Efecto de aldehídos alifáticos productos de lipoperoxidacion sobre la estructura química y función de la insulina

Tesis (Maestría en Ciencias en Farmacología), Instituto Politécnico Nacional, SEPI, ESM, 2008, 1 archivo PDF, (52 páginas). tesis.ipn.m

Diabetes Mellitus and Pregnancy: An Insight into the Effects on the Epigenome

Worldwide, diabetes mellitus represents a growing health problem. If it occurs during pregnancy, it can increase the risk of various abnormalities in early and advanced life stages of exposed individuals due to fetal programming occurring in utero. Studies have determined that maternal conditions interfere with the genotypes and phenotypes of offspring. Researchers are now uncovering the mechanisms by which epigenetic alterations caused by diabetes affect the expression of genes and, therefore, the development of various diseases. Among the numerous possible epigenetic changes in this regard, the most studied to date are DNA methylation and hydroxymethylation, as well as histone acetylation and methylation. This review article addresses critical findings in epigenetic studies involving diabetes mellitus, including variations reported in the expression of specific genes and their transgenerational effects

Efectos en músculo por administración de glucocorticoides en modelo murino

Los corticoesteroides son fármacos que se utilizan frecuentemente de manera crónica en diversas condiciones, de manera puntual los glucocorticoides resultan de gran utilidad en un espectro muy amplio de patologías, sin embargo, los efectos adversos no siempre son considerados para su administración, existen efectos en todos los tejidos, incluido de manera importante el tejido muscular, donde pueden provocar desde atrofia hasta facilitar procesos infecciosos

Reverse Screening of Boronic Acid Derivatives: Analysis of Potential Antiproliferative Effects on a Triple-Negative Breast Cancer Model In Vitro

It has been demonstrated that different organoboron compounds interact with some well-known molecular targets, including serine proteases, transcription factors, receptors, and other important molecules. Several approaches to finding the possible beneficial effects of boronic compounds include various in silico tools. This work aimed to find the most probable targets for five aromatic boronic acid derivatives. In silico servers, SuperPred, PASS-Targets, and Polypharmacology browser 2 (PPB2) suggested that the analyzed compounds have anticancer properties. Based on these results, the antiproliferative effect was evaluated using an in vitro model of triple-negative breast cancer (4T1 cells in culture). It was demonstrated that phenanthren-9-yl boronic acid and 6-hydroxynaphthalen-2-yl boronic acid have cytotoxic properties at sub-micromolar concentrations. In conclusion, using in silico approaches and in vitro analysis, we found two boronic acid derivatives with potential anticancer activity

Oxidative stress biomarkers and their relationship with cytokine concentrations in overweight/obese pregnant women and their neonates

Abstract Background Oxidative damage present in obese/overweight mothers may lead to further oxidative stress conditions or inflammation in maternal and cord blood samples. Thirty-four pregnant women/newborn pairs were included in this study to assess the presence of oxidative stress biomarkers and their relationship with serum cytokine concentrations. Oxidative stress biomarkers and antioxidant enzymes were compared between the mother/offspring pairs. The presence of 27 cytokines was measured in maternal and cord blood samples. Analyses were initially performed between all mothers and newborns and later between normal weight and mothers with overweight and obesity, and diabetic/non-diabetic women. Results Significant differences were found in biomarker concentrations between mothers and newborns. Additionally, superoxide-dismutase activity was higher in pre-pregnancy overweight mothers compared to those with normal weight. Activity for this enzyme was higher in neonates born from mothers with normal pregestational weight compared with their mothers. Nitrites in overweight/obese mothers were statistically lower than in their offspring. Maternal free fatty acids, nitrites, carbonylated proteins, malondialdehyde and superoxide dismutase predicted maternal serum concentrations of IL-4, IL-13, IP-10 and MIP-1β. Arginase activity in maternal plasma was related to decreased concentrations of IL-4 and IL-1β in cord arterial blood. Increased maternal malondialdehyde plasma was associated with higher levels of IL-6 and IL-7 in the offspring. Conclusions Oxidative stress biomarkers differ between mothers and offspring and can predict maternal and newborn cytokine concentrations, indicating a potential role for oxidative stress in foetal metabolic and immunologic programming. Moreover, maternal obesity and diabetes may affect maternal microenvironments, and oxidative stress related to these can have an impact on the placenta and foetal growth

Potent Anti-Inflammatory Activity of Carbohydrate Polymer with Oxide of Zinc

Pebisut is a biological adhesive composed of naturally occurring carbohydrates combined with zinc oxide (ZnO) initially used as a coadjutant for healing of anastomoses. Likewise some works demonstrated that carbohydrate complexes exerts anti-inflammatory activity and it is widely known that ZnO modulate inflammation. However, the direct effects of Pebisut on isolated cells and acute inflammatory responses remained to be investigated. The present study evaluated anti-inflammatory effect of Pebisut using lipopolysaccharide (LPS) stimulated human mononuclear cells, chemotaxis, and cell infiltration in vivo in a murine model of peritonitis. Our data show that human cells treated with different dilutions of Pebisut release less IL-6, IL-1β, and IL-8 after LPS stimuli compared with the control treated cells. In addition, Pebisut lacked chemotactic activity in human mononuclear cells but was able to reduce chemotaxis towards CCL2, CCL5, and CXCL12 that are representative mononuclear cells chemoattractants. Finally, in a murine model of peritonitis, we found less number of macrophages (F4/80+) and T lymphocytes (CD3+) in peritoneal lavages from animals treated with Pebisut. Our results suggest that Pebisut has anti-inflammatory activity, which might have a beneficial effect during anastomoses healing or wounds associated with excessive inflammation

Vitamin D Deficiency, Excessive Gestational Weight Gain, and Oxidative Stress Predict Small for Gestational Age Newborns Using an Artificial Neural Network Model

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R2 = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application