Instituto Nacional de Perinatología

To examine the cross-sectional relationship between dietary intake and epigenetic age acceleration, as well as the prospective relationship between epigenetic age acceleration and cardiometabolic parameters measured two years later. In 526 adolescents aged 7-18 years (average age 14.50) residing in Mexico City, dietary intake was assessed using a semi-quantitative food frequency questionnaire. Adherence to three dietary patterns was derived from principal component analysis. Blood leukocyte DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip, from which epigenetic age acceleration was calculated for six epigenetic clocks: Horvath, Skin-Blood, PhenoAge, GrimAge, Pediatric-Buccal-Epigenetic (PedBE), and Wu. Nine cardiometabolic parameters were assessed two years after assessment of diet and epigenetic age acceleration. Linear regression models for sex-stratified associations were examined. Among males, the Meat & Starchy foods pattern was positively associated with Wu epigenetic age acceleration, showing a 0.096-year increase, while folate intake in females was associated with a 0.004-year decelerated GrimAge. Prospective analysis showed positive associations between epigenetic age acceleration and fat distribution and insulin resistance, particularly in males. In females, only GrimAge acceleration was associated in the expected manner with increased waist circumference (β=0.62cm), BMI (β=0.25kg/m2), fasting insulin (β=0.86 μIU/mL), and insulin resistance (β=0.21). Skin-Blood acceleration was associated with decreased HDL in males, and PedBE acceleration was associated with triglycerides in both sexes, though in opposing directions. Adolescent diet was not strongly associated with baseline epigenetic age acceleration. However, epigenetic age acceleration was associated prospectively with fat distribution and insulin resistance.

Export Most of the available pharmacological strategies of pain relief use drugs that have monomodal mechanisms of analgesia. However, pain treatment requires combinations of drugs with nonredundant mechanisms of action to improve pain management and reduce the adverse effects produced by high doses of individual drugs. This study aimed to investigate, through isobolographic analysis, whether statins can modify the antinociceptive effect produced by diclofenac. The above was measured by the formalin test in rats, a murine animal model of acute inflammatory pain. Animals were administered with diclofenac (0.3, 1, 3 and 10 mg/kg; p.o.), atorvastatin (1, 3, 10 and 30 mg/kg; p.o.), pravastatin (1, 3, 10 and 30 mg/kg; p.o.), rosuvastatin (1, 3, 10 and 30 mg/kg; p.o.), or calculated combinations of diclofenac with the different statins. The effective doses 30 (ED30) were calculated for diclofenac and statins, and subsequently, the isobolographic analysis of each one of the combinations was performed, thus determining their respective ED30. The experimental ED30 values of antinociception for diclofenac coadministered with atorvastatin, pravastatin, or rosuvastatin were 0.27 ± 0.01, 1.30 ± 0.08, and 0.59 ± 0.08, respectively, while the corresponding theoretical ED30 values of antinociception were 5.08 ± 0.33, 5.30 ± 0.33, and 6.64 ± 0.3, respectively, being statistically higher (P < 0.05) theoretical ED30 values than their corresponding experimental ED30 values. The above suggests that statins enhance the antinociceptive effect of diclofenac. These pharmacological combinations may help treat pain.

Total body water (TBW) undergoes substantial physiological expansion during pregnancy, reflecting coordinated cardiovascular, renal, and endocrine adaptations required to support maternal metabolism, uteroplacental perfusion, and fetal growth. These changes involve not only an overall increase in body water but also shifts in the distribution of extracellular water (ECW) and intracellular water (ICW), which influence maternal body composition, the interpretation of biochemical biomarkers affected by hemodilution, and pregnancy-related clinical outcomes. Despite its physiological and clinical relevance, the regulation and assessment of body-water compartments during pregnancy remain insufficiently integrated within nutritional and clinical research. This narrative review synthesizes current knowledge on the physiological regulation of TBW and its compartments across gestation and provides a critical analysis of the methodological approaches used to assess body-water distribution in pregnant populations. We review the mechanisms underlying plasma volume expansion, interstitial fluid accumulation, and tissue hydration, and discuss their implications for fetal growth, hypertensive disorders of pregnancy, and gestational diabetes mellitus. We also examine the principles, strengths, and limitations of the main techniques used to assess TBW and body-water compartments during pregnancy. Isotope dilution using stable isotopes (2H2O and H218O) remains the reference method for TBW assessment, whereas bioelectrical impedance-based approaches, including bioelectrical impedance analysis (BIA), bioelectrical impedance spectroscopy (BIS), and bioelectrical impedance vector analysis (BIVA), offer practical alternatives for longitudinal monitoring of fluid redistribution during gestation. By integrating physiological and methodological perspectives, this review provides a framework for understanding body-water dynamics during pregnancy and for selecting appropriate approaches to assess maternal body composition and hydration.

There is limited knowledge about the sexually dimorphic effects of manganese (Mn) on children’s temporal cognition (i.e., time perception), an important component of executive function, and whether impacts differ by sex. We proposed that the effects of prenatal Mn exposure on children’s ability to perceive time could be best assessed using a multi-media biomarker (MMB) to estimate cumulative exposure. Children aged 6–7 from Mexico City were administered a temporal response differentiation task, an operant test in which a reward is provided if they correctly hold a lever down between 10 and 14 s (s). Short (< 10s) and long holds (> 14s) were incorrect and not rewarded. Blood and urinary Mn levels were assessed from mothers in the 2nd and 3rd trimesters. A covariate-adjusted generalized weighted quantile sum (WQS) regression estimated the effect of a Mn MMB index (combining blood and urine biomarkers into a single metric) on temporal cognitive performance. Sex-stratified models were also assessed. Higher prenatal Mn MMB index, representing higher exposure levels, was significantly associated with impaired performance across multiple cognitive timing measures. When examining Mn exposure in sex-stratified analyses, girls exhibited significantly poorer performance than boys. Among girls, higher prenatal Mn MMB index was associated with fewer timing holds (β = -2.14; 95%CI: -3.57, -0.72), fewer total holds (β = -2.11; 95%CI: -4.18, -0.04), and lower timing accuracy, reflected in total holds excluding durations of 2s or less (β = -1.29; 95%CI: -1.49, -1.09), and greater variability in lever hold durations for total holds (β = 0.67; 95%CI: 0.09, 1.24). High Mn exposure impacts temporal assessment pathways with greater impacts in girls. Our results also highlight the necessity of assessing sex as a biological factor in prenatal Mn exposure, as the sex specificity of results was clear in the stratified models. Results may reflect sex-specific susceptibility via dopamine signaling, neurodevelopmental timing, and/or hormonal influences, warranting further research on these mechanisms.

The thymus is a vital organ for T-cell development that undergoes significant changes during malaria infection, including atrophy and disrupted structure, which weaken immune responses. This study examines the mechanisms behind thymic atrophy during Plasmodium chabaudi AS infection, focusing on cellular and molecular changes across different parasitemia stages. Our results show that thymic atrophy is marked by a substantial decrease in thymus weight and cellularity, especially at 20%-30% parasitemia levels. A significant loss of DP and SP thymocytes mainly causes this atrophy. Histological analysis revealed notable cortical shrinkage and DNA fragmentation in thymic cells, indicating increased apoptosis. Elevated serum cytokines and chemokines, including IFN-γ, TNF-α, IL-6 and CXCL9, were observed throughout the infection, with higher levels correlating with the degree of thymic atrophy. Also, early release of thymocytes into peripheral tissues, especially the spleen, worsened the decrease in thymic cellularity. However, after parasitemia resolved, the thymus recovered, restoring its structure and thymocyte populations. These results highlight the complex interaction between parasite-induced inflammation and immune cell behaviour, suggesting that even though P. c. chabaudi AS infection is not lethal, a prolonged parasitic burden can cause severe thymic dysfunction, possibly impairing immune system function.

Although neuronal hyperexcitability is the primary mechanism underlying seizure activity in epilepsy, little is known about how different neuronal mechanisms at different organizational levels contribute to network hyperexcitability in the human epileptic brain. In this study, we determined a series of cellular and synaptic properties of Layer V pyramidal neurons from neocortical tissue of patients with drug-resistant epilepsy that may contribute to the hyperexcitable state associated with epilepsy. Using the whole cell, patch-clamp technique, and extracellular recordings, we determined the passive and active electrophysiological properties of Layer V pyramidal neurons with regular spiking phenotypes from temporal, parietal, and frontal neocortices surgically resected from individuals with drug-resistant epilepsy. Also, the glutamatergic strength, the synaptic coupling between presynaptic volleys and field excitatory postsynaptic potentials, and short-term, frequency-dependent plasticity were determined. Our data revealed that pyramidal neurons exhibit minimal spontaneous synaptic activity, similar resting membrane potentials, and input resistance values among the temporal, parietal, and frontal neocortices. Although frontal neurons were more hyperexcitable than temporal and parietal neurons, the firing output was comparable to that previously observed in non-pathological human tissue. In contrast, the extracellular recordings uncovered significant decoupling between presynaptic excitability and postsynaptic activity and the lack of short-term depression in response to gamma-range (30 Hz) repetitive stimulation. Our data suggest that neocortical Layer V pyramidal neurons from individuals with drug-resistance epilepsy, particularly intratelencephalic-2 neurons, which exhibit regular firing, are not necessarily hyperexcitable at the somatic level. Instead, synaptic alterations, such as synaptic decoupling and the lack of frequency-dependent short-term depression, may significantly contribute to the hyperexcitable state observed during seizure activity.

Exacerbated inflammation in pregnancy can be detrimental in many aspects and can result in spontaneous abortion, intrauterine growth restriction, or preterm delivery. The inflammatory cascade may be triggered by pathogen molecular motifs or by damage-associated molecular patterns. These danger signals can be found in viral or bacterial antigens, tissue breakdown products, excess adipose tissue, and pollutants, among others. Endogenous danger signals can also be released after exposure to nutrient overload. Mechanistically, both pathogen- and damage-associated molecular patterns are recognized by pattern recognition receptors on host cells, triggering signalling pathways that culminate in immune activation. The resultant inflammation can alter homeostasis at the feto-maternal interface, posing a risk to the continuation of pregnancy and imprinting fetal developmental pathways. A maternal healthy diet can help prevent and mitigate inflammation. The adequate selection of foods is of utmost importance especially during pregnancy, which involves choosing natural products while avoiding ultra-processed foods, saturated fats, and refined carbohydrates. Plant-based diets, particularly those rich in whole grains, fruits and vegetables, are especially important since they contain numerous bioactive compounds with anti-inflammatory and anti-oxidant properties. In this review, we explore the potential of natural dietary products to elicit anti-inflammatory effects during pregnancy, with a particular focus on key dietary constituents such as monounsaturated fatty acids, phytochemicals (such as polyphenols, terpenoids, and alkaloids), and vitamins. The aim was to provide an up-to-date narrative review integrating the impact of these compounds upon immunological, metabolic, placental, and fetal responses, emphasizing the anti-inflammatory potential of natural dietary products in the context of maternal health.

IntroductionSerotonin (5-hydroxytryptamine [5-HT]) plays a fundamental role in fetal neurodevelopment. While 5-HT is synthesized in the fetal brain, the placenta contributes significantly to fetal 5-HT levels during early gestation. However, little is known about the influence of placental serotonergic components on early neurodevelopmental outcomes. In this study, we have evaluated the association between the expression of key components of the placental serotonergic system and neurodevelopmental status in infants of mother–child dyads enrolled in the Origen Bioquímico y Epigenético del Sobrepeso y la Obesidad (OBESO) perinatal cohort at the first month of life.MethodsWe analyzed 5-HT concentrations in maternal serum, umbilical cord serum, and placental tissue, and investigated the expression of key proteins of the serotonergic system in the placenta. All samples were obtained from full-term healthy pregnancies. 5-HT levels were measured by ELISA, and protein expression in placental tissue was evaluated by Western blot. Neurodevelopment was assessed at 1 month of age using the Bayley Infant Development Scale III (BSID-III). Infants with two or more BSID-III domain scores ≤ 7 were grouped as having altereded neurodevelopment.ResultsPlacentas from infants with altered neurodevelopment exhibited higher expression of tryptophan hydroxylase types 1 and 2 (TPH1 and TPH2)—the rate-limiting enzymes in 5-HT synthesis—as well as the serotonin transporter (SERT), compared to those from infants with normal neurodevelopment. In contrast, expression of monoamine oxidase-A (MAO-A), the primary degrading enzyme, was significantly lower in the altered group. Interestingly, 5-HT levels and the expression of 5-HT1E and 5-HTR5A receptors were similar between groups.ConclusionThese findings suggest that dysregulation of the placental serotonergic system, independent of total 5-HT levels, could be associated with early neurodevelopmental impairments, highlighting the importance of placental serotonin signaling in fetal brain development.