Ciencias Exactas y Ciencias de la Salud
Permanent URI for this collectionhttps://hdl.handle.net/11285/551039
Pertenecen a esta colección Tesis y Trabajos de grado de las Maestrías correspondientes a las Escuelas de Ingeniería y Ciencias así como a Medicina y Ciencias de la Salud.
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- Administration of resveratrol and cyclosporine a nanoparticles in a hypoxia/reoxygenation model(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-06) Hernández Fontes, Paulina; LOZANO GARCIA, OMAR; 486173; ; Lozano García, Omar; tolmquevedo, emipsanchez; Mayolo Deloisa, Karla P.; Cholula Díaz, Jorge L.; Santillán Zerón, Moíses; Escuela de Medicina y Ciencias de la Salud; Campus Monterrey; García Rivas, Gerardo de JesúsIschemia reperfusion (I/R) injury remains as a neglected therapeutic target, limiting the benefits on morbidity and mortality of early reperfusion therapies. In this work, two separate poly(lactic-co-glycolic) acid (PLGA) nanoparticles incorporating resveratrol (Resv-NPs), a phytoalexin with strong antioxidant potential, and cyclosporine A (CsA-NPs), a pharmacological inhibitor of the mitochondrial permeability transition pore (mPTP), were developed. These molecules present limitations in their pharmacokinetic profiles which obstruct them from being effectively applied as a treatment for I/R injury. In a H9c2 rat cardiomyoblast model of hypoxia/reoxygenation injury, free drugs were compared with their encapsulated counterparts through the assessment of cell viability. In terms of the latter, Resv-NPs appeared to have an equivalent protection than that of free Resv, however, CsA-NPs appeared to widen CsA narrow therapeutic window under the conditions here reported. mPTP opening was assessed through a Ca2+ retention capacity (CRC) assay, where encapsulation appeared to improve Resv-induced inhibition of pore opening at a concentration of 0.1 μM, while both free and encapsulated CsA groups appeared to prevent mPTP opening. The potential in vivo applications of these nanoformulations as well as the perspectives of this work are described.
- The role of the mitochondrial calcium uniporter in the process of arrhythmogenesis in a murine model of acute catecholamine overload(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-05-22) Salazar Ramírez, Felipe de Jesús; SALAZAR RAMIREZ, FELIPE DE JESUS; 876167; García Rivas, Gerardo de Jesús; emipsanchez; Alves Figueiredo, Hugo Jorge; Rojas Martínez, Augusto; Ramos Mondragón, Roberto; Escuela de Medicina y Ciencias de la Salud; Campus MonterreySudden cardiac death by fulminant ventricular arrhythmias remains a concern in population with cardiac risk. Recently, the mitochondrion has been implied to be a central player in Ca2+ mishandling, with its dysfunction leading up to arrhythmogenesis. A possible starting event that could lead to most changes seen in cardiac disfunction is mitochondrial Ca2+ overload. The following research study focuses on demonstrating the effects of mitochondrial Ca2+ influx inhibition in arrhythmogenesis. A murine model of acute catecholamine (isoproterenol) overload was treated previously with mitochondrial Ca2+ transport inhibitor Ru360. Ru360 treated mice showed a complete abolishment of ventricular tachycardia and ventricular fibrillation. To characterize the possible mechanisms of action, heart mitochondria were isolated and mitochondrial function was assessed. Mitochondrial Ca2+ transport inhibition preserved mitochondrial function and membrane integrity as demonstrated by a higher respiratory control and calcium retention capacity when compared to isoproterenol-treated mice which appears to be caused by a reduced oxidative stress as a trend to preserve reduced thiol groups was shown. Given the positive results obtained in abolishing ventricular arrhythmias by inhibiting mitochondrial Ca2+ transport, it is precise to continue the characterization of the mechanisms by which this therapy exerts its effects. To fully demonstrate its efficacy and characterize its mechanism of action may lead up to a new therapeutic target and therapy that could set the bases to clinical research in the near future.
- Characterizing the role of mitochondrial Ca2+ overload and permeability transition during the BCR-dependent activation of murine B lymphocytes(2017-12-05) Torres Quintanilla, Alejandro Daniel; González Castillo, Elena Cristina; García Rivas, Gerardo; Maravillas Montero, José Luis; Torre Amione, GuillermoMitochondria have proved their role as major players for immunometabolism, regulating cell function by metabolic signals. Indeed, mitochondrial function during lymphocyte activation goes beyond ATP supply, as recent evidence shows that mitochondrial Ca2+ uptake and mitochondrial ROS (mROS) production regulate lymphocyte activation. Furthermore, the adaptive immune response depends on the differentiation of lymphocytes into various subsets. Whether metabolic signals determine lymphocyte differentiation has just began to be explored. Interestingly, recent evidence shows that mitochondrial signals determine B lymphocyte differentiation into memory cells. During lymphocyte activation, Ca2+ uptake into mitochondria has proven to be an important mechanism of regulation. However, if mitochondrial Ca2+ uptake capacity impacts B cell differentiation and activation is not yet determined. Here, we have generated an in vitro model of B lymphocyte mitochondrial Ca2+ overload to explore whether this mechanism is involved in B cell activation. Primary mice B lymphocytes were subjected to activation or thapsigargin treatment to induce Ca2+ overload. The effect on the expression of activation surface marker CD69 was explored using flow cytometry. Mitochondrial contribution was explored by Ca2+ uptake inhibition using Ru360 or treatment with the mitochondrial antioxidant MitoTEMPO. Mitochondrial membrane potential, Ca2+ uptake, and content were determined. Results show that our in vitro model effectively induces mitochondrial Ca2+ overload, as seen by higher Ca2+ content and mitochondrial membrane depolarization. Moreover, mitochondrial Ca2+ overload contributes to the expression of CD69 via mROS production. Lastly, results suggest that during BCR-dependent activation, mitochondria take up Ca2+ to increase mROS production that can alter the signaling cascade. The in vitro model generated herein, should allow for further exploration of whether mitochondrial Ca2+ overload impacts B cell differentiation.