Ciencia e Ingeniería en Alimentos y Biotecnología

URI permanente para esta comunidadhttp://repositorio.uta.edu.ec/handle/123456789/412

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Propuesta de una quimioteca de compuestos relacionados estructuralmente y diseñados para el tratamiento la enfermedad de Huntington
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2024-08)
Sanchez Guayta, Kevin Joel
;
Galarza Galarza, Cristian Fernando
Huntington's disease (HD) is an inherited neurodegenerative disorder that affects movement, cognition and behaviour. It is characterised by uncontrollable chorea movements, difficulty speaking and swallowing, memory and thinking problems, and mood swings. HD progresses over time and usually results in death 15-20 years after diagnosis; treatment focuses on controlling symptoms. Medications can help relieve chorea movements, muscle stiffness and psychiatric problems. Physiotherapy and speech therapy may also be helpful. Research into HD is ongoing, with the goal of finding new therapies and, ultimately, a cure. Scientists are using various methods, such as bioinformatics and computer science, to identify genes and proteins that may be involved in the disease. In this study, these methods were used to identify 20 elite genes potentially implicated in HD. The researchers also identified several promising therapeutic targets, including DRD2, PDE10A and CNR1. These findings provide new insights into the molecular basis of HD and may lead to the development of new treatments. HD research is encouraging and there is steady progress towards understanding and treating this devastating disease. Scientists are working hard to find a cure, and with continued support, it is hoped that one day this goal will be achieved.
Identificación de posibles dianas terapéuticas para la Enfermedad de Parkinson mediante la aplicación de métodos in silico
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2024-02)
Chimbo Gavilanes, Klever Javier
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Galarza Galarza, Cristian Fernando
In the exploration of possible therapeutic targets to treat Parkinson's disease through computational chemistry, drug design using docking tools is employed. This process is based on the analysis of genes such as LRRK2, where the main objective is to identify the most optimal binding sites in terms of energetic stability, considering them as possible ideal locations for protein action. In this context, virtual screening makes it possible to verify whether the complexes formed between the protein and the ligand represent a potential avenue for the investigation of a disease-specific drug. The analysis of several disease databases, such as MalaCards, Harmonizome, KEGG, OMIM, Unitpro, Disgenet, GeneReviews and Orphanet, has allowed the identification of key genes in Parkinson's disease. These genes are of great importance since, among numerous candidates, those with similarities in molecular processes and common dysfunctions were selected. The grouping and categorization of these genes facilitated the creation of a biological network of interactions using Cytoscape, accompanied by a bibliographic investigation of the metabolic pathways and the relationships between them, thanks to this approach, mutations in the LRRK2 gene were identified to then search for possible druggable sites in this molecule, with the aim of forming protein-ligand complexes. Thus, existing drugs or ligands can be analyzed by screening and evaluation of toxicological properties. In this bioinformatics study of therapeutic targets, I point out that the main ligand Losulazine presents a higher affinity of pharmacological interaction with the LRRK2 gene.
Evaluación de posibles dianas terapéuticas para el cáncer de colon aplicando Pipeline Bioinformático como base para el diseño de fármacos asistido por computador
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2023-09)
Jácome Campos, Mario Fabricio
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Galarza Galarza, Cristian Fernando
Colon cancer is a common type of malignant tumor in the gastrointestinal tract, accounting for about 13 percent of all tumors. Its development is influenced by epigenetic changes, genetic and environmental factors. However, current methods for diagnosing and treating this disease are often expensive, making access to treatment difficult for many patients. To identify the genes that are expressed or inhibited in colon cancer, differential expression analysis was performed using R. These genes were contrasted with databases such as: OMIM, Malacards, Harmonizome, and KEGG. The most relevant genes are grouped according to their biochemical alteration, with this information biological interaction networks are created through Cytoscape to identify proteins that are altered within the disease process. For the identification of the targets, the DrugBank database was used, through DoGSiteScorer the drugable sites were identified, virtual screening is performed through MTiopenScreen to find possible ligands that present high binding affinity. The interaction networks obtained from STITCH allow the identification of the drug that is linked to the metabolic pathways to analyze the protein-ligand interactions. The drug etoposide was identified, and its pharmacokinetic and toxicity properties are assessed by bioinformatics predictions using QSAR VEGA and pkCSM models. The toxicity and hepatotoxicity were found to be negative, suggesting that this could be a viable candidate for the development of drugs targeting the SMAD2 and CASP9 genes.
Identificación de posibles dianas terapéuticas en Alzheimer utilizando pipeline bioinformático combinado para aplicarlas al diseño de fármacos asistidos por computadora
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Biotecnología, 2023-09)
Barriga Sanchez, Luis Leonardo
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Galarza Galarza, Cristian Fernando
Bioinformatics has a potential biotechnological use because it allows the study of genetically complex diseases using different tools. The aim of this project was to analyze transcriptomic data related to Alzheimer's disease (AD) for the identification of potential therapeutic targets and computer-aided drug design. This was done through the application of a multilevel analysis of biological interaction networks, molecular docking, and evaluation of the pharmacokinetic properties of selected drugs. The analyses indicated a total of 507 and 478 genes with high and low expression, respectively, present in brains with different stages of AD. The results of the protein-protein interaction and miRNA-miRNA network analysis identified only one biomarker, hsa-mir-34a-5p, for the diagnosis of AD and asymptomatic AD in cancer patients. Survival analysis revealed that CDK6 and CD44 are potential therapeutic targets for AD. Additionally, the established pipeline also identified CCND1 as another potential therapeutic target. The drug-gene interaction networks reflected four potential drug candidates for repurposing in the treatment of AD: Estradiol, Trichostatin A, Doxorubicin, and Dorsomorphin. Molecular docking demonstrated that Estradiol and Trichostatin A can inhibit the CCND1 protein, while Dorsomorphin induces inhibition of CDK6, because of their free energy of binding is lower than the reference. The evaluation of pharmacokinetic properties indicated that only Trichostatin A can be used for the treatment of AD in humans.
Búsqueda de posibles dianas terapéuticas para el cáncer papilar de tiroides (PTC)
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos y Biotecnología. Carrera de Ingeniería Bioquímica, 2022-09)
Lagua Mainato, Christian Orley
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Galarza Galarza, Cristian Fernando
In the search for possible therapeutic targets through computational chemistry for papillary thyroid cancer (PTC), the design of drugs with docking tools is based on the analysis of the BRAF gene, where the best binding sites are mainly identified. Regarding energy stability, therefore, the virtual screening allowed to verify the drugability of said complexes that were created between protein and ligand, this represents a potential avenue of research for the development of an optimal and specific drug for said disease. The analysis within the databases of diseases such as MalaCards, Harmonizome, KEGG, OMIM, Unitpro, Disgenet, GeneReviews and Orphanet allowed to know the main genes that lead the carcinogenesis process in PTC, certain genes presented common dysfunctions so that it was possible to group and categorize them to then create a biological network of interaction with the help of Cytoscape and subsequently the metabolic pathways of these genes and the relationship between them were investigated bibliographically. In this way, the mutations that this target gene presents and the alterations in its metabolic pathway were identified. Finally, the mutations that the BRAF gene suffers were found to subsequently identify possible drugable sites that can create protein-ligand complexes, so that the existing drugs currently they were analyzed by screening and subsequent analysis of toxicological properties. Therefore, this bioinformatic study allowed to determine that the ligands Entrectinib, Bms-833923, Afacifenacin, Floxacrine, Olaparib, Nolpitantium, Aleplasinin present pharmacological potential for the BRAF gene.
Actividad antioxidante de dos extractos de Arracacia xanthorrhiza (ecotipos Baños y Quinchicoto) y su efecto citotóxico in vitro sobre células HeLa
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos. Carrera de Ingeniería Bioquímica, 2018-08)
Moya Arízaga, Jenny Maribel
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Carrero Castillo, Yendy Nayghit
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López Hernández, Orestes Darío
Evidencias biofísicas de la formación del heteroreceptor de Oxitocina - Colecistoquinina B
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos. Carrera de Ingeniería Bioquímica, 2018-05)
Tayo Montenegro, Andrés Sebastián
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Pérez Betancourt, Yunys
The neuropeptides oxytocin (OX) and cholecystokinin (CCK) are widely implicated in the physiological and pathophysiological response of anxiety, fear and depression. Thus, its membrane receptors are specific targets to which drugs are targeted. Actually, it has been described that both the formation of homodimers and heterodimers of membrane receptors coupled to G proteins (GPCR) and the allosteric regulation that takes place between the involved protomers, represent new more specific and effective therapeutic options. Therefore, the objective of this study was to demonstrate the formation of a heterodimer among these receptors. In this work, HeLa cells were used for transient expression of fluorescently labeled receptors. Microscopy analysis showed the coexpression of receptors in discrete regions of the cytoplasmic membrane. In addition, proximity ligation assays confirmed the biophysical interaction of the receptors elucidating the formation of the OxTR / CCKB heteroreceptor. These findings could become a starting point to explore the use of this heteroreceptor as a new strategy for the treatment of anxiety disorders.
Formación del heteroreceptor oxitocina - serotonina 5-HT1A: relevancia de la interacción receptor-receptor en el tratamiento de trastornos de ansiedad
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos. Carrera de Ingeniería Bioquímica, 2017-04)
Manjarrés Raza, Darwin Israel
;
Romero Fernández, Wilber
Anxiety and depression disorders represent the mental pathologies of higher prevalence in the population making it is a serious public health problem worldwide. It has now been reported that both homodimer and heterodimer formation and allosteric regulation occurring among the protomers involved in receptor-receptor interactions represent important therapeutic targets for the treatment of mental illness. The present investigation was based on demonstrating the physical interaction between the oxytocin receptor (OxTR) and the serotonin 5-HT1A receptor (5-HT1AR). The results show the expression of OxTR-GFP and 5-HT1AR-YFP receptors in the cytoplasmic membrane of HeLa cells. In addition, it is demonstrated through a technique with the biophysical basis that these receptors colocalize in the discrete zones of the cell membrane as well, the treatment of HeLa cells that coexpress both receptors with a specific agency of 5-HT1AR (8-OH- DPAT, 10nM) induce the internalization of OxTR. The results indicate the formation of an OxTR / 5-HT1AR heterodimer and suggest that there is a positive regulation in the receptor-receptor interaction, therefore this heteroreceptor may constitute a therapeutic target for anxiety and depression disorders.
Regulación alostérica en el heteroreceptor oxitocina - cannabinoide CB1: una nueva estrategia terapéutica para el tratamiento de trastornos de ansiedad
(Universidad Técnica de Ambato. Facultad de Ciencia e Ingeniería en Alimentos. Carrera de Ingeniería Bioquímica, 2017-04)
Carvajal Tapia, Cristian Omar
;
Romero Fernández, Wilber
G-protein coupled membrane receptors (GPCRs) can establish interactions between two or more receptors. It has been described that allosteric regulation may exist in these receptor-receptor interactions. Therefore, the formation of these complex structures and the regulation among the protomers involved in the protein-protein interaction represent therapeutic targets for anxiety, fear, and depression treatments. HeLa cells that transiently express oxytocin (OxTR) and cannabinoid CB1R (CB1R) receptors are a worthy study model of protein-protein interactions. The results indicate that these receptors co-localize in specific areas of the cell membrane, which could suggest the formation of the OxTR / CB1R heteroreceptor. In addition, the administration of anandamide, a specific CB1R agonist, induces the internalization of OxTR, which would indicate a positive allosteric regulation between OxTR and CB1R. The data obtained represent the first evidence of the OxTR / CB1R heteroreceptor formation and the nature of the allosteric regulation that takes place in this complex structure. Therefore, this heteromer could establish a target for the design of new drugs for the treatment of anxiety disorders.

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