Association between maternal cardiometabolic markers and fetal growth in non-complicated pregnancies: a secondary analysis of the PRINCESA cohort.

The objective of this study was to evaluate the association of maternal cardiometabolic markers trajectories (glucose, triglycerides (TG), total cholesterol, systolic blood pressure (SBP) and diastolic blood pressure (DBP)) with estimated fetal weight trajectories and birth weight in Mexican pregnant women without medical complications. Cardiometabolic marker trajectories were characterized using group-based trajectory models. Mixed-effect and linear regression models were estimated to assess the association of maternal trajectories with estimated fetal weight and birth weight. The final sample comprised 606 mother-child dyads. Two trajectory groups of maternal cardiometabolic risk indicators during pregnancy were identified (high and low). Fetuses from women with higher values of TG had higher weight gain during pregnancy ( ß ^ = 24.00 g; 95%CI: 12.9, 35.3), were heavier at the sixth month ( ß ^ =48.24 g; 95%CI: 7.2, 89.7) and had higher birth weight ( ß ^ = 89.08 g; 95%CI: 20.8, 157.4) than fetuses in the low values trajectory. Fetuses from mothers with high SBP and DBP had less weight in the sixth month of pregnancy ( ß ^ = - 42.4 g; 95%CI: - 82.7, - 2.1 and ß ^ = - 50.35 g; 95%CI: - 94.2, - 6.4), and a higher DBP trajectory was associated with lower birth weight ( ß ^ = - 101.48 g; 95%CI: - 176.5, - 26.4). In conclusion, a longitudinal exposition to high values of TG and BP was associated with potentially adverse effects on fetal growth. These findings support the potential modulation of children's phenotype by maternal cardiometabolic conditions in pregnancies without medical complications.

Effects of PM10 Airborne Particles from Different Regions of a Megacity on In Vitro Secretion of Cytokines by a Monocyte Line during Different Seasons.

Several epidemiological studies have demonstrated that particulate matter (PM) in air pollution can be involved in the genesis or aggravation of different cardiovascular, respiratory, perinatal, and cancer diseases. This study assessed the in vitro effects of PM10 on the secretion of cytokines by a human monocytic cell line (THP-1). We compared the chemotactic, pro-inflammatory, and anti-inflammatory cytokines induced by PM10 collected for two years during three different seasons in five different Mexico City locations. MIP-1α, IP-10, MCP-1, TNF-α, and VEGF were the main secretion products after stimulation with 80 µg/mL of PM10 for 24 h. The THP-1 cells showed a differential response to PM10 obtained in the different sites of Mexico City. The PM10 from the north and the central city areas induced a higher pro-inflammatory cytokine response than those from the south. Seasonal pro-inflammatory cytokine secretion always exceeded anti-inflammatory secretion. The rainy-season-derived particles caused the lowest pro-inflammatory effects. We concluded that toxicological assessment of airborne particles provides evidence supporting their potential role in the chronic exacerbation of local or systemic inflammatory responses that may worsen the evolution of some chronic diseases.

DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.

The P2X7 receptor (P2X7R) stands out within the purinergic family as it has exclusive pharmacological and regulatory features, and it fulfills distinct roles depending on the type of stimulation and cellular environment. Tonic activation of P2X7R promotes cell proliferation, whereas sustained activation is associated with cell death. Yet strikingly, prolonged P2X7R activation in rat cerebellar granule neurons and astrocytes does not affect cell survival. The intracellular pathways activated by P2X7Rs involve proteins like MAPKs, ERK1/2 and p38, and interactions with growth factor receptors could explain their behavior in populations of rat cerebellar cells. In this study, we set out to characterize the intracellular mechanisms through which P2X7Rs and Trk receptors, EGFR (epidermal growth factor receptor) and BDNFR (brain-derived neurotrophic factor receptor), regulate the dual-specificity phosphatase DUSP1. In cerebellar astrocytes, the regulation of DUSP1 expression by P2X7R depends on ERK and p38 activation. EGFR stimulation can also induce DUSP1 expression, albeit less strongly than P2X7R. Conversely, EGF was virtually ineffective in regulating DUSP1 in granule neurons, a cell type in which BDNF is the main regulator of DUSP1 expression and P2X7R only induces a mild response. Indeed, the regulation of DUSP1 elicited by BDNF reflects the balance between both transcriptional and post-transcriptional mechanisms. Importantly, when the regulation of DUSP1 expression is compromised, the viability of both astrocytes and neurons is impaired, suggesting this phosphatase is essential to maintain proper cell cytoarchitecture and functioning.

Programming of neural progenitors of the adult subependymal zone towards a glutamatergic neuron lineage by neurogenin 2.

Although adult subependymal zone (SEZ) neural stem cells mostly generate GABAergic interneurons, a small progenitor population expresses the proneural gene Neurog2 and produces glutamatergic neurons. Here, we determined whether Neurog2 could respecify SEZ neural stem cells and their progeny toward a glutamatergic fate. Retrovirus-mediated expression of Neurog2 induced the glutamatergic lineage markers TBR2 and TBR1 in cultured SEZ progenitors, which differentiated into functional glutamatergic neurons. Likewise, Neurog2-transduced SEZ progenitors acquired glutamatergic neuron hallmarks in vivo. Intriguingly, they failed to migrate toward the olfactory bulb and instead differentiated within the SEZ or the adjacent striatum, where they received connections from local neurons, as indicated by rabies virus-mediated monosynaptic tracing. In contrast, lentivirus-mediated expression of Neurog2 failed to reprogram early SEZ neurons, which maintained GABAergic identity and migrated to the olfactory bulb. Our data show that NEUROG2 can program SEZ progenitors toward a glutamatergic identity but fails to reprogram their neuronal progeny.

Metabolomic Phenotype of Hepatic Steatosis and Fibrosis in Mexican Children Living with Obesity.

Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.

The pregnancy research on inflammation, nutrition, & city environment: systematic analyses study (PRINCESA) cohort, 2009-2015.

The Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses Study (PRINCESA) cohort was set up to evaluate associations between air pollution and birth outcomes among pregnant persons in Mexico City. Specifically, the study was designed to improve air pollution exposure assessment and elucidate biological mechanisms underlying associations between maternal exposures and adverse pregnancy outcomes. Pregnant persons (all women) (N = 935) between ages 18-45 who lived and/or worked in metropolitan Mexico City, Mexico, from 2009 to 2015 and liveborn singleton infants (N = 815) of participants who completed follow-up were enrolled in the cohort. We followed participants monthly from enrollment to delivery and the following categories of data were obtained: demographic, medical and obstetric history, geo-referenced data, repeated measures on daily activity patterns, reported food intake, anthropometric, clinical and obstetric data, 20 serum and 20 cervicovaginal cytokines, and lower reproductive tract infection. Repeated ultrasound measures of fetal parameters and infant birth data are also included in the study's database. In addition, PRINCESA investigators calculated air pollution exposure measures for six pollutants measured by the Mexico City Atmospheric Monitoring System (SIMAT). These estimates utilize participants' addresses to account for spatial variation in exposure (nearest monitor, inverse distance weighting, and kriging) and are available daily during pregnancy for participants. To date, associations between environmental and nutritional impacts on maternal and child health outcomes have been evaluated. PRINCESA has a comprehensive database of maternal and infant data and biological samples and offers collaboration opportunities to study associations between environmental and other factors, including nutrition and pregnancy outcomes.

An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers.

BACKGROUND: Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM. METHODS: A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM. RESULTS: Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873-0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015-0.25 µmol/L and of C5:1 with a range of 0.015-0.19 µmol/L. CONCLUSION: Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.

Associations between Air Pollution Exposure and Blood Pressure during Pregnancy among PRINCESA Cohort Participants.

High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 µm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for "below the median" or "above the median", where the beta estimate is the change in BP at a pollutant's median versus BP at the pollutant's minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP.

Longitudinal large-scale changes in maternal circulating microRNAs associated with gestation-related compartments, fetal sex, and growth during and post-pregnancy.

Circulating microRNAs (c-miRNAs) during pregnancy could provide information regarding the functional status of the mother and fetus. However, it remains unclear which pregnancy-related processes are actually reflected by changes c-miRNAs. Here, we used large-scale c-miRNA profiling of maternal plasma during and post-pregnancy, and compared it with that of non-pregnant women. Fetal growth measurements and fetal sex data were used to identify associated changes in these transcripts. Surprisingly, c-miRNA subpopulations with prominent expression in maternal/fetal compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found to be under-expressed in circulation throughout pregnancy relative to non-pregnant plasma profiles. Furthermore, we found a bias in global c-miRNA expression in association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth. Our results demonstrate the existence of specific temporal changes in c-miRNA populations associated with specific pregnancy-related compartments and processes, including fetal sex, and growth.

Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex.

BACKGROUND: M1 macrophages involved in pro-inflammatory processes can be induced by low-density lipoproteins (LDL), giving rise to foam cells. In the atheroma plaque, it has been identified that males present more advanced lesions associated with infiltration. Therefore, our study aims to investigate sex-related changes in the transcriptome of M1 macrophages during the internalization process of LDL particles. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy male and female subjects were separated using Hystopaque, and monocytes were isolated from PBMCs using a positive selection of CD14+ cells. Cells were stimulated with LDL 10 µg/mL, and the transcriptional profile of M1 macrophages performed during LDL internalization was determined using a Clariom D platform array. RESULTS: Chromosome Y influences the immune system and inflammatory responses in males expressing 43% of transcripts in response to LDL treatment. Males and females share 15 transcripts, where most correspond to non-coding elements involved in oxidative stress and endothelial damage. CONCLUSIONS: During LDL internalization, male monocyte-derived M1 macrophages display more marked proinflammatory gene expression. In contrast, female M1 macrophages display a more significant number of markers associated with cell damage.

Post-transcriptional control of a stemness signature by RNA-binding protein MEX3A regulates murine adult neurogenesis.

Neural stem cells (NSCs) in the adult murine subependymal zone balance their self-renewal capacity and glial identity with the potential to generate neurons during the lifetime. Adult NSCs exhibit lineage priming via pro-neurogenic fate determinants. However, the protein levels of the neural fate determinants are not sufficient to drive direct differentiation of adult NSCs, which raises the question of how cells along the neurogenic lineage avoid different conflicting fate choices, such as self-renewal and differentiation. Here, we identify RNA-binding protein MEX3A as a post-transcriptional regulator of a set of stemness associated transcripts at critical transitions in the subependymal neurogenic lineage. MEX3A regulates a quiescence-related RNA signature in activated NSCs that is needed for their return to quiescence, playing a role in the long-term maintenance of the NSC pool. Furthermore, it is required for the repression of the same program at the onset of neuronal differentiation. Our data indicate that MEX3A is a pivotal regulator of adult murine neurogenesis acting as a translational remodeller.

Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study.

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1ß, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57-1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693-0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

Effect of the B-amyloid peptide on microglia activation: ATP release / Efecto del péptido B-amiloide en la activación de la microglía: liberación de ATP

Estudios previos han mostrado un papel clave de las células microgliales en los procesos neuroinflamatorios asociados con algunas enfermedades neurodegenerativas, como la enfermedad de Alzheimer (EA). La microglía detecta varios tipos de moléculas difusibles que regulan el múltiple repertorio de funciones microgliales. Entre ellos, los nucleótidos extracelulares, actuando sobre los receptores P2 microgliales, llevan a cabo un papel central. En este sentido, el receptor P2X7 ionotrópico ha sido reconocido como un regulador clave de las respuestas inflamatorias mediadas por la microglia. Se sabe que la microglía libera ATP y otros nucleótidos al medio extracelular. Aunque se han propuesto varios mecanismos, tales como la liberación a través de conexinas o panexinas, no se puede descartar un origen vesicular para estos nucleótidos liberados, basándose en la actividad del transportador vesicular de nucleótidos (VNUT).En este trabajo hemos analizado si la expresión de VNUT y el receptor P2X7, así como la liberación de ATP, podrían modificarse en la microglía reactiva. Para lograr la activación de la microglía estimulamos las células con el lipopolisacárido (LPS). Además, analizamos el efecto del péptido β1-amiloide, β1-42, que puede activar también las células microgliales, sobre la expresión de VNUT y la liberación de ATP en la microglía. (AU)

Previous studies have shown a key role of microglial cells in the neuroinflammatory processes associated with some neurodegenerative diseases, such as Alzheimer’s disease (AD). Microglia sense several types of diffusible molecules that regulate the multiple repertoire of microglial functions. Among them, extracellular nucleotides, acting on microglial P2 receptors, have central roles. In this sense, the ionotropic P2X7 receptor has gained recognition as a key regulator of microglial-mediated inflammatory responses. It is known that microglia releases ATP and other nucleotides to the extracellular medium. Although several mechanisms, such as release trough conexins or panexins, has been proposed, a vesicular origin for this released nucleotides, relying on the activity of the vesicular nucleotide transporter (VNUT), cannot be ruled out.In this work we evaluated whether the expression of VNUT and the P2X7 receptor, as well as the ATP release, could be modified in the reactive microglia. To achieve microglia activation we stimulated the cells with the lipopolysaccharide (LPS). Moreover, we analyzed the effect of the β-amyloid peptide β1-42, which is also able to activate the microglial cells, on the expression of VNUT and the ATP release in the microglia. (AU)

Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México / Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico

Objetivos: Describir la asociación entre las enfermedades crónicas no transmisibles y la edad, con la hospitalización, desenlaces clínicos graves y las defunciones por COVID-19 en los casos confirmados en población mexicana, comparando las tres primeras olas epidemiológicas de la pandemia en México. Diseño: Se realizó un análisis transversal utilizando el Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral para COVID-19. Emplazamiento: Sistema de Vigilancia Epidemiológica de Enfermedad Respiratoria Viral en México (SISVER). Participantes: Población mexicana confirmada para SARS-CoV-2 registrada en el SISVER. Mediciones principales: Los desenlaces graves analizados fueron hospitalización, neumonía, necesidad de ventilación mecánica, ingreso a la UCI y defunción. Se evaluó la asociación (odds ratio [OR]) entre los desenlaces y las variables clínicas, comparando las tres olas epidemiológicas en México. Resultados: Una edad mayor de 65 años se asocia a un mayor porcentaje de hospitalización, neumonía, y notablemente, con el total de defunciones, independientemente del efecto de las comorbilidades crónicas. Existe interacción entre la edad en conjunto con la obesidad, la cual se asocia con la hospitalización y neumonía. Estos hallazgos fueron consistentes a lo largo de las tres olas epidemiológicas.Conclusión: La obesidad, EPOC y la diabetes en interacción con la edad se asocian con peores desenlaces clínicos, primordialmente con defunciones en los pacientes con COVID-19.(AU)

Objectives: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. Design: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. Emplacement: Mexico's Epidemiological Surveillance System for Respiratory Diseases. Participants: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. Primary measurements: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. Results: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. Conclusion: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.(AU)

[Risk factors for COVID-19 severe complications comparing three major epidemiological waves: An approach from primary health care in Mexico]. / Factores de riesgo para complicaciones graves de COVID-19, comparando tres olas epidemiológicas. Un enfoque desde la atención primaria en México.

OBJECTIVES: To describe the association between chronic noncommunicable diseases and age with hospitalization, death and severe clinical outcomes for COVID-19 in confirmed cases within the mexican population, comparing the first three epidemiological waves of the pandemic in Mexico. DESIGN: We performed an analysis using Mexico's Government Epidemiological Surveillance System database for COVID-19. EMPLACEMENT: Mexico's Epidemiological Surveillance System for Respiratory Diseases. PARTICIPANTS: Mexican population confirmed with SARS-CoV-2 registered on Mexico's Epidemiological Surveillance System for Respiratory Diseases. PRIMARY MEASUREMENTS: The analysed severe outcomes were hospitalization, pneumonia, use of mechanical ventilation, intensive care unit admission and death. The association (odds ratio) between the outcomes and clinical variables was evaluated, comparing the three epidemiological waves in Mexico. RESULTS: Age over 65 is associated with a higher ratio of hospitalization and pneumonia, independent of the effect of chronic comorbidities. There is an interaction between age and obesity, which is associated with hospitalization, pneumonia and highly associated with death. These findings were consistent throughout the three epidemiological waves. CONCLUSION: Obesity, COPD and diabetes in interaction with age, are associated with worse clinical outcomes and, more importantly, death in patients with COVID-19.

Nucleotide-Induced Nanoscale Changes in the Mechanical Properties of Rat Cerebellar Astrocytes: Selective Stimulation and Blocking of the Purinergic Receptor P2X7.

As members of the family of nucleotide receptors, P2X7 receptors are of particular interest due to their unique structural and pharmacological characteristics. As ATP-gated ionic channels, P2X7 receptors in their activation elicit membrane depolarization; extracellular calcium influx; and activation of several downstream intracellular signaling pathways, some of them independent of the ionic channel activity. Further interactions of P2X7 receptors and cytoskeleton-related proteins have also been confirmed, and we previously described the effects of P2X7 receptor stimulation on the morphology of rat cerebellar astrocytes. In the present work, we used time-lapse video microscopy and atomic force microscopy (AFM) to elucidate the effects of P2X7 receptor stimulation on the morphology, migratory capabilities, and mechanical properties of rat cerebellar astrocytes in vitro. Stimulation of P2X7 receptors with the selective agonist BzATP specifically caused an increase in cell size, motility, and number of membrane protrusions of the astrocytes in culture. These effects were reverted when cells were previously treated with the competitive antagonist of P2X7R, A 438079. AFM analysis also showed an increase in cell stiffness and viscosity after P2X7 receptor stimulation. Surprisingly, these effects on the mechanical properties of the cell were not blocked by the treatment with the antagonist. Fluorescence microscopy analysis of the actin cytoskeleton showed an increase in actin stress fibers after BzATP treatment, an effect that again was not blocked by previous treatment with the antagonist, further confirming that the effects of P2X7 receptors on the cytoskeleton of astrocytes are, at least in part, independent of the ionic channel activity.

Sex-differential RXRα gene methylation effects on mRNA and protein expression in umbilical cord of the offspring rat exposed to maternal obesity.

Maternal obesity (MO) induces negative consequences in the offspring development. Adiposity phenotype is associated with maternal diet at early pregnancy and DNA methylation marks in the RXRα promotor at birth. Glucocorticoids play an important role in the regulation of metabolism through the activation of nuclear hormone receptors such as the RXRα protein. The aim of the study was to analyze steroid hormone changes at the end of pregnancy in the obese mother and RXRα gene methylation in the umbilical cord. For this purpose, in a well-established MO model, female Wistar rats were fed either standard chow (controls: C) or high-fat obesogenic diet (MO) before and during pregnancy to evaluate at 19 days of gestation (19 dG): 1) maternal concentration of circulating steroid hormones in MO and C groups, 2) maternal and fetal weights, 3) analysis of correlation between hormones concentration and maternal and fetal weights, 4) DNA methylation status of a single locus of RXRα gene near the early growth response (EGR-1) protein DNA binding site, and 5) RXRα mRNA and protein expressions in umbilical cords. Our results demonstrate that at 19 dG, MO body weight before and during pregnancy was higher than C; MO progesterone and corticosterone serum concentrations were higher and estradiol lower than C. There were not differences in fetal weight between male and female per group, therefore averaged data was used; MO fetal weight was lower than C. Positive correlations were found between progesterone and corticosterone with maternal weight, and estradiol with fetal weight, while negative correlation was observed between corticosterone and fetal weight. Additionally, male umbilical cords from MO were hypermethylated in RXRα gene compared to male C group, without differences in the female groups; mRNA and protein expression of RXRα were decreased in F1 male but not in female MO compared to C. In conclusion, MO results in dysregulation of circulating steroid hormones of the obese mothers and low fetal weight in the F1, modifying DNA methylation of RXRα gene as well as RXRα mRNA and protein expression in the umbilical cord in a sex-dependent manner.

Asociación de la exposición a contaminantes atmosféricos con indicadores epidemiológicos de morbilidad y mortalidad por Covid-19 en el Valle de México.

OBJETIVO: Analizar la asociación de la concentración de con-taminantes atmosféricos y los indicadores epidemiológicos de Covid-19 en la Zona Metropolitana del Valle de México (ZMVM). Material y métodos. Se diseñó un estudio epidemiológico ecológico. Se utilizaron modelos lineales tipo Poisson para variables de conteo y modelos lineales de efectos aleatorios en variables continuas para cuantificar la asociación entre los contaminantes atmosféricos y los indicadores de Covid-19. Los datos obtenidos fueron del 28 de febrero de 2020 al 30 de junio de 2021. La exposición a contaminantes se estratificó por estaciones climáticas. RESULTADOS: Los contaminantes que tuvieron asociación significativa con indicadores de morbilidad y mortalidad fueron CO, NOX, O3 y PM10. En la estación seca fría el CO y el NOX tuvieron efecto sobre los casos diarios confirmados y las defunciones diarias. Las PM10 se asociaron con efecto en los indicadores de casos diarios confirmados, incidencia diaria, porcentaje de hospitalizados y la tasa de letalidad. CONCLUSIONES: Los resultados sugieren una asociación entre el comportamiento epidemiológico de Covid-19 y la exposición a CO, NOX, O3 y PM10, en la que se encontró un mayor efecto en la estación seca-fría en la ZMVM.

Sensor Data Analytics: Challenges and Methods for Data-Intensive Applications.

Sensors have become a key element for the development of the Information Society [...].

Sera from women with different metabolic and menopause states differentially regulate cell viability and Akt activation in a breast cancer in-vitro model.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-ß/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-ß and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.