Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.

Once thought of in terms of bioenergetics, mitochondria are now widely accepted as both the orchestrator of cellular health and the gatekeeper of cell death. The pulmonary disease field has performed extensive efforts to explore the role of mitochondria in regulating inflammation, cellular metabolism, apoptosis, and oxidative stress. However, a critical component of these processes needs to be more studied: mitochondrial network dynamics. Mitochondria morphologically change in response to their environment to regulate these processes through fusion, fission, and mitophagy. This allows mitochondria to adapt their function to respond to cellular requirements, a critical component in maintaining cellular homeostasis. For that reason, mitochondrial network dynamics can be considered a bridge that brings multiple cellular processes together, revealing a potential pathway for therapeutic intervention. In this review, we discuss the critical modulators of mitochondrial dynamics and how they are affected in pulmonary diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), and pulmonary arterial hypertension (PAH). A dysregulated mitochondrial network plays a crucial role in lung disease pathobiology, and aberrant fission/fusion/mitophagy pathways are druggable processes that warrant further exploration. Thus, we also discuss the candidates for lung disease therapeutics that regulate mitochondrial network dynamics.

Bio-directed Chemical Study of Pleurotus ostreatus Spent Substrate and Its Nematicidal Activity.

PURPOSE: In the present study, the nematicidal activity of the chemical fractionation of the spent substrate of the edible mushroom Pleurotus ostreatus against eggs and L3 larvae of Haemonchus contortus was evaluated. METHODS: The hydroalcoholic extract of the spent substrate was subjected to a bipartition with ethyl acetate giving two fractions: one aqueous (F. Ac) and one organic (F. AcOET). Both fractions were evaluated against eggs and L3 larvae at different concentrations (5, 2.5, 1.25, 0.625 and 0.3125 mg/mL) and 2% methanol, PBS and thiabendazole (5 mg/mL) as controls. Chemical fractionation of F. AcOET was performed in open column chromatography where 76 fractions were obtained and when analyzed by thin layer chromatography (TLC) were grouped into 11 mixtures (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11). These mixtures were evaluated at 10 mg/mL against eggs and L3 larvae. The data obtained were analyzed by ANOVA and a Tukey test in the SAS V9 program. RESULTS: The results showed that, in the evaluation of F. AcOET and F. Ac, for the inhibition of egg hatching, the highest percentages were 78.80 and 76.89% at 5 mg/mL, respectively. As for the percentage of larval mortality, F. AcOET obtained 60.91 and F. Ac 29.77% at 5 mg/mL. The results of the evaluations of the mixtures showed that mixtures R4, R5 obtained 100 and 95.41% larval mortality and mixtures R6 and R7 presented 100% inhibitory activity of egg hatching, so these were analyzed by gas chromatography mass spectrometry finding compounds such as vanillin, ß-sitosterol, ρ-methyl ρ-hydroxycinnamate and ρ-hydroxybenzaldehyde. CONCLUSION: The results of the present study demonstrate that the spent substrate of P. ostreatus has potential anthelmintic activity against H. contortus. Moreover, by reusing and taking advantage of this substrate, its environmental pollution effects can be reduced.

Fauna silvestre con valor de uso en la Reserva de la Biosfera Sierra de Huautla, Morelos, México / Wild fauna with use value in the Biosphere Reserve Sierra de Huautla, Morelos, Mexico

Resumen El objetivo de este trabajo fue sistematizar las especies apropiadas, formas de apropiación y valores de uso asignados a la fauna silvestre en comunidades de la Reserva de la Biosfera Sierra de Huautla, México, mediante un análisis documental y trabajo de campo. Se registraron 46 especies con valor de uso pertenecientes a 31 familias. La clase con mayor número de especies apropiadas son las aves (42.5%), seguidas de los mamíferos (34%). El 64% de las especies se apropian con fines alimentarios y el 38.3% se utilizan para el tratamiento de enfermedades en la medicina tradicional. Otros usos son adornos, amuletos, elaboración de herramientas y como animal de compañía. La apropiación de fauna silvestre se realiza por medio de la cacería, la recolección y la pesca. Las armas de fuego como la escopeta es el principal instrumento para la cacería. También se utilizan perros, machetes, resorteras, tarrayas, anzuelos, nudos corredizos y se capturan manualmente. La apropiación puede ser una actividad oportunista u organizada por medio de las arreadas, espiadas, lampareadas, campeadas, acorralamiento y recolección manual. La apropiación de fauna silvestre es una actividad culturalmente arraigada en las comunidades de la reserva. Sin embargo, el análisis de la relación sociedad-fauna en la región es limitado, por lo que es necesario generar información que promueva el manejo sostenible del recurso faunístico.

Abstract The aims of this paper were the systematization of appropriated species, appropriation forms and assigned use values of wildlife species in the Biosphere Reserve of the Sierra de Huautla, Mexico, by means of documentary analysis and field work. We recorded 46 species with use value pertaining to 31 families. Birds accounted for the highest number of appropriated species (42.5%), followed by mammals (34%). Of the total species, 64% are appropriated for alimentary purposes and are used in the treatment of diseases in traditional medicine. Others are used as ornaments, talismans, in tool manufacture and as pet animals. Wildlife appropriation is achieved by hunting, collection and fishing. Fire arms such as shotguns are the main instrument used in hunting. Dogs, machetes, slingshots, nets, hooks, slipknots, are also used, or they are captured by hand. Appropriation can be an opportunistic or organized activity by means of "arreadas" (herding), "espiadas" (opportunistic observation), "lampareadas" (spotlighting), "campeadas" (scouring), "acorralamiento" (cornering) and manual collection. Wildlife appropriation is a culturally rooted activity in the reserve communities. Nevertheless, the analysis of the relationship society-fauna in the region is limited and this is why the generation of information that may enable a sustainable management of the faunistic resource is necessary.

Activation of the mechanosensitive Ca2+ channel TRPV4 induces endothelial barrier permeability via the disruption of mitochondrial bioenergetics.

Mechanical ventilation is a life-saving intervention in critically ill patients with respiratory failure due to acute respiratory distress syndrome (ARDS), a refractory lung disease with an unacceptable high mortality rate. Paradoxically, mechanical ventilation also creates excessive mechanical stress that directly augments lung injury, a syndrome known as ventilator-induced lung injury (VILI). The specific mechanisms involved in VILI-induced pulmonary capillary leakage, a key pathologic feature of VILI are still far from resolved. The mechanoreceptor, transient receptor potential cation channel subfamily V member 4, TRPV4 plays a key role in the development of VILI through unresolved mechanism. Endothelial nitric oxide synthase (eNOS) uncoupling plays an important role in sepsis-mediated ARDS so in this study we investigated whether there is a role for eNOS uncoupling in the barrier disruption associated with TRPV4 activation during VILI. Our data indicate that the TRPV4 agonist, 4α-Phorbol 12,13-didecanoate (4αPDD) induces pulmonary arterial endothelial cell (EC) barrier disruption through the disruption of mitochondrial bioenergetics. Mechanistically, this occurs via the mitochondrial redistribution of uncoupled eNOS secondary to a PKC-dependent phosphorylation of eNOS at Threonine 495 (T495). A specific decoy peptide to prevent T495 phosphorylation reduced eNOS uncoupling and mitochondrial redistribution and preserved PAEC barrier function under 4αPDD challenge. Further, our eNOS decoy peptide was able to preserve lung vascular integrity in a mouse model of VILI. Thus, we have revealed a functional link between TRPV4 activation, PKC-dependent eNOS phosphorylation at T495, and EC barrier permeability. Reducing pT495-eNOS could be a new therapeutic approach for the prevention of VILI.

Plantas útiles de los huertos frutícolas tradicionales de Coatetelco, Morelos, México, frente al potencial emplazamiento minero / Useful plants of the traditional fruit orchards of Coatetelco, Morelos, Mexico, in front of the potential mining site

La pérdida de los procesos productivos tradicionales vigentes en los huertos familiares tradicionales debido a los emplazamientos mineros pone en riesgo la producción de las plantas con valor de uso medicinal y alimentario, cuya cosecha permite mitigar la pobreza entre las familias de las comunidades campesinas e indígenas. El objetivo del presente trabajo fue determinar las plantas con valores de uso que mitigan la desigualdad social de los habitantes de Coatetelco, Morelos, México. Mediante técnicas etnobiológicas, se registró una riqueza de 99 especies de plantas correspondientes a 88 géneros y 48 familias botánicas. Se registraron ocho valores de uso, de los cuales destaca el medicinal con 49.5% y el alimentario con 47.5%. Además de los usos antes mencionados, destacan funciones ecosistémicas que aseguran agua, aire limpio y alimentos orgánicos del territorio a las zonas urbanas del sur del estado. Los conocimientos tradicionales expresados en los valores de uso de las plantas aportan elementos susceptibles de integrarse a políticas públicas que garanticen la conservación de la diversidad biológica y cultural para la reproducción social de las comunidades nahuas del Poniente de Morelos, México.