Function and expression of N-acetyltransferases 1 and 2 are altered in lymphocytes in type 2 diabetes and obesity.

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited. An increased enzyme expression and a diminished NAT2 enzymatic activity were found in cells of T2D patients compared to the control group, while NAT1 was negatively correlated with body fat percentage and BMI. In contrast, Sirtuin inhibition increased NAT2 activity, while Sirtuin agonism decreased its activity in both groups. The analysis of NAT2 SNPs showed a higher frequency of rapid acetylation haplotypes in T2D patients compared to the control group, possibly associated as a risk factor for diabetes. The enzymatic expression of CD3+NAT2+ cells was higher in the rapid acetylators group compared to the slow acetylators group. The levels and activity of NAT1 were associated with total cholesterol and triglycerides. Meanwhile, CD3+NAT2+ cells and NAT2 activity levels were associated with HbA1c and glucose levels. The results indicate that NAT2 could be involved in metabolic processes related to the development of T2D, due to its association with glucose levels, HbA1c, and the altered SIRT-NAT axis. NAT1 may be involved with dyslipidaemias in people who are overweight or obese.

Clinical Significance of the Lipid Profile Ratios and Triglyceride Glucose Index in the Diagnosis of Metabolic Syndrome.

Introduction: Metabolic syndrome (MetS) is a pathophysiological condition defined by a set of metabolic alterations such as hypertriglyceridemia, hyperglycemia, hypertension, low HDL-c levels, and visceral obesity. Its presence identifies people with an increased risk of developing cardiovascular diseases and type 2 diabetes; however, the lack of practical and reliable methods for its diagnosis limits the identification of people with this condition. In this sense, the objective of this study was to analyze the diagnostic utility of markers derived from the lipid profile [triglyceride-glucose (TyG) index and the ratios total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-c), triglyceride (TG)/HDL-c, low-density lipoprotein cholesterol/HDL-c, fasting blood glucose (FBG)/HDL-c, and white blood cell/HDL-c] in the determination of MetS. Methods: A retrospective study was designed that included 619 individuals. A logistic regression model was used to evaluate the associations of the different markers with MetS, and the cutoff points of the markers were determined through an analysis of receiver operating characteristic curves and the Youden Index. Results: A positive and significant association was observed between all markers and the presence of MetS. The cutoff values for the markers that best predicted MetS were TyG ≥ 4.8 (sensitivity = 91.4%, specificity = 74.3%), TC/HDL-c ≥ 3.7 (sensitivity = 74.3%, specificity = 75.7%), TG/HDL-c ≥ 3.3 (sensitivity = 82.5%, specificity = 84.0%), and FBG/HDL-c ≥ 2.0 (sensitivity = 85.1%, specificity = 79.7%). Conclusion: Our study demonstrated the diagnostic relevance of the different markers in detecting MetS, suggesting that these ratios may be useful in clinical practice for the opportune and accurate diagnosis of MetS.

miR-21, miR-221, miR-29 and miR-34 are distinguishable molecular features of a metabolically unhealthy phenotype in young adults.

Discrepancies between the measurement of body mass index (BMI) and metabolic health status have been described for the onset of metabolic diseases. Studying novel biomarkers, some of which are associated with metabolic syndrome, can help us to understand the differences between metabolic health (MetH) and BMI. A group of 1469 young adults with pre-specified anthropometric and blood biochemical parameters were selected. Of these, 80 subjects were included in the downstream analysis that considered their BMI and MetH parameters for selection as follows: norm weight metabolically healthy (MHNW) or metabolically unhealthy (MUNW); overweight/obese metabolically healthy (MHOW) or metabolically unhealthy (MUOW). Our results showed for the first time the differences when the MetH status and the BMI are considered as global MetH statures. First, all the evaluated miRNAs presented a higher expression in the metabolically unhealthy group than the metabolically healthy group. The higher levels of leptin, IL-1b, IL-8, IL-17A, miR-221, miR-21, and miR-29 are directly associated with metabolic unhealthy and OW/OB phenotypes (MUOW group). In contrast, high levels of miR34 were detected only in the MUNW group. We found differences in the SIRT1-PGC1α pathway with increased levels of SIRT1+ cells and diminished mRNA levels of PGCa in the metabolically unhealthy compared to metabolically healthy subjects. Our results demonstrate that even when metabolic diseases are not apparent in young adult populations, MetH and BMI have a distinguishable phenotype print that signals the potential to develop major metabolic diseases.

Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

Influence of feeding practices in the composition and functionality of infant gut microbiota and its relationship with health.

Establishing the infant's gut microbiota has long-term implications on health and immunity. Breastfeeding is recognized as the best practice of infant nutrition in comparison with formula feeding. We evaluated the effects of the primary feeding practices by analyzing the infant growth and the potential association with gut diseases. A cross-sectional and observational study was designed. This study included 55 mothers with infants, who were divided according to their feeding practices in breastfeeding (BF), formula feeding (FF), and combined breast and formula feeding (CF). Anthropometric measurements of the participants were recorded. Additionally, non-invasive fecal samples from the infants were collected to analyze the microbiota by sequencing, immunoglobulin A (IgA) concentration (ELISA), and volatile organic compounds (gas chromatography with an electronic nose). Results showed that the microbiota diversity in the BF group was the highest compared to the other two groups. The IgA levels in the BF group were twice as high as those in the FF group. Moreover, the child´s growth in the BF group showed the best infant development when the data were compared at birth to the recollection time, as noted by the correlation with a decreased concentration of toxic volatile organic compounds. Interestingly, the CF group showed a significant difference in health status when the data were compared with the FF group. We conclude that early health practices influence children's growth, which is relevant to further research about how those infants' health evolved.

Dynamical changes in the expression of GABAergic and purinergic components occur during the polarization of THP-1 monocytes to proinflammatory macrophages.

The monocytes are key components of innate immunity, as they can differentiate into phagocytic cells or macrophages with proinflammatory or anti-inflammatory phenotypes. The gamma-aminobutyric acid (GABA) and adenosine triphosphate (ATP), two known neurotransmitters, are two environmental signals that contribute to the differentiation of monocytes into macrophages and their subsequent polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. Although monocytes and macrophages express proteins related to GABA and ATP-mediated response (GABAergic and purinergic systems, respectively), it is unknown whether changes in their expression occur during monocyte activation or their differentiation and polarization into macrophages. Therefore, we evaluated the expression levels of GABAergic and purinergic signaling components in the THP-1 monocyte cell line and their changes during monocyte activation, differentiation, and polarization to M1 proinflammatory macrophages. Our results showed that activated monocytes are characterized by increased expression of two GABAergic components, the GABA transporter 2 (GAT-2) and the glutamic acid decarboxylase (GAD)-67, an enzyme involved in GABA synthesis. Also, monocytes showed a pronounced expression of the purinergic receptors P2X4 and P2X7. Interestingly, during differentiation, monocytes increased the expression of the ß2 subunit of GABA A-type receptor (GABA-AR), while the purinergic receptors P2X1 and P2X1del were reduced. In contrast, proinflammatory M1 macrophages showed a reduced expression in the α4 subunit of GABA-AR and GAD67, while P2X4 and P2X7 were overexpressed. These results indicate that dynamical changes in the GABAergic and purinergic components occur during the transition from monocytes to macrophages. Since GABA and ATP are two neurotransmitters, our results suggest that monocytes and macrophages respond to neurotransmitter-induced stimulation and may represent a path of interaction between the nervous and immune systems during peripheral inflammation and neuroinflammation development.

Soluble receptor for advanced glycation end-products (sRAGE) in childhood obesity: association with gene expression of RAGE and cardiometabolic markers / Receptor soluble para productos finales de glicación avanzada (sRAGE) en la obesidad infantil:asociación con la expresión génica de RAGE y marcadores cardiometabólicos

Introduction: advanced glycation end-products (AGEs) interact with the receptor for AGEs (RAGE). Full-length RAGE is associated with intracellular signal transduction, and soluble-RAGE (sRAGE) lacks the transmembrane and cytoplasmic domains, acting as a competitive inhibitor ofAGEs-RAGE binding. sRAGE levels in healthy children are associated with cell surface expression of RAGE. However, the expression of RAGE hasnot been explored in childhood obesity.Objective: the study aim was to evaluate the sRAGE levels and the gene expression of RAGE in children and its association with cardiometabolicmarkers.Methods: this is a cross-sectional study with 6-11-year children, 20 with overweight and 20 with obesity. Anthropometric measurements includedwaist circumference (cm) (WC), neck circumference (NC), weight (kg), fat mass (%), trunk fat (kg), muscular mass (kg), height (cm), and bodymass index (BMI) (kg/m2). Blood samples following an overnight fast were collected to measure glucose (mg/dl) and lipid profile with colorimetricmethods. sRAGE was determined in serum using the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription (RT-qPCR)was performed to analyze RAGE transcripts in peripheral blood mononuclear cells isolated by Ficoll®-Hypaque.Results: we found higher RAGE (p = 0.0315) and lower sRAGE (p = 0.0305) levels in the obesity group. sRAGE level showed a negative correlation with RAGE (r = -0.35) and BMI (r = -0.24), and positive with HDL-cholesterol (r = 0.29). Regression analysis suggests that HDL-C andRAGE levels are predictors of sRAGE levels.Conclusions: expression of RAGE is associated with lower sRAGE levels in childhood obesity. Moreover, obese children show higher cardiometabolic risk markers, and a positively associated with sRAGE. (AU)

Introducción: los productos finales de glicación avanzada (AGE) interactúan con el receptor de AGE (RAGE). El RAGE de longitud completaestá asociado con la transducción de señales intracelulares y el RAGE soluble (sRAGE) carece de los dominios transmembrana y citoplásmico,actuando como un inhibidor competitivo de la unión de AGE-RAGE. Los niveles de sRAGE en niños sanos están asociados con la expresión deRAGE en la superficie celular. Sin embargo, la expresión de RAGE no se ha explorado en la obesidad infantil.Objetivo: el objetivo del estudio fue evaluar los niveles de sRAGE y la expresión génica de RAGE en niños y su asociación con marcadorescardiometabólicos.Métodos: se trata de un estudio transversal con niños de seis a once años, 20 con sobrepeso y 20 con obesidad. Las medidas antropométricasincluyeron la circunferencia de la cintura (cm) (CC), la circunferencia del cuello (NC), el peso (kg), la masa grasa (%), la grasa del tronco (kg),la masa muscular (kg), la altura (cm) y el índice de masa corporal (IMC) (kg/m2). Se tomaron muestras de sangre después de una noche deayuno para medir glucosa (mg/dl) y el perfil de lípidos con métodos colorimétricos. Los sRAGE se determinaron en suero utilizando un ensayoinmunoabsorbente ligado a enzimas (ELISA). Se realizó una transcripción inversa cuantitativa (RT-qPCR) para analizar los transcritos de RAGE encélulas mononucleares de sangre periférica aisladas por Ficoll®-Hypaque.Resultados: encontramos niveles más altos de RAGE (p = 0,0315) y más bajos de sRAGE (p = 0,0305) en el grupo de obesidad. El nivel de sRAGE mostró una correlación negativa con RAGE (r = -0,35) e IMC (r = -0,24), y positiva con el colesterol HDL (r = 0,29). El análisis de regresión sugiere que los niveles de HDL-C y RAGE predicen los niveles de sRAGE.Conclusiones: la expresión de RAGE se asocia con niveles más bajos de sRAGE en la obesidad infantil. ... (AU)

Soluble receptor for advanced glycation end-products (sRAGE) in childhood obesity: association with gene expression of RAGE and cardiometabolic markers.

Introduction: Introduction: advanced glycation end-products (AGEs) interact with the receptor for AGEs (RAGE). Full-length RAGE is associated with intracellular signal transduction, and soluble-RAGE (sRAGE) lacks the transmembrane and cytoplasmic domains, acting as a competitive inhibitor of AGEs-RAGE binding. sRAGE levels in healthy children are associated with cell surface expression of RAGE. However, the expression of RAGE has not been explored in childhood obesity. Objective: the study aim was to evaluate the sRAGE levels and the gene expression of RAGE in children and its association with cardiometabolic markers. Methods: this is a cross-sectional study with 6-11-year children, 20 with overweight and 20 with obesity. Anthropometric measurements included waist circumference (cm) (WC), neck circumference (NC), weight (kg), fat mass (%), trunk fat (kg), muscular mass (kg), height (cm), and body mass index (BMI) (kg/m2). Blood samples following an overnight fast were collected to measure glucose (mg/dl) and lipid profile with colorimetric methods. sRAGE was determined in serum using the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription (RT-qPCR) was performed to analyze RAGE transcripts in peripheral blood mononuclear cells isolated by Ficoll®-Hypaque. Results: we found higher RAGE (p = 0.0315) and lower sRAGE (p = 0.0305) levels in the obesity group. sRAGE level showed a negative correlation with RAGE (r = -0.35) and BMI (r = -0.24), and positive with HDL-cholesterol (r = 0.29). Regression analysis suggests that HDL-C and RAGE levels are predictors of sRAGE levels. Conclusions: expression of RAGE is associated with lower sRAGE levels in childhood obesity. Moreover, obese children show higher cardiometabolic risk markers, and a positively associated with sRAGE.

Introducción: Introducción: los productos finales de glicación avanzada (AGE) interactúan con el receptor de AGE (RAGE). El RAGE de longitud completa está asociado con la transducción de señales intracelulares y el RAGE soluble (sRAGE) carece de los dominios transmembrana y citoplásmico, actuando como un inhibidor competitivo de la unión de AGE-RAGE. Los niveles de sRAGE en niños sanos están asociados con la expresión de RAGE en la superficie celular. Sin embargo, la expresión de RAGE no se ha explorado en la obesidad infantil. Objetivo: el objetivo del estudio fue evaluar los niveles de sRAGE y la expresión génica de RAGE en niños y su asociación con marcadores cardiometabólicos. Métodos: se trata de un estudio transversal con niños de seis a once años, 20 con sobrepeso y 20 con obesidad. Las medidas antropométricas incluyeron la circunferencia de la cintura (cm) (CC), la circunferencia del cuello (NC), el peso (kg), la masa grasa (%), la grasa del tronco (kg), la masa muscular (kg), la altura (cm) y el índice de masa corporal (IMC) (kg/m2). Se tomaron muestras de sangre después de una noche de ayuno para medir glucosa (mg/dl) y el perfil de lípidos con métodos colorimétricos. Los sRAGE se determinaron en suero utilizando un ensayo inmunoabsorbente ligado a enzimas (ELISA). Se realizó una transcripción inversa cuantitativa (RT-qPCR) para analizar los transcritos de RAGE en células mononucleares de sangre periférica aisladas por Ficoll®-Hypaque. Resultados: encontramos niveles más altos de RAGE (p = 0,0315) y más bajos de sRAGE (p = 0,0305) en el grupo de obesidad. El nivel de sRAGE mostró una correlación negativa con RAGE (r = -0,35) e IMC (r = -0,24), y positiva con el colesterol HDL (r = 0,29). El análisis de regresión sugiere que los niveles de HDL-C y RAGE predicen los niveles de sRAGE. Conclusiones: la expresión de RAGE se asocia con niveles más bajos de sRAGE en la obesidad infantil. Además, los niños obesos muestran marcadores de riesgo cardiometabólico más elevados y una asociación positiva con sRAGE.

Fluoroquinolone Analogs, SAR Analysis, and the Antimicrobial Evaluation of 7-Benzimidazol-1-yl-fluoroquinolone in In Vitro, In Silico, and In Vivo Models.

Structure-activity relationship (SAR) studies allow the evaluation of the relationship between structural chemical changes and biological activity. Fluoroquinolones have chemical characteristics that allow their structure to be modified and new analogs with different therapeutic properties to be generated. The objective of this research is to identify and select the C-7 heterocycle fluoroquinolone analog (FQH 1-5) with antibacterial activity similar to the reference fluoroquinolone through in vitro, in silico, and in vivo evaluations. First, SAR analysis was conducted on the FQH 1-5, using an in vitro antimicrobial sensibility model in order to select the best compound. Then, an in silico model mechanism of action analysis was carried out by molecular docking. The non-bacterial cell cytotoxicity was evaluated, and finally, the antimicrobial potential was determined by an in vivo model of topical infection in mice. The results showed antimicrobial differences between the FQH 1-5 and Gram-positive and Gram-negative bacteria, identifying the 7-benzimidazol-1-yl-fluoroquinolone (FQH-2) as the most active against S. aureus. Suggesting the same mechanism of action as the other fluoroquinolones; no cytotoxic effects on non-bacterial cells were found. FQH-2 was demonstrated to decrease the amount of bacteria in infected wound tissue.

A systematic review of the protein composition of whole saliva in subjects with healthy periodontium compared with chronic periodontitis.

CONTEXT: Periodontitis is a chronic multifactorial inflammatory disease linked to oral microbiota dysbiosis. This disease progresses to infection that stimulates a host immune/inflammatory response, with progressive destruction of the tooth-supporting structures. OBJECTIVE: This systematic review aims to present a robust critical evaluation of the evidence of salivary protein profiles for identifying oral diseases using proteomic approaches and summarize the use of these approaches to diagnose chronic periodontitis. DATA SOURCES: A systematic literature search was conducted from January 1st, 2010, to December 1st, 2022, based on PICO criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching the three databases Science Direct, Scopus, and Springer Link. STUDY SELECTION: According to the inclusion criteria, eight studies were identified to analyze the proteins identified by proteomics. RESULTS: The protein family S100 was identified as the most abundant in patients with chronic periodontitis. In this family, an increased abundance of S100A8 and S100A9 from individuals with the active disease was observed, which strongly relates to the inflammatory response. Moreover, the ratio S100A8/S100A9 and the metalloproteinase-8 in saliva could differentiate distinct periodontitis groups. The changes in protein profile after non-surgical periodontal therapy improved the health of the buccal area. The results of this systematic review identified a set of proteins that could be used as a complementary tool for periodontitis diagnosis using salivary proteins. CONCLUSION: Biomarkers in saliva can be used to monitor an early stage of periodontitis and the progression of the disease following therapy.

Altered Arylamine N-acetyltransferase 1 and miR-1290 Levels in Childhood Acute Lymphoblastic Leukemia: A Pilot Study.

BACKGROUND/AIM: Arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) are drug-metabolizing enzymes that play a key role in the development of acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: This study evaluated NAT1 and NAT2 mRNA and protein expression and their enzymatic activity in peripheral blood mononuclear cells (PBMC) from patients with ALL (n=20) and healthy children (n=19) and explored the mechanisms that regulate these enzymes in ALL such as microRNAs (miR-1290, miR-26b) and SNPs. RESULTS: PBMC from patients with ALL showed a decrease in NAT1 mRNA and protein expression. In addition, NAT1 enzymatic activity was decreased in patients with ALL. There was no influence of SNP 559 C>T or 560 G>A on low NAT1 activity. The lower expression of NAT1 might be related to the loss of acetylated histone H3K14 in the NAT1 gene promoter in patients with ALL and the higher relative expression of miR-1290 in the plasma of patients with relapsed ALL compared with healthy controls. There were significantly fewer CD3+/NAT1+ double-positive cells in patients who relapsed compared with control subjects. Based on a t-distributed stochastic neighbor embedding algorithm, CD19+ cells that reappeared in patients with relapse showed low NAT1 expression. In contrast, for NAT2, there were no significant results. CONCLUSION: The expression and function of NAT1 and miR-1290 levels could be involved in modulating immune cells altered in ALL.

The role of arylamine N-acetyltransferases in chronic degenerative diseases: Their possible function in the immune system.

Since their discovery, arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2, respectively) have been associated with the metabolism of xenobiotics. NAT2 is the main factor in the therapeutic success of tuberculosis treatment due to its role in the biotransformation of isoniazid. However, researchers have started to investigate the possible participation of NAT1 and NAT2 (NATs) in carcinogenesis, although the mechanisms have not been elucidated fully. NATs enzymatic activity is essential in some types of cancer, such as breast cancer and acute lymphoblastic leukemia. Whether NAT1 and/or NAT2 participate in insulin resistance level in diabetes mellitus or in the immune system remains to be explored. Therefore, it is clear that its role in cell physiology has more implications than just metabolizing compounds.

Implementation and evaluation of an educational intervention to prevent risk factors for the development of non-communicable diseases in Mexican families of suburban communities.

Non-communicable diseases (NCD), are not transmitted from person to person, are long-lasting and usually of slow evolution. Worldwide cause 71% deaths, in Mexico during 2016 were the cause of 80% of registered deaths; population in socioeconomic disadvantage is more vulnerable. It is urgent to develop strategies that can prevent NCD, thus, the objective of this study was to design, implement and evaluate an educational intervention strategy (EI), to prevent and control risk factors for the development NCD in families of two vulnerable communities. The research design was mixed, the stages were developed based on a risk communication (RC) model and was performed in three stages: 1) EI Design, 2) Implementation and 3) Evaluation of the intervention. In the contextualization, risk factors were found in the participants who were integrated in the design of the educational strategy. The EI implemented was effective in increasing knowledge about NCD and practice of healthy habits, such as increasing the consumption of fruits and vegetables. Additionally, the guidance of EI at the family level has the advantage of creating a support network for these changes. However, pending issues remain, such as the design of effective strategies to reduce the consumption of sugars and sugary drinks.

An Analysis COVID-19 in Mexico: a Prediction of Severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes a mild illness in most cases; forecasting COVID-19-associated mortality and the demand for hospital beds and ventilators are crucial for rationing countries' resources. OBJECTIVE: To evaluate factors associated with the severity of COVID-19 in Mexico and to develop and validate a score to predict severity in patients with COVID-19 infection in Mexico. DESIGN: Retrospective cohort. PARTICIPANTS: We included 1,435,316 patients with COVID-19 included before the first vaccine application in Mexico; 725,289 (50.5%) were men; patient's mean age (standard deviation (SD)) was 43.9 (16.9) years; 21.7% of patients were considered severe COVID-19 because they were hospitalized, died or both. MAIN MEASURES: We assessed demographic variables, smoking status, pregnancy, and comorbidities. Backward selection of variables was used to derive and validate a model to predict the severity of COVID-19. KEY RESULTS: We developed a logistic regression model with 14 main variables, splines, and interactions that may predict the probability of COVID-19 severity (area under the curve for the validation cohort = 82.4%). CONCLUSIONS: We developed a new model able to predict the severity of COVID-19 in Mexican patients. This model could be helpful in epidemiology and medical decisions.

Differential Expression of AhR in Peripheral Mononuclear Cells in Response to Exposure to Polycyclic Aromatic Hydrocarbons in Mexican Women.

The exposure to air pollutants causes significant damage to health, and inefficient cooking and heating practices produce high levels of household air pollution, including a wide range of health-damaging pollutants such as fine particles, carbon monoxide and PAHs. The exposure to PAHs has been associated with the development of neoplastic processes, asthma, genotoxicity, altered neurodevelopment and inflammation. The effects on the induction of proinflammatory cytokines are attributed to the activation of AhR. However, the molecular mechanisms by which the PAHs produce proinflammatory effects are unknown. This study was performed on a group of 41 Mexican women from two rural communities who had stoves inside their houses, used wood as biomass fuel, and, thus, were vulnerable. According to the urinary 1-OHP concentration, the samples were stratified into two groups for determination of the levels of TNF-α, AhR, CYP1B1, miR-125b and miR-155 expression. Our results showed that the CYP1B1, TNF-α, miR-125b and miR-155 expression levels were not statistically different between women with the lowest and highest levels of 1-OHP. Interestingly, high levels of PAHs promoted augmented expression of AhR, which is a protein involved in the modulation of inflammatory pathways in vivo, suggesting that cell signaling of AhR may be implicated in several pathogenesis processes.

Revealing the contribution of astrocytes to glutamatergic neuronal transmission.

Research on glutamatergic neurotransmission has focused mainly on the function of presynaptic and postsynaptic neurons, leaving astrocytes with a secondary role only to ensure successful neurotransmission. However, recent evidence indicates that astrocytes contribute actively and even regulate neuronal transmission at different levels. This review establishes a framework by comparing glutamatergic components between neurons and astrocytes to examine how astrocytes modulate or otherwise influence neuronal transmission. We have included the most recent findings about the role of astrocytes in neurotransmission, allowing us to understand the complex network of neuron-astrocyte interactions. However, despite the knowledge of synaptic modulation by astrocytes, their contribution to specific physiological and pathological conditions remains to be elucidated. A full understanding of the astrocyte's role in neuronal processing could open fruitful new frontiers in the development of therapeutic applications.

Changes in PPAR-γ Expression Are Associated with microRNA Profiles during Fetal Programming due to Maternal Overweight and Obesity.

BACKGROUND: There has been a global increase in the prevalence of obesity in pregnant women in recent years. Animal studies have shown that intrauterine environment associated with maternal obesity leads to epigenetic changes. However, the effects of epigenetic changes occurring before birth in response to maternal conditions have not been clearly characterized in humans. OBJECTIVE: The aim of the study was to analyze peroxisome proliferator-activated receptor (PPAR)-γ expression in cell cultures from newborns from mothers with overweight and obesity, in response to in vitro metabolic challenges and their relationship with microRNA profile and cytokine expression. Methods/Study design: The profile of circulating microRNAs from 72 mother-child pairs (including healthy infants born to normal weight [n = 35], overweight [n = 25], and obese [n = 12] mothers) was determined through real-time PCR, and the PPAR-γ expression in peripheral blood mononuclear cell cultures from offspring was analyzed after in vitro challenges. RESULTS: miR-146a, miR-155, and miR-378a were upregulated in overweight mothers, while miR-378a was upregulated in obese mothers compared to normal weight mothers. In children from overweight mothers, miR-155 and miR-221 were downregulated and miR-146a was upregulated, while offspring of mothers with obesity showed downregulation of miR-155, miR-221, and miR-1301. These microRNAs have direct or indirect relation with PPAR-γ expression. In vitro exposure to high triglyceride and exposure to miR-378a induced a higher expression of PPAR-γ in cells from offspring of mothers with overweight and obesity. In contrast, cells from offspring of mothers with obesity cultured with high glucose concentrations showed PPAR-γ downregulation. IL-1ß, IL-6, and TNF-α expression in cells of offspring of overweight and obese mothers differed from that of offspring of normal weight mothers. Limitation of our study is the small sample size. CONCLUSION: The blood microRNA profile, and in vitro PPAR-γ and inflammatory cytokine expression in cells of newborn infants are associated with maternal obesity indicating that epigenetic marks may be established during intrauterine development. Key Message: Neonatal microRNA profile is associated with maternal weight. Neonatal microRNA profile is independent of maternal microRNA profile. PPAR-γ expression in newborn cell cultures is affected by maternal weight.

Prevalencia de la prediabetes y sus comorbilidades en la población pediátrica mexicana / Prevalence of prediabetes and its comorbidities in the Mexican pediatric population

Objetivo: la prediabetes es un estado que se observa antes de la diabetes de tipo 2. La actual epidemia de obesidad puede ser una causa del aumento de la incidencia de la prediabetes. En México existen políticas públicas para el manejo de las enfermedades no comunicables. Sin embargo, la obesidad continúa aumentando. Nuestro objetivo fue elaborar un diagnóstico de prediabetes en la población pediátrica mexicana y contrastar la proporción de comorbilidades que presentaban los niños con y sin prediabetes. Metodología: se realizó un estudio transversal analítico de 569 participantes de 4 a 19 años de edad procedentes de escuelas públicas. Se tomaron variables antropométricas (peso, talla y circunferencia de la cintura) y clínicas (presión arterial), así como indicadores bioquímicos (glucosa, perfil lipídico y ácido úrico). Resultados: el 8,6 % de la población presentaba prediabetes. Las variables de mayor prevalencia de alteración fueron los triglicéridos, seguidos de la presión arterial sistólica. Los hombres tenían prevalencias más altas de prediabetes, presión arterial elevada e hiperuricemia. Los niños con prediabetes tenían mayor riesgo de presentar cifras elevadas de circunferencia de la cintura, presión arterial y ácido úrico. Conclusiones: la población pediátrica mexicana tiene una prevalencia elevada de prediabetes. Además, se encontró que el grupo con prediabetes tiene mayor riesgo de presentar cifras elevadas de triglicéridos, presión arterial, ácido úrico y colesterol total. (AU)

Background: prediabetes is a state observed before type-2 diabetes. Nowadays the obesity epidemic could be due to a rise in the incidence of prediabetes. Mexico has public policies for the management of non-communicable diseases. However, obesity rates continue to increase. The aim of this study was to elaborate on a diagnosis of prediabetes in the pediatric Mexican population, and compare the proportions of comorbidities that children with and without prediabetes had. Methods: a cross-sectional study was performed with 569 participants of 4 to 19 years of age from public schools. Anthropometric (weight, height, and waist circumference), clinical (blood pressure), and biochemical (fasting glucose, lipidic profile, and uric acid) variables were collected. Results: in all, 8.6 % of the population had prediabetes. Variables with the highest altered prevalence included triglycerides and systolic blood pressure. Boys had higher rates of prediabetes, altered BP, and hyperuricemia than girls. Children with prediabetes had a greater risk of elevated waist circumference, blood pressure, and uric acid measures. Conclusions: the Mexican pediatric population had elevated rates of prediabetes. Furthermore, the group with prediabetes had a higher risk of presenting high values of triglycerides, blood pressure, uric acid, and total cholesterol. (AU)

[Prevalence of prediabetes and its comorbidities in the Mexican pediatric population]. / Prevalencia de la prediabetes y sus comorbilidades en la población pediátrica mexicana.

INTRODUCTION: Background: prediabetes is a state observed before type-2 diabetes. Nowadays the obesity epidemic could be due to a rise in the incidence of prediabetes. Mexico has public policies for the management of non-communicable diseases. However, obesity rates continue to increase. The aim of this study was to elaborate on a diagnosis of prediabetes in the pediatric Mexican population, and compare the proportions of comorbidities that children with and without prediabetes had. Methods: a cross-sectional study was performed with 569 participants of 4 to 19 years of age from public schools. Anthropometric (weight, height, and waist circumference), clinical (blood pressure), and biochemical (fasting glucose, lipidic profile, and uric acid) variables were collected. Results: in all, 8.6 % of the population had prediabetes. Variables with the highest altered prevalence included triglycerides and systolic blood pressure. Boys had higher rates of prediabetes, altered BP, and hyperuricemia than girls. Children with prediabetes had a greater risk of elevated waist circumference, blood pressure, and uric acid measures. Conclusions: the Mexican pediatric population had elevated rates of prediabetes. Furthermore, the group with prediabetes had a higher risk of presenting high values of triglycerides, blood pressure, uric acid, and total cholesterol.

INTRODUCCIÓN: Objetivo: la prediabetes es un estado que se observa antes de la diabetes de tipo 2. La actual epidemia de obesidad puede ser una causa del aumento de la incidencia de la prediabetes. En México existen políticas públicas para el manejo de las enfermedades no comunicables. Sin embargo, la obesidad continúa aumentando. Nuestro objetivo fue elaborar un diagnóstico de prediabetes en la población pediátrica mexicana y contrastar la proporción de comorbilidades que presentaban los niños con y sin prediabetes. Metodología: se realizó un estudio transversal analítico de 569 participantes de 4 a 19 años de edad procedentes de escuelas públicas. Se tomaron variables antropométricas (peso, talla y circunferencia de la cintura) y clínicas (presión arterial), así como indicadores bioquímicos (glucosa, perfil lipídico y ácido úrico). Resultados: el 8,6 % de la población presentaba prediabetes. Las variables de mayor prevalencia de alteración fueron los triglicéridos, seguidos de la presión arterial sistólica. Los hombres tenían prevalencias más altas de prediabetes, presión arterial elevada e hiperuricemia. Los niños con prediabetes tenían mayor riesgo de presentar cifras elevadas de circunferencia de la cintura, presión arterial y ácido úrico. Conclusiones: la población pediátrica mexicana tiene una prevalencia elevada de prediabetes. Además, se encontró que el grupo con prediabetes tiene mayor riesgo de presentar cifras elevadas de triglicéridos, presión arterial, ácido úrico y colesterol total.

Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients.

PURPOSE: Resistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance. MATERIALS: A total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: ABCB1 rs1045642 (3435 C > T) and ABCG2 rs2231142 (421 G > T). RESULTS: In clinical response evaluation, significant associations were found between the ABCB1 C3435T genotype and breast cancer chemoresistant and chemosensitive patients (p < 0.05). In the early clinical response, patients with genotype C/C or C/T were more likely to be chemosensitive to neoadjuvant therapy than patients with genotype T/T (OR = 4.055; p = 0.0064). Association analysis between the ABCB1 gene polymorphism and the pathologic response to FAC chemotherapy showed that the C/C + C/T genotype was a protective factor against chemoresistance (OR = 3.714; p = 0.0104). Polymorphisms in ABCG2 indicated a lack of association with resistance to chemotherapy (p = 0.2586) evaluating the clinical or pathological response rate to FAC neoadjuvant chemotherapy. CONCLUSION: The early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced breast cancer patients of the Mexican population.