Mauro Manuel Martínez Pacheco

Aldose reductase (AR) is a key enzyme in the polyol pathway and has been widely implicated in the development of diabetic complications, including cataract formation. In this work, a series of structurally modified 1,4-dihydropyridine (DHP) derivatives were evaluated as potential AR inhibitors. The compounds were obtained with high purity and subjected to enzymatic screening, exhibiting IC₅₀ values ranging from 1.11 ± 0.07 to 55.34 ± 0.06 µM. The unsubstituted DHP scaffold exhibited intrinsic activity, whereas substitution at the 4-phenyl ring modulated inhibition in a nonlinear manner, reflecting the combined influence of steric and electronic factors on enzyme interactions. Kinetic analysis revealed mixed-type inhibition, indicating that the inhibitory behavior of the DHP derivatives cannot be explained solely by simple competition with the substrate. Molecular docking using the AR–NADP complex identified favorable binding poses and interactions with residues involved in ligand recognition and stabilization, although no direct correlation was observed between predicted docking scores and experimental inhibitory potency. A representative compound (DHP3, IC₅₀ = 1.11 ± 0.07 µM) was elected for ex vivo evaluation in a rabbit lens model under hyperglycemic conditions. Treatment reduced glucose-induced lens opacity by 89.1%, estimated by image-based analysis, and decreased sorbitol accumulation by 57.48% relative to hyperglycemic control, indicating modulation of the polyol pathway at the tissue level. In contrast, no significant changes were detected in calcium content. These findings support the potential of DHP derivatives as a scaffold for aldose reductase inhibition and highlight their ability to attenuate early alterations associated with hyperglycemia in lens tissue. Further studies are required to expand biological validation and optimize their inhibitory profile.

¿Alguna vez has escuchado de una enfermedad que "secuestra" los recuerdos? El culpable es un desorden neurológico llamado Alzheimer. Para entender cómo funciona esta enfermedad, nos podemos imaginar que nuestro cuerpo es una fábrica liderada por múltiples jefes que trabajan en el cerebro a los que llamamos neuronas. Las neuronas son las células básicas del sistema nervioso que transmiten señales entre diferentes partes del cuerpo a través de neurotransmisores. Los neurotransmisores son sustancias químicas que facilitan la comunicación entre neuronas a través de la hendidura sináptica, donde se liberan y se unen a receptores en la membrana dela neurona receptora, alterando su estado y provocando una respuesta. Existen más de 40 neurotransmisoresen el sistema nervioso humano, cada uno con funciones específicas, como la acetilcolina, la dopamina y la serotonina, que juegan un papel crucial en procesos como el aprendizaje, el control de emociones y la regulación del movimiento, así como formar y guardar nuestros recuerdos como si fueran "documentos" a través de los cuales se almacena la información. En este artículo descubrirás como se pierden estos documentos y cómo podemos hacer que se queden por más tiempo al aumentar los niveles del neurotransmisor acetilcolina.

Introducción La madera es altamente susceptible al daño por agentes microbianos como los hongos xilófagos. Por ello, la industria se ha esforzado por mantener las estructuras de madera en condiciones mecánicamente funcionales; sin embargo, la contaminación ambiental y la responsabilidad social para minimizar los riesgos a la salud humana han obligado a la búsqueda de nuevas estrategias. Objetivo Definir las condiciones en las cuales los aceites esenciales de Syzygium sp. y Citrus sp. preservan la madera de Pinus sp. ante el daño por Trametes versicolor y Gloeophyllum trabeum mediante el diseño experimental Box-Behnken. Materiales y métodos El experimento se diseñó con tres factores: aceite esencial de Syzygium sp. (AES), aceite esencial de Citrus sp. (AEC) y tiempo (6, 9 y 12 meses), así como tres niveles por factor -1, 0 y +1. La variable de respuesta fue la compresión paralela en probetas (ISO 3345) de madera de Pinus sp. Resultados La madera de pino, expuesta a los hongos xilófagos evaluados, requiere una concentración de 6.25 % de AES y 6.25 % de AEC con el fin de mantener una resistencia estándar de 355.5 kg·cm^-2 en compresión paralela. Este efecto preservante perduraría entre los 8.4 y 8.7 meses según el agente xilófago. Conclusión Los aceites esenciales de Syzygium sp. y Citrus sp. son candidatos para ser empleados como preservantes de la madera. El efecto inhibitorio de sustancias químicas de origen natural contra organismos del deterioro de la madera es importante en el avance científico para migrar a tecnologías amigables con nuestro entorno.

The lens cells of humans with chronic hyperglycemia show a progressive accumulation of sorbitol by aldose reductase catalysis that ends with cell lysis. Therefore, this work aims to explore metabolites in native plants that prevent cataracts through inhibition of the enzyme aldose reductase. The scrutiny was performed using bioinformatics, chemicals, enzymes, and cataract ex vivo prevention techniques. Eleven Eupatorium spp. were the natural resources explored. Five of them were selected to continue with the phytochemical scrutiny. Twelve pure phytometabolites were obtained with an inhibitory effect on the enzyme. Nine of them were subject to the accepted heuristic rules for drug-likeness. With this analysis, a possible active principle emerged a phenolic compound: methylripariochromene A. An apparent mixed catalytic mechanism carries out the inhibition of enzyme catalysis. Molecular docking and molecular dynamic simulations helped us understand their coupling in the active site of AR, finding an agreement between experimental and computational data. Methylripariochromene A prevented experimental cataract formation in rabbit lens cultured ex vivo.

Enterolobium cyclocarpum heartwood is prized for furniture making because of its natural durability. In this process, up to 50% of the heartwood is discarded in the sawmill. Which contains extractives that can be used to emulate the natural durability and give protection to soft or rapidly deteriorating wood. Pinewood in service and several items made up mainly of cellulose are subject to deterioration caused by xylophage boring insects and other biotic agents. The purpose of this research was to demonstrate that the E. cyclocarpum heartwood aqueous extract protects dry pinewood against the damage caused by the termite Incisitermes marginipennis (Latreille) (Isoptera: Kalotermitidae) a borer insect. The removal of pigments from the aqueous extract, which initially stained the wood dark brown, made it possible to preserve the natural color of the wood, an important characteristic for the commercialization of wooden products. In addition to the protective properties, the phenolic compounds in the extract contributed to reducing degradation caused by light and other factors, delaying the aging of the wood. The proposal to use E. cyclocarpum residues to prepare a cheap and easy-to-prepare aqueous extract offers a sustainable and economical solution for wood preservation. These compounds can be applied in various biological areas, due to their antitumor, antimicrobial and antioxidant properties. Offering an ecologically correct and economically viable alternative to traditional preservatives, aligning with sustainability and environmental preservation trends. In conclusion, for indoor use, E. cyclocarpum heartwood colourless aqueous extract is an alternative to protect pinewood of drywood termite Incisitermes marginipennis due to manool presence.

Fungal holocellulases are interesting for their possible applications in the bioconversion of corn crop residues into molecules with technological significance. Holocellulase (xylanases and cellulases) production from Fusarium solani and Aspergillus sp. with corn stover as a carbon source was compared using a Box–Wilson design. The fungal holocellulase production was different in both fungi. For F. solani, the maximum endoxylanase and β-xylosidase activities were 14.15 U/mg and 0.75 U/mg at 84 h of fermentation on 350 g/L corn stover, while Aspergillus sp. was 5.90 U/mg and 0.03 U/mg, respectively, at 156 h and 1000 g/L corn stover. The production of holocellulases in both fungi was reduced with increasing carbon sources. The nitrogen source induced the holocellulases in Aspergillus sp., but not in F. solani. Interestingly, when verifying the optimal culture conditions, the production of endoxylanases by F. solani was higher when compared to the predicted value. With regard to the endoxylanase and β-xylosidase activities of Aspergillus sp., these were close to the predicted values. Based on the optimization model, F. solani and Aspergillus sp. produce an interesting holocellulolytic activity in a growth medium with corn stover as the only carbon source. The fermentation time and the amount of corn stover required to obtain maximum holocellulase production are possible advantages for Fusarium solani and Aspergillus sp., respectively.

This study analyzed the role of blood serum in enhancing the mitochondrial metabolism and virulence of Mucorales through rhizoferrin secretion. We observed that the spores of clinically relevant Mucorales produced in the presence of serum exhibited higher virulence in a heterologous infection model of Galleria mellonella. Cell-free supernatants of the culture broth obtained from spores produced in serum showed increased toxicity against Caenorhabditis elegans, which was linked with the enhanced secretion of rhizoferrin. Spores from Mucoralean species produced or germinated in serum showed increased respiration rates and reactive oxygen species levels. The addition of non-lethal concentrations of potassium cyanide and N-acetylcysteine during the aerobic or anaerobic growth of Mucorales decreased the toxicity of the cell-free supernatants of the culture broth, suggesting that mitochondrial metabolism is important for serum-induced virulence. In support of this hypothesis, a mutant strain of Mucor lusitanicus that lacks fermentation and solely relies on oxidative metabolism exhibited virulence levels comparable to those of the wild-type strain under serum-induced conditions. Contrary to the lower virulence observed, even in the serum, the ADP-ribosylation factor-like 2 deletion strain exhibited decreased mitochondrial activity. Moreover, spores produced in the serum of M. lusitanicus and Rhizopus arrhizus that grew in the presence of a mitophagy inducer showed low virulence. These results suggest that serum-induced mitochondrial activity increases rhizoferrin levels, making Mucorales more virulent.

Natural color influences the decision to acquire a wood product. Sapstain is a fungal deterioration of pinewood that affects its aesthetic attributes and generally causes its rejection. The aim was to control the sapstain on pinewood with citrus essential oils. Causal agents of sapstain on pinewood were identified by molecular methods to genus level as Alternaria sp., Hypocrea sp., Trichoderma sp., and Geosmithia sp. Citrus essential oils were tested to control the fungal growth. For the treated pinewood probes, the adsorption and retention of citrus essential oils, fungal adhesion, and wood satin as fungal growth indicators were determined. The composition of the essential oils was determined by gas chromatography. Fungi were sensible to essential oils rich in D-limonene, γ-terpinene, α-terpineol, geraniol, eugenol, or β-bisabolene. Absorption and retention data suggest that 12.37±1.62 kg/m3 is the minimal amount to inhibit the fungal adhesion and growth on pinewood. Citrus essential oils control sapstain in pinewood, but poor retention should be improved.

Introducción: La madera es propensa a ser utilizada como fuente de carbono por especies de hongos que la dañan. La durabilidad de la madera ha sido categorizada de acuerdo con la pérdida de peso sin considerar la disminución de las propiedades fisicoquímicas y mecánicas inherentes. Objetivo: Evaluar cómo afecta la pérdida de peso a las propiedades fisicoquímicas y mecánicas de la madera de Pinus pseudostrobus Lindl. expuesta al hongo de pudrición café Gloeophyllum trabeum (Pers.) Murrill. Materiales y métodos: Piezas de madera aserrada de P. pseudostrobus se inocularon con 50 mL de G. trabeum (10 6 UFC∙mL -1 ). Periódicamente (cero, tres, seis y nueve meses), y con la ayuda de una máquina universal de ensayo, se analizó la compresión paralela, la flexión estática (FE) y la compresión perpendicular a la fibra (CPF); además, se cuantificó la holocelulosa, celulosa y lignina. Resultados y discusión: Después de nueve meses de interacción con G. trabeum, las piezas de madera fueron resistentes a la degradación, considerando únicamente la pérdida de peso. No obstante, las propiedades químico-mecánicas mostraron que el hongo produjo adelgazamiento y ruptura de las células del tejido ocasionando disminución significativa de FE (100 a 56 N∙mm -2 ) y CPF (42.2 a 20.2 N∙mm -2 ), lo cual redujo su resistencia a los esfuerzos mecánicos. Conclusiones: La madera expuesta a la degradación por hongos está afectada significativamente en sus propiedades mecánicas, inhabilitándola para la construcción. Los daños no se reflejan en la estética del material, lo cual es alarmante, ya que el usuario común de la madera de pino no podría notar el problema.