Cortisol Research Articles

Abstract 4119210: Differential Proteomic Expression of IGFßP-1 and IGFßP-2 in Primary Angioplasty for Acute Myocardial Infarction

Introduction: Insulin growth factor (IGF) binding protein-1 and 2 (IGFBP-1 and 2) are implicated in acute myocardial infarction (AMI) and have been suggested as predictors of mortality and development of heart failure. The IGF axis has been shown to play roles in cell proliferation and apoptosis. We analysed the serum IGFBP-1 and 2 levels in AMI before and after percutaneous coronary intervention (PCI) and correlated this with cardiac magnetic resonance (CMR) imaging to better establish their significance as biomarkers in AMI. Methods: Patients with AMI who presented to Royal Free Hospital, London, were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation, 24h and 72h following primary PCI. All underwent both admission and follow-up CMR at 6 months to assess for myocardial oedema, left ventricular volumes and function, and assessment of scar. Results: Proteomic evaluation in 20 AMI patients (male 95%; median age 59) revealed significant reduction in the average IGFBP-1 values at discharge compared with presentation, from 5.93 to 4.52 (24% reduction, p=0.003). Conversely, the average IGFBP-2 values at discharge significantly increased from 7.66 to 8.29 (8% increase, p=0.001). Higher discharge IGFBP-2 value was also correlated with increased indexed left ventricle end diastolic volume (LVEDV) at 6-month follow-up (R=0.54, p=0.032). Discussion: IGFBP-1 and 2 showed significant change following intervention for AMI. IGFBP-1 is a stress hormone, which is directly and indirectly activated by cytokines, dysglycaemia and vasopressin activation. Its subsequent reduction following PCI in AMI indicates relative resolution of inflammation, but this was not correlated with changes in infarct size or LV function at follow-up. IGFBP-2 showed significant upregulation, and higher values at discharge were significantly correlated with increased LDEDV at follow-up, suggesting adverse clinical outcomes within this setting. This data suggests differential roles of IGFBP-1 and 2 in the pathogenesis of AMI.

Abstract 4119195: Proteomic Analysis of Primary Angioplasty in Acute Myocardial Infarction: Implications for Left Ventricular Remodelling and Recovery of Function

Introduction: Acute myocardial infarction (AMI) is a leading global cause of mortality. Following primary percutaneous coronary intervention (PCI), 25% require hospitalisation for symptomatic heart failure. Further understanding of the molecular pathogenesis and the temporal relationship of the protein profile associated with ischaemic insult and subsequent cardiac remodelling is required to improve risk stratification following AMI. Methods: 20 patients with AMI presenting to Royal Free Hospital in London were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation and at 24 and 72 hours following primary PCI. All underwent initial CMR on admission and at 6 month follow up to assess for myocardial oedema, left ventricular volumes and function and assessment of scar. Results: Proteomic biomarkers that increased on discharge following AMI were: IGFBP2 (8% increase, p=0.001), MMP-10 (5% increase, p=0.001), TIMP4 (14.4% increase, p<0.001), CSF-1 (3.4% increase, p<0.001), CHI3L1 (15% increase, p<0.001), ST2 (19% increase, p=0.001), TGF-alpha (17% increase, p=0.001), IL6 (38% increase, p<0.001), and NT-proBNP (93% increase, p<0.001). The only biomarker that significantly decreased was IGFBP-1 (24% decrease, p=0.003). Notably, increased post-PCI biomarkers correlated with reduced infarct size at follow-up, including CCL23 (R=-0.6, p=0.016), IL6 (R=-0.051, p=0.04), NT-proBNP (R=-0.72, p=0.002). High biomarkers at initial presentation associated with reduced left ventricular end diastolic volume (LVEDV) were CSF-1 (R=-0.64, p=0.03) and CCL23 (R=-0.76, p=0.006). Discussion: Following AMI, we observed increase in proteins implicated in inflammation, angiogenesis and tissue repair. IGFBP1 as a stress hormone significantly decreased after PCI. Markers that showed linear association with reduced cardiac preload measured by LVEDV were linked with angiogenesis promotion and resolution of inflammation.

Sex-dependent effects of early life sensory overstimulation on later life behavioral function in rats

AbstractChildren today are immersed in electronic technology shortly after birth as they now begin regularly watching television earlier than they did in the past. Many new programs geared towards infants contain lots of lights, color, and sounds, which may constitute a form of sensory overstimulation (SOS) that leads to cognitive and behavioral changes in children and adolescents. Here, we examined the impact of early life SOS exposure on later life behavioral and cognitive function in rodents by exposing developing male and female rats to excessive audiovisual stimulation from postnatal days (PND) 10–40 and assessing anxiety-like behavior, social motivation, compulsive behavior, and spatial learning/cognition from PND 50–60. To evaluate potential SOS effects on hypothalamic–pituitary–adrenal (HPA)-axis function, levels of the stress hormone corticosterone (CORT) were measured at 3 timepoints (e.g., PND 23, 41, 61) post-SOS exposure. Sensory overstimulated males exhibited reduced anxiety-like and compulsive behavior compared to controls, whereas females exhibited reduced social motivation but enhanced spatial learning/cognition compared to controls. No differences in baseline CORT levels were found at any age tested, suggesting no impact of early life SOS on later life basal HPA-axis function. Our results demonstrate sex-specific effects of early life SOS on distinct behavioral domains in early adult rats.

Renal endowment in men and women: start from the beginning.

The development of the human kidney leads to the establishment of nephron endowment through a process influenced by both genetic and environmental factors. There is individual variability regarding nephron endowment and factors including aging and pathological conditions contribute to the decline in the number of nephrons, impacting renal function. Genetic determinants, such as mutations in crucial developmental genes like Pax2, and epigenetic mechanisms mediated by key enzymes including sirtuin 3, play critical roles in the regulation of the number of nephrons, with implications for kidney disease susceptibility. Sexual dimorphism significantly influences kidney development and function, with the number of nephrons being significantly lower in females, consistent with lower female birth weight, which is considered a surrogate for nephron endowment. Also, although females have fewer nephrons, they experience a slower decline in GFR compared to males. Gender disparity in chronic kidney disease progression has been attributed to factors such as metabolism, oxidative stress, renal hemodynamics, and sex hormones. Understanding the complexities of nephron endowment variability, genetic determinants, and sexual dimorphism in kidney development and function is crucial for elucidating the mechanisms underlying individual kidney disease susceptibility and progression. Further research in this field holds promise for the development of personalized approaches to kidney disease prevention, management, and treatment.

Increasing student well-being through a positive psychology intervention: changes in salivary cortisol, depression, psychological well-being, and hope.

The significant prevalence of mental health problems among children and adolescents is a major concern worldwide. The current study evaluates the impact of a year-long, school-based intervention, Flourishing Students, on adolescents' salivary cortisol levels, depressive symptoms, psychological well-being, and hope. Utilizing a cluster randomized design with intervention and control classes, 72 students engaged in 32 well-being lessons during academic year 2016-2017, whereas 68 students followed their standard curriculum. Depressive symptoms and psychological well-being were assessed at three time points, while the stress hormone cortisol and hope were measured at two. The results showed a slight increase in cortisol levels from baseline to post-intervention during school hours in the control group, whereas no change occurred in the intervention group. Additionally, total cortisol levels at post-intervention were slightly lower among intervention-group students compared with control group students. Questionnaire data revealed significant interaction effects on psychological well-being and hope from baseline to post-intervention, and on depression and psychological well-being from baseline to the 5-month follow-up. The intervention group scored lower in depressive symptoms and higher in psychological well-being and hope compared with the control group. These findings underscore the essential role of comprehensive assessment methods in evaluating intervention efficacy in well-being programs.

Ashwagandha and stress

Ashwagandha, also known as Withania somnifera, is an adaptogen gaining popularity as a natural stress reducer. Stress is a common phenomenon caused by factors such as lifestyle, work pressure or social conflict, and has a negative impact on both mental and physical health. In response to these challenges, more and more people are looking for natural solutions, and adaptogens such as ashwagandha offer support in dealing with stress without significant side effects. Scientific research shows that ashwagandha can lower levels of the stress hormone cortisol and improve results on tests assessing stress, anxiety and depression. Numerous studies conducted on both animals and humans confirm its beneficial effects on mental and physical health, including improvement of cognitive functions, sleep quality and emotional well-being. The mechanism of action of ashwagandha includes regulation of the HPA axis, reduction of glucocorticoids and modulation of the immune system. Despite promising results, further research is needed to fully understand its mechanism of action, assess long-term effects, and investigate possible interactions with other drugs. Ashwagandha seems to be a safe and effective agent in the fight against stress, but it is recommended to consult a doctor before starting supplementation.

Impact of Chronic Moderate Psychological Stress on Skin Aging: Exploratory Clinical Study and Cellular Functioning.

Skin is continuously exposed to environmental external and internal factors, including psychological stress (PS). PS has been reported to trigger different dermatoses such as psoriasis, atopic dermatitis, vitiligo, alopecia areata, and acne through the release of cortisol and epinephrine. To clinically explore PS-induced measurable skin aging signs in subjects with moderate versus mild chronic PS, and to investigate the effect of chronic PS on DNA damage at cellular level. In vitro stress tests with cortisol and epinephrine, and with cortisol only on extracellular matrix (ECM) synthesis, as well as on normal human skin fibroblast and keratinocyte functioning, including skin barrier and wound healing were performed. Moderately stressed subjects in the context of the clinical study had a significantly decreased antioxidant potential and impacted skin barrier integrity, as well as significantly increased signs of microrelief alterations (skin texture and fine lines) reaching an increased severity of about 32.9%. At a cellular level, DNA integrity, ECM synthesis, wound healing, and skin barrier parameters were impacted by increased stress hormone levels. The clinical exploratory studies presented herewith, as well as the study of cell functioning under stress, have provided evidence that chronic PS significantly affects skin homeostasis and triggers skin aging.

Stress induces nucleobindin-1 mRNA and nesfatin-1-like peptide stimulates cortisol secretion in goldfish

Stress is a state of disrupted homeostasis triggered by physical or psychological stimuli that elicit adaptive responses at the molecular and cellular levels. In fish, the hypothalamus-pituitary-interrenal (HPI) axis mediates stress responses. Nesfatin-1 and a nesfatin-1-like peptide (NLP), derived from nucleobindin-1 (NUCB1), have been implicated in stress hormone regulation in mammals. This study investigated the cell-specific expression of NUCB1/NLP in HPI tissues and its effects on stress response in goldfish (Carassius auratus). NUCB1 mRNA is abundant in the hypothalamus, pituitary, and several other peripheral tissues of goldfish. NUCB1/NLP-like immunoreactivity was found in the brain and pituitary, co-localized with corticotropin-releasing factor receptor 1 (CRF-R1) in the hypothalamus, and with adrenocorticotrophic hormone (ACTH) in the pituitary. In vivo netting and restraint stress increased nucb1 and crf-r1 mRNAs in the brain and acth mRNA in the pituitary, as determined by RT-qPCR. Intraperitoneal injection of NLP increased cortisol in circulation, crf-r1 mRNA in the brain and acth mRNA in the pituitary. These findings suggest that NUCB1/NLP is a new player in mediating the endocrine stress response of goldfish through the HPI axis.

Genome-Wide Analysis of HECT E3 Ligases Members in Phyllostachys edulis Provides Insights into the Role of PeHECT1 in Plant Abiotic Stress Response

Homology to E6-AP Carboxy Terminus (HECT) E3 ubiquitin ligases play pivotal roles in plant growth, development, and responses to abiotic stresses. However, the function of HECT genes in Phyllostachys edulis (P. edulis) remains largely uninvestigated. In this study, a comprehensive genome-wide analysis of the HECT E3 ubiquitin ligases gene family in P. edulis was conducted, aiming to elucidate its evolutionary relationships and gene expansion. Analysis of gene structure, conserved motifs and domains, and synteny genome regions were performed. Furthermore, cis-elements in HECT gene promoters that respond to plant hormones and environmental stresses were identified and corroborated by expression data from diverse abiotic stress conditions and hormone treatments. Based on the co-expression network of PeHECTs under cold and dehydration stresses, PeHECT1 was identified as a key candidate gene associated with abiotic stress tolerance. Overexpression of PeHECT1 in tobacco leaves significantly upregulated genes related to reactive oxygen species (ROS) detoxification and polyamine biosynthesis. Yeast one-hybrid (Y1H), electrophoretic mobility shift assay (EMSA), and dual-luciferase (dual-LUC) assays suggested that the transcription factor ETHYLENE RESPONSE FACTOR 3 (PeERF3) bound to the dehydration-responsive element (DRE) of the promoter of PeHECT1 and activated its transcription activity. Phylogenetic analysis indicated that PeHECT1 in P. edulis exhibited a close association with the diploid herbaceous bamboo Olyra latifolia, followed by the divergence of rice and bamboo. In summary, this study enhances our comprehensive understanding of the HECT E3 ubiquitin ligases gene family in P. edulis and highlights the potential role of PeHECT1 in plant abiotic stress response.

Hormones in Malaria Infection: Influence on Disease Severity, Host Physiology, and Therapeutic Opportunities.

Human malaria, caused by Plasmodium parasites, is a fatal disease that disrupts the host's physiological balance and affects the neuroendocrine system. This review explores how malaria influences and is influenced by hormones. Malaria activates the Hypothalamus-Pituitary-Adrenal axis, leading to increased cortisol, aldosterone, and epinephrine. Cortisol, while reducing inflammation, aids parasite survival, whereas epinephrine helps manage hypoglycemia. The Hypothalamus-Pituitary-Gonad and Hypothalamus-Pituitary-Thyroid axes are also impacted, resulting in lower sex and thyroid hormone levels. Malaria disrupts the renin-angiotensin-aldosterone system (RAAS), causing higher angiotensin-II and aldosterone levels, contributing to edema, hyponatremia and hypertension. Malaria-induced anemia is exacerbated by increased hepcidin, which impairs iron absorption, reducing both iron availability for the parasite and red blood cell formation, despite elevated erythropoietin. Hypoglycemia is common due to decreased glucose production and hyperinsulinemia, although some cases show hyperglycemia due to stress hormones and inflammation. Hypocalcemia, and hypophosphatemia are associated with low Vitamin D3 and parathyroid hormone but high calcitonin. Hormones such as DHEA, melatonin, PTH, Vitamin D3, hepcidin, progesterone, and erythropoietin protects against malaria. Furthermore, synthetic analogs, receptor agonists and antagonists or mimics of hormones like DHEA, melatonin, serotonin, PTH, vitamin D3, estrogen, progesterone, angiotensin, and somatostatin are being explored as potential antimalarial treatments or adjunct therapies. Additionally, hormones like leptin and PCT are being studied as probable markers of malaria infection.

Efficacy of anesthetics in an echinoderm based on multifaceted stress biomarkers

Animal care committees remain ambiguous on the need for anesthetics during experimental procedures on invertebrate taxa due to long-standing questioning of their sentience and pain perception. When used, anesthetizing procedures for invertebrates have commonly been adapted from those developed for vertebrates, under the largely unverified assumption that they afford the same benefits. The present study formally tested the efficacy of four common anesthetics of aquatic invertebrates (ethanol, MgCl2, clove oil, MS-222) using behavioural (reaction to physical contact and presence of a predator), physiological (respiration rate), cellular (coelomocytes), and hormonal (cortisol) biomarkers in the holothuroid Cucumaria frondosa (Echinodermata). While subjects recovered from exposures to all anesthetics tested, their responses differed markedly. Ethanol did not immobilize the individuals and concurrently increased their respiration rate, and cellular and hormonal stress markers. MgCl2 and clove oil reduced the behavioural and physiological responses, and decreased the cellular markers, but increased the cortisol levels. Only MS-222 fully immobilized the treated individuals and decreased their respiration rate, both during exposure and throughout ulterior interactions with a predator, while keeping coelomocyte counts and cortisol concentrations at baseline levels. MS-222 thus appears to induce the loss of sensation, representing a promising anesthetic and sedative in soft-bodied aquatic invertebrates.

Ionizing radiation has negligible effects on the age, telomere length and corticosterone levels of Chornobyl tree frogs.

The accident that occurred at the Chornobyl nuclear power plant (Ukraine, 1986) contaminated a large extension of territory after the deposition of radioactive material. It is still under debate whether the chronic exposure to the radiation levels currently present in the area has long-term effects on organisms, such as decreases in longevity. Here, we investigate whether current levels of radiation in Chornobyl negatively impact the age of the Eastern tree frog Hyla orientalis. We also explore whether radiation induces changes in an ageing marker, telomere length or the stress hormone corticosterone. We found no effect of total individual absorbed radiation (including both external and internal exposure) on frog age (n = 197 individuals sampled in 3 consecutive years). We also did not find any relationship between individual absorbed radiation and telomere length, nor between individual absorbed radiation and corticosterone levels. Our results suggest that radiation levels currently experienced by Chornobyl tree frogs may not be high enough to cause severe chronic damage to semi-aquatic vertebrates such as this species. This is the first study addressing age and stress hormones in Chornobyl wildlife, and thus future research will confirm if these results can be extended to other taxa.

Psychological and Biological Stress Pathways as Common Mechanisms Underlying a Psycho-Neurological Symptom Cluster in Cancer Patients: Perceived Stress, Cortisol, and ACTH

ObjectiveThis study aimed to examine (a) whether psychological stress is associated with experiencing multiple psycho-neurological symptoms (depression, cognitive impairment, fatigue, sleep disturbance, and pain) as a cluster and (b) whether stress hormones (adrenocorticotropic hormone [ACTH] and cortisol) are associated with psychological stress and symptom cluster experience. MethodsThis cross-sectional study analyzed data from 133 patients with hematologic cancer awaiting chemotherapy. Enzyme-linked immunosorbent assays analyzed the morning stress hormone levels (ACTH and cortisol). Latent profile analyses identified the group experiencing a psycho-neurological symptom cluster. Factors influencing the experience of the psycho-neurological symptom cluster were included as covariates and analyzed using multinomial logistic regression. ResultsThirty-three percent (n=44) experienced all five psycho-neurological symptoms as a cluster and experienced each symptom in a higher severity than those who did not experience the symptom cluster (ps <.05). Thereby, this group legitimately experienced the psycho-neurological symptom cluster. The major determinant of this group was the perceived psychological stress (OR = 8.05, 95% CI = 3.08; 20.99). Further, each symptom demonstrated a positive association with stress levels (correlation r ranged from 0.22 to 0. 56, all ps < 0.05). Participants with higher stress were more likely to experience the symptom cluster. Stress hormones levels (ACTH and cortisol) were neither associated with the symptom cluster experience nor with psychological stress levels. ConclusionsPsychological stress, rather than biological stress response, is involved in experiencing the psycho-neurological symptom cluster. Managing stress levels would help alleviate this symptom cluster.

Copper sulfate-induced stress in Spinach: Metabolic pathway disruption and plant response

Copper sulfate (CuSO4) stress profoundly affects plant growth by interfering with key metabolic pathways. This disruption leads to significant alterations in various physiological parameters, ultimately impacting the overall health and productivity of the plant. This study assessed the impact of CuSO4 stress on spinach (Spinacia oleracea L.) through a pot experiment using CuSO4 concentrations of 0, 75, 125, and 175 ppm. We noticed that at 75 ppm, CuSO4 improved plant height and the concentration of soluble sugar and ascorbic acid compared to the control. Additionally, amino acid, phenol, proline, fresh weight, and moisture content peaked at 175 ppm. Conversely, at 125 and 175 ppm, plant height, dry weight, leaf area, and concentrations of ascorbic acid and sugar significantly decreased. Moreover, at 175 ppm, there were substantial decreases in chlorophyll a (14.8%), chlorophyll b (73.6%), carotenoids (15%), and photosynthetic rates compared to the control. However, the chlorophyll a to chlorophyll b ratio increased by 29.53% at 175 ppm. In addition, protein and phenol contents diminished at 75 and 125 ppm. Elevated CuSO4 levels increased non-protein thiol levels while reducing the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione peroxidase. Stress hormones such as abscisic acid, jasmonic acid, and ethylene increased with CuSO4 stress, whereas growth hormones indol-acetic acid and gibberellic acid declined. This study demonstrates that spinach shows improved growth and metabolic function at 75 ppm CuSO4, indicating tolerance to mild stress. However, higher CuSO4 concentrations (125 and 175 ppm) significantly reduce growth parameters, chlorophyll content, and enzyme activities, highlighting the need for careful CuSO4 management in agriculture to avoid adverse effects on plant health and productivity.

Sibling presence during fostering ameliorates endocrine stress profile changes in a social rodent species (Octodon degus) in a sex-specific manner

During early life, disruption of the parent-offspring bond can substantially impact development of offspring physiology and behavior. In rodents, it has been well-documented that parental separation, reduction in parental care, and cross-fostering can affect development of the endocrine stress response. For social species, however, several social factors may mitigate the stress of cross-fostering, such as remaining with other known adult caregivers or siblings. In this study, we cross-fostered a social rodent species (Octodon degus) with or without their siblings at postnatal day (PND) 8 and measured their endocrine stress response immediately after fostering (PND9) and at weaning (PND28). We found that female singly-fostered offspring displayed elevated baseline cortisol levels and reduced weight gain immediately after fostering. At weaning, female singly-fostered offspring continued to display elevated baseline cortisol levels compared to non-fostered female offspring, while singly-fostered males demonstrated weaker cortisol negative feedback strength compared to male offspring that were not fostered or were fostered with their siblings. These results suggest that sibling presence may help mitigate the stress of fostering, and that future studies should further examine other social conditions that may help reduce developmental consequences of long-term parental bond disruption.

Unveiling the camelina MBOAT gene family: Phylogenetic insights and regulatory landscape

The membrane-bound O-acyltransferase (MBOAT) gene family comprises enzymes responsible for transferring acyl groups to various lipid molecules. Some members of the MBOAT gene family and their functions have been extensively studied in the model plant Arabidopsis. However, research on the MBOAT gene family in camelina is still limited. In this study, 54 MBOATs were identified on 17 chromosomes and one unidentified scaffold in camelina, including seven newly identified genes. A total of 149 MBOATs were identified in 10 other species. Six subgroups of these MBOATs with different conservation were classified by phylogenetic analysis, showing diversification between monocots and dicots. Detailed analysis of the motif composition, evolutionary relationships, and gene structures of CsaMBOATs are presented. The results of the syntenic analysis suggest that the evolution of CsaMBOAT gene family is primarily driven by segmental and tandem duplications, and that there is a stronger collinearity within dicots. In addition, analysis of CsaMBOAT gene promoter cis-elements reveals a possible transcriptional regulation and tissue-specific expression, highlighting potential role in plant stress responses and hormone signaling. Furthermore, both the transcriptome and RT-qPCR data revealed the changes in the expression levels of DGAT1 during salt stress treatment. Subsequent analyses indicated that DGAT1 influenced the ratio of fatty acid fractions in the plants. Importantly, a large number of transcription factors involved in the regulation of CsaMBOAT gene expression were identified by WGCNA analysis, and the transcriptional data confirmed that the NAC032 and CAMMTA6 genes play a role upstream of DGAT1. This study not only identified the members of the MBOAT in camelina, but also provided insights and clues into its regulatory mechanisms.

Emerging roles of auxin in plant abiotic stress tolerance.

Plants are continuously attacked by several biotic and abiotic factors. Among abiotic factors, heat, cold, drought, and salinity are common stresses. Plants produce several hormones as their main weapon in fightback against these stresses. Among these hormones, the role of auxin is well established in regulating plant growth and development at various scales. However, in recent literature, the important role of auxin in abiotic stress tolerance has emerged. Several auxin signalling and transport mutants exhibit heat, drought, and salinity-related phenotypes. Among them, auxin-mediated hypocotyl elongation and root growth in response to increased heat are of importance due to the continuous rise in global temperature. Auxin is also involved in regulating and recruiting specialized metabolites like aliphatic glucosinolate to defend themselves from drought stress. Aliphatic glucosinolate (A-GLS) regulates guard cell closure using auxin, which is independent of the major abiotic stress hormone abscisic acid. This regulatory mechanism serves as an additional layer of guard cell movement to protect plants from drought. Transferring the aliphatic glucosinolate pathway into non-brassica plants such as rice and soybean holds the promise to improve drought tolerance. In addition to these, post-translational modification of auxin signalling components and redistribution of auxin efflux transporters are also playing important roles in drought and salt tolerance and, hence, may be exploited to breed drought-tolerant crops. Also, reactive oxygen species, along with peptide hormone and auxin signalling, are important in root growth under stress. In conclusion, we summarize recent discoveries that suggest auxin is involved in various abiotic stresses.

Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction

The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS.

Characterization of Cytoskeletal Profilin Genes in Plasticity Elongation of Mesocotyl and Coleoptile of Maize Under Diverse Abiotic Stresses

The plasticity elongation of mesocotyl (MES) and coleoptile (COL) largely determines the morphology of maize seedlings under abiotic stresses. The profilin (PRF) proteins play a pivotal role in cytoskeleton dynamics and plant development via regulating actin polymerization. However, little is known about whether and how the expression of the ZmPRF gene family regulates MES and COL elongation in maize under adverse abiotic stresses. Here, a total of eight ZmPRF gene members were identified in the maize genome. They were mainly located in the cytoplasm, chloroplast, and mitochondrion, and clearly divided into four classes, based on phylogenetic analysis. Segmental duplication was the main driver for the expansion of ZmPRF genes. Ka/Ks analysis indicated that most ZmPRF genes were intensely purified and selected. Promoter cis-element analysis suggested their potential roles in response to growth and development, stress adaption, hormone response, and light response. The protein–protein interaction network and two independent RNA-sequencing analyses revealed that eight ZmPRF genes and their thirty-seven interacting genes showed varied expression patterns in MES and COL of three maize genotypes under different sowing depths, 24-epibrassinolide application, and light spectral-quality treatments, of which ZmPRF3.3 was a potential core conserved gene for breeding application. Moreover, the quantitative real-time PCR (qRT-PCR) verified that the relative expression levels of most ZmPRF genes in MES and COL under above treatments were significantly correlated with the plasticity elongation of MES and COL in maize. Therefore, these results perform a comprehensive overview of the ZmPRF family and will provide valuable information for the validation of the function of ZmPRF genes in maize development under diverse abiotic stress.

Ethanol-activated microglial exosomes induce MCP1 signaling mediated death of stress-regulatory proopiomelanocortin neurons in the developing hypothalamus

BackgroundMicroglia, a type of resident immune cells within the central nervous system, have been implicated in ethanol-activated neuronal death of the stress regulatory proopiomelanocortin (POMC) neuron-producing β-endorphin peptides in the hypothalamus in a postnatal rat model of fetal alcohol spectrum disorders. We determined if microglial extracellular vesicles (exosomes) are involved in the ethanol-induced neuronal death of the β-endorphin neuron via secreting elevated levels of the chemokine monocyte chemoattractant protein 1 (MCP1), a key regulator of neuroinflammation.MethodsWe employed an in vitro model, consisting of primary culture of hypothalamic microglia prepared from postnatal day 2 (PND2) rat hypothalami and treated with or without 50 mM ethanol for 24 h, and an in vivo animal model in which microglia were obtained from hypothalami of PND6 rats fed daily with 2.5 mg/kg ethanol or control milk formula for five days prior to use. Exosomes were extracted and characterized with nanosight tracking analysis (NTA), transmission electron microscopy and western blot. Chemokine multiplex immunoassay and ELISA were used for quantitative estimation of MCP1 level. Neurotoxic ability of exosome was tested using primary cultures of β-endorphin neurons and employing nucleosome assay and immunocytochemistry. Elevated plus maze, open field and restraint tests were used to assess anxiety-related behaviors.ResultsEthanol elevated MCP1 levels in microglial exosomes both in vitro and in vivo models. Ethanol-activated microglial exosomes when introduced into primary cultures of β-endorphin neurons, increased cellular levels of MCP1 and the chemokine receptor CCR2 related signaling molecules including inflammatory cytokines and apoptotic genes as well as apoptotic death of β-endorphin neurons. These effects of microglial exosomes on β-endorphin neurons were suppressed by a CCR2 antagonist RS504393. Furthermore, RS504393 when injected in postnatal rats prior to feeding with ethanol it reduced alcohol-induced β-endorphin neuronal death in the hypothalamus. RS504393 also suppressed corticosterone response to stress and anxiety-like behaviors in postnatally alcohol-fed rats during adult period.ConclusionThese data suggest that alcohol exposures during the developmental period elevates MCP1 levels in microglial exosomes that promote MCP1/CCR2 signaling to increase the apoptosis of β-endorphin neurons and resulting in hormonal and behavioral stress responses.