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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- Immunomodulatory effect of a nutraceutical mixture in a mouse model of metabolic syndrome(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2021-05-28) Gastélum Estrada, Alejandro; Serna Saldívar, Sergio Román Othón; puelquio; Santacruz López, Yolanda Arlette; School of Engineering and Sciences; Campus Monterrey; Canales Aguirre, Alejandro ArturoCOVID-19 has impacted global community since its appearance in December 2019, with consequences in health, economic, employment, among many others that have created scenarios known as “new normality”. Along pharmacological measures, preventive ones have also been proposed including the change of diet patterns, increasing physical activities and others. In this work, nutraceuticals are explored for assessing their potential as COVID-19 preventers that could extrapolate to other new diseases or pandemics. Specifically, a nutraceutical mixture was tested in C57BL/6J mice, which is a model for obesity and metabolic syndrome, to evaluate immunomodulation potential by measuring the effect on blood indicators and immune biomarkers. Nutraceuticals evaluated include vitamins (C, D and E), minerals (selenium and zinc) and other ingredients as coenzyme Q10, microencapsulated probiotics, broccoli sprout powder and black bean coat flour as sources of sulforaphane and flavonoids, respectively. All of them have been widely studied and attributed with immunomodulatory properties, each one of them are explained and detailed in the second chapter. Results of blood indicators show a low effect on blood cells concentration and lipid profile, with no consistent differences between male and female individuals. No significant effect was determined in coagulation time. Some of the observed changes such as increase of erythrocytes and leukocyte in males of the supplemented group may suggest a heterogeneous effect between male and female mice, but more studies would be needed. While no significant effects were observed in lymphocyte-T analysis, the most relevant result was obtained in IL-1 evaluation, which level significantly increased in the obese-no supplemented group in comparison with the healthy group, but the increase was countered and even got to lower levels compared to healthy mice when the nutraceutical supplement was included in the diet. This result may suggest a higher effect of the nutraceuticals in inflammation processes rather than in blood cell levels.
- High-Protein Diets Effect on Metabolic Profiles, Gut Microbiota and Inflammation Markers in a Murine Model(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020-12-18) Bárcena Lozano, Laura; Santacruz López, Yolanda Arlette; tolmquevedo; Zabala Arcos, Judith; School of Engineering and Sciences; Campus Monterrey; Serna Saldívar, Sergio OthónDietary food is a key factor that limits the composition of microbial communities in the gut. Extreme diets cause a gut microbiota dysbiosis, modifying immunological markers and being able to produce inflammation in diverse organs. Specialized diets for losing weight and gaining muscle mass, and a raising economical support to obtain meat products in the market have doubled the recommended protein consumption amongst the population. The aim of this work was to elucidate the effects over metabolic profiles, gut microbial communities and inflammation markers that a high-protein diet, vegetal- and animal- based, can cause in a murine model. 27 male mice of 17 weeks of life (Mus musculus C57BL/6) divided in 3 groups: 1) vegetal, 2) animal and 3) standard were fed ad libitum with a high-protein diet (25- 30 %) for 7.5 weeks, following the directions of CICUAL and the Vivarium of Tecnológico de Monterrey. Mice were weighted every week. After the experimental phase, epididymal fat was measured in every group. Also, cecum samples were analysed by qPCR to evaluate the changes in gut microbiota (total bacteria, Bifidobacterium, Lactobacillus, Enterobacteria). Blood samples were collected to obtain serum, and the inflammation markers TNF-α, IL-6 and IL-10 and were analysed by Milliplex® MAP technology and the CRP by ELISA. The statistical tool Minitab® was used to process the results through ANOVA and transforming the data when necessary. Vegetal-based protein diet individuals had more epididymal fat than the rest of the groups. Moreover, they showed a higher IL-10 production as well as the CG. Nevertheless, microbial communities were compromised in the animal-based protein diet, showing signs of dysbiosis, although not presenting excessive production of inflammatory cytokines. Therefore, metabolism of a protein excess with similar amino acid profile may have negative consequences in amino acid utilization and formation of by-products, gut microbiota profiles and inflammation in gut depending on the protein source.
- Identification and Association of Fatty Acid Profile and Inflammation in Pediatric Type 2 Diabetes Mellitus and Metabolic Syndrome(Instituto Tecnológico y de Estudios Superiores de Monterrey, 2020) Navarro Guerra, Mariana; ELIZONDO MONTEMAYOR, LUZ LETICIA; 253956; CARVAJAL AGUILERA, KARLA GUADALUPE; 20316; GONZALEZ CASTILLO, ELENA CRISTINA; 167407; HERNANDEZ BRENES, CARMEN; 26334; Elizondo Montemayor, Luz Leticia; RR; García Rivas, Gerardo Jesús; Carvajal Aguilera, Karla Guadalupe; González Castillo, Elena Cristina; School of Medicine and Health Sciences; Campus Monterrey; Hernández Brenes, CarmenPlasma fatty acid composition reflects dietary intake, as well as endogenous metabolism of fatty acids, which may be impaired in metabolic diseases. In adults, analysis of plasma fatty acids and their metabolism have been used to characterize their role in inflammation and obesity-related diseases such as Type 2 Diabetes Mellitus (T2DM), however evidence in the pediatric population is scarce. To the best of knowledge, there are no studies in T2DM pediatric patients focused on the quantification of fatty acid profiles and their potential relationship with inflammation markers. The objective of this study was to determine the association between the plasma fatty acid composition and inflammatory markers in pediatric Mexican patients with T2DM, Metabolic syndrome (MetS) and healthy controls (HC). Anthropometric and biochemical parameters were determined. Plasma fatty acid profiles were quantified by gas chromatography and plasma cytokines by flow-cytometry. Univariate and multivariate statistical analyses were conducted to establish differences and relationships between response variables investigated in the clinical groups. Patients with T2DM and MetS had distinct fatty acid profiles despite similarities between anthropometric and metabolic parameters. Higher proportions of C8:0 and n-6 polyunsaturated fatty acids (PUFA), lower n-3 PUFA and estimated delta-5-desaturase (D5D) activity could place MetS patients at higher risk of developing T2DM and cardiovascular disease. Despite having higher proportions of anti-inflammatory n-3 PUFAs, patients with T2DM had a pro-inflammatory profile characterized by higher proportions of C16:0 and elevated chemokines MCP-1, IL-8 and IL-18 concentrations. Higher percent contributions of odd chain saturated fatty acid (OCSFA) C17:0 were observed in plasma of patients with MetS and T2DM; its metabolic significance requires further research but a possible protective role in the reduction of inflammation seems to be supported by prior literature. Plasma monounsaturated fatty acids (MUFA) 18:1 n-9 and 16:1 n-7 appear to have a dual role in inflammation depending on the obese state. Characterization of the fatty acid profiles of a pediatric population with MetS and T2DM generated new knowledge of specific compounds such as C8:0 and C17:0, which may play a role in progression of obesity induced IR and inflammation to T2DM.
- The role of irisin on the polarization of monocyte-derived macrophages from pediatric patients with type 2 diabetes mellitus(Instituto Tecnológico y de Estudios Superiores de Monterrey) González Gil, Adrián Marcelo; Elizondo Montemayor, Luz Leticia; puelquio; García Rivas, Gerardo de Jesús; Estrada, Manuel; Genevieve Brunck, Marion Emilie; School of Medicine and Health Sciences; Campus Monterrey; González Castillo, Elena CristinaIrisin is a novel peptide hormone released from skeletal muscle following acute bouts of physical exercise. Besides its originally described role on adipose tissue browning, its direct antiinflammatory properties have been recently described. Specifically, when murine RAW264.7 macrophages were pre-treated with irisin, both gene and protein expression of key proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, decrease following exposure to lipopolysaccharide (LPS), while levels of the anti-inflammatory cytokine IL-10 increase. These changes have been linked to decreased TLR4 protein expression and activity of NF-ΚB. As well, in murine models, irisin has been described to favor an alternatively activated M2 macrophage phenotype, both from a M0 unstimulated state and a M1 classical proinflammatory state. Recently, the importance of an anti-inflammatory microenvironment to maintain the differentiation and function of brown adipose tissue has been emphasized in preclinical models, which could imply that irisin exerts its global metabolic effects indirectly through its action on adipose tissue macrophages, at least partially. Thus, irisin and its downstream pathways could represent a novel therapeutic target in type 2 diabetes mellitus (T2DM), a disease state characterized by a systemic low-grade proinflammatory state and lower circulating levels of irisin compared with healthy controls. In humans, evidence shows that M1 macrophage infiltrates in adipose tissue originate from circulating monocytes, but no studies have described the role of irisin on any type of human immune cell. Using monocyte-derived macrophages (MDMs) obtained from peripheral blood mononuclear cells (PBMCs) from a previously characterized cross-sample of pediatric T2DM patients (n=15) and matched healthy controls (n=8), we sought to determine differences in MDM immunophenotypes between groups, their response to in vitro treatment with recombinant human irisin, and to correlate patients’ basal monocyte subsets with their clinical and biochemical parameters and MDM phenotypes. In order to standardize the procedures previous to testing cryopreserved samples of T2DM and control pediatric patients, blood was obtained from one healthy adult individual. In this subject, in vitro irisin treatment significantly increased CD163 MFI. T2DM subjects had higher proportions of circulating intermediate monocytes (IMs) relative to healthy controls, which correlated positively with body fat percentage and the inflammatory marker hs-CRP and negatively with HDL-c. MDMs from T2DM subjects had similar polarization profiles compared with controls when exposed to IL-4 and IFN-γ and LPS. However, macrophage polarization capacity, as measured by M1 (CD80) and M2 (CD163, CD200R) marker MFI, was significantly associated with basal monocyte proportions when considering all participants. Upon irisin treatment, CD163 upregulation was no longer observed in MDMs from patient samples, but a trend towards decreased NF-κB activation was noted. Our results provide preliminary evidence in favor of irisin’s anti-inflammatory role in human macrophages but must be replicated in future studies with larger sample sizes. On the other hand, increased IMs in pediatric T2DM might suggest enhanced monocyte migration and differentiation to macrophages in obese white adipose tissue or to vascular atherosclerotic lesions early in disease evolution, which warrants future longitudinal and mechanistic studies.