Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

Editorial for the Special Issue "Food and Microbial Bioprocesses".

The aim of this Special Issue was to provide readers with a holistic, systematic, and integrative approach to microbial processes involved in the production of selected foods, nutraceuticals, and bioactive materials by using modern biotechnological tools [...].

Assessing the effects of oxytocin in changes of core body temperature during LPS-induced endotoxemia: A novel approach using Extended Poincaré Plot Analysis.

Oxytocin has shown cardioprotective effects during inflammation and may modify the core body temperature changes in LPS-induced endotoxemia. Notably, the time series analysis of core body temperature fluctuations may indicate thermoregulation alterations. This study aims to assess the effects of oxytocin on changes in the core body temperature by analyzing the fluctuations of the temperature time series of endotoxemic rats. Twelve hours of continuous core body temperature fluctuations time series were obtained from adult male Dark Agouti rats implanted with a telemetric transmitter under the following treatment: lipopolysaccharide (LPS); oxytocin (O); lipopolysaccharide + oxytocin (LPS + O), and vehicle or control (C). The temperature fluctuations time series were analyzed using the Extended Poincaré Plot Analysis (EPPA), a novel approach for measuring nonlinear features, to compute the autocorrelation by Pearson's correlation coefficient r, the standard deviation perpendicular to the line of identity (SD1), and the standard deviation parallel to the line of identity (SD2). The autocorrelation of the temperature fluctuations assessed by Pearson's coefficient was significantly higher in the LPS group compared to control rats (C). Likewise, the co-administration of oxytocin during endotoxemia (LPS + O) significantly reduced the autocorrelation and increased the short-term variability (SD1) of temperature fluctuations compared to those recorded with a single dose of LPS. Thus, we concluded that oxytocin may introduce thermoregulatory changes under LPS-induced endotoxemia. The EPPA is a simple and powerful approach to assess physiological variability that can provide valuable insights into changes in thermoregulation.

Impact of Normal and Overweight Pregnancy in GLUT4 and Glucose-Dependent Vascular Contractility.

INTRODUCTION: Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats. METHODS: Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10-9 to 10-4M) using standard (11 mm) or without (0 mm) glucose Krebs solution. GLUT4 density in the aortas was measured using the en face method. RESULTS: Aortas from overweight pregnant animals (PHD) showed increased Phe-induced vasoconstriction (p < 0.05 vs. pregnant standard diet [PSD]), which was endothelium-independent. The contraction decreased significantly in the absence of glucose. In contrast, vessels from pregnant SD rats maintained their contraction in glucose-free Krebs solution. 5-HT increases PHD aortic contraction only in the absence of glucose. The fetal aortas from PHD mothers showed blunted vasoconstriction. Overweight significantly reduced GLUT4 expression in maternal and fetal aortas (p < 0.05 vs. PSD). CONCLUSIONS: Aortic contractility is independent of glucose uptake during healthy pregnancy. In contrast, overweight pregnancy increases contractility. This increase depends directly on smooth muscle glucose uptake and inversely on GLUT-4 density. The increased contraction observed in the vasculature of overweight mothers was inverted in the fetal aortas.

Protective Effect of Alginate Microcapsules with Different Rheological Behavior on Lactiplantibacillus plantarum 299v.

Alginate encapsulation is a well-known technique used to protect microorganisms from adverse conditions. However, it is also known that the viscosity of the alginate is dependent on its composition and degree of polymerization and that thermal treatments, such as pasteurization and sterilization, can affect the structure of the polymer and decrease its protection efficiency. The goal of this study was to evaluate the protective effect of encapsulation, using alginates of different viscosities treated at different temperatures, on Lactiplantibacillus plantarum 299v under in vitro gastrointestinal conditions and cold storage at 4 °C and -15 °C, respectively. Steady- and dynamic-shear rheological tests were used to characterize the polymers. Thermal treatments profoundly affected the rheological characteristics of alginates with high and low viscosity. However, the solutions and gels of the low-viscosity alginate were more affected at a temperature of 117 °C. The capsules elaborated with high-viscosity alginate solution and pasteurized at 63 °C for 30 min provided better protection to the cells of L. plantarum 299v under simulated gastrointestinal and cold storage conditions.

Chronic resveratrol administration reduces oxidative stress and brain cell loss and improves memory of recognition in old rats.

The cognitive functions of people over 60 years of age have been diminished, due to the structural and functional changes that the brain has during aging. The most evident changes are at the behavioral and cognitive level, with decreased learning capacity, recognition memory, and motor incoordination. The use of exogenous antioxidants has been implemented as a potential pharmacological option to delay the onset of brain aging by attenuating oxidative stress and neurodegeneration. Resveratrol (RSVL) is a polyphenol present in various foods, such as red fruits, and drinks, such as red wine. This compound has shown great antioxidant capacity due to its chemical structure. In this study, we evaluated the effect of chronic RSVL treatment on oxidative stress and cell loss in the prefrontal cortex, hippocampus, and cerebellum of 20-month-old rats, as well as its impact on recognition memory and motor behavior. Rats treated with RSVL showed an improvement in locomotor activity and in short- and long-term recognition memory. Likewise, the concentration of reactive oxygen species and lipid peroxidation decreased significantly in the group with RSVL, coupled with an improvement in the activity of the antioxidant system. Finally, with the help of hematoxylin and eosin staining, it was shown that chronic treatment with RSVL prevented cell loss in the brain regions studied. Our results demonstrate the antioxidant and neuroprotective capacity of RSVL when administered chronically. This strengthens the proposal that RSVL could be an important pharmacological option to reduce the incidence of neurodegenerative diseases that affect older adults.

Frecuencia de factores de riesgo cardiovascular modificables en estudiantes universitarios de carreras de salud

Introducción: las enfermedades cardiovasculares son la principal causa de muerte por enfermedades no transmisibles. La detección de los factores de riesgo cardiovascular modificables juega un rol importante en la prevención de la morbimortalidad cardiovascular. Objetivos: describir la frecuencia de factores de riesgo cardiovascular modificables en estudiantes de carreras de salud en la Universidad Politécnica y Artística del Paraguay, filial San Lorenzo. Metodología: diseño observacional, descriptivo, de corte trasversal. Los datos fueron obtenidos por una encuesta telemática durante el año 2022. Resultado: participaron 134 estudiantes, con predomino de mujeres: 104 (78%) con edad promedio de 25 ± 7 años, mayoría de la carrera de medicina 44 (33%). Los factores de riesgo cardiovascular encontrados fueron: sedentarismo en 83 (62%) participantes, hábito alimentario no saludable en 128 (95%), tabaquismo en 7 (5%), hipertensión arterial en 7 (5%), diabetes mellitus tipo 2 en 3 (2%), dislipidemia en 4 (3%). Hubo pérdida de datos para IMC en 62 casos, por lo que no se ha analizado la frecuencia de sobrepeso ni obesidad. La muestran estudiada presentó al menos 1 factor de riesgo cardiovascular 131 participantes (98%). La sumatoria de factores de riesgo cardiovascular por sujeto, muestra alto porcentaje 42,5% y 39,5% para 2 y 3 factores de riesgo asociados, respectivamente. Conclusión: en la muestra estudiada, a pesar de ser jóvenes y en formación en materias de salud, existe una alta frecuencia de al menos un factor de riesgo cardiovascular modificable. Los factores de riesgo cardiovascular más frecuentes fueron el hábito alimentario no saludable y sedentarismo. Llama la atención que a pesar de ser una población joven, la hipertensión, diabetes y dislipidemia ya se encuentran presentes suponiendo una carga alta y precoz de riesgo cardiovascular.

Introduction: Cardiovascular diseases are the main cause of death due to non-communicable diseases. The detection of modifiable cardiovascular risk factors plays an important role in the prevention of cardiovascular morbidity and mortality. Objectives: To describe the frequency of modifiable cardiovascular risk factors in health career students at the Polytechnic and Artistic University of Paraguay, San Lorenzo branch. Methodology: Observational, descriptive, cross-sectional design. The data was obtained by a telematic survey during the year 2022. Result: One hundred thirty-four students participated, with a predominance of women: 104 (78%) with an average age of 25 ± 7 years, most of them were from the medical career 44 (33%). The cardiovascular risk factors found were: sedentary lifestyle in 83 (62%) participants, unhealthy eating habits in 128 (95%), smoking in 7 (5%), arterial hypertension in 7 (5%), type 2 diabetes mellitus in 3 (2%), and dyslipidemia in 4 (3%). There was loss of data for BMI in 62 cases, so the frequency of overweight or obesity has not been analyzed. The sample studied presented at least 1 cardiovascular risk factor in 131 participants (98%). The sum of cardiovascular risk factors per subject shows a high percentage of 42.5% and 39.5% for 2 and 3 associated risk factors, respectively. Conclusion: In the studied sample, despite being young and in training in health matters, there is a high frequency of at least one modifiable cardiovascular risk factor. The most frequent cardiovascular risk factors were unhealthy eating habits and a sedentary lifestyle. It is striking that, despite being a young population, hypertension, diabetes, and dyslipidemia are already present, assuming a high and early burden of cardiovascular risk.

Recommended food supplies under conditions of natural and provoked catastrophes.

Natural catastrophes include those of biological origin as the pandemic provoked by virus SARS CoV2, earthquakes, flooding and hurricanes among others, while provoked ones are mainly those related to wars and social movements. These situations may cause food shortage and challenge food safety and security systems. In this review, strategies to produce foods aimed to alleviate food needs before, during and after catastrophic conditions are described based on the supply of various processed, intermediate and low moisture foods and three categories of food supplies are depicted based on the nature of the adverse conditions, Also, relevant patents on on innovative food preparations and containers for disaster areas are discussed. Innovation to produce appropriate and nutritious foods for disaster zones may include food bags containing individual packages of high protein, high fiber/vitamins and carbohydrate/oils ingredients in dried/vitreous state. Additionally, the role of food structure on food preservation is mentioned in the context of ready to eat, nutritious and sensory acceptable food supplies during natural or provoked catastrophes is also reported.

Influence of environmental awareness on the willingness to pay for green products: an analysis under the application of the theory of planned behavior in the Peruvian market.

Introduction: This paper aimed to build a predictive model through an empirical study to examine the influence of environmental awareness (EA) on attitude (ATT) and perceived behavioral control (PBC), as well as to determine the influence of the three variables of the theory of planned behavior (TPB) on willingness to pay (WP) for green products in the Peruvian market. Methods: A total of 405 Peruvian consumers were surveyed. Most of them were between the ages of 18 and 30 and single. To test the hypotheses, partial least squares (PLS-SEM) were used using the SamrtPls4 software. The results show the significant positive effect of EA on ATT and PBC. The positive and significant effect of ATT, SN, and PBC on WP was also tested A total of 405 Peruvian consumers were surveyed. Most of them were between 18 and 30 years old and single. To test the hypotheses, partial least squares (PLS-SEM) was used using SamrtPls4 software. Results: The results show the positive and significant effect of AD on ATT and PBC. The positive and significant effect of ATT, SN and PBC on WP was also tested. Discussion: The research provides antecedents that allow evaluation of the possibility that companies and governments adjust the dissemination strategies and related public policies regarding the impact of environmentally responsible behavior in order to contribute to the development of environmental awareness as a variable that promotes the disposition of consumers to pay for environmentally friendly products.

Hypertrophic cardiomyopathy in a patient with secondary hypoparathyroidism: A case report.

Parathyroid hormone (PTH) has direct and indirect actions on cardiovascular cells. The effects of chronic hypoparathyroidism on cardiac morphology, function, and conduction are still unclear. Low PTH states are associated with multiple manifestations in the heart, acute or chronic. Acute hypocalcemic cardiomyopathy is a transient dilated cardiomyopathy with reduced ejection fraction and diffuse left ventricular hypokinesia. Chronic hypoparathyroidism-associated cardiomyopathy is a rare disease that may cause reduced myocardial tension, cardiac cavity enlargement, arrhythmias, and congestive heart failure. Here, we describe a 73-year-old woman with chronic hypoparathyroidism and hypocalcemia, who developed a hypertrophic cardiomyopathy, and not a dilated hypocalcemia-associated cardiomyopathy, which would be usually the case.

Adiposity affects emotional information processing.

Obesity is a worldwide epidemic associated with severe health and psychological wellbeing impairments expressed by an increased prevalence of affective disorders. Emotional dysfunction is important due to its effect on social performance. The aim of the present narrative review is to provide a general overview of human research exploring emotional information processing in overweight and obese people. Evidence suggests that obesity is associated with an attenuation of emotional experience, contradictory findings about emotion recognition, and scarce research about automatic emotional information processing. Finally, we made some concluding considerations for future research on emotional information processing in overweight and obese people.

Social complexity as a driving force of gut microbiota exchange among conspecific hosts in non-human primates.

The emergent concept of the social microbiome implies a view of a highly connected biological world, in which microbial interchange across organisms may be influenced by social and ecological connections occurring at different levels of biological organization. We explore this idea reviewing evidence of whether increasing social complexity in primate societies is associated with both higher diversity and greater similarity in the composition of the gut microbiota. By proposing a series of predictions regarding such relationship, we evaluate the existence of a link between gut microbiota and primate social behavior. Overall, we find that enough empirical evidence already supports these predictions. Nonetheless, we conclude that studies with the necessary, sufficient, explicit, and available evidence are still scarce. Therefore, we reflect on the benefit of founding future analyses on the utility of social complexity as a theoretical framework.

Chronic-Antibiotics Induced Gut Microbiota Dysbiosis Rescues Memory Impairment and Reduces ß-Amyloid Aggregation in a Preclinical Alzheimer's Disease Model.

Alzheimer's disease (AD) is a multifactorial pathology characterized by ß-amyloid (Aß) deposits, Tau hyperphosphorylation, neuroinflammatory response, and cognitive deficit. Changes in the bacterial gut microbiota (BGM) have been reported as a possible etiological factor of AD. We assessed in offspring (F1) 3xTg, the effect of BGM dysbiosisdysbiosis in mothers (F0) at gestation and F1 from lactation up to the age of 5 months on Aß and Tau levels in the hippocampus, as well as on spatial memory at the early symptomatic stage of AD. We found that BGM dysbiosisdysbiosis with antibiotics (Abx) treatment in F0 was vertically transferred to their F1 3xTg mice, as observed on postnatal day (PD) 30 and 150. On PD150, we observed a delay in spatial memory impairment and Aß deposits, but not in Tau and pTau protein in the hippocampus at the early symptomatic stage of AD. These effects are correlated with relative abundance of bacteria and alpha diversity, and are specific to bacterial consortia. Our results suggest that this specific BGM could reduce neuroinflammatory responses related to cerebral amyloidosis and cognitive deficit and activate metabolic pathways associated with the biosynthesis of triggering or protective molecules for AD.

Voluntary physical activity improves spatial and recognition memory deficits induced by post-weaning chronic exposure to a high-fat diet.

Childhood and adolescent exposure to obesogenic environments has contributed to the development of several health disorders, including neurocognitive impairment. Adolescence is a critical neurodevelopmental window highly influenced by environmental factors that affect brain function until adulthood. Post-weaning chronic exposure to a high-fat diet (HFD) adversely affects memory performance; physical activity is one approach to coping with these dysfunctions. Previous studies indicate that voluntary exercise prevents HFD's detrimental effects on memory; however, it remains to evaluate whether it has a remedial/therapeutical effect when introduced after a long-term HFD exposure. This study was conducted on a diet-induced obesity mice model over six months. After three months of HFD exposure (without interrupting the diet) access to voluntary physical activity was provided. HFD produced weight gain, increased adiposity, and impaired glucose tolerance. Voluntary physical exercise ameliorated glucose tolerance and halted weight gain and fat accumulation. Additionally, physical activity mitigated HFD-induced spatial and recognition memory impairments. Our data indicate that voluntary physical exercise starting after several months of periadolescent HFD exposure reverses metabolic and cognitive alterations demonstrating that voluntary exercise, in addition to its known preventive effect, also has a restorative impact on metabolism and cognition dysfunctions associated with obesity.

Squalene-Rich Amaranth Oil Pickering Emulsions Stabilized by Native α-Lactalbumin Nanoparticles.

The stabilization of Pickering emulsions by nanoparticles has drawn great interest in the field of food science and technology. In this study, α-Lactalbumin nanoparticles prepared by the desolvation and cross-linking method from protein solutions with initial pH values of 9 and 11 were used to stabilize squalene-rich amaranth oil Pickering o/w emulsions. The effect of different concentrations of nanoparticles on the size, size distribution, ζ potential, and emulsion stability was evaluated using dynamic light scattering, electron microscopy, and light backscattering. Dependence of the emulsions' droplet size on the nanoparticle concentration was observed, and the critical coverage ratio was reached when 5-10% nanoparticles concentration was used. Our findings suggest that α-LA nanoparticles at a 10% concentration can be used as novel stabilizers for Pickering emulsions to provide protection for beneficial lipophilic bioactive compounds. This is the first time that native α-LA nanoparticles have been used as stabilizers of Pickering emulsions.

Vaginal Microbiota Is Stable and Mainly Dominated by Lactobacillus at Third Trimester of Pregnancy and Active Childbirth: A Longitudinal Study of Ten Mexican Women.

In healthy women at reproductive age, the vaginal microbiota is mainly dominated by Lactobacillus bacteria during pregnancy and non-pregnancy stages. However, little is known about longitudinal changes within the vaginal microbiota composition from the third trimester of pregnancy to childbirth in healthy women. Thus, we conducted an exploratory longitudinal study of vaginal microbiota composition of 10 Mexican pregnant women, sampling from the same volunteer at two-time points: third trimester of pregnancy and active childbirth. Vaginal bacterial microbiota was characterized by V3-16S rDNA libraries by high-throughput sequencing and bioinformatics methods. Out of ten, vaginal microbiota from eight women was dominated by the Lactobacillus genus at both time points, whereas the other two women showed vaginal microbiota composition with high abundance of genera Gardnerella, Prevotella, and members of the Atopobiaceae family, without any preterm birth correlation. Importantly, we found no statistically significant differences in relative abundances, absolute reads count, alpha and beta diversity between the third trimester of pregnancy, and active childbirth time points. However, compared to the third trimester of pregnancy, we observed a trend with higher absolute reads counts for Gardnerella, Faecalibaculum, Ileibacterium, and Lactococcus genus at active childbirth and lower absolute reads count of Lactobacillus genus. Our results suggest that the vaginal microbiota composition is stable, and Lactobacillus genus is the dominant taxa in Mexican women's vagina at the third trimester of pregnancy and childbirth.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Postnatal exposure to lipopolysaccharide combined with high-fat diet consumption induces immune tolerance without prevention in spatial working memory impairment.

High-fat diet (HFD) consumption has been related to metabolic alterations, such as obesity and cardiovascular problems, and has pronounced effects on brain plasticity and memory impairment. HFD exposure has a pro-inflammatory effect associated with microglial cell modifications in the hippocampus, a region involved in the working memory process. Immune tolerance can protect from inflammation in periphery induced by HFD consumption, when the immune response is desensitized in development period with lipopolysaccharide (LPS) exposure, maybe this previously state can change the course of the diseases associated to HFDs but is not known if can protect the hippocampus's inflammatory response. In the present study, male mice were injected with LPS (100 µg.kg-1 body weight) on postnatal day 3 and fed with HFD for 16 weeks after weaning. Ours results indicated that postnatal exposure to LPS in the early postnatal developmental stage combined with HFD consumption prevented glycemia, insulin, HOMA-IR, microglial process, and increased pro-inflammatory cytokines mRNA expression, without changes in body weight gain and spatial working memory with respect vehicle + HFD group. These findings suggest that HFD consumption after postnatal LPS exposure induces hippocampal immune tolerance, without prevention in spatial working memory impairment on male mice.

Computational Molecular Characterization of the Interaction of Acetylcholine and the NMDA Receptor to Explain the Direct Glycine-Competitive Potentiation of NMDA-Mediated Neuronal Currents.

The activation of N-methyl-d-aspartate receptor (NMDAR) is triggered by the closure of bilobed (D1 and D2) clamshell-like clefts upon binding glycine (Gly) and glutamate. There is evidence that cholinergic compounds modulate NMDAR-mediated currents via direct receptor-ligand interactions; however, molecular bases are unknown. Here, we first propose a mechanistic structure-based explanation for the observed ACh-induced submaximal potentiation of NMDA-elicited currents in striatal neurons by predicting competitive inhibition with Gly. Then, the model was validated, in principle, by confirming that the coapplication of Gly and ACh significantly reduces these neuronal currents. Finally, we delineate the interplay of ACh with the NMDAR by a combination of computational strategies. Crystallographic ACh-bound complexes were studied, revealing a similar ACh binding environment on the GluN1 subunit of the NMDAR. We illustrate how ACh can occupy X-ray monomeric open, dimeric "semiopen" cleft conformations obtained by molecular dynamics and a full-active cryo-EM NMDAR structure, explaining the suboptimal NMDAR electrophysiological activity under the "Venus Flytrap model". At an evolutionary biology level, the binding mode of ACh coincides with that of the homologous ornithine-bound periplasmic LAO binding protein complex. Our computed results indicate an analogous mechanism of action, inasmuch as ACh may stabilize the GluN1 subunit "semiclosed" conformations by inducing direct and indirect D1-to-D2 interdomain bonds. Additionally, an alternative binding site was detected, shared by the known NMDAR allosteric modulators. Experimental and computed results strongly suggest that ACh acts as a Gly-competitive, submaximal potentiating agent of the NMDAR, possibly constituting a novel chemotype for multitarget-directed drug development, e.g., to treat Alzheimer's, and it may lead to a new understanding of glutamatergic neurotransmission.

Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production.

CONTEXT: The chronic exposure to Cadmium (Cd) constitute an risk to develop hypertension and cardiovascular diseases associated with the increase of oxidative stress. OBJECTIVE: In this study, we investigate the role of metabolic changes produced by exposure to Cd on the endothelial dysfunction via oxidative stress. METHODS: Male Wistar rats were exposed to Cd (32.5-ppm) for 2-months. The zoometry and blood pressure were evaluated, also glucose and lipids profiles in serum and vascular reactivity evaluated in isolated aorta rings. RESULTS: Rats exposed to Cd showed an increase of blood pressure and biochemical parameters similar to metabolic syndrome. Additionally, rats exposed to Cd showed a reduced relaxation in aortic rings, which was reversed after the addition of SOD and apocynin an inhibitor of NADPH. CONCLUSION: The Cd-exposition induced hypertension and endothelial injury by that modifying the vascular relaxation and develop oxidative stress via NADPH oxidase, superoxide and loss nitric oxide bioavailability.