Search Results (779)

The autonomic nervous system (ANS) regulates internal organ function to maintain homeostasis. Dysautonomias are ANS disorders involving reduced or excessive sympathetic or parasympathetic activity and can be associated with metabolic syndrome and eating disorders such as binge eating disorder (BED). The ANS exhibits synaptic plasticity phenomena, including long-term potentiation (LTP) and neurotransmitter expression changes, which may influence autonomic function. BED is defined as recurrent, compulsive intake of large amounts of high-calorie food in a short time. Here, we examined dysautonomia in a rat BED model induced by cycles of food restriction and access to highly caloric food, and assessed whether exercise prevents these alterations. After confirming BED induction, we characterized LTP in the superior cervical ganglion (SCG) and analyzed acetylcholine (ACh) and GABA expression and their co-localization/segregation. BED rats exhibited impaired LTP and increased GABA expression. Voluntary aerobic exercise prevented BED onset and the associated changes in LTP and GABA. We propose that BED-associated dysautonomia proceeds at least in the ganglionic sympathetic cholinergic transmission, with reduced sympathetic activity. These results may contribute to a better understanding of the autonomic disorder associated with BED and support exercise as a protective intervention. Full article

The blood–brain barrier (BBB) restricts the entry of therapeutic agents into the brain cardiovascular regulatory region, potentially contributing to drug-resistant hypertension. Objective: The objective of this study was to overcome this limitation by modifying PEGylated liposomes with transferrin (Tf) to facilitate Tf receptor binding at the BBB and penetratin (Pen), a cell-penetrating peptide, to enhance neuronal uptake. Methods: This study evaluated the efficacy of Tf-Pen-liposomes in delivering angiotensin-converting enzyme 2 (ACE2) or EGFP (control) genes across the BBB in rats. In addition, the therapeutic effect of intravenous administration of Tf-Pen-Lip carrying plasmid DNA encoding ACE2 (Tf-Pen-Lip-pACE2) was tested in a neurogenic hypertension model induced by intracerebroventricular (ICV) infusion of angiotensin II (Ang II) via osmotic pump implantation and brain cannulation. Results: Conjugation with Tf and Pen significantly enhanced liposome-mediated gene transfection in cultured cells and increased transport across an in vitro BBB model. In vivo, intravenous administration of Tf-Pen-Lip-pACE2 or Tf-Pen-Lip-pGFP successfully elevated ACE2 or EGFP expression, respectively, in the hypothalamic paraventricular nucleus (PVN). Chronic ICV infusion of Ang II produced a sustained increase in blood pressure and heart rate, accompanied by sympathetic overactivation and elevated arginine vasopressin (AVP) secretion, hallmarks of neurogenic hypertension. Notably, intravenous Tf-Pen-Lip-pACE2 treatment dramatically attenuated Ang II–induced neurogenic hypertension, whereas Tf-Pen-Lip-pGFP had no effect on pressor responses, sympathetic activity, or AVP secretion. Conclusions: This dual-functionalized liposomal delivery system effectively transported the ACE2 gene across the BBB into the brain, increased ACE2 expression, and markedly attenuated neurogenic hypertension following systemic administration. Full article

Background/Objectives: This study aimed to objectively assess fatigue levels using facial expressions. Methods: This study included 25 female nurses aged between 30 and 50 years. We compared their subjective and objective fatigue levels after a night shift, when accumulated fatigue was assumed, with those after a day off, when recovery was expected. Fatigue levels were subjectively assessed using questionnaires and were also quantified by the Visual Analog Scale (VAS). Objective evaluations included (1) the degree of eye-opening, (2) the maximum distance and speed of facial skin movement by tracking changes in coordinate values of facial markers on the skin during intentional smiling, and (3) analysis of high-frequency (HF) components and the low frequency-to-high frequency (LF/HF) ratio in heart rate variability (HRV). Results: After a night shift, compared to after a day off, subjective assessments of mental and physical fatigue in the questionnaires and VAS values of own fatigue were significantly elevated. Concurrently, objective evaluations revealed that the degree of eye-opening, along with the maximum movement distance and speed of the lower eyelid, cheek, and mouth corners during intentional smiling, were significantly reduced. Furthermore, the HF component, an index of parasympathetic activity, significantly decreased, whereas the LF/HF ratio, an index of sympathetic activity, significantly increased. Additionally, significant correlations were observed between subjective VAS estimation of fatigue levels and each objective parameter examined. Conclusions: Measuring facial parameters is an effective method for objectively assessing facial expressions of fatigue, and these changes are mediated through reduced parasympathetic nervous activity and increased sympathetic nervous activity during fatigue. Full article

Background: Optimizing training load and recovery is crucial for achieving peak performance in competitive wrestling, a sport characterized by high physical, technical, and psychological demands. Methods: This study compared the effects of two different training programs—one emphasizing high-intensity interval training (HIIT) sessions and the other based on traditional volume-oriented training—on both competitive performance and autonomic regulation measured by heart rate variability (HRV). A total of 24 elite wrestlers were divided into two equal groups, each following a different weekly training regimen over a 3-month period. HRV was recorded using a wearable 3-channel ECG Holter before training, immediately after training, and during recovery phases (up to 2 h post-exercise). HRV parameters were analyzed to assess training-induced stress and recovery status. Competitive performance was evaluated using official national championship scores and ranking positions. Results: Both training programs improved competitive performance, the HIIT-based regimen induced greater short-term suppression of parasympathetic activity (RMSSD: −32% vs. −14%; HF power: −40% vs. −18%) and increased sympathetic dominance (LF/HF: +56% vs. +22%) after training. Wrestlers in the HIIT group achieved a mean competition score of 17.92 ± 4.50 points, compared to 15.08 ± 6.26 points in the volume-oriented group. These acute autonomic shifts may provide a higher readiness for intense and explosive actions, which is advantageous in short and dynamic matches. In contrast, the volume-oriented program induced smaller acute autonomic changes but showed a slower recovery to baseline. Conclusions: These findings suggest that HRV-derived measures can serve as sensitive indicators of training load tolerance, recovery capacity, and stress susceptibility in combat sports athletes. This study highlights the value of integrating HRV monitoring into the periodization of combat training to individualize the load, prevent overtraining, and optimize performance outcomes. Full article

Bone immunity represents a dynamic interface where skeletal homeostasis intersects with systemic immune regulation. We synthesize emerging paradigms by contrasting two functionally distinct microenvironments: the marrow cavity, a hematopoietic and immune cell reservoir, and cancellous bone, a metabolically active hub orchestrating osteoimmune interactions. The marrow cavity not only generates innate and adaptive immune cells but also preserves long-term immune memory through stromal-derived chemokines and survival factors, while cancellous bone regulates bone remodeling via macrophage-osteoclast crosstalk and cytokine gradients. Breakthroughs in lymphatic vasculature identification challenge traditional views, revealing cortical and lymphatic networks in cancellous bone that mediate immune surveillance and pathological processes such as cancer metastasis. Central to bone immunity is the neuro–immune–endocrine axis, where sympathetic and parasympathetic signaling bidirectionally modulate osteoclastogenesis and macrophage polarization. Gut microbiota-derived metabolites, including short-chain fatty acids and polyamines, reshape bone immunity through epigenetic and receptor-mediated pathways, bridging systemic metabolism with local immune responses. In disease contexts, dysregulated immune dynamics drive osteoporosis via RANKL/IL-17 hyperactivity and promote leukemic evasion through microenvironmental immunosuppression. We further propose the “brain–gut–bone axis” as a systemic regulatory framework, wherein vagus nerve-mediated gut signaling enhances osteogenic pathways, while leptin and adipokine circuits link marrow adiposity to inflammatory bone loss. These insights redefine bone as a multidimensional immunometabolic organ, integrating neural, endocrine, and microbial inputs to maintain homeostasis. By elucidating the mechanisms of immune-driven bone pathologies, this work highlights therapeutic opportunities through biomaterial-mediated immunomodulation and microbiota-targeted interventions, paving the way for next-generation treatments in osteoimmune disorders. Full article

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Wound healing is impaired under diabetic conditions due to reduced angiogenesis, thereby increasing the risk of wound-healing complications. Studies have shown that inhibition of α- and β-adrenoceptors delays wound healing. This study investigates the effects of topical salbutamol (TS) on STZ-induced diabetic wound healing in rats. The rats were divided into two initial groups: non-diabetic and diabetic. Diabetes mellitus was induced in the second group with STZ (65 mg/kg). Excision wounds were inflicted on the dorsal thoracic region, 1–1.5 cm away from the vertebral column on either side, following anesthesia on all groups. Group 2 was subdivided into untreated diabetic wounds, low-dose-TS-treated diabetic wounds (6.25 mg/mL), medium-dose-TS-treated diabetic wounds (12.5 mg/mL), and high-dose-TS-treated diabetic wounds (25 mg/mL), and were monitored for 14 days. Percentage wound contraction and the time required for complete wound closure were observed and recorded. In addition, oxidative stress and inflammatory markers such as NO, CRP, MPO, TGF-β1, TNF-α, IL-6, IL-1β, NO, and hexosamine were estimated in wound exudates and tissue over 14 days. TS treatment resulted in 100% wound contraction in all treated wounds within 14 days compared to untreated non-diabetic and diabetic wounds. Increased NO, TGF-β1, and hexosamine activity was observed in TS-treated wounds when compared to untreated diabetic wounds. In addition, TS treatment decreased the activity of IL-1β, TNF-α, IL-6, CRP, and MPO, all of which were elevated in the untreated diabetic wounds. The current study shows that the application of TS significantly improved diabetic wound contraction and aided the healing process. Angiogenic markers, such as TGF-β1 and NO, were prominently increased, supporting the role of sympathetic nerve stimulation in angiogenesis. Full article

Heart failure (HF) remains a leading cause of morbidity and mortality globally, with increasing prevalence driven by aging populations and comorbidities such as diabetes mellitus. Recent advances have highlighted sodium-glucose cotransporter-2 (SGLT2) inhibitors, particularly empagliflozin and dapagliflozin, as effective agents in HF management across a broad spectrum of ejection fractions. Initially developed for glycemic control in type 2 diabetes, both drugs have demonstrated significant cardiovascular benefits, including reductions in HF hospitalizations and improvements in symptoms and quality of life. Their mechanisms extend beyond glucose lowering, involving natriuresis, osmotic diuresis, improved myocardial energetics, reduced sympathetic activation, and anti-inflammatory effects. While empagliflozin and dapagliflozin share a core renal mechanism via selective SGLT2 inhibition, subtle differences in pharmacokinetics, potency, and tissue selectivity may influence their clinical profiles. Emerging evidence suggests empagliflozin may confer stronger benefits in heart failure with reduced ejection fraction (HFrEF), while dapagliflozin could offer enhanced efficacy in heart failure with preserved ejection franction (HFpEF), although head-to-head comparisons are lacking. This review synthesizes current evidence comparing the mechanisms of action and clinical performance of empagliflozin and dapagliflozin in HF, providing insight into agent selection and future directions in therapy personalization. Full article

Heart failure (HF) is a growing public health concern, driven by the increasing prevalence of obesity, diabetes, and aging. Despite therapeutic advances, HF continues to be associated with high morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for glycemic control in type 2 diabetes, have demonstrated cardiovascular benefits in clinical trials. Recent studies, including STEP-HFpEF and SUMMIT, have shown improvement in symptoms and weight loss in patients with HF with preserved ejection fraction (HFpEF). GLP-1 RAs are involved in multiple biological pathways relevant to heart failure pathophysiology. These include pathways related to sympathetic nervous system activity, inflammatory cytokine signaling, oxidative stress, calcium handling, natriuretic peptide signaling, and cardiac metabolism. GLP-1 receptor agonists modulate vascular pathways involving nitric oxide signaling, endothelial function, and renal sodium handling, contributing to improved hemodynamics and neurohormonal balance. Together, these actions intersect with key neurohormonal and cellular processes contributing to chronic heart failure progression. This review explores the mechanistic overlap between GLP-1 receptor signaling and heart failure pathophysiology. This mechanistic overlap suggests a plausible role for these agents as adjunctive treatments in heart failure, especially in metabolically driven phenotypes. While direct cardiac effects remain incompletely defined, systemic metabolic and anti-inflammatory actions provide a mechanistic basis for observed clinical benefits. Full article

Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. Although grape seed extract (GSE) supplementation has been shown to increase nitric oxide production and modify sympathetic output, there is limited evidence on its potential beneficial effects on PHRR. We investigated the effect of GSE supplementation on PHRR during sympathetic overactivation induced by muscle metaboreflex activation (MMA) in young individuals. Participants were randomly assigned, via a double-blind, cross-over design, to either receive GSE (300 mg, two capsules) or PL (300 mg, two capsules), with a washout period of at least 72 h. between trials. A submaximal exercise test was performed using a cycle ergometer combined with an isometric handgrip exercise using a handgrip dynamometer and blood flow occlusion by placing a cuff over the brachial artery of the dominant arm. PHRR was measured at 5 s. intervals throughout the experiment. The PHRR was evaluated between GSE and PL at every min. for 300 s. PHRR kinetics significantly improved following GSE supplementation (74.3 ± 7.5 s) compared with the PL condition (86.2 ± 10.4 s). Our results suggest that GSE is effective in improving HRR kinetics during heightened sympathetic activity induced by MMA in young individuals (p = 0.034; ES = 0.4). Thus, regular treatment with GSE may provide a nonpharmacological intervention to reduce sympathetic hyperactivity in conditions where excessive sympathetic activity is consistently present. Full article

Background: As we age, our autonomic function declines, resulting in altered autonomic balance during postural transitions. These changes can affect the dynamic interplay between sympathetic and parasympathetic modulation, compromising short-term compensatory responses to active standing. Objectives: This study aimed to compare heart rate variability (HRV) at baseline, cardiac parasympathetic modulation (CPM), and cardiac baroreflex gain (CRG) between younger adults (YA) and older adults (OA) following active standing orthostatic stress. A secondary objective was to analyze the incidence of orthostatic intolerance (OI) symptoms. Methods: Participants (n = 76) completed sit-to-stand and lie-to-stand maneuvers with continuous beat-to-beat blood pressure and heart rate (HR, electrocardiogram). HRV at baseline was analyzed in both time and frequency domains. CPM was measured by the HR 30:15 ratio on standing. CBG was determined as the ratio of HR and SBP changes (ΔHR/ΔSBP) at specific phase time points (30 s, 60 s, 180 s, and 420 s). Results: At baseline, OA showed reduced Standard Deviation of RR intervals (SDRR), Root Mean Square of Successive Differences (RMSSD), low-frequency (LF), and high-frequency (HF) power, and elevated LF/HF ratio (all p < 0.05), indicating a shift toward sympathetic dominance. During active standing orthostatic stress, OA demonstrated a lower HR30:15 ratio and CBG in later phases (phases 2–4) (all p < 0.05). Also, OA reported more symptoms (14%) of OI than YA (0%) (p = 0.041). Conclusions: These findings indicate that older adults have impaired autonomic function characterized by reduced HRV, CPM and CBG responses. These impairments lead to diminished autonomic regulation under active-standing orthostatic stress and a higher incidence of OI symptoms. Full article

Chronic stress disrupts neuroimmune homeostasis and initiates CNS inflammation. This paper examines the molecular and cellular mechanisms that connect stress to the interplay among the nervous, endocrine, and immune systems, with a focus on the role of the NLRP3 inflammasome in neuroinflammatory processes. It discusses the dynamics of HPA axis, stress-induced changes in glucocorticoid and mineralocorticoid signaling, sympathetic nervous system activation, and the contribution of pro-inflammatory cytokines in brain immune activation. The NLRP3 inflammasome is described in terms of its structure, activation via a two-signal model, and its role in IL-1β and IL-18 maturation in neurons, microglia, and astrocytes. Preclinical evidence highlights the therapeutic potential of targeting NLRP3 in stress-related disorders, underscoring its key role in their pathophysiology. Full article

Recent clinical studies and scientific literature increasingly support the use of essential oils (EOs) as adjuncts in enhancing sports performance and recovery. They have demonstrated potential in modulating mood, alleviating fatigue, facilitating muscle recovery, and contributing to the overall physiological and psychological well-being of athletes. Specifically, EOs such as peppermint and eucalyptus exhibit analgesic and anti-inflammatory properties, making them beneficial for managing exercise-induced muscle soreness and discomfort. Conversely, oils like lavender are recognized for their anxiolytic and sedative effects, which may improve sleep quality and promote relaxation. But both are essential for effective post-exercise recovery. As such, their strategic application may represent a valuable, complementary approach within the broader context of sports medicine and athletic training. Although EOs have been used for centuries in traditional medicine of various cultures to support physical performance, scientific research in the field of sports medicine remains still limited. Preliminary findings suggest promising effects on fatigue reduction, sleep, sympathetic activity, and endurance improvement. However, results are inconsistent, with some studies even showing no significant differences compared to placebo. Further rigorous research is needed to establish the efficacy and mechanisms of EOs in athletic settings. Full article

The bone and brain, though distinct in structure and function, share remarkable physical, molecular, and developmental similarities. Emerging evidence reveals dynamic bidirectional crosstalk between these systems mediated by hormones, cytokines, extracellular vesicles (EVs), and neural signals. Bone-derived factors such as osteocalcin (OCN), lipocalin-2, and fibroblast growth factor (FGF) 23 influence cognitive functions, mood, and neurogenesis, while brain- and nerve-derived mediators, including leptin, serotonin, and sympathetic signals, modulate bone remodeling. Inflammation and aging disrupt this communication, contributing to cognitive decline, osteoporosis, and other age-related disorders. Stem cells and EVs have also been implicated as mediators in this axis, offering insights into regenerative strategies. Molecular signaling pathways and transcriptional regulators, such as Wnt/β-catenin, leptin, receptor activator of nuclear factor kappa-B ligand (RANKL), sclerostin (SOST), and nuclear factor kappa-B (NF-κB), play critical roles in maintaining bone–brain homeostasis. Additionally, shared biomarkers and pathological links between neurodegeneration and bone loss suggest new diagnostic and therapeutic opportunities. Studies support this inter-organ communication, yet further mechanistic and translational research is needed. This review highlights the molecular basis of bone–brain crosstalk, emphasizing inflammation, aging, and regulatory pathways, with a focus on future directions in biomarker discovery and therapeutic targeting. Understanding this crosstalk may help in early diagnosis and dual-targeted interventions for both bone and brain disorders. Full article

Neonatal rodent cardiomyocytes (CMs) are a mainstay of in vitro cardiac research, yet their immature phenotype limits the study of key physiological processes such as excitation–contraction coupling (ECC) and sympathetic modulation. Here, we present a defined low-glucose, serum-free (LGSF) culture protocol that drives the structural and functional maturation of neonatal CMs and supports their integration into functional neuro-cardiac co-cultures. After 15 days in LGSF conditions, CMs exhibit elongated morphology, organized sarcomeres, polarized connexin-43, mitochondrial redistribution, and sarcoplasmic reticulum (SR) development, all closely resembling features of adult cells. These structural hallmarks were paralleled by enhanced Ca²⁺ handling, with increased SR contribution and reduced spontaneous activity, indicative of a mature ECC phenotype. When co-cultured with sympathetic neurons (SN), CMs established anatomically distinct neuro-cardiac junctions. Notably, nicotine stimulation triggered spatially restricted, reversible increases in CM Ca²⁺ transients, confined to varicosity-contacted cells. Pharmacological analysis revealed subtype-specific roles for β₁- and β₂-adrenergic receptors, and uncovered evidence of functional crosstalk between them. Our study defines a reproducible culture framework that advances CM maturation and enables the high-resolution interrogation of synaptic-like sympathetic modulation. This approach opens new avenues for mechanistic studies and drug testing in developmentally relevant neuro-cardiac systems. Full article