Enrique González-Vergara

Over the last 30 years, many studies have examined polyoxidometalates as a treatment for various illnesses. Many substances that contain decavanadate have been proposed as potential therapies for diabetes, cancer, and Alzheimer's disease. Currently, there are 8 functional proteins in the Protein Data Bank (PDB) that bind decavanadate (V ₁₀ ). These are the human cell cycle protein CksHs1, the transient receptor potential cation channel (TRPM4), two ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), acid phosphatase, tyrosine kinase, and, more recently, HEWL (lysozyme) and RNase A. The interaction sites of the decavanadate anion with these proteins are mostly made up of side chains, such as arginine, lysine, and histidine. The histaminium dication served as a small biomimetic model to elucidate the noncovalent interactions between decavanadate and histidine residues in proteins. Here we report the synthesis and crystallization of histaminium decavanadate and its characterization using FTIR, Raman, ⁵¹ V-NMR, TGA, and X-ray diffraction. To gain insights into the non-covalent interactions of decavanadate in protein environments, the interaction energy between the decavanadate anion and histaminium counterions was calculated using DFT methods. To better understand the non-covalent interactions in these adducts, studies were carried out using the Quantum Theory of Atoms in Molecules (QTAIM) and Non-covalent Interaction-Reduced Density Gradient (NCI-RDG). Based on their interaction energies, decavanadate can interact with histaminium through hydrogen bonds, electrostatic forces, and van der Waals forces. The compound exhibits strong hydrogen bond interactions, which significantly enhance its stability. Decavanadate holds considerable promise as a potential treatment for diabetes, cancer, and neurological protection. Consequently, additional research is required to elucidate its interactions with proteins.

Diabetes is a complex condition that requires continuous medical care and risk-reduction strategies. Therefore, technological improvements and the development of new insulins are necessary. This work aimed to develop insulin functionalized with vanadate (V1) or decavanadate (DV10) and probe its effectiveness on glucose and lipid homeostasis in a like-T1D murine model. Seven different molar combinations of HUMALOG ^® 75/25 insulin with V1 or DV10 were characterized using molecular docking, UV/visible, and FT-IR spectroscopy, confirming stable interactions between V1 or DV10 with the insulin. Then, a like-T1D model was generated in Wistar rats. The acute pharmacodynamics and pharmacokinetics of functionalized insulin were evaluated. Ins-V1 9:1 and 7:3 ratios demonstrated functional bioequivalence to commercial Lispro insulin, reducing glycemia by approximately 67.7% and 60%, within 60 min. The ins-DV10 3:7 and 5:5 ratios exhibited lower average glycemia than Lispro ( p < 0.01), indicating greater cumulative efficacy. In the long term (30 days), the ins-V1 and ins-DV10 combination administered successfully reversed hyperglycemia and dyslipidemia. Treatments enhanced glycogen storage by 50%–80% and reduced tissue steatosis by 22%–62.5% in the liver, muscle, heart, and kidney. Ins-DV10 (3:7 and 1:9) were better than any ins-V1 combination. Remarkably, acute V1 treatment alone improved dyslipidemia and hyperglycemia, but in the long term, DV10 alone showed the greatest efficacy in both serum and tissues. In conclusion, functionalization with a higher proportion of DV10 significantly enhances the pharmacokinetics and pharmacodynamics of lispro-protamine insulin. Therefore, it could be considered a treatment strategy for managing glucose and lipid homeostasis in diabetes.

La bioinformática es un campo que comenzó con la investigación de macromoléculas como proteínas y ácidos nucleicos. Utiliza técnicas computacionales, matemáticas y estadísticas para analizar, interpretar y generar datos biológicos, con aplicaciones en biología, genómica y biotecnología. La BI ha sido una herramienta vital en el desarrollo de varias disciplinas, incluidas la genómica, la nutrigenómica, la transcriptómica, la metabolómica y la epigenómica. Los programas de medicina deberían formar profesionales de la salud capaces de interactuar con las ciencias ómicas para una mejor visualización, entendimiento, diagnóstico y tratamiento de las enfermedades, por lo que su presencia en los planes de estudio universitarios, está ampliamente justificada. Varias bases de datos en ciencias de la salud, como PDB, NCBI y PubMed, se utilizan para estudios de enfermedades genéticas, entre otras. Junto con la inteligencia artificial, la minería de datos y el aprendizaje automático, se están produciendo resultados más confiables, mejorando la calidad del producto y permitiendo la adquisición de conocimientos para resolver problemas biomédicos. Al permitir comprender y aprovechar el vasto volumen de datos biológicos generados en la medicina moderna, la bioinformática es una herramienta fundamental para los estudiantes del área de la salud.

COVID-19 has caused over seven million deaths globally due to its high transmission rate. The virus responsible for the disease requires a transmembrane protease serine type II (TMPRSS2-7MEQ) to infiltrate host cells and has been linked to several cancers, particularly prostate cancer. To investigate COVID-19 potential therapies, a series of Casiopeina-like copper complexes containing 1,10-Phenanthroline and amino acids were investigated as TMPRSS2 inhibitors. The molecular structures of twelve Phenanthroline copper complexes were calculated, and their global reactivity indices were analyzed using DFT and conceptual DFT methods. Three molecular docking algorithms were employed to identify the most effective inhibitors by examining their interactions with amino acid residues in the target protein’s catalytic activity triad (Asp345, His296, and Ser441). All complexes are docked above the catalytic site, blocking the interaction with substrates. The Phenanthroline complexes showed better interactions than the Bipyridine complexes, likely due to increased hydrophobic contacts. Analogs’ cationic nature and amino acids’ basic side chains bring them near the active site by interacting with Asp435. The top complexes in this study contain Ornithine, Lysine, and Arginine, making them promising alternatives for researching new drugs for COVID-19 and cancers like prostate cancer.

Actualmente, en materia de cuidado existen muchos desafíos, incluyendo que los familiares y amigos cuidadores asuman responsabilidades esenciales de atención médica, frecuentemente sin capacitación ni apoyo inadecuados, exponiéndose a riesgos que perjudican su salud por desempeñar una actividad agobiante y estresante. El bienestar del cuidador es pieza fundamental del equipo multidisciplinario que participa en el complejo proceso del trasplante de progenitores hematopoyéticos. En este artículo se exponen algunos datos sobre la pequeña, pero creciente población de cuidadores, su función, sus principales necesidades de salud, y finalmente algunas estrategias de intervención que se han investigado y reportado como exitosas en términos de salud.

During the last three decades, numerous investigations have been conducted on polyoxidovanadates to treat several illnesses and inhibit enzymes. Numerous decavanadate compounds have been proposed as potential therapies for Diabetes mellitus, Cancer, and Alzheimer’s disease. Only six relevant functional proteins interacting with decavanadate, V₁₀, have been deposited in the PDB. These are acid phosphatase, tyrosine kinase, two ecto-nucleoside triphosphate diphosphohydrolases (NTPDases), the human transient receptor potential cation channel (TRPM4), and the human cell cycle protein CksHs1. The interaction sites in these proteins mainly consist of Arginine and Lysine, side chains binding to the decavanadate anion. To get further knowledge regarding non-covalent interactions of decavanadate in protein environments, guanidinium and spermidinium decavanadates were synthesized, crystallized, and subjected to analysis utilizing various techniques, including FTIR, Raman, ⁵¹V-NMR, TGA, and X-ray diffraction. The DFT calculations were employed to calculate the interaction energy between the decavanadate anion and the organic counterions. Furthermore, the Quantum Theory of Atoms in Molecules (QTAIM) and Non-covalent Interaction-Reduced Density Gradient (NCI-RDG) analyses were conducted to understand the non-covalent interactions present in these adducts. Decavanadate can engage in electrostatic forces, van der Waals, and hydrogen bond interactions with guanidinium and spermidinium, as shown by their respective interaction energies. Both compounds were highly stabilized by strong hydrogen bond interactions N−H···O and weak non-covalent interactions C−H···O. In addition, the interactions between guanidinium and spermidinium cations and decavanadate anion form several stable rings. This study provides new information on non-covalent intermolecular interactions between decavanadate and small biomimetic models of arginine and lysine lateral chains in protein environments.

Citrulline (C₆H₁₃N₃O₃) is an amino acid found in the body as a zwitterion. This means its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, citrulline possesses a terminal ureido group on its aliphatic chain, which also appears to coordinate. Here, two new mixed complexes of citrulline were made with 1,10-phenanthroline and 2,2′-bipyridine. These compounds, once dissolved in water, gave aquo-complexes that were subject to DFT studies and in vitro toxicity studies on cancer cell lines (HeLa, MDA-MB-231, HCT 15, and MCF7) showed promising results. Docking studies with DNA were also conducted, indicating potential anticancer properties.

Citrulline is a non-protein amino acid that acts as a metabolic intermediate in the urea cycle and arginine synthesis. It is present in some foods, although its name derives from watermelon (Citrullus vulgaris), from which it was first identified. Under normal conditions, Citrulline exists as a zwitterion in aqueous solutions since its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, Citrulline possesses in the aliphatic chain a terminal ureide group, which could also coordinate. Although Citrulline is comparable to other classical amino acids, its coordination chemistry has yet to be explored. Only two metal complexes have been reported, and the copper complex is a polymeric and insoluble material. As part of our search for active Casiopeina^® analogs, we created a more soluble complex by combining 2,2′-Bipyridine into a new mixed material, resulting in the mononuclear complex [Cu(Bipy)(Citr)(H₂O)(NO₃)]·H₂O. Single-crystal X-ray diffraction, spectroscopic methods (FT-IR, UV-Vis, Raman), and mass spectrometry characterized the material. Interestingly, both isomers of Citrulline, R(D), and S(L) are present in the same crystal. In addition, the molecular structure and electronic properties of the complex were calculated using density functional theory (DFT). Non-covalent interactions were characterized using the atoms-in-molecules (AIM) approach and Hirshfeld surface (HS) analysis. This ternary complex containing Citrulline and 2,2′-Bipyridine will be used for docking calculations and preliminary biological studies using calf thymus DNA (CT-DNA) and plasmid pUC19 as a first approximation to cytotoxic activity against cancer cell lines.

The development of composite materials with thermo-optical properties based on smart polymeric systems and nanostructures have been extensively studied. Due to the fact of its ability to self-assemble into a structure that generates a significant change in the refractive index, one of most attractive thermo-responsive polymers is poly(N-isopropylacrylamide) (PNIPAM), as well as its derivatives such as multiblock copolymers. In this work, symmetric triblock copolymers of polyacrylamide (PAM) and PNIPAM (PAM_x-b-PNIPAM_y-b-PAM_x) with different block lengths were prepared by reversible addition−fragmentation chain-transfer polymerization (RAFT). The ABA sequence of these triblock copolymers was obtained in only two steps using a symmetrical trithiocarbonate as a transfer agent. The copolymers were combined with gold nanoparticles (AuNPs) to prepare nanocomposite materials with tunable optical properties. The results show that copolymers behave differently in solution due to the fact of variations in their composition. Therefore, they have a different impact on the nanoparticle formation process. Likewise, as expected, an increase in the length of the PNIPAM block promotes a better thermo-optical response.