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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- Validation of machine learning supervised algorithms applied for drug-target identification in cannabinoid receptors(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2023) Rodríguez Villanueva, Ramón Martín; Contreras Torres, Flavio Fernando; VMLSAADTICR; López Aguayo, Servando; Medel Cobaxin, Héctor Javier; Rodríguez López, Carlos Eduardo; Escuela de Ingeniería y Ciencias; Campus Monterrey; Velasco Bolom, José LuisThe exploration of natural products (NPs) forms a fundamental framework in the pharmaceutical industry. In recent decades, the efficiency of discovering new drugs from NPs has been dramatically enhanced through the use of computational approaches. In this context, Machine Learning (ML) methods stand out as valuable tools for classifying, categorizing, and predicting the properties of NPs. ML methods play a crucial role in expediting drug discovery processes, offering enhanced insights and efficiency in harnessing the potential of natural compounds. In this thesis, we adopted a target-based approach paradigm guided by a hypothesis that delineates the molecular mechanisms of interaction between drugs and their respective targets. The molecular targets of interest in this study are the cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are of interest in the context of energy metabolism and food intake. We utilized the COCONUT database, containing approximately 400,000 molecules, to explore the chemical space of natural products (NPs). In particular, we optimized ML algorithms such as Support Vector Machine, Random Forest, and Deep Neural Networks by employing various training and testing splits, along with the respective parameters for each method. The algorithms underwent validation based on scoring metrics such as the F1_Score, accuracy, and Receiver Operating Characteristics curves to evaluate the performance of binary classification models. The Random Forest (RF) algorithm was chosen as the top-performing model based on scoring metrics. It was then utilized to predict active molecules associated with the cannabinoid CB1 and CB2 receptors. The predictions were guided by selecting NPs based on the criteria of functional similarity.
- Synthesis, characterization, and structural determination of ferrispinels(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2022-06-14) Murrieta Muñoz, Ana Cecilia; CONTRERAS TORRES, FLAVIO FERNANDO; 132171; Contreras Torres, Flavio Fernando; puelquio/mscuervo, emipsanchez; Medel Cobaxin, Héctor Javier; Rodríguez Macías, Fernando Jaime; Lozano García, Omar; School of Engineering and Sciences; Campus MonterreySpinel (AB2X4) crystalline system is typically characterized by a distribution of cations that can move from tetrahedral (A) to octahedral (B) sites. This movement also involves the X anions rearrangement into the cubic lattice. Accordingly, spinels can exhibit A-sites and B-sites distribution characterized by a partial to total cell inversion degree (x=1). We are interested in Zn-ferrites due to their chemical and thermal stability, ferrimagnetic properties, and earth abundance. ZnFe2O4 shows the unitary cell for a typical spinel structure; however, some previous reports suggested that this spinel can be inverted at the nanoscale regime. Hence, it is expected that ZnFe2O4 nanoparticles might show a ferrimagnetic behavior, which is an outstanding property for several applications, including high-density magnetic data storage and water splitting. The structural determination and microstructure properties are of great value in analyzing the cell inversion degree for particles synthesized following a proposed experimental design. In this Thesis, we synthesized nano and sub-micro, beam-like, and amorphous particles using a hydrothermal method varying the proportion of reactants, reaction time, and reagents. The morphology and size of the as-prepared particles were characterized by scanning electron microscopy. Atomic chemical composition and elemental stoichiometry were determined using energy-dispersive X-ray and inductively coupled plasma optical emission spectroscopy. Raman spectroscopy measurements indicate redshifts notably observed for the symmetric mode. Such wavenumber increments suggest that the frequency of phonons interacting with the incident photon is decreasing, probably due to the improved crystallinity during annealing treatments. The crystalline evolution was followed by X-ray diffraction. At the same time, lattice parameters were obtained from Rietveld refinements, and microstructure properties were assessed via Williamson-Hall type fittings. The cell parameter is estimated to be about 8.44 nm. The crystallite sizes range from 9 to 65 nm, and the microstrain is less than 0.2%. Finally, the degree of inversion of the crystalline system was evaluated using the Bertaut method. The cell inversion degree follows as 0.85 (400 °C), 0.67 (600 °C), and 0.38 (800 °C), suggesting that the annealing process helps to restore a standard spinel structure. Our simple synthesis method facilitates the tuning of the size and shape of particles, which appropriately leads to improved crystallinity as observed from structural parameters and cell inversion degrees. In this way, we assisted in evaluating and comparing the synthesis parameters to obtain ZnFe2O4 particles with different cell inversion degrees, sizes, and microstrain. We believe that this analysis could be replicated in other spinel structures and might help evaluate the relationship between their structure and magnetic properties.
- Toxicological evaluation of the TiO2 anatase and rutile crystalline phases in H9c2 cardiac cells(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-12-05) Santos Aguilar, Pamela; CONTRERAS TORRES, FLAVIO FERNANDO; 132171; Contreras Torres, Flavio Fernando; emipsanchez; Lozano García, Omar; Silva Platas, Christian Iván; Salas Treviño, Daniel; School of Engineering and Sciences; Campus Monterrey; García Rivas, Gerardo de JesúsAlthough TiO2 particles constitute a highly used material in consumer products, including food and pharmaceutical industries, considerable experimental evidence suggests that TiO2 particle exposure could be harmful and cause adverse health effects. Generally, the most studied factor for toxicity is size as nano, and fine particles are considered more toxic than bulk forms. The second structural factor most studied is the crystalline phase. The TiO2 rutile phase is considered a more inert phase than the highly active, high-refractive-index anatase phase. The cytotoxicity of TiO2-anatase has been related to that these particles can induce higher production of reactive oxygen species (ROS), which is a trigger of apoptosis pathway and alteration of mitochondrial membrane potential in cells. However, such a toxicological susceptibility to the TiO2-anatase phase may differ from the one initiated by the TiO2-rutile phase, suggesting a different cell death mechanism, which is not known at the detail. In this thesis, a series of experimental measurements were carried out to analyze TiO2-anatase and TiO2-rutile submicron-sized particles' physical properties. The TiO2 particles in anatase phase were transformed to rutile phase through a heating process, and then both were analyzed by Raman spectroscopy, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), dynamic light scattering (DLS), and zeta potential. The evaluation of the toxicity of TiO2 particles in H9c2 cardiac cells to identify the role of the crystalline phase that may pose a health risk in a dose-dependent manner is the main objective of this study. The TiO2-anatase and TiO2-rutile particles' toxicity assessment was conducted in vitro, evaluating the metabolic activity, the plasma membrane integrity, mitochondrial superoxide production, and intracellular redox state. The particles' characterization by XRD and Raman spectroscopy confirmed the successful transformation of anatase particles to the rutile phase through a heating process. By DLS, it was confirmed that the hydrodynamic particle diameter was 166 nm and 468 nm for anatase and rutile, respectively. At the same time, further analysis by XLPA methods: Williamson-Hall and Warren Averbach showed that the apparent crystallite size of anatase is larger than for rutile. SEM microscopy identified that anatase particles had a spheric-like shape while for rutile were slightly more elongated. H9c2 cells show metabolic activity inhibition of 50% at an approximate value of 30 μg/mL when exposed to either anatase or rutile particles for 24 h. However, the dose-dependent inhibition at lower or higher values of the IC50 is dependent on the crystalline structure. Neither anatase phase nor rutile phase reduces the number of viable cells through necrosis; however, cell death has been categorized as early or late apoptosis for both particles. No significant alteration of the intracellular redox state at any particle exposure concentration between 0.3 μg/mL – 30 μg/mL was observed. On the other hand, for anatase, a 3-fold increase in mitochondrial superoxide production at 30 μg/mL was found, indicating that the intrinsic mitochondrial apoptotic pathway might mediate the apoptosis. However, for rutile, there is no increase in mitochondrial ROS production, suggesting that the cell death mechanism is dependent on a different metabolic pathway independent of the mitochondria.