The imbalance in the dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratio contributes to chronic low-grade inflammation, a key pathological basis for degenerative musculoskeletal conditions such as osteoporosis and osteoarthritis. While individual reviews have explored aspects of ω-3 PUFAs in bone or muscle, a comprehensive narrative review integrating their multidimensional mechanisms with translational evidence across orthopedics and sports medicine is less common. This review consolidates evidence from fundamental science, clinical trials, and translational research, employing an interdisciplinary approach to systematically elucidate their mechanisms and application values. ω-3 PUFAs exert multi-layered anti-inflammatory and pro-repair effects through mechanisms including cell membrane remodeling, reprogramming of lipid mediator profiles (promoting the generation of specialized pro-resolving mediators), and inhibition of key pathways such as NF-κB and the NLRP3 inflammasome. Clinical studies indicate that ω-3 PUFA supplementation can improve bone metabolic markers, alleviate pain in osteoarthritis, and reduce inflammation and muscle loss in the perioperative period. In sports medicine, ω-3 PUFAs enhance muscle anabolic metabolism, optimize energy utilization, promote recovery, and demonstrate neuroprotective potential. Their extended application value lies in regulating the "bone-muscle axis," providing targeted nutritional support for athletes, and serving as a nutritional countermeasure in extreme environment medicine. Statement of Significance: This review constructs an integrative framework linking molecular mechanisms to clinical translation, positioning ω-3 PUFAs as key physiological modulators for musculoskeletal health and delineating future directions for precision nutrition-based intervention strategies.
Self-assembled herbal bioactive materials (SAHBMs) represent a rapidly advancing frontier integrating phytochemistry, supramolecular chemistry, and biomedical engineering. By leveraging the intrinsic pharmacological activity and self-organization of herbal compounds, SAHBMs offer improved solubility, stability, and therapeutic efficacy. Despite growing interest, existing studies remain largely narrative and subjective. This study employs bibliometric mapping to provide a systematic, data-driven overview of the field. Publications related to SAHBMs (2000 to June 2025) were retrieved from the Web of Science Core Collection, yielding 1085 records. Analyses were conducted using VOSviewer, CiteSpace, Pajek, SCImago Graphica, and R-based visualizations to assess publication dynamics, institutional and national contributions, collaboration and citation networks, journal dissemination, keyword evolution, and disease associations. Annual publications increased markedly over time, with China contributing 57.1% of outputs, while France and Germany achieved higher citation impact. Collaboration networks highlighted active China-United States partnerships. Core institutions included the Chinese Academy of Sciences and China Agricultural University, while prolific authors such as Wang Penglong and Huang Xuemei shaped research trajectories. Thematic clustering revealed dual disciplinary cores in nanoscience/materials and pharmacology/medicine. Co-cited works emphasized antibacterial, anti-inflammatory, and oncological applications. Keyword bursts such as "wound healing", "drug delivery system", and "regenerative medicine" highlighted evolving thematic emphases and application-oriented research attention. This first bibliometric analysis of SAHBMs delineates global trajectories, intellectual anchors, and emerging frontiers. Challenges remain in stability, biokinetics, and the generation of evidence needed for further preclinical development. Future progress will depend on artificial intelligence-assisted molecular design, advanced preclinical modeling, and strengthened global collaboration. Bibliometric trends suggest that SAHBMs is evolving as a nanomaterials-oriented research field, with increasing attention to self-assembled nanostructures, self-assembly mechanisms, and functional biomedical applications such as carrier-free drug delivery and regenerative medicine.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multisystemic disorder characterized by severe, persistent fatigue not alleviated by rest and worsened by minimal exertion, often accompanied by post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and autonomic disturbances. Despite decades of research, its pathophysiology remains incompletely understood, and skeletal muscle involvement has only recently gained attention. This review aims to provide a historical and pathophysiological synthesis of ME/CFS, emphasizing the pivotal role of skeletal muscle in the onset and persistence of symptoms, and to integrate molecular, cellular, and pathophysiological evidence into a coherent explanatory framework. This is a narrative review of published literature (1990-2025) with critical integration of clinical, biochemical, and experimental data on oxidative stress, mitochondrial dysfunction, Excitation-Contraction (E-C coupling) dysregulation, and muscle secretome alterations in ME/CFS also in relation to post-viral syndromes (e.g., Long COVID). Evidence consistently points to mitochondrial oxidative stress, redox imbalance, impaired Ca2+ handling, and altered signaling pathways in skeletal muscle of patients with ME/CFS. Historical milestones show an evolution from psychogenic interpretations toward recognition of ME/CFS as a biological disorder with neuromuscular and metabolic underpinnings. ME/CFS can be interpreted as a skeletal muscle-metabolic disorder characterized by oxidative distress, mitochondrial dysfunction, and impaired energy regulation, leading to the clinical picture of exercise intolerance and post-exertional malaise. Integrating basic and clinical research through a translational approach provides the foundation for new diagnostic tools, targeted therapies, and biomarkers.
The mechanical environments endured by the human body profoundly influence life activities across different scales, from single molecules to complicated systems. Gaining insight into the mechanical factors and their biological implications is crucial for deciphering physiological and pathological processes and advancing innovations in drug development and therapeutic approaches for various diseases. Recently, we have witnessed rapid advances in biomechanics and mechanobiology, which, however, are not fully recognized by the clinical community and effectively integrated into medical decision-making, highlighting a translational gap between mechano-based discovery and therapeutic application. Here, we first provide a comprehensive review of research progress in biomechanics and mechanobiology, focusing on key areas such as the cardiovascular system, bone and joints, ocular tissues, liver, lung, the craniomandibular system, cancer, and immunology. We demonstrate how mechanical cues drive health and disease across biological levels, offering insights into complex physiological and pathological mechanisms. Further, we explore the diverse applications of biomechanics and mechanobiology in disease diagnosis, treatment, and rehabilitation. Mechanical insights fuel medical innovations through advanced diagnostic tools, novel therapies, and effective rehabilitation protocols, enhancing clinical outcomes. Looking ahead, we outline future directions of biomechanics and mechanobiology, emphasizing interdisciplinary integration, artificial intelligence, model development, and extreme environments, which hold the promise to deepen scientific understanding and propel technological innovations. This review highlights the transformative potential of biomechanics and mechanobiology in driving scientific and clinical advancements and helps bridge the long-standing gap between biomechanical research and clinical practice.
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Current guidelines discourage sports participation for athletes with arrhythmogenic cardiomyopathy (ACM). However, the evidence that exercise is a disease-accelerator is most compelling for PKP2-mediated ACM. This study aims to examine management, return-to-play (RTP) decisions, outcomes, and phenotype evolution among athletes with genotype-positive ACM. A retrospective review of electronic medical record of 1,229 patients in our Arrhythmogenic/Dilated Cardiomyopathy Registry was used to identify self-identified athletes. They were evaluated, risk stratified, and treated at Mayo Clinic Windland Smith Rice Genetic Heart Rhythm Clinic between July 2000 and February 2025. A total of 138 genotype-positive athletes with ACM were identified (58 women [42%], mean age of 31 ± 19 years, plakophilin [PKP2]-ACM [n = 61; 44%], desmoplakin [DSP]-ACM [n = 32; 23%]). After diagnosis of ACM, 34 athletes (25%) experienced at least 1 breakthrough cardiac event (BCE), accounting for a total of 68 events, and 6 patients experienced 14 BCEs following physician-approved RTP. During a median follow-up of 25 months (IQR: 6-71), the overall event rate for the entire cohort was 7.9 BCEs per 100 patient-years (95 % CI: 5.8-10.5), and the event rate after physician-approved RTP was 14.6 per 100 patient-years (95% CI: 7.8-24.9). During RTP period, one-half of these BCEs occurred during sports participation, whereas the remainder occurred at rest or unknown context. This is the first single-center cohort of patients with ACM being empowered to RTP and remain athletes. These athletes have exhibited higher rates of BCEs and disease conversion/progression than our athletes with a variety of other genetic heart diseases. Further studies are needed to determine how to further guide safe sports participation in genetically mediated ACM.
Comprehensive bibliometric analysis of magnetic resonance imaging applications in multiple sclerosis research remains scarce despite exponential growth. This study maps 25-year global MS-MRI trends (2000-2024) to identify transformative shifts. We analyzed 8,038 publications from the Web of Science Core Collection using VOSviewer, Bibliometrix, and CiteSpace. Machine learning clustering quantified collaboration networks, while dual-map overlays and burst detection quantified interdisciplinary bridges and paradigm shifts. Publication growth showed three phases: steady (2005-2011, +6.2%/year), accelerated (2011-2021, peak 480 publications), and stabilization (2022-2024), with recent decline linked to diagnostic criteria simplification and artificial intelligence-driven consolidation. The USA dominated total output (24.2%), while the UK led international collaboration (44.2% multi-country publications). China's unique focus on psychoneuroimmunology contrasts with Western clinical-translational priorities. The strongest interdisciplinary link connected Neurology/Sports/Ophthalmology and Molecular/Biology/Genetics fields (Z-score = 5.3). Artificial intelligence drove paradigm shifts, with deep learning showing the highest keyword burst strength (413.27). Central authors (e.g., Massimo Filippi, Frederik Barkhof) bridged magnetic resonance imaging biomarkers and therapeutic innovation. MS-MRI research is evolving from descriptive observations to AI-driven precision medicine. Future success relies on a closed-loop paradigm integrating ultra-high-field MRI and multi-omics. This analysis reveals: (1) Magnetic resonance imaging-artificial intelligence-biomarker integration resolves clinical-radiological paradoxes, enabling dynamic patient stratification; (2) ultra-high-field magnetic resonance imaging and multi-omics provide a roadmap for precision neurology in therapy personalization; (3) global collaboration synergies may democratize advanced multiple sclerosis care.
Tumour necrosis factor-α (TNF-α) is a central pro-inflammatory cytokine whose biogenesis, secretion, and signalling are tightly interconnected with cellular protein-quality control systems. Current evidence shows that TNF-α maturation, co-translational and post-modifications, ER-luminal folding and trimerisation, Golgi trafficking, and ectodomain shedding by ADAM17 are constrained by ER chaperones and ER-associated degradation (ERAD). Furthermore, TNF-α signalling reciprocally interfaces with the proteostasis network (PN) largely through inflammatory stress pathways such as NF-κB-dependent transcriptional control of chaperones, ubiquitin-proteasome components, and autophagy regulators. However, dysregulation of this bidirectional crosstalk mechanistically contributes to disease, including chronic inflammatory disorders, cancer, and degenerative diseases. In this study we provide a synthesis of the current literature on pathways related to protein homeostasis control that determines whether TNF-α exposure is adaptive or proteotoxic. We also discuss the translational implications this could have by including rational combinations of TNF-α targeted blockers with PN modulators (chemical chaperones, proteasome or autophagy modulators), which reduce the proteotoxic burden. Therefore, understanding the crosstalk between TNF-α signalling and components of the PN system promises new mechanistic insights and translational targets for TNF-α-driven diseases.
Sarcopenia and osteoarthritis are two common musculoskeletal disorders that often coexist, posing significant challenges in clinical management. These conditions share underlying mechanisms such as chronic inflammation, metabolic dysfunction, and biomechanical stress, which accelerate musculoskeletal degeneration. Sarcopenia, characterized by muscle loss and weakness, and osteoarthritis, marked by cartilage degradation and joint dysfunction, frequently overlap, leading to increased disability and reduced quality of life. The presence of both conditions creates a detrimental cycle where muscle weakness exacerbates joint pain, and joint dysfunction further weakens muscles. This comorbidity complicates treatment, requiring integrated strategies that address both muscle and joint pathology. Advances in personalized therapies, driven by multi-omics technologies, are crucial in targeting these interconnected conditions more effectively. Precision medicine, using genetic, metabolic, and physiological data, can help tailor treatments and improve patient outcomes. Furthermore, the integration of adaptive interventions, digital twin models, and real-time feedback systems will play key roles in refining individualized treatment plans. Multi-omics integration and real-world evidence are also transforming how clinical trials are designed and how we assess disease progression, moving away from structural markers to functional and patient-centered outcomes. Effective interventions must involve early detection, personalized approaches, and interdisciplinary care, aiming to break the cycle of degeneration and improve patients' functional independence and quality of life. This review identifies the biomechanical, metabolic, and epigenetic "vicious cycles" that drive the comorbidity of sarcopenia and osteoarthritis. By integrating multi-omics data, digital twin modeling, and real-time biomechanical feedback, this work provides a framework for clinical precision medicine. The clinical significance lies in identifying a "mechanical window of opportunity" for early intervention-using personalized exercise and nutritional strategies to restore joint homeostasis and prevent irreversible functional decline.
Repetitive head impacts (RHI) from contact sports may cause a unique pattern of white matter hyperintensities (WMH) on T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), termed RHI-associated WMH (RHI-WMH). These lesions are punctate, circular, and located at the gray-white matter boundary, an area vulnerable to trauma-related damage. We investigated the association of RHI with these lesions in two aging cohorts: (1) former American football players versus asymptomatic unexposed men and (2) individuals with RHI from various contact sports versus non-RHI participants. RHI-WMH were assessed using visual ratings and a novel automated quantification pipeline. Individuals with RHI had greater RHI-WMH by both detection methods in both cohorts. RHI-WMH were associated with plasma neurofilament light and p-tau231, and flortaucipir positron emission tomography (PET) uptake. RHI-WMH may represent a new supportive biomarker for the detection of RHI-related neuropathologies later in life.
Background: Μetabolic syndrome (MetS)-comprises central adiposity, elevated blood pressure, dyslipidaemia, and dysglycaemia, increasing the risk of type 2 diabetes and cardiovascular disease. Exercise training improves cardiorespiratory fitness and several MetS components, but real-world effectiveness is limited by poor adherence, restricted supervision, and insufficient personalisation. Objective: This scoping review mapped the clinical intervention evidence on technology-enhanced exercise and structured physical activity relevant to MetS, while distinguishing direct MetS evidence from translational evidence. Methods: In accordance with PRISMA-ScR, we searched PubMed and extended the search to Scopus and Web of Science; a supplementary IEEE Xplore search and a post hoc Embase check were also conducted. Eligible studies were interventions using web-based delivery, wearables, telemonitoring/mobile health (mHealth), artificial intelligence (AI) coaching, virtual reality (VR)/exergaming, or continuous glucose monitoring (CGM) alongside exercise training or structured physical activity. Results: Nineteen studies met the eligibility criteria. The evidence base was weighted toward wearable/app-based feedback and telemonitoring/mHealth/web-based approaches, with fewer studies on VR/exergaming, CGM-enabled exercise, and AI coaching. Most studies were randomised or cluster-randomised, but interventions were usually short term. Across categories, technology most consistently supported adherence, self-monitoring, accountability, remote supervision, and, in selected cases, physiology-informed personalisation. Direct MetS evidence was strongest for wearables with structured feedback, telemonitoring, mHealth, and web-based delivery, whereas AI coaching and CGM were supported by adjacent translational evidence. Conclusions: Technology-enhanced exercise and structured physical activity show promising but heterogeneous and still preliminary potential for MetS management. Key limitations include short follow-up, uneven representation across categories, inconsistent reporting of exercise dose/intensity fidelity and adverse events, and limited equity and implementation outcomes.
This study investigated whether the accuracy of 3D-guided osteotomies is influenced by surgeon experience. Two types of experience were assessed: (1) general surgical experience, defined as self-reported years in practice as an orthopaedic trauma surgeon, and (2) prior use of patient-specific guides (PSGs). Secondary aim was to evaluate whether accuracy varies by anatomical location. 24 orthopaedic-trauma surgeons performed 75 corrective osteotomies on cadaveric long-bones (43 single-cut, 32 double-cut; 107 cuts in total). Each osteotomy was preoperatively planned on CT-derived 3D-reconstructions, and PSGs were manufactured to guide the cuts. Postoperative CT-scans were used to compare planned and executed osteotomy planes. Surgeons completed a questionnaire reporting years of practice and annual PSG usage. A Spearman’s rank-order correlation was used to test differences in accuracy versus experience, a Kruskal-Wallis test was performed to explore differences across anatomical locations. General surgical experience ranged from 0 to 25 years (median 9), and PSG-usage from 0 to 20 cases annually (median 2). No association was found between general surgical experience and osteotomy accuracy (p = 0.406 and p = 0.548). In contrast, PSG-experience correlated with improved accuracy for angular and translational deviation of the osteotomy plane (p = 0.027 and p = 0.029). In addition, midshaft osteotomies of the lower extremity showed smaller angular deviations but larger translational errors compared with metaphyseal (p < 0.001 and p = 0.003). Experience with PSGs, rather than general surgical experience, improves accuracy in 3D-guided osteotomies, highlighting the need for training and repeated use. In contrast to metaphyseal, midshaft lower-extremity osteotomies are executed less accurately because fewer anatomical reference points are available. The online version contains supplementary material available at 10.1007/s00068-026-03179-4.
Osteoarthritis (OA) and osteoporosis (OP) are prevalent musculoskeletal disorders with substantial global health and economic burdens. Imaging is central to their diagnosis and monitoring, yet manual interpretation is vulnerable to inter-reader variability and workload-related fatigue. Artificial intelligence (AI), including machine learning (ML) and deep learning (DL), provides data-driven approaches to enhance the accuracy, efficiency, and objectivity of image interpretation. This review summarizes AI-assisted imaging advances for OA and OP over the past decade and discusses translational opportunities and challenges. A literature search was conducted in Web of Science, PubMed, and Scopus for English-language studies published between January 2015 and August 2025. Search terms included osteoarthritis, osteoporosis, X-ray, computed tomography (CT), magnetic resonance imaging (MRI), machine learning, deep learning, detection, classification, and diagnosis. Titles and abstracts were screened, and selected full texts were reviewed to summarize advances and diagnostic performance across modalities. Across X-ray, CT, and MRI, ML/DL approaches enable more objective quantification of OA- and OP-related abnormalities. Using public and cohort-based datasets, studies have evolved from radiomics-based ML pipelines to end-to-end DL frameworks for screening, classification, and grading. For OA, radiographs dominate Kellgren-Lawrence (KL) grading and large-scale screening, complemented by MRI for early tissue biomarkers and CT for quantifying subchondral bone remodeling. For OP, X-ray/CT captures bone texture and trabecular microarchitecture to support detection and classification, with MRI mainly used to assess marrow- and soft-tissue-related markers. Overall, DL typically improves automation and representation learning, while ML remains interpretable and competitive in smaller datasets. Emerging studies suggest that multimodal fusion and longitudinal modeling for progression assessment and prediction may further improve performance. AI-assisted imaging is reshaping OA and OP assessment by enabling earlier detection and more objective longitudinal monitoring. However, clinical translation is hindered by limited interpretability of many DL models and substantial data heterogeneity. Future research should prioritize standardized multicenter datasets and explainable AI frameworks. Prospective clinical studies and rigorous external validation are needed to bridge the gap between research and practice and to advance personalized musculoskeletal care.
ObjectiveThe meniscus has poor intrinsic healing capacity, particularly in avascular regions. Meniscal injury is strongly associated with progressive knee dysfunction, chronic pain, and accelerated osteoarthritis development. Current treatments, such as allografts and partial meniscectomy, are limited by donor scarcity and secondary joint degeneration. Therefore, this study aimed to develop a regenerative meniscal scaffold with integrated biomechanical and biological functionality.MethodsA biomimetic composite scaffold was fabricated via low-temperature three-dimensional printing using poly(D,L-lactic acid-co-trimethylene carbonate) and bacterial cellulose. Native meniscal architecture was reproduced using micro-computed tomography-based modeling, and interconnected porosity was designed to promote cell infiltration. Material integration employed dichloromethane as a shared solvent, enabling dual-ink (poly(D,L-lactic acid-co-trimethylene carbonate) + bacterial cellulose) co-printing. Scaffold performance was assessed using scanning electron microscopy morphology, porosity and water absorption assays, mechanical testing, Fourier-transform infrared spectroscopy, and in vitro cytocompatibility studies with rat bone mesenchymal stem cells.ResultsThe scaffold exhibited a tensile modulus of 16.6 MPa and compressive modulus of 2.97 MPa, closely matching native meniscal mechanics. Porosity reached 63.57% ± 5.72%, supporting cell adhesion, while water absorption exceeded 138% after 7 days. Notably, the scaffold exhibited temperature-responsive shape memory behavior, allowing minimally invasive implantation and anatomic recovery at 37°C. Bone mesenchymal stem cells exhibited 95% viability (live/dead staining), significant proliferation (cell counting kit-8), and spontaneous chondrogenic differentiation (SRY-box transcription factor 9/collagen type II (SOX9/COLII) expression) without exogenous induction.ConclusionThis three-dimensional-printed poly(D,L-lactic acid-co-trimethylene carbonate)/bacterial cellulose composite scaffold integrates biomimetic mechanics, shape-memory functionality, and pro-chondrogenic bioactivity, offering a promising strategy for meniscal regeneration. Further in vivo studies are warranted to confirm long-term efficacy and clinical translational potential.
Inflammatory processes drive a heterogeneous spectrum of diseases, including cardiovascular (CV), neurodegenerative, autoimmune, rare, and viral disorders, which together account for a major global disease burden. Despite diverse clinical manifestations, these conditions share systemic endothelial dysfunction (ED) as a common pathophysiological hallmark. The retina, accessible through non-invasive imaging, provides a unique window into systemic microvascular health. Over the past decades, retinal vessel analysis (RVA), both static and dynamic, has emerged as a robust tool for detecting and predicting microvascular alterations in inflammatory diseases. Large population-based cohorts, including the Atherosclerosis Risk in Communities (ARIC, n>9,000 participants) study and the Rotterdam Study (n>5,000), have shown that retinal diameter changes independently predict incident CV events and all-cause mortality. Recent UK Biobank (n>45,000) analyses further demonstrate incremental value in stroke prediction beyond traditional risk factors (AUC 0.739 to 0.752; p<0.001). Other retinal imaging modalities, such as optical coherence tomography angiography (OCTA) and adaptive optics (AO), provide complementary high-resolution structural data on capillary architecture and perfusion integrity. The retinal vascular phenotype reflects both shared and disease-specific mechanisms of ED. Therefore, accurate interpretation of retinal biomarkers requires an understanding of the molecular pathways that shape ED across disease entities, thereby forming the conceptual foundation of oculomics. We synthesize current evidence linking systemic ED to retinal microvascular structure and function across major categories of inflammatory disease. We integrate findings from static and dynamic RVA, OCTA, and AO, discuss their mechanistic interpretation within the emerging framework of oculomics, and critically evaluate challenges for clinical translation. Finally, we outline how artificial intelligence (AI) may facilitate robust, scalable implementation of retinal biomarkers for risk stratification, disease monitoring, and outcome prediction. This review moves beyond modality-specific descriptions to propose a unified biological and translational framework for retinal biomarkers.
To determine the independent effects of moderate-intensity exercise training and intermittent normobaric hypoxic exposure, and whether their combination provides additional improvements in body composition, energy metabolism, and glucose homeostasis in high-fat diet (HFD)-induced obese mice. Male ICR mice were fed an HFD for 7 weeks to induce obesity, then assigned to sedentary normoxia (SED+NOR), sedentary hypoxia (SED+HYP), exercise normoxia (EXE+NOR), or combined exercise plus hypoxia (EXE+HYP) for 5 weeks. Hypoxic exposure was applied under normobaric conditions by reducing inspired oxygen fraction (FiO₂ = 12%) for 12 h/day during the inactive phase, whereas exercise was performed during the active phase as speed-defined moderate-intensity treadmill running (5 d/wk) under normoxia. Body composition was assessed by DXA before and after the intervention. Glucose regulation was evaluated using fasting blood glucose, circulating insulin levels, OGTT, and HOMA-IR. Resting gas exchange and substrate oxidation were assessed to characterize energy metabolism. Skeletal muscle proteins related to substrate metabolism and glucose transport were measured by immunoblotting. Exercise training and intermittent hypoxic exposure improved obesity-associated metabolic impairments via distinct mechanisms. Exercise primarily reduced fat mass and improved glucose tolerance, accompanied by increased skeletal muscle GLUT4 abundance. Hypoxic exposure improved insulin sensitivity and systemic glucose regulation (lower insulin and HOMA-IR), despite limited effects on body weight. Notably, the combined EXE+HYP intervention produced the most pronounced overall improvements, including greater benefits in body composition and resting carbohydrate utilization compared with either intervention alone. In skeletal muscle, EXE+HYP increased oxidative metabolism-related protein expression relative to sedentary HFD controls. Intermittent normobaric hypoxic exposure and moderate-intensity exercise training provide complementary metabolic benefits in HFD-induced obese mice, and their combination yields additional improvements in key markers of body composition and glucose homeostasis. These findings support integrating hypoxic exposure with exercise as a potential non-pharmacological strategy to optimize metabolic health and motivate further mechanistic and translational studies.
Psychoneuroimmunology (PNI) research is a thriving field that integrates the growing knowledge about the complex interactions between neuroendocrine mediators and immune function into medicine and psychology. The aim of this BBI-Health special issue was to promote this research, it's creativity and the forward-thinking of future key opinion leaders in the PNI field of psychoneuroimmunology. Contributing researchers were invited to present new ideas and innovations that map out the future trajectory of our discipline. Together, their contributions show that PNI is becoming a trans-diagnostic, trans-methodological field that closes the psychosomatic division between the mind (our thoughts, feelings, and behaviors) and the body (its physiological states from health to illness). Their diverse views covered in this special issue highlight the ideas and contributions of the next generation of researchers who are helping to shape this field. Covered topics range from the role of stress in early development through the participation of the brain in chronic inflammation and immune contributions to depression, to insights from psychoneuroimmune research into dysregulated brain-body interactions going awry in chronic communicable and non-communicable diseases alike. They also explore biomarkers that indicate when adaptive neuroendocrine-immune stress responses shift toward maladaptive patterns, helping to guide treatment strategies that prevent or reduce such outcomes. Taken together, these contributions provide an informative glimpse into a prosperous research future that upholds a central science belief: knowledge is the key to a better life.
Oxidative stress, mitochondrial dysfunction, and autophagy imbalance form a vicious cycle driving intervertebral disc degeneration (IVDD). However, comprehensive therapeutic strategies remain limited. To address this, we engineered a biomimetic nanoparticle (NPCM@CeO2-RAPA) by encapsulating cerium oxide (CeO2) and rapamycin (RAPA) within a nucleus pulposus cell membrane (NPCM) shell. This biomimetic encapsulation enabled precise targeting of nucleus pulposus cells through membrane fusion. In vitro studies demonstrated that while CeO2 alone alleviated oxidative stress and partially restored mitochondrial function, and RAPA individually modulated autophagy, the combined treatment NPCM@CeO2-RAPA exhibited superior therapeutic effects. In vivo, the composite nanoparticle significantly suppressed catabolic activity and attenuated IVDD progression in a puncture-induced rat IVDD model. These findings highlight NPCM@(CeO2-RAPA) as a precise and synergistic nanotherapeutic with strong translational potential for IVDD management.
Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by multifactorial pathological mechanisms, and remains a significant clinical challenge. Exosome therapy represents a future direction for delaying OA progression, yet its efficacy is often compromised by inflammatory microenvironment within the joints. To overcome these limitations, we present a novel combinatorial therapeutic platform that alleviates OA through a multi-targeted strategy, including the scavenging of reactive oxygen species (ROS), suppression of macrophage-driven inflammation, and inhibition of chondrocyte ferroptosis. This platform combines dental pulp stem cells-derived exosomes (Exo) with hollow mesoporous cerium oxide nanozymes, which were first loaded with curcumin and subsequently coated with hyaluronic acid, termed HA@Cur@CeO2. In vitro, this combination reduced intracellular ROS and promoted macrophage polarization toward the anti-inflammatory M2 phenotype, thereby remodeling the OA microenvironment and halting the inflammatory cascade. Additionally, Exo and HA@Cur@CeO2 nanozymes complementarily modulated ALOX12-and GPX4-dependent ferroptosis pathways in chondrocytes, with the combined approach yielding superior anti-ferroptotic effects. For in vivo assessment, Exo and HA@Cur@CeO2 were encapsulated within a chitosan/β-glycerophosphate hydrogel to achieve sustained release (Exo/HA@Cur@CeO2/Gel). This formulation significantly reduced inflammation, chondrocyte ferroptosis, cartilage degeneration, and subchondral bone remodeling, ultimately slowing OA progression. With excellent biocompatibility, this innovative combinatorial therapeutic strategy represents a comprehensive approach for enhancing Exo efficacy in OA treatment with promising translational potential.
Paediatric athletes are not simply 'mini adults'. Most existing recommendations for cardiac screening in paediatric athletes are primarily based on evidence in adults and are designed for adult athletes. Paediatric-specific recommendations are needed due to the specifics of cardiac physiology, maturation and growth, age-related disease expression, modified diagnostic pathways, training adaptations, and to address relevant ethical considerations. This clinical consensus document from the European Association of Preventive Cardiology (EAPC) of the ESC and the Association for European Paediatric and Congenital Cardiology (AEPC) introduces specific advice for paediatric athletes for the first time, based on expert consensus, and where available, data from paediatric athlete populations. Members of the writing group voted anonymously on key advice statements, with ≥80% agreement required for consensus. All advice in this document applies to paediatric athletes aged <16 years, including those under 12 years of age. This document advises that cardiac screening of paediatric athletes with personal and family medical history, physical examination and 12-lead resting electrocardiogram (ECG) should be performed and should start no later than the age of 12 years. Implementing a screening programme requires ensuring the availability of necessary healthcare resources. One transthoracic echocardiogram may be appropriate to identify high-risk structural cardiac diseases not identifiable on ECG, provided appropriate infrastructure for baseline diagnostic assessments is in place. This document also includes suggested definitions of normal, borderline and abnormal ECG findings in paediatric athletes. Detailed advice is provided for further evaluation if suspicious findings are identified on initial tests. This document highlights that further research is required to optimise screening strategies, accurately assess and quantify the risk of sudden cardiac death and provide evidence-based eligibility recommendations for paediatric athletes with cardiac disease. It is also noted that increased opportunities for paediatric sports cardiology training are required to provide adequate medical care for the paediatric athlete population.