Guadalupe Estrada-Gutierrez

Endothelial dysfunction is a hallmark of vascular injury and a central event in cardiovascular and inflammatory diseases. It is characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress, and disruption of endothelial barrier integrity. Activated neutrophils contribute to this process through the generation of reactive oxygen species and other oxidative mediators. Here, we investigated whether L-arginine, the principal substrate for endothelial NO synthase (eNOS), attenuates neutrophil-induced endothelial injury. Primary human umbilical vein endothelial cells (HUVECs) were exposed to sustained L-arginine supplementation initiated at passage 1 and subsequently challenged with activated neutrophils. Neutrophil exposure reduced stable NO metabolites (NOx), decreased eNOS phosphorylation at Ser1177, increased oxidant-sensitive DCF fluorescence, induced oxidative damage to lipids, proteins, and nucleic acids, disrupted PECAM-1/CD31-associated junctional organization, and increased endothelial permeability. Sustained L-arginine supplementation increased NOx accumulation in neutrophil-exposed cultures, partially preserved eNOS Ser1177 phosphorylation, attenuated oxidative damage, and improved endothelial barrier integrity. Catalase reduced oxidant-sensitive fluorescence and permeability, supporting a ROS-dependent component of the injury model. Targeted PCR array analysis identified neutrophil-associated changes in oxidative stress-related gene-expression patterns; however, direct comparison between L-arginine-supplemented and non-supplemented neutrophil-exposed cultures showed no statistically significant gene-expression changes after Benjamini–Hochberg FDR correction. These findings indicate that L-arginine attenuates neutrophil-induced endothelial injury primarily through biochemical, functional, and structural mechanisms, whereas transcriptional findings should be interpreted as exploratory and hypothesis-generating. Additional studies are required to determine the translational relevance of L-arginine supplementation as a potential approach to preserve endothelial function under oxidative and inflammatory stress.

Background: Lead (Pb) exposure remains a significant public health concern, particularly among women of childbearing age, because of its adverse effects on maternal–child health. Although lead-glazed ceramics (LGC) for cooking or storing food are a well-recognized source of Pb exposure in Mexico, other environmental and household sources remain insufficiently characterized. Objective: To identify environmental and household factors associated with elevated blood lead levels (BLLs) among women of childbearing age participating in a community-based screening in Mexico City. Methods: We conducted a cross-sectional analysis of 158 women aged 18–40 years. Capillary BLLs were measured using the LeadCare^® II system. Participants completed a structured questionnaire assessing potential Pb sources of exposure. Elevated BLL was defined as ≥3.5 µg/dL. Associations between exposure sources and elevated BLL were evaluated using multivariable logistic regression adjusted for sociodemographic and lifestyle factors. Shapley decomposition was used to estimate the relative contribution of each exposure source to the model. Results: The prevalence of elevated BLLs was 31%. Women reporting both past and current use of LGC had higher odds of elevated BLLs than women who had never used LGC (adjusted OR = 9.43; 95% CI: 1.85–48.15). Living in or regularly visiting a recently remodeled home (adjusted OR = 3.21; 95% CI: 1.45–7.11) and living near a highway (adjusted OR = 2.41; 95% CI: 1.07–5.48) were also independently associated with elevated BLLs. LGC use was the largest contributor to the model performance (47.46%), followed by home remodeling (31.78%) and proximity to highways (20.76%). Conclusions: Our findings support LGC as an important source of Pb exposure while identify home remodeling and residential proximity to highways as additional sources associated with elevated BLLs. Together, these findings broaden the understanding of Pb exposure pathways among women of childbearing age and support the need for prevention and screening strategies.

Background: The role of adipokines in childhood glycemia is poorly understood. We investigate the longitudinal association between adipokines and glycemia in a cohort of children in Mexico City. Methods: Children from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort (948 children, 52% male) were followed longitudinally from birth. Leptin, adiponectin, glucose, and HbA _1c were measured at four, six, and eight years, and fasting insulin at eight years. Adiponectin to leptin ratio (ALR) and HOMA2 indices were computed. Longitudinal associations were examined by linear mixed models and cross-sectional associations were examined by multivariable linear regression. All models were adjusted for maternal and child covariates. Findings: Between ages four and eight years, average levels of leptin increased from 3·2 to 10·8 ug/mL; adiponectin dropped from 15·7 to 13·7 ng/mL; and ALR dropped from 9·1 to 3·1 ug/ng. Longitudinally, across timepoints four, six, and eight years after birth, there was no association between adipokines and glycemia. However, the cross-sectional analysis at age 8 years found an association between leptin and insulin (1·0, 95% CI: 1·0; 1·1), HOMA2-B (1·0, 95% CI: 1·0; 1·0), HOMA2-IR (1·0, 95% CI: 1·0; 1·1), and HOMA2-S (0·9, 95% CI: 0·9; 0·9). Interpretation: Further investigation is needed to understand the role of adipokines in the development of T2DM in children and the factors that may alter adipokine metabolism.

Background: Metabolomic profiling can uncover metabolic differences among seemingly healthy children, providing opportunities for personalized medicine and early detection of risk biomarkers for future metabolic disorders. This study aimed to identify and internally validate metabotypes in apparently healthy schoolchildren using targeted serum metabolomics and to assess the external validity of this metabotype classification tool in two separate groups of children. Methods: Data from schoolchildren aged 6–11 years were analyzed in two phases. In the first phase, we developed and validated a classification tool using targeted serum metabolomics in healthy children. Metabotypes were identified through unsupervised clustering with a self-organizing map, followed by assessment of cluster stability and classification accuracy. In the second phase, we tested the tool’s consistency by applying it to two additional groups: the same children from phase 1 after a 10-month physical activity intervention, and a separate group diagnosed with metabolic syndrome. Results: Three metabotypes were identified in healthy children: METBA (balanced profile), METLI (high lipid and glucose levels), and METAA (high amino acid levels). Internal validation showed strong cluster stability (ARI = 0.79) and high classification accuracy (0.95). After the intervention, 55% of children were reclassified, indicating diverse metabolic responses to physical activity. Among children with metabolic syndrome, 83% were classified as METLI and 13% as METAA. Conclusions. This tool revealed serum metabolomic diversity, enabling classification of healthy children into three distinct metabotypes. It also detects changes in metabotype classification associated with a physical activity intervention and identifies the majority of children diagnosed with metabolic syndrome within two groups. This supports the potential use of metabotypes as biomarkers and eventually for personalized interventions.

Background/Objectives: Vitamin D deficiency has been associated with an increased risk of adverse perinatal outcomes (APOs). This study aimed to examine whether vitamin D deficiency during the first trimester of pregnancy is linked to the development of gestational diabetes mellitus (GDM) in a Mexican population. Methods: A total of 404 pregnant women from the Biochemical and Epigenetic Origin of Overweight and Obesity (OBESO) cohort were included. Maternal vitamin D levels were measured between 11 and 14 weeks of gestation. Vitamin D deficiency was defined as a level below 20.0 ng/mL. The primary goal was to compare APOs between Group 1 (women with vitamin D deficiency) and Group 2 (women without vitamin D deficiency). Adjusted odds ratio (aOR) for APOs—including GDM, preeclampsia, preterm birth, miscarriage, cesarean section, and neonatal size—were calculated, adjusting for pregestational body mass index (BMI) and obesity, with 95% confidence interval (95% CI). Results: Vitamin D deficiency was present in 40.5% of women. Pre-pregnancy BMI and obesity were significantly higher in women with deficiency; other baseline characteristics did not differ between groups. Women with vitamin D deficiency had a higher risk of GDM (aOR 2.04, 95% CI 1.14–3.65, p = 0.01). No association was found between vitamin D deficiency and other APOs. Conclusions: The incidence of vitamin D deficiency in the first trimester was 40.5%. Early pregnancy vitamin D deficiency increases the risk of GDM among Mexican women. These findings highlight the importance of monitoring and supplementing vitamin D during pregnancy to reduce the risk of GDM.

Introduction: Serotonin (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 Bioquı́mico y Epigenético del Sobrepeso y la Obesidad (OBESO) perinatal cohort at the first month of life. Methods: We 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. Results: Placentas 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. Conclusion: These 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.

Background: Depression and anxiety during pregnancy are global public health issues, as both are linked to adverse outcomes for mothers and their newborns. This study aimed to determine the prevalence of depression and anxiety during pregnancy and identify the factors associated with these conditions in Mexican women. Methods: This prospective cohort study included 288 participants. The Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory were applied during the second trimester of pregnancy. The factors associated with depression and anxiety were analyzed. Results: The prevalence of depression and anxiety was 20.5% (95% confidence interval (CI) 16.1–25.7) and 22.2% (95% CI 17.8–27.3), respectively. The factors independently associated with an increased risk of depression, expressed as adjusted odds ratios with (95% CI), were anxiety, 10.8 (5.4–21.6), p = 0.0001, and educational level, secondary school and high school, 2.6 (1.10–6.14). In contrast, a bachelor’s degree was associated with a lower risk of depression, 0.38 (0.16–0.90), p = 0.03. The factors independently associated with a higher risk of anxiety were depression, 11.2 (5.6–22.1), and having children, 3.1 (1.6–6.1), p = 0.03. Conclusions: Our results show that one in five pregnant women exhibit clinical symptoms of depression or anxiety, and one in eight women have both conditions simultaneously. These findings highlight the importance of routine mental health screening and assessment during pregnancy. The factors linked to depression include anxiety and having completed secondary or high school education, while depression and having children were associated with anxiety.

Neuroactive steroids synthesized within the maternal-placental-fetal unit play a crucial role in fetal neurodevelopment by regulating cell proliferation, migration, and myelination, neurogenesis, gliogenesis, and synaptogenesis, ultimately shaping brain maturation. Dysregulation of neuroactive steroid metabolism, receptor signaling, and downstream pathways has been linked to neurodevelopmental and mood disorders. Maternal overweight and obesity, increasingly prevalent worldwide, induce profound metabolic and hormonal adaptations that may interfere with neuroactive steroid synthesis and function. These disturbances are associated with a higher risk of autism spectrum disorder, attention deficit hyperactivity disorder, and cognitive impairments in offspring, frequently with sex-specific effects. Despite these observations, the impact of obesity on neuroactive steroid levels and their regulatory roles during pregnancy remains poorly understood. This review synthesizes preclinical and clinical evidence on the biosynthesis, mechanisms of action, and neurodevelopmental effects of neuroactive steroids during the critical window of fetal programming. Furthermore, it highlights a current knowledge on how maternal overweight and obesity alter neuroactive steroid metabolism within the maternal–placental–fetal unit and explores their potential contribution to adverse neurodevelopmental outcomes. Addressing these knowledge gaps may uncover novel biomarkers and therapeutic targets to improve neurodevelopmental trajectories in populations increasingly exposed to maternal metabolic comorbidities.