (LDLT) started in Egypt in 2001, with more than 5000 cases transplanted since then. In Egypt using only ABO compatible donor is the practice in all cases, and up till now, the only oncological indication for LDLT is hepatocellular carcinoma (HCC). The optimal management of the transplant recipient relies on understanding and proper utilization of immunosuppression regimens. The clinician should be aware of how to maintain the delicate balance between under-immunosuppression, leading to graft rejection, and over-immunosuppression, leading to the consequences of immunodeficiency such as sepsis and malignancy. The aim of this consensus is to provide clinical guidance to transplant physicians, transplant surgeons, clinical pharmacologists and nurses about immunosuppression in LDLT recipients. Main body These national recommendations on immunosuppression in adult LDLT were developed by an experience exchange between the 22 centers currently undergoing LDLT in Egypt. A group of experts in liver transplantation from all over Egypt participated in the review of literature for different aspects related to these recommendations and, then they shared in formulation of several statements. In the United Conference on Hepato-gastroenterology and Infectious Diseases (UCHID) (2022), voting on these statements was done. Conclusion Comprehensive national guidance is provided regarding the general principles of liver transplant immunosuppression, types of immunosuppression (IS), established IS drugs, types of rejection and their management, treatment of special groups, immunosuppression minimization, immune tolerance and complete IS withdrawal and the role of liver biopsy in orchestrating immunosuppression.
This study reports the design, fabrication, and characterization of a novel carbon paste electrode integrated with graphene and copper oxide nanohybrid (Gr/CuONPs/CPE) for the sensitive and selective voltammetric determination of the serotonin reuptake inhibitor paroxetine (PAR). Modification of the electrode surface with Gr/CuONPs nanohybrid facilitated a more efficient electrochemical oxidation of PAR at 1.046 V in BR buffer (pH 6) based on the synergistic electrocatalytic effect of the nanohybrid components and the enhanced electroactive surface area provided by the nanostructure. The electroanalytical investigations combined with molecular orbital calculations revealed a diffusion-controlled mechanism through oxidation of the pyrimidine nitrogen atom (N6), accompanied with the transfer of two protons/one electron. At the optimized Gr/CuONPs ratio within the nanohybrid, the cited electrode demonstrated a linear response within the PAR concentrations ranged from 0.066 to 4.939 & micro;g mL-1 and an limit of detection value of 45.4 ng mL-1. The Gr/CuONPs/CPE exhibited extended storage stability with excellent fabrication and electrochemical measurement reproducibility. Based on the environmental impact of PAR, the developed voltammetric procedure was effectively applied for monitoring of PAR residues in surface water samples and marketed formulations with acceptable recoveries. The green analytical metrics (Analytical Eco-Scale and Analytical GrEEness metric approach) were evaluated, highlighting the method's environmental friendliness of the suggested voltammetric procedures.
