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Introducción: la percepción de la salud es un predictor significativo de mortalidad, de actitudes hacia la muerte y de cumplimiento de tratamientos durante la enfermedad; cómo se observan las personas en bienestar físico actual, futuro y adaptación psicológica; por tanto, tiene un papel importante en la conducta promotora de salud. Lo descrito motivó la reflexión sobre esos conceptos y la actuación de los pacientes con diabetesmellitus tipo 2 (PDMT2), enfermedad que representa un problema de salud pública mundial. Propósito: determinar el efecto de los factores personales (biológicos, psicológicos y socioculturales) sobre el resultado de conducta (estilo de vida) de los pacientes con diabetes mellitus tipo 2. Marco teórico: “Modelo de promoción de la salud” de Pender (1). Metodología: diseño descriptivo-correlacional, en una muestra de 125 pacientes. Resultados: la variable factores personales mostró efecto sobre la variable estilo de vida (nutrición, ejercicio, responsabilidad en salud y manejo adecuado del estrés) (F cal = 4.780 R2 38,7, p = ,001). Conclusión: los resultados apoyan la relación entre los conceptos seleccionados del “Modelo de promoción de la salud” de Pender (2003) y muestran que la percepción de salud de los PDMT2 promueve cambios de la conducta promotora (estilo de vida), por lo que se cree que los pacientes pueden actuar, corresponsablemente con el equipo de salud, para mejorar el control del padecimiento y evitar o retrasar complicaciones.Introduction: Perceived Health is a significant predictor of mortality, attitude towards death, adherence to treatments during illnesses; i.e. the way people see themselves in their current and future condition and in their psychological adaptation to it. Therefore, it plays an important role on health promoting behavior. This study made us ponder about these concepts and about habits of patients with type 2 diabetes mellitus (PDMT2), which represents a global health problem. Purpose: to determine the effect of personal conditions (biological, psychological and social-cultural) over the behavior (life style) of patients with type 2 diabetes mellitus. Theoretical Framework: “Pender’s health promotion model” (1). Methodology: descriptive-co-relational design in a sample of 125 patients. Results: the personal condition variables (biological, psychological and social-cultural) had an impact on the lifestyle variable (nutrition, exercise, health related responsibility and appropriate stress management) (F cal, = 4.780 R2 38,7, p = 0,001). Conclusion: results support the relationship between concepts selected from “Pender’s health promotion model” (2003) and those that show that health perception of PDMT2 promotes changes in motor behavior (i.e. in lifestyle). Therefore, patients are able to act, in co-responsibility with the health team, to improve control of their illness and to avoid or to delay complications.Introdução: a saúde pode predizer a mortalidade, bem como as atitudes a respeito da morte, a adesão aos tratamentos durante a doença, a forma como as pessoas se observam em bem-estar físico atual, futuro e a adaptação psicológica. Portanto, a saúde tem um papel importante na conduta voltada à promoção da saúde. O descrito anteriormente levantou a reflexão sobre esses conceitos e sobre a atuação dos pacientes com diabetes tipo 2, doença que representa um problema de saúde pública mundial. Objetivo: determinar o efeito dos fatores pessoais (biológicos, psicológicos e sócio-culturais) no resultado de conduta (estilo de vida) dos pacientes com diabetes mellitus tipo 2 (PDMT2). Bases teóricas: “Modelo de promoção da saúde de Pender” (1). Metodologia: análise descritivo – correlacional, numa amostra de 125 pacientes. Resultados: a variável de fatores pessoais (biológicos, psicológicos y sócio-culturais) mostrou efeitos na variável estilo de vida (nutrição, exercício físico, responsabilidade com a saúde e gestão adequada do estresses) (F cal, = 4.780 R2 38,7, p = 0,001). Conclusão: os resultados demonstram a relação entre os conceitos selecionados do “Modelo de promoção da saúde” de Pender (2003) e provam que a promoção da saúde nos PDMT2 determina mudanças da conduta (estilo de vida). Por esta razão se considera que os PDMT2 podem agir, junto com sua equipe médica, para melhorar o controle da doença evitando ou retardando o aparecimento de complicações.

Oxidative stress and the activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome have been linked to insulin resistance in skeletal muscle. In immune cells, the exacerbated generation of reactive oxygen species (ROS) activates the NLRP3 inflammasome, by facilitating the interaction between thioredoxin interacting protein (TXNIP) and NLRP3. However, the precise role of ROS/TXNIP-dependent NLRP3 inflammasome activation in skeletal muscle during obesity-induced insulin resistance remains undefined. Here, we induced insulin resistance in C57BL/6J mice by feeding them for 8 weeks with a high-fat diet (HFD) and explored whether the ROS/TXNIP/NLRP3 pathway was involved in the induction of insulin resistance in skeletal muscle. Skeletal muscle fibers from insulin-resistant mice exhibited increased oxidative stress, as evidenced by elevated malondialdehyde levels, and altered peroxiredoxin 2 dimerization. Additionally, these fibers displayed augmented activation of the NLRP3 inflammasome, accompanied by heightened ROS-dependent proximity between TXNIP and NLRP3, which was abolished by the antioxidant N-acetylcysteine (NAC). Inhibition of the NLRP3 inflammasome with MCC950 or suppressing the ROS/TXNIP/NLRP3 pathway with NAC restored insulin-dependent glucose uptake in muscle fibers from insulin-resistant mice. These findings provide insights into the mechanistic link between oxidative stress, NLRP3 inflammasome activation, and obesity-induced insulin resistance in skeletal muscle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females ( n = 19-16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE.

Asthma is the most common chronic disease among children, with more than 300 million cases worldwide. Over the past several decades, asthma incidence has grown, and epidemiological studies identify the modernized lifestyle as playing a strong contributing role in this phenomenon. In particular, lifestyle factors that modify the maternal gut microbiome during pregnancy, or the infant microbiome in early life, can act as developmental programming events which determine health or disease susceptibility later in life. Microbial colonization of the gut begins at birth, and factors such as delivery mode, breastfeeding, diet, antibiotic use, and exposure to environmental bacteria influence the development of the infant microbiome. Colonization of the gut microbiome is crucial for proper immune system development and disruptions to this process can predispose a child to asthma development. Here, we describe the importance of early-life events for shaping immune responses along the gut-lung axis and why they may provide a window of opportunity for asthma prevention., (© 2024 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Pregnancy is a finely tuned process, with the health and well-being of the developing fetus determined by the metabolic status and dietary intake of the mother. The maternal gut microbiome is remodeled during pregnancy, and this, coupled with the maternal nutrient intake during gestation shapes the production of metabolites that can cross the placenta and affect fetal development. As posited by the Developmental Origins of Health and Disease Hypothesis, such environmental influences can have major effects on the developing organ systems. When occurring at particularly sensitive gestational time points, these developmental programming events can have long lasting effects on offspring adaptation to the postnatal environment, and major health implications later in life. This review will summarize current knowledge on how pregnancy and maternal dietary intake intrinsically and extrinsically modify maternal gut microbiota composition and metabolite production. Further, we will assess how these factors shape the fetal landscape and ultimately contribute to offspring health. DOHaD, fetal development, metabolites, microbiome, nutrition, pregnancy, short-chain fatty acids., (© 2023 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Purpose: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19., Participants: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence., Findings to Date: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up., Future Plans: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024., Trial Registration Number: NCT04537338., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma risk in the offspring. Pregnant/lactating mice were treated daily, from gestation day 6 to postnatal day 21, with an oral suspension of 106, 107 or 108 colony-forming units of a live preparation of the probiotic E. faecalis (Symbioflor®1). At weaning, offspring were subjected to an ovalbumin-induced experimental asthma protocol. Faeces were collected from the mothers and offspring at several different time points to determine SCFA concentrations. It was found that maternal supplementation with E. faecalis did not alter litter size, sex ratio or offspring weight, and was associated with an increase in SCFAs in offspring faeces at weaning and after allergy induction. However, allergic offspring from E. faecalis supplemented mothers showed no difference in asthma severity when compared with allergic offspring from control mothers. In conclusion, although maternal perinatal supplementation with low-dose E. faecalis was associated with increased faecal SCFAs in the offspring, it did not protect against offspring asthma. This is may be because SCFA concentrations were not increased to an immunoprotective level. We recommend that future studies concentrate on probiotic supplementation in high-risk cases, for instance, to repair gut dysbiosis resulting from antibiotic use in pregnant mothers or their infants., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antibiotic use during pregnancy is associated with increased asthma risk in children. Since approximately 25% of women use antibiotics during pregnancy, it is important to identify the pathways involved in this phenomenon. We investigate how mother-to-offspring transfer of antibiotic-induced gut microbial dysbiosis influences immune system development along the gut-lung axis. Using a mouse model of maternal antibiotic exposure during pregnancy, we immunophenotyped offspring in early life and after asthma induction. In early life, prenatal-antibiotic exposed offspring exhibited gut microbial dysbiosis, intestinal inflammation (increased fecal lipocalin-2 and IgA), and dysregulated intestinal ILC3 subtypes. Intestinal barrier dysfunction in the offspring was indicated by a FITC-dextran intestinal permeability assay and circulating lipopolysaccharide. This was accompanied by increased T-helper (Th)17 cell percentages in the offspring's blood and lungs in both early life and after allergy induction. Lung tissue additionally showed increased percentages of RORγt T-regulatory (Treg) cells at both time points. Our investigation of the gut-lung axis identifies early-life gut dysbiosis, intestinal inflammation, and barrier dysfunction as a possible developmental programming event promoting increased expression of RORγt in blood and lung CD4 + T cells that may contribute to increased asthma risk., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Objetivo: Estimar la prevalencia e identificar determinantes de la infección por el virus del papiloma humano (VPH) en mujeres jóvenes (18-25 años). Material y métodos. Se analizaron datos de 5 871 mujeres sexualmente activas a quienes se les realizó una entrevista y toma de muestras cervicouterinas para detección de VPH y citología durante la visita de reclutamiento del Ensayo de Vacunación contra VPH16/18 en Costa Rica. Se calculó la prevalencia total para cualquier tipo de VPH y tipos oncogénicos, no oncogénicos y específicos, con intervalos de confianza al 95% (IC95%). Se utilizó regresión logística múltiple paso-a-paso para identificar determinantes asociados con la infección., Resultados: La prevalencia total de VPH fue 50.0% (IC95% 48.8,51.3) y por tipos oncogénicos fue 33.8% (IC95% 32.6,35.0). El VPH-16 fue el tipo más prevalente (8.3%, IC95% 7.6,9.0). Los determinantes asociados con un alto riesgo de infección prevalente por VPH oncogénicos fueron no estar casada/unión libre, >1 compañero sexual, infección concomitante por Chlamydia trachomatis, y entre aquéllas con un único compañero sexual en su vida, un compañero con antecedente de múltiples compañeras sexuales. Conclusión. Se confirma la asociación de las infecciones por VPH oncogénicos con el comportamiento sexual de la mujer y se destacan los comportamientos del compañero sexual.

Dysfunction of the aging heart is a major cause of death in the human population. Amongst other tasks, mitochondria are pivotal to supply the working heart with ATP. The mitochondrial inner membrane (IMM) ultrastructure is tailored to meet these demands and to provide nano-compartments for specific tasks. Thus, function and morphology are closely coupled. Senescent cardiomyocytes from the mouse heart display alterations of the inner mitochondrial membrane. To study the relation between inner mitochondrial membrane architecture, dynamics and function is hardly possible in living organisms. Here, we present two cardiomyocyte senescence cell models that allow in cellular studies of mitochondrial performance. We show that doxorubicin treatment transforms human iPSC-derived cardiomyocytes and rat neonatal cardiomyocytes in an aged phenotype. The treated cardiomyocytes display double-strand breaks in the nDNA, have β-galactosidase activity, possess enlarged nuclei, and show p21 upregulation. Most importantly, they also display a compromised inner mitochondrial structure. This prompted us to test whether the dynamics of the inner membrane was also altered. We found that the exchange of IMM components after organelle fusion was faster in doxorubicin-treated cells than in control cells, with no change in mitochondrial fusion dynamics at the meso-scale. Such altered IMM morphology and dynamics may have important implications for local OXPHOS protein organization, exchange of damaged components, and eventually the mitochondrial bioenergetics function of the aged cardiomyocyte., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Neuronal Ca 2+ signals generated through the activation of Ca 2+ -induced Ca 2+ release in response to activity-generated Ca 2+ influx play a significant role in hippocampal synaptic plasticity, spatial learning, and memory. We and others have previously reported that diverse stimulation protocols, or different memory-inducing procedures, enhance the expression of endoplasmic reticulum-resident Ca 2+ release channels in rat primary hippocampal neuronal cells or hippocampal tissue. Methods and Results: Here, we report that induction of long-term potentiation (LTP) by Theta burst stimulation protocols of the CA3-CA1 hippocampal synapse increased the mRNA and protein levels of type-2 Ryanodine Receptor (RyR2) Ca 2+ release channels in rat hippocampal slices. Suppression of RyR channel activity (1 h preincubation with 20 μM ryanodine) abolished both LTP induction and the enhanced expression of these channels; it also promoted an increase in the surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR1 and GluR2 and caused a moderate but significant reduction of dendritic spine density. In addition, training rats in the Morris water maze induced memory consolidation, which lasted for several days after the end of the training period, accompanied by an increase in the mRNA levels and the protein content of the RyR2 channel isoform. Discussion: We confirm in this work that LTP induction by TBS protocols requires functional RyR channels. We propose that the increments in the protein content of RyR2 Ca 2+ release channels, induced by LTP or spatial memory training, play a significant role in hippocampal synaptic plasticity and spatial memory consolidation., Competing Interests: Author IV-U is currently employed by company IVIRMA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Valdés-Undurraga, Lobos, Sánchez-Robledo, Arias-Cavieres, SanMartín, Barrientos, More, Muñoz, Paula-Lima, Hidalgo and Adasme.)

Objective: To describe the presence of obstructive sleep apnea syndrome (OSAS) in children with craniofacial anomalies (CFA), associate biodemographic characteristics and polygraph variables, and analyze the therapeutic management decided after the sleep study and the evaluation by a multidisciplinary team., Patients and Method: Retrospective study. Polygraphs were performed on patients aged between 1 month and 19 years with CFA. An initial and projected management was established categorized into ventilatory support, tracheostomy, surgery, dental, and medical treatment. Descrip tive and inferential statistics were performed, evaluating the association between demographic and polygraph variables and therapeutic management., Results: 34 patients were included with a median age of 4.0 years (IQR 0.9 - 6.5). Diagnosis was 41.2% cleft lip and palate, 35.3% craniosynostosis, and 23.5% micrognathia. Polygraphs were altered in 70.6% of the cases; of these, 26.5% were diagnosed as mild, 5.9% moderate, and 38.2% severe OSAS. There was an association between minimum satu ration and diagnosis of OSAS (p = 0.0036), and in the presence of OSAS with the initial management applied (p=0.0013). There was no significant relationship between the different types of CFA with the initial therapeutic management (p = 0.6565). Initial and projected managements, respectively: Venti latory support (11.8% and 2.9%), tracheostomy (11.8% and 0%), surgery (35.2% and 26.5%), dental (20.6% and 53%), and medical treatment (20.6% and 17.6 %)., Conclusions: 70% of the patients with CFA presented OSAS. The greatest severity was found in Cleft Lip and Palatine and Craniosynostosis. Therapeutic management was mainly oriented towards initial surgical and planned dental treatments based on the diagnosis of OSAS and not on the type of CFA.

Histamine (HA) is a potent mediator that plays a central role in inflammation and allergy, acting through four G-protein-coupled receptors (i.e. H 1 -H 4 ). HA is an accepted promoter of type 2 immunity in CD4 + T cells during hypersensitivity. Previously, we demonstrated that HA can promote antigen cross-presentation, inducing the activation of antigen-specific CD8 + T cells in an asthmatic murine model. Non-classical CD8+ T-cell profiles, such as Tc2 or Tc17, are associated with allergic disease persistence and chronicity. In this paper, we focus on the role of the H 3 receptor (H 3 R) and the H 4 receptor (H 4 R) in the development of allergic contact dermatitis. We were able to show that induction of the type 2 profiles associated with interleukin 13 production, both by CD4 and CD8 lymphocytes, depend on the interaction of HA with H 3 R and H 4 R. Blocking both receptors using the selective H 3 /H 4 receptor antagonist thioperamide or the selective H 4 R ligand JNJ777120 reduces the inflammatory response, inducing an immunosuppressive profile associated with the increased proportion of FOXp3 + regulatory T lymphocytes and CD11b + Gr-1 + myeloid suppressor cells. Interestingly, in dendritic cells, only H 4 R blockade, and not H 3 R blockade, is capable of modulating most of the inflammatory effects observed in our model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alcain, Infante Cruz, Barrientos, Vanzulli, Salamone and Vermeulen.)

In this paper, we present integrated lead-free energy converters based on a suitable MEMS fabrication process with an embedded layer of LiNbO 3 . The fabrication technology has been developed to realize micromachined self-generating transducers to convert kinetic energy into electrical energy. The process proposed presents several interesting features with the possibility of realizing smaller scale devices, integrated systems, miniaturized mechanical and electromechanical sensors, and transducers with an active layer used as the main conversion element. When the system is fabricated in the typical cantilever configuration, it can produce a peak-to-peak open-circuit output voltage of 0.208 V, due to flexural deformation, and a power density of 1.9 nW·mm -3 ·g -2 at resonance, with values of acceleration and frequency of 2.4 g and 4096 Hz, respectively. The electromechanical transduction capability is exploited for sensing and power generation/energy harvesting applications. Theoretical considerations, simulations, numerical analyses, and experiments are presented to show the proposed LiNbO 3 -based MEMS fabrication process suitability. This paper presents substantial contributions to the state-of-the-art, proposing an integral solution regarding the design, modelling, simulation, realization, and characterization of a novel transducer.

HPV vaccination of adolescent girls is the most effective measure to prevent cervical cancer. The World Health Organization recommends that adolescent girls receive two doses of vaccine but only a small proportion of girls from regions with the highest disease burden are vaccinated because of cost and logistical considerations. Our Costa Rica HPV Vaccine trial suggested that one dose of the bivalent HPV vaccine provides robust and lasting protection against persistent HPV infections for over a decade. Data from a post-licensure trial of the quadrivalent vaccine in India also suggested that a single dose may be effective in reducing cervical cancer risk. To formally compare one versus two doses of the bivalent and nonavalent HPV vaccines, we implemented a large, randomized, double-blind trial to investigate the non-inferiority of one compared to two vaccine doses in the prevention of new HPV16/18 infections that persist 6 or more months. Bivalent and nonavalent vaccines will be evaluated separately. The trial enrolled and randomized (1:1:1:1 to 1- and 2-dose arms of the bivalent and nonavalent vaccines) 20,330 girls 12 to 16 years old residing in Costa Rica. Trial participants are followed every 6 months for up to 5 years. We also aim to estimate vaccine efficacy by comparing the rates of 6 month persistent infection in unvaccinated women with the rates in the follow-up visits of trial participants. We included one survey of unvaccinated women at the start of the study (N = 4452) and will include another survey concomitant with follow up visits of trial participants at year 4.5 (planned N = 3000). Survey participants attend two visits 6 months appart. Herein, we present the rationale, design, and enrolled study population of the ESCUDDO trial. ClinicalTrials.gov Identifier: NCT03180034., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Galectin-1 (gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, is differentially expressed at the feto-maternal interface and appears to be functionally polyvalent, with a wide range of biological activities. However, the contributions of maternal and/or feto-placental gal-1 to the signaling networks promoting a healthy pregnancy are still being elucidated. This chapter discusses the methods commonly employed to study the maternal or feto-placental contribution of gal-1 during pregnancy in mice. The methods described here can be used to decipher the specific role of each source, e.g., maternal and/or feto-placental derived gal-1 in the orchestration of pregnancy-associated processes., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Menkhorst, Than, Jeschke, Barrientos, Szereday, Dveksler and Blois.)

Problem: Proper placental development is pivotal to ensure healthy pregnancy outcomes. Among the multiple cellular mechanisms involved in the orchestration of this process, little is known on the role of alternative splicing events in the modulation of trophoblast cell biology. Here, we evaluated the expression of the alternative splicing regulator Rbfox2 in the pre- and post-placentation period in mouse pregnancies in both healthy and pathological settings., Method of Study: Immunofluorescence analysis of Rbfox2 expression in mouse implantation sites collected during the pre-placentation period (E5-E7) and post-placentation (E13)., Results: We identified a progressive increase of Rbfox2 levels throughout the peri-implantation period with a shift from a cytoplasmatic expression on E5-E6 to a predominantly nuclear expression on E7, together with a prominent expression of this factor in both subcellular compartments of the primitive placenta. Our results further showed that in contrast to healthy gestations, Rbfox2 expression decreased in preeclamptic models during the post-placentation period. Finally, we further demonstrated enhanced expression of Rbfox2 proteins in allogeneic pregnancy compared to syngeneic models., Conclusions: Our findings uncover a novel role for Rbfox2-controlled splicing events in the modulation of trophoblast function, with potential implications for the pathogenesis of preeclampsia and other pregnancy complications originated from defective placentation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction The human papillomavirus induces the formation of lesions in different epithelia. Several studies describe an association of class II human leukocyte antigen with genital lesions, implying that they could also be related to the presence of common warts. The goal of this work was to determine the frequency of human leukocyte antigens (HLA)-DQA1 and HLA-DQB1 in Mexicans with common warts. Methods Thirty-two patients with a diagnosis of common warts, without any other systemic disease, and 100 healthy subjects from the same geographic area were recruited. The second exon of the HLA-DQA1 and HLA-DQB1 loci was typed by dot-blot and chemiluminescence. Results Alleles DQA1*03:01:01 (P = 0.021) and DQB1*03:02 (P = 0.036) were associated with the presence of skin warts. DQA1*04:01-DQB1*04:02 (P = 0.009) and DQA1*03:01:01-DQB1*03:02 (P = 0.044) were the most frequent haplotypes in patients. Conclusion In conclusion, the results of our study showed that the alleles DQA1 *03:01:01, DQB1*03:02, DQA1 *04:01, and DQB1*04:02 were associated with susceptibility to common warts, while DQA1*05:01 was significantly diminished in them. Consequently, the haplotypes DQA1*04:01-DQB1*04: 02 and DQA1*03:01:01-DQB1*03:02 were found to be associated with susceptibility, and DQA1*05:01-DQB1*03:01 increased significantly in controls. Therefore, the alleles of the DQA1 and DQB1 genes that are associated with susceptibility could be presenting human papillomavirus (HPV) peptides to T lymphocytes that activate a Th2-type response (anti-inflammatory cytokines), which allows the development of skin warts in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sánchez-Barrientos et al.)

Low-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3 inflammasome activation in skeletal muscle has not been reported. Here, we evaluated the NLRP3 inflammasome components and their role in GLUT4 translocation impairment in skeletal muscle during IR. Male C57BL/6J mice were fed with a normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. The protein levels of NLRP3, ASC, caspase-1, gasdermin-D (GSDMD), and interleukin (IL)-1β were measured in both homogenized and isolated fibers from the flexor digitorum brevis (FDB) or soleus muscle. GLUT4 translocation was determined through GLUT4 myc -eGFP electroporation of the FBD muscle. Our results, obtained using immunofluorescence, showed that adult skeletal muscle expresses the inflammasome components. In the FDB and soleus muscles, homogenates from HFD-fed mice, we found increased protein levels of NLRP3 and ASC, higher activation of caspase-1, and elevated IL-1β in its mature form, compared to NCD-fed mice. Moreover, GSDMD, a protein that mediates IL-1β secretion, was found to be increased in HFD-fed-mice muscles. Interestingly, MCC950, a specific pharmacological NLRP3 inflammasome inhibitor, promoted GLUT4 translocation in fibers isolated from the FDB muscle of NCD- and HFD-fed mice. In conclusion, we found increased NLRP3 inflammasome components in adult skeletal muscle of obese insulin-resistant animals, which might contribute to the low-grade chronic metabolic inflammation of skeletal muscle and IR development.

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPAR γ ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Carla Basualto-Alarcón et al.)

Introduction: Background: it is well known that moderate or vigorous physical exercise produces an increase in free radicals. Aim: the aims of this study were to observe changes in malondialdehyde and antioxidant vitamins after a maximum incremental test, and to relate malondialdehyde and antioxidant vitamin values to performance parameters. Methods: eighty-four male athletes participated in this study. Participants performed a maximum incremental test until exhaustion on a treadmill. Malondialdehyde in plasma and antioxidant vitamins in plasma and erythrocytes were determined before and after the test. Results: in plasma, there was a decrease in malondialdehyde after the test. In erythrocytes, results showed increases in vitamin C and decreases in vitamin E after the test. Maximal oxygen uptake values were associated positively with vitamin C and negatively with malondialdehyde levels before the test. On the other hand, maximal oxygen uptake, total test time, and total test distance were positively related to the malondialdehyde values obtained after the test. Conclusions: a maximum incremental test did not produce any changes in plasma vitamins in athletes. However, it increased the levels of vitamin C in erythrocytes and decreased malondialdehyde values in plasma and vitamin E in erythrocytes. The levels of malondialdehyde, vitamin C and vitamin E were related to performance parameters. These results may be linked to the adaptation of antioxidant systems due to regular training.

Pregnancies carried by women with chronic hypertension are at increased risk of superimposed preeclampsia, but the placental pathways involved in disease progression remain poorly understood. In this study, we used the stroke-prone spontaneously hypertensive rat (SHRSP) model to investigate the placental mechanisms promoting superimposed preeclampsia, with focus on cellular stress and its influence on galectin-glycan circuits. Our analysis revealed that SHRSP placentas are characterized by a sustained activation of the cellular stress response, displaying significantly increased levels of markers of lipid peroxidation (i.e., thiobarbituric acid reactive substances (TBARS)) and protein nitration and defective antioxidant enzyme expression as early as gestation day 14 (which marks disease onset). Further, lectin profiling showed that such redox imbalance was associated with marked alterations of the placental glycocode, including a prominent decrease of core 1 O-glycan expression in trophoblasts and increased decidual levels of sialylation in SHRSP placentas. We also observed significant changes in the expression of galectins 1, 3 and 9 with pregnancy progression, highlighting the important role of the galectin signature as dynamic interpreters of placental microenvironmental challenges. Collectively, our findings uncover a new role for the glycoredox balance in the pathogenesis of superimposed preeclampsia representing a promising target for interventions in hypertensive disorders of pregnancy.

Among multiple mechanisms, low-grade inflammation is critical for the development of insulin resistance as a feature of type 2 diabetes. The nucleotide-binding oligomerization domain-like receptor family (NOD-like) pyrin domain containing 3 (NLRP3) inflammasome has been linked to the development of insulin resistance in various tissues; however, its role in the development of insulin resistance in the skeletal muscle has not been explored in depth. Currently, there is limited evidence that supports the pathological role of NLRP3 inflammasome activation in glucose handling in the skeletal muscle of obese individuals. Here, we have centered our focus on insulin signaling in skeletal muscle, which is the main site of postprandial glucose disposal in humans. We discuss the current evidence showing that the NLRP3 inflammasome disturbs glucose homeostasis. We also review how NLRP3-associated interleukin and its gasdermin D-mediated efflux could affect insulin-dependent intracellular pathways. Finally, we address pharmacological NLRP3 inhibitors that may have a therapeutical use in obesity-related metabolic alterations.

Several anthropometric and performance parameters related to aerobic metabolism are associated with performance in endurance runners and are modified according to the training performed. The objective of this study was to investigate the ergospirometric and body composition changes in endurance runners during a sports season in relation to their training. Twenty highly trained men endurance runners performed an incremental test until exhaustion (initial, and at 3, 6, and 9 months) on a treadmill to determine maximal oxygen consumption (VO 2 max), second ventilatory threshold (VT 2 ), and their associated running speeds. Skinfolds, perimeters, and weights were measured. No changes were obtained in VO 2 max or VT 2 during the study, although their associated running speeds increased ( p < 0.05) after 3 months of the study. Decreases in fat mass ( p < 0.05) and muscle mass ( p < 0.05) were observed at the end of the season (9 months). Changes occurred in the different skinfolds according to the characteristics of the training performed during the season. In conclusion, vVO 2 max and vVT 2 increase with a greater volume of kilometres trained and can be adversely affected by loss of muscle mass.

Galectin (gal)-1, -3, and -9 are members of a family of glycan binding proteins that mediate complex interactions between decidual, inflammatory and trophoblast cells modulating several processes during gestation, control of the maternal immune system, and parturition. Their immunomodulatory role in preterm birth and postnatal expression in preterm infants is unknown. We performed a single center prospective study of 170 preterm infants with a gestational age below 35 weeks. Peripheral venous blood samples were collected during the neonatal period and galectin-1, -3, and -9 were determined by ELISA. We noted a strong decline of circulating gal-1 and -3 levels but not gal-9 from birth to day 7 of life. There was an inverse correlation of gal-1 and -3 levels at birth with gestational age. Gal-1 levels were remarkably increased in infants born to amniotic infection syndrome (AIS), which was also observed for gal-9 levels. Infants who developed early-onset sepsis had higher levels of gal-3 at day 1 as compared to unaffected infants. Our observational data imply that galectin-1, -3, and -9 levels are elevated in preterm infants born in an inflammatory milieu such as AIS or EOS. Future studies need to address whether galectins mediate inflammation-induced preterm birth and could therefore be a target for clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Faust, Freitag, Barrientos, Hartel and Blois.)

Background: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake-via AMP-activated protein kinase (AMPK)-after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR)., Methods: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of β-myosin heavy chain (β-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR)., Results: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated β-mhc, Hk2 and Pfk2 mRNA levels., Conclusion: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Several essential trace minerals play an important role in the endocrine system; however, toxic trace minerals have a disruptive effect. The aim of this research was to determine basal concentrations and the possible correlations between trace minerals in plasma and several plasma hormones in runners. Sixty high-level male endurance runners (21 ± 3 years; 1.77 ± 0.05 m; 64.97 ± 7.36 kg) participated in the present study. Plasma hormones were analyzed using an enzyme-linked immunosorbent assay (ELISA) and plasma trace minerals were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). Correlations and simple linear regression were used to assess the association between trace minerals and hormones. Plasma testosterone concentrations were inversely correlated with manganese (r = -0.543; β = -0.410; p < 0.01), selenium (r = -0.292; β = -0.024; p < 0.05), vanadium (r = -0.406; β = -1.278; p < 0.01), arsenic (r = -0.336; β = -0.142; p < 0.05), and lead (r = -0.385; β = -0.418; p < 0.01). Plasma luteinizing hormone (LH) levels were positively correlated with arsenic (r = 0.298; β = 0.327; p < 0.05) and cesium (r = 0.305; β = 2.272; p < 0.05), and negatively correlated with vanadium (r = -0.303; β = -2.467; p < 0.05). Moreover, cortisol concentrations showed significant positive correlations with cadmium (r = 0.291; β = 209.01; p < 0.05). Finally, insulin concentrations were inversely related to vanadium (r = -0.359; β = -3.982; p < 0.05). In conclusion, endurance runners living in areas with high environmental levels of toxic minerals should check their concentrations of anabolic hormones.

Problem: From conception, a delicate regulation of galectins, a family of carbohydrate-binding proteins, is established to ensure maternal immune tolerance in pregnancy. Though galectin-3 (gal-3), the only chimera-type galectin, is abundantly expressed at the feto-maternal interface; the physiological role of this lectin during pregnancy remains to be fully elucidated and requires further investigation., Method of Study: In this study, we analyzed serum gal-3 levels during the course of healthy gestation. Trophoblast functions were evaluated upon gal-3 exogenous stimulation using trophoblastic cell lines (e.g. , HIPEC65, SGHPL-4, and BeWo cells). Finally, we investigated variations in peripheral gal-3 levels associated with the development of spontaneous abortion and gestational diabetes mellitus (GDM)., Results: Gal-3 circulating levels increased as normal pregnancy progressed. In vitro experiments showed that exogenous gal-3 positively regulated trophoblast functions inducing invasion, tube formation, and fusion. Compared with normal pregnant women, circulating gal-3 levels were significantly decreased in patients who developed GDM., Conclusion: Our results reveal a physiological role for gal-3 during pregnancy, promoting proper trophoblast functions associated with healthy gestation. GDM is associated with a failure to increase circulating gal-3 levels late in gestation. Thus, dysregulation of gal-3 may indicate a contribution of the chimera-type lectin to this adverse pregnancy outcome., (© 2020 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Early postnatal life is characterized by a critical time period in which the developing neonatal immune system transitions from passive immunity, induced by protective maternal antibodies, to the competence of a fully functioning immune system. The inflammatory capability of both maternal and neonatal antibodies is governed by N-linked glycosylation of the Fc region, and though this has been examined extensively in adults, there is currently little information regarding antibody glycosylation patterns during early postnatal life. To characterize the murine IgG Fc glycosylation profile during early life, we used nano-LC-ESI-Qq-TOF mass spectrometry analysis to assess subclass specific Asn-297 glycosylation patterns in the serum of BALB/c mice from 5-60 days of age. From birth to adulthood, we observed a decline in proinflammatory Fc glycosylation in all IgG subclasses. This was shown by significantly reduced agalactosylated and monogalactosylated structures combined with increased sialylation after weaning at 45 and 60 days of age. This information indicates that the transition between neonatal life and adulthood in mice is accompanied by reduction of inflammatory IgG antibodies. Our study contributes to a growing body of literature indicating the importance of IgG Fc glycosylation and its association with inflammation during different life stages.

The aim of this study was to determine the possible correlations between essential and toxic trace elements of plasma with several anthropometric and body composition parameters and performance in endurance runners. Sixty-five high-level middle and long-distance runners (21  ±  3 years; 1.77 ± 0.05 m; 64.97 ± 7.36 kg; VO 2 max. 67.55 ± 4.11 mL/min/kg) participated in the present study. Abdominal, subscapular, iliac crest, triceps, front thigh and medial calf skinfold thicknesses and an incremental test until exhaustion were recorded. Body, fat, muscle and bone mass were estimated. Plasma trace elements were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). Correlations and simple linear regression were used to assess the relationship between trace elements and several variables. Different skinfolds, fat mass, muscle mass and bone mass correlated positively and negatively with trace elements such as copper, manganese, selenium, vanadium, zinc, lithium, rubidium, strontium, arsenic, beryllium and lead. Lithium was related with performance. In conclusion, endurance training causes changes in the body concentrations of several trace elements that trigger modifications in body composition that may be interesting, if confirmed in the future, for the control of metabolic diseases such as obesity.

The aim of this study was to determine the possible changes in plasma of several hormones such as Luteinizing Hormone, Testosterone, Cortisol and Insulin in endurance runners during the sports season. Twenty-one high-level male endurance runners (22 ± 3.2 years, 1.77 ± 0.05 m) participated in the study. Basal plasma hormones were measured at four moments during the season (initial, 3, 6 and 9 months), and were analyzed using ELISA (enzyme-linked immunosorbent assay). Testosterone and Luteinizing Hormone (LH) suffered very significant decreases ( p < 0.01) at 3 months compared with the beginning and an increase ( p < 0.05) at 6 and 9 months compared with 3 months. Insulin level was significantly lower ( p < 0.05) at 3, 6 and 9 months compared with the initial test. Insulin and cortisol were associated inversely (r = 0.363; β = -0.577; p = 0.017) and positively (r = 0.202; β = 0.310; p = 0.043), respectively, with the amount of km per week performed by the runners. There was a significant association between km covered at a higher intensity than the anaerobic threshold and I (r = 0.580; β = -0.442; p = 0.000). Our findings indicate that testosterone, LH and insulin were more sensitive to changes in training volume and intensity than cortisol in high-level endurance runners. Basal testosterone and LH concentrations decrease in athletes who perform a high volume of aerobic km in situations of low energy availability.

Growing evidence suggests that galectins, an evolutionarily conserved family of glycan-binding proteins, fulfill key roles in pregnancy including blastocyst implantation, maternal-fetal immune tolerance, placental development, and maternal vascular expansion, thereby establishing a healthy environment for the growing fetus. In this review, we comprehensively present the function of galectins in shaping cellular circuits that characterize a healthy pregnancy. We describe the current understanding of galectins in term and preterm labor and discuss how the galectin-glycan circuits contribute to key immunological pathways sustaining maternal tolerance and preventing microbial infections. A deeper understanding of the glycoimmune pathways regulating early events in preterm birth could offer the broader translational potential for the treatment of this devastating syndrome.

Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR. The objective of this study was to investigate the contribution of galectin-3 (gal-3), a β-galactoside binding protein involved in pregnancy, placental function and fetal growth. We demonstrated that lack of gal-3 during mouse pregnancy leads to placental dysfunction and drives FGR in the absence of a maternal preeclampsia syndrome. Analysis of gal-3 deficient dams revealed placental inflammation and malperfusion, as well as uterine natural killer cell infiltration with aberrant activation. Our results also show that FGR is associated with a failure to increase maternal circulating gal-3 levels during the second and third trimester in human pregnancies. Placentas from human pregnancies affected by FGR displayed lower gal-3 expression, which correlated with placental dysfunction. These data highlight the importance of gal-3 in the promotion of proper placental function, as its absence leads to placental disease and subsequent FGR.

Immune cells [e. g., dendritic cells (DC) and natural killer (NK) cells] are critical players during the pre-placentation stage for successful mammalian pregnancy. Proper placental and fetal development relies on balanced DC-NK cell interactions regulating immune cell homing, maternal vascular expansion, and trophoblast functions. Previously, we showed that in vivo disruption of the uterine NK cell-DC balance interferes with the decidualization process, with subsequent impact on placental and fetal development leading to fetal growth restriction. Glycans are essential determinants of reproductive health and the glycocode expressed in a particular compartment (e.g., placenta) is highly dependent on the cell type and its developmental and pathological state. Here, we aimed to investigate the maternal and placental glycovariation during the pre- and post-placentation period associated with disruption of the NK cell-DC dynamics during early pregnancy. We observed that depletion of NK cells was associated with significant increases of O- and N-linked glycosylation and sialylation in the decidual vascular zone during the pre-placental period, followed by downregulation of core 1 and poly-LacNAc extended O-glycans and increased expression of branched N-glycans affecting mainly the placental giant cells and spongiotrophoblasts of the junctional zone. On the other hand, expansion of DC induced a milder increase of Tn antigen (truncated form of mucin-type O-glycans) and branched N-glycan expression in the vascular zone, with only modest changes in the glycosylation pattern during the post-placentation period. In both groups, this spatiotemporal variation in the glycosylation pattern of the implantation site was accompanied by corresponding changes in galectin-1 expression. Our results show that pre- and post- placentation implantation sites have a differential glycopattern upon disruption of the NK cell-DC dynamics, suggesting that immune imbalance early in gestation impacts placentation and fetal development by directly influencing the placental glycocode., (Copyright © 2020 Borowski, Tirado-Gonzalez, Freitag, Garcia, Barrientos and Blois.)

The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid hormone levels and their cardio-specific actions, which are critical factors involved in the prevalence and features of age-associated cardiovascular disease. In women, estrogens have been described as cardioprotective agents, while in men, testosterone is the main sex steroid hormone. The effects of testosterone as a metabolic regulator and cardioprotective agent in aging men are poorly understood. With advancing age, testosterone levels gradually decrease in men, an effect associated with increasing fat mass, decrease in lean body mass, dyslipidemia, insulin resistance and adjustment in energy substrate metabolism. Aging is associated with a decline in metabolism, characterized by modifications in cardiac function, excitation-contraction coupling, and lower efficacy to generate energy. Testosterone deficiency -as found in elderly men- rapidly becomes an epidemic condition, associated with prominent cardiometabolic disorders. Therefore, it is highly probable that senior men showing low testosterone levels will display symptoms of androgen deficiency, presenting an unfavorable metabolic profile and increased cardiovascular risk. Moreover, recent reports establish that testosterone replacement improves cardiomyocyte bioenergetics, increases glucose metabolism and reduces insulin resistance in elderly men. Thus, testosterone-related metabolic signaling and gene expression may constitute relevant therapeutic target for preventing, or treating, age- and gender-related cardiometabolic diseases in men. Here, we will discuss the impact of current evidence showing how cardiac metabolism is regulated by androgen levels in aging men., (Copyright © 2020 Barrientos, Llanos, Basualto-Alarcón and Estrada.)

Ellagic acid, a naturally occurring phenol found in a variety of fruits and nuts has been shown to possess anti-inflammatory properties. However, the mechanism of action behind its anti-inflammatory action is unclear. Using human Jurkat T cells, our study examined the effects of ellagic acid (EA) on Ca 2+ handling, in particular, store-operated Ca 2+ entry (SOCE), a process critical to proper T cell function. We observed that the acute addition of EA-induced Ca 2+ release with an EC 50 of 63 μM. The Ca 2+ release was significantly attenuated by Xestospongin C, a known inhibitor of the Inositol 1,4,5-trisphosphate receptor (IP 3 R) channel and was unaffected by the phospholipase C (PLC) inhibitor, U73122. Furthermore, chronic incubation of Jurkat T cells with EA not only decreased the ATP-induced Ca 2+ release but also diminished the SOCE-mediated Ca 2+ influx in a dose-dependent manner. This inhibition was confirmed by reduced Mn 2+ entry rates in the EA-treated cells. The ATP-induced Ca 2+ entry was also attenuated in EA-treated HEK293 cells transiently transfected with SOCE channel Orai1-myc and ER-sensor stromal interaction molecule (STIM1) (HEK STIM/Orai ). Moreover, EA treatment interfered with the Orai1 and STIM1 coupling by disrupting STIM1 puncta formation in the HEK STIM/Orai cells. We observed that EA treatment reduced cytokine secretion and nuclear factor of activated T-cell transcriptional activity in stimulated T cells. Hence, by inhibiting SOCE mediated Ca 2+ influx, EA decreased downstream activation of pro-inflammatory mediators. These results suggest a novel target for EA-mediated effects and provide insight into the mechanisms underlying EA-mediated anti-inflammatory effects., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.

The current information about the effect of physical exercise on the body concentrations of several minerals is still limited, both in the acute (short-term) and adaptive (long-term) responses. So, this manuscript aims, on the one hand, to assess the possible differences on basal levels of cobalt (Co), copper (Cu), and manganese (Mn) concentrations in serum and urine between athletes and sedentary participants and, on the other hand, to evaluate the effect of an acute progressive physical exercise until voluntary exhaustion on the serum and urinary concentrations of Co, Cu, and Mn. Two groups participated in this survey, one was formed by untrained, sedentary males (CG; n = 26), and the other group was constituted by national endurance (long and middle distances) athletes (AG; n = 21). All participants were from the same region of Spain. Participants of both groups performed a physical test on a treadmill, reaching voluntary exhaustion. Blood and urine samples of each participant were collected before and at after the tests. Once obtained and processed, the concentrations of Co, Cu, and Mn elements were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The differences in the studied variables were evaluated using a mixed model by means of an ANOVA and Bonferroni post hoc tests. In the comparison of the pre-test values between groups, the results showed that serum concentrations of Mn were significantly lower in CG than in AG (p < 0.01). In urine, Co and Mn levels were significantly higher among CG participants (p < 0.01) than among AG ones, while in the case of Cu, the values were lower (p < 0.01) in the CG than in the AG. Regarding the effects of the effort tests, no significant changes were found among the participants of the CG. It was observed that the serum concentrations of Co (p < 0.05) and Cu (p < 0.01) decreased after the test among the AG participants. Also, the results showed that there were no statistical differences in Co and Mn values (expressed in μg/g creatinine). However, the urinary post-test Cu concentrations were lower (p < 0.05) among AG participants. In basal conditions, serum concentrations of Mn were significantly lower in CG than in AG. In urine, Co and Mn levels were significantly higher among CG participants and Cu level was significantly lower in CG, a fact which may reflect adaptive responses to exercise. An incremental exercise to exhaustion in AG produces a decrease in Co and Cu serum concentrations, as well as in urinary excretion of Cu.

Galectins are a phylogenetically conserved family of soluble β-galactoside binding proteins, consisting of 15 different types, each with a specific function. Galectins contribute to placentation by regulating trophoblast development, migration, and invasion during early pregnancy. In addition, galectins are critical players regulating maternal immune tolerance to the embedded embryo. Recently, the role of galectins in angiogenesis during decidualization and in placenta formation has gained attention. Altered expression of galectins is associated with abnormal pregnancies and infertility. This review focuses on the role of galectins in pregnancy-associated processes and discusses the relevance of galectin-glycan interactions as potential therapeutic targets in pregnancy disorders.

The aim of the present study was to determine changes occurring in serum and urine concentrations of essential trace elements with proven essentiality (molybdenum, selenium, and zinc) as a result of performing an acute physical activity until exhaustion in middle- and long-distance runners who live in the same area of Extremadura (Spain). Twenty-one Spanish national middle- and long-distance runners and 26 sedentary students of a similar age were recruited for the study. Both groups ran on a treadmill until exhaustion, starting at a speed of 10 and 8 km/h, respectively, and increasing the speed at 1 km/h every 400 m, without modifying the slope, always within the recommended parameters. Serum and urine samples were obtained from all subjects before and after the tests. Analysis of trace metals was performed by inductively coupled plasma mass spectrometry (ICP-MS). Resting serum and urinary concentrations between groups were compared using the Student t test, and the Wilcoxon test was used to analyze the trends of changes before and after the effort. The results showed that molybdenum concentrations were significantly higher in athletes than in controls (p < 0.01). Selenium (p < 0.05) and zinc (p < 0.01) concentrations were significantly lower in athletes than in controls. When we compared the serum concentrations before and after the test in the controls, only in the case of selenium (p = 0.006), a significant increase was observed after the test. However, this signification disappears with the corrections for hematocrit. Athletes' serum concentrations of Se (p = 0.004) and Zn (p = 0.005) lowered at the end of the test. Also, the results showed that there were no statistical urinary concentration (expressed in μg/g creatinine) changes in Mo and Se. Zn urinary concentration increased at the end of exercise (p = 0.018), since an incremental exercise to exhaustion in middle- and long-distance elite athletes produces a decrease in Se and Zn serum concentrations but Zn urinary concentration increased. In conclusion, athletes show higher serum concentrations of molybdenum and lower serum concentrations of selenium and zinc than sedentary subjects. Additionally, a treadmill test until exhaustion provokes a decrease in serum concentration of selenium and zinc and a higher excretion of urinary zinc. Serum concentrations of Se and Zn should be carried out in order to avoid any possible deficit cases and to establish the optimal supplementation.

Background: The main objective of this study was to observe any changes and possible adaptations produced in MDA and antioxidants vitamins on plasma and erythrocytes in endurance male athletes among an athletic season (12 months)., Methods: Twenty three long and middle distance male athletes participated in this study. Basal MDA on plasma and antioxidant vitamins in plasma and erythrocytes were measured at four moments along the season (0, 3, 6 and 9 months). Fatty acid concentrations in erythrocytes were obtained to determine lipid peroxidation indexes., Results: In plasma, vitamin C suffered significant decreases at 3 and 6 months compared with the begin (P<0.01), and an increase at 9 months, compared with 3 months. On the other hand, vitamin A level was significantly lower at 9 months compared with the other periods (P<0.01 compared with 0 and 6 months; P<0.05 compared with 3 months). In erythrocytes, significant decreases were observed in vitamin E among the season at 6 months and an increase from 6 to 9 months (P<0.05). Vitamin A suffers a significant decrease in both for competitive periods, at 3 and 9 months, compared with the beginning of the season. The most of changes in lipid peroxidation indexes were produced along the firsts 3 months., Conclusions: 1) Physical training improves the antioxidant systems in order to reduce lipid peroxidation in trained athletes along the season; 2) PUFA/SFA ratios seem more reliable than MDA to observe oxidative stress.