Jesús Magdiel García-Díaz

Heart and vascular complications now rank among the leading health threats facing individuals with HIV, a reality that continues even when modern drug regimens successfully silence viral replication. Sustained immune system overdrive and persistent low-grade systemic inflammation appear central to this heightened vulnerability. This narrative review integrates current understanding of how inflammatory signaling molecules, particularly interleukins, connect to heightened cardiovascular danger in HIV-positive populations, while exploring mechanistic underpinnings, cohort-derived evidence, and prospective treatment possibilities. Elevated concentrations of proinflammatory messengers such as IL-6 and IL-18, alongside indicators of myeloid cell activation including sCD14 and sCD163, characterize the HIV-positive state and independently forecast arterial disease progression, clinical cardiac events, and shortened survival. Notably, this inflammatory signature endures despite pharmacologically induced viral quiescence. Disturbances in protective lipoprotein function, heightened clotting propensity, and leakage of gut-derived bacterial components into the bloodstream each amplify vascular injury. Inflammatory cytokines occupy a central position in HIV-associated cardiovascular pathobiology, serving dual roles as disease predictors and candidate treatment targets. Importantly, recent evidence from the REPRIEVE randomized clinical trial demonstrated that pitavastatin therapy reduced major adverse cardiovascular events by approximately 35% in people living with HIV receiving antiretroviral therapy, highlighting inflammation-modulating strategies as a new foundation of cardiovascular prevention in this population.

Background: Two novel copper(II) coordination complexes, PH-Cu [(1,10-phenanthroline)(malonato)copper(II)] and PC-Cu [(1,10-phenanthroline)(cyclobutane-1,1-dicarboxylato)copper(II)], were synthesized and evaluated as potential anticancer agents, aiming to characterize structural properties, explore antiproliferative activity and generate mechanistic hypotheses through experimental and computational approaches. Methods: Complexes were characterized by EPR, FTIR-ATR, and ESI-MS, with preliminary SC-XRD data for PH-Cu. Antiproliferative activity was evaluated against six human cancer cell lines using the MTT assay (24 h). Subcellular effects were assessed by fluorescence microscopy and RT-qPCR. Computational studies included DFT geometry optimization, target prediction, molecular docking, and ADMET profiling. Results: Based on spectroscopic and spectrometric data and comparison with analogous Cu(II) complexes, a distorted square-pyramidal coordination geometry was proposed; this assignment was not confirmed by SC-XRD. Both complexes exhibited potent antiproliferative activity, with PH-Cu showing the highest potency in HeLa cells (IC₅₀ = 4.22 µM). Under the same conditions, cisplatin showed substantially lower activity (HepG2: 191.1 µM; Caco-2: 129.6 µM; NCI-H69: >333.3 µM; HeLa: 21.9 µM). Fluorescence microscopy at 18 h revealed pyknosis, karyorrhexis, and microtubule disorganization, consistent with regulated cell death. RT-qPCR of PH-Cu indicated intrinsic apoptotic pathway engagement (BAX +3.20-fold; BCL2 to 0.39-fold of control). DFT-optimized bond lengths were consistent with crystallographic data for analogous complexes. Molecular docking suggested PRKCG, RELA (p65), Caspase-3, and α/β-tubulin as interaction candidates, while ADMET profiling predicted favorable intestinal absorption (>92.8%) and low BBB permeability. Conclusions: These results suggest that the [Cu(phen)] unit constitutes the primary pharmacophore, with the dicarboxylate co-ligand as a modulator of the antiproliferative profile, suggesting promising anticancer pharmacological potential.

Drug discovery is a complex and expensive process in which only a small proportion of candidate molecules reach clinical approval. Computational methods, particularly computer-aided drug design (CADD), have become fundamental to accelerate and optimize early stages of discovery by integrating chemical, biological, and pharmacokinetic information into predictive models. This review outlines a complete computational workflow for chemical compound analysis, covering molecular structure generation, database selection, evaluation of absorption, distribution, metabolism, excretion and toxicity (ADMET), target prediction, and molecular docking. It focuses on freely accessible and web-based tools that enable reproducible, cost-effective, and scalable in silico studies. Key platforms such as PubChem, ChEMBL, RDKit, SwissADME, TargetNet, and SwissDock are highlighted as examples of how different resources can be integrated to support rational compound design and prioritization. The article also discusses essential methodological principles, data curation strategies, and common limitations in virtual screening and docking analyses. Finally, it explores future directions in computational drug discovery, including the incorporation of artificial intelligence, multi-omics integration, and quantum simulations, to enhance predictive accuracy and translational relevance.

Backgroud. Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the ectopic presence of endometrial-like tissue. Although genome-wide association studies (GWAS) have identified susceptibility variants, their tissue-specific regulatory impact remains poorly understood. Objective. To functionally characterize endometriosis-associated variants by exploring their regulatory effects as expression quantitative trait loci (eQTLs) across six physiologically relevant tissues: peripheral blood, sigmoid colon, ileum, ovary, uterus, and vagina. Methods. GWAS-identified variants were cross-referenced with tissue-specific eQTL data from the GTEx v8 database. We prioritized genes either frequently regulated by eQTLs or showing the strongest regulatory effects (based on slope values, which indicate the direction and magnitude of the effect on gene expression). Functional interpretation was performed using MSigDB Hallmark gene sets and Cancer Hallmarks gene collections. Results. A tissue specificity was observed in the regulatory profiles of eQTL-associated genes. In the colon, ileum, and peripheral blood, immune and epithelial signaling genes predominated. In contrast, reproductive tissues showed the enrichment of genes involved in hormonal response, tissue remodeling, and adhesion. Key regulators such as MICB, CLDN23, and GATA4 were consistently linked to hallmark pathways, including immune evasion, angiogenesis, and proliferative signaling. Notably, a substantial subset of regulated genes was not associated with any known pathway, indicating potential novel regulatory mechanisms. Conclusions. This integrative approach highlights the com-plexity of tissue-specific gene regulation mediated by endometriosis-associated variants. Our findings provide a functional framework to prioritize candidate genes and support new mechanistic hypotheses for the molecular pathophysiology of endometriosis.