Search Results (180)

In the face of population aging, sarcopenia has emerged as a significant muscle disorder characterized by the progressive loss of muscle mass, strength, and function. Chronic inflammation, oxidative stress, and mitochondrial dysfunction contribute to sarcopenia and help explain its association with comorbidities such as type 2 diabetes, obesity, and neurodegenerative diseases. Despite extensive research, there remains a need to integrate current knowledge on interventions that target these interconnected mechanisms. This review synthesizes recent evidence on the effects of resistance exercise, nutritional supplementation (high-protein intake, leucine, vitamin D, omega-3 fatty acids), and probiotic use on muscle function and inflammatory status in older adults with sarcopenia. Literature was critically analyzed to evaluate the efficacy of multicomponent strategies. The reviewed studies consistently report that combining resistance training with anti-inflammatory nutrition and targeted supplementation improves muscle strength, reduces pro-inflammatory cytokines, and supports mitochondrial function. These findings suggest that an integrated, multicomponent approach represents a promising strategy for attenuating the progression of sarcopenia and reducing its associated comorbidities. Full article

Physical exercise is a potent non-pharmacological strategy for the prevention and management of chronic non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular diseases, obesity, and certain cancers. Growing evidence demonstrates that the benefits of exercise extend beyond its physiological effects and are largely mediated by coordinated molecular and cellular adaptations. This review synthesizes current knowledge on the key mechanisms through which exercise modulates metabolic health, emphasizing intracellular signaling pathways, epigenetic regulation, and myokine-driven inter-organ communication. Exercise induces acute and chronic activation of pathways such as AMPK, PGC-1α, mTOR, MAPKs, and NF-κB, leading to enhanced mitochondrial biogenesis, improved oxidative capacity, refined energy sensing, and reduced inflammation. Additionally, repeated muscle contraction stimulates the release of myokines—including IL-6, irisin, BDNF, FGF21, apelin, and others—that act through endocrine and paracrine routes to regulate glucose and lipid metabolism, insulin secretion, adipose tissue remodeling, neuroplasticity, and systemic inflammatory tone. Epigenetic modifications and exercise-responsive microRNAs further contribute to long-term metabolic reprogramming. Collectively, these molecular adaptations establish exercise as a systemic biological stimulus capable of restoring metabolic homeostasis and counteracting the pathophysiological processes underlying NCDs. Understanding these mechanisms provides a foundation for developing targeted, personalized exercise-based interventions in preventive and therapeutic medicine. Full article

Background: Gastrointestinal (GI) involvement is the most frequent visceral complication of systemic sclerosis (SSc), affecting up to 90% of patients, yet it remains poorly understood compared to pulmonary or cutaneous manifestations. The aim of this review is to integrate current knowledge on the cellular mechanisms underlying GI disease in SSc and to identify research priorities. Methods: A narrative literature review was conducted through a systematic PubMed search up to September 2025, complemented by manual reference screening. Results: Histopathological and functional evidence consistently demonstrates that neuromuscular alterations, including degeneration of enteric neurons, loss of interstitial cells of Cajal, and smooth muscle atrophy, can precede fibrosis, challenging the traditional “fibrosis-first” paradigm. Fibroblast and myofibroblast activation are present in gastric and colonic samples, sustained by profibrotic mediators such as TGF-β, CTGF, and endothelin-1, although the cellular origins of these stromal cells remain uncertain. Additional pathogenic contributions include autonomic dysfunction, barrier dysfunction with dysbiosis, impaired vascular reserve of vessels perfusing the gut, and functional autoantibodies targeting interneural and neuromuscular function and communication. Compared with skin and lung, the GI tract displays less fibrosis and fewer inflammatory infiltrates, but immune-derived mediators and autoantibodies suggest distinct immunopathogenic pathways are activated. Conclusions: Collectively, these findings depict GI involvement in SSc as a multi-compartmental process integrating neural, epithelial, endothelial, stromal, and immune alterations. Addressing the lack of validated biomarkers, mechanistic models, and biomarker-stratified trials will be essential to move beyond symptomatic care and toward precision medicine approaches for SSc-related GI disease. Full article

Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2’s role in these processes. This review aims to summarize current knowledge on SHP2/PTPN11 biology, its role in immune regulation, cancer progression, and vascular homeostasis, and to discuss emerging therapeutic strategies targeting this pathway. The concept of using SHP2 inhibitors with immune checkpoint inhibitors (ICIs) is being investigated to address ICI resistance and to improve anti-tumor efficacy substantially. SHP2 is also being studied in non-cancer cell contexts, and signaling responses can differ by large magnitudes depending on the biological context and stimuli. Under normal circumstances, SHP2 promotes vascular homeostasis in endothelial cells (ECs) and myeloid cells and inhibits inflammation, and the reduction in SHP2 activity by oxidative stress, such as in atherosclerosis or diabetes, upregulates inflammation. In contrast, in response to radiation, the fibrotic response and subsequent lung injury were increased by endothelial SHP2 induction via Notch-Jag1 signaling. Vascular smooth muscle cells SHP2 act as a pro-atherogenic effector by enhancing ERK/MAPK signaling, and the upregulation of mitochondria localized SHP2 can also induce cellular senescence-associated inflammation by upregulating mitochondrial reactive oxygen species. Taken together, the two opposite signaling effects of SHP2 suggest that both the immune and vascular system responses appear to be more modulated by the redox, cell, and compartment-specific signaling of SHP2. More studies are needed for mitigating cardiovascular toxicity to patients, particularly with ICI-based treatment regimens. Full article

Aberrant activation of innate immunity promotes the development of pulmonary arterial hypertension (PAH); however, the role of pattern recognition by Toll-like receptors (TLRs) within the pulmonary vasculature remains unclear. To consolidate knowledge (as of June 2025) about TLRs and their interactions with viruses in PAH and to identify therapeutic implications. A narrative review of experimental and clinical studies investigating ten TLRs in the context of the pulmonary vascular microenvironment and viral infections. Activation of TLR1/2, TLR4, TLR5/6, TLR7/8, and TLR9 converges on the MyD88–NF-κB/IL-6 axis, thereby enhancing endothelial-mesenchymal transition, smooth muscle proliferation, oxidative stress, thrombosis, and maladaptive inflammation, ultimately increasing pulmonary vascular resistance. Conversely, TLR3, through TRIF–IFN-I, preserves endothelial integrity and inhibits vascular remodeling; its downregulation correlates with PAH severity, and poly (I:C) restitution has been shown to improve hemodynamics and right ventricular function. HIV-1, EBV, HCV, endogenous retrovirus K, and SARS-CoV-2 infections modulate TLR circuits, either amplifying pro-remodeling cascades or attenuating protective pathways. The “TLR rheostat” is shaped by polymorphisms, ligand biochemistry, compartmentalization, and biomechanical forces. The balance between MyD88-dependent signaling and the TRIF–IFN-I axis determines the trajectory of PAH. Prospective therapeutic strategies may include TLR3 agonists, MyD88/NF-κB inhibitors, modulation of IL-6, and combination approaches integrating antiviral therapy with targeted immunomodulation in a precision approach. Full article

This review synthesizes current knowledge on the roles of X-box binding protein 1 (XBP1) in development and regenerative medicine. XBP1 is defined as a key transcription factor that regulates biological processes from embryogenesis to adult tissue homeostasis via both endoplasmic reticulum(ER) stress-dependent and independent mechanisms. Evidence for its regulatory role in cell fate determination and tissue maintenance across multiple systems is presented. The therapeutic potential of targeting XBP1 is explored, particularly for the regeneration of skeletal muscle, skin, and bone. Critical future research priorities are outlined, such as deciphering the precise functions of the Inositol requiring enzyme 1 (IRE1α)/XBP1 signaling axis and evaluating the long-term safety of its modulation. XBP1 is thus confirmed as a prime target for advancing developmental biology and pioneering new regenerative therapies. Full article

As a key piece of equipment in badminton, the surface treatment technology of rackets has garnered significant attention in the fields of material science and sports engineering. This study is the first to systematically review research on racket coatings, integrating interdisciplinary knowledge on the classification of functional coatings, their performance-enhancing principles, and their relationship with competitive levels, thereby addressing a gap in theoretical research in this field. This study focuses on four major functional coating systems: superhydrophobic coatings (to improve environmental adaptability and reduce air resistance), anti-scratch coatings (to prolong the life of the equipment), vibration-damping coatings (to optimise vibration damping performance), and strength-enhancing coatings (to safeguard structural stability). In badminton, differences in player skill levels and usage scenarios lead to variations in racket materials, which, in turn, result in different preparation processes and performance effects. The use of vibration-damping materials alleviates the impact force on the wrist, effectively preventing sports injuries caused by prolonged training; leveraging the aerodynamic properties of superhydrophobic technology enhances racket swing speed, thereby improving hitting power and accuracy. From the perspective of performance optimization, coating technology improves athletic performance in three ways: nanocomposite coatings enhance the fatigue resistance of the racket frame; customized damping layers reduce muscle activation delays; and surface energy regulation technology improves grip stability. Challenges remain in the industrial application of environmentally friendly water-based coatings and the evaluation system for coating lifespan under multi-field coupling conditions. Future research should integrate intelligent algorithms to construct a tripartite optimization system of “racket-coating-user” and utilize digital sports platforms to analyze its mechanism of influence on professional athletes’ tactical choices, providing a theoretical paradigm and technical roadmap for the targeted development of next-generation smart badminton rackets. Full article

Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL, is a common yet underrecognized electrolyte disturbance in critically ill patients, with prevalence estimates reaching up to 80%. This review explores the intricate bidirectional relationship between hypophosphatemia and hyperventilation, emphasizing its profound implications for respiratory function and critical care management. Hypophosphatemia impairs oxygen delivery by depleting 2,3-diphosphoglycerate (2,3-DPG), disrupts central respiratory drive, and weakens respiratory muscles, leading to hyperventilation, ventilatory failure, and prolonged mechanical ventilation. Conversely, hyperventilation exacerbates hypophosphatemia through respiratory alkalosis, triggering intracellular phosphate shifts and metabolic cascades that rapidly deplete serum levels. This cycle creates significant challenges for ventilator weaning and increases morbidity and mortality. Underlying mechanisms include impaired ATP synthesis, altered chemoreceptor sensitivity, and systemic inflammatory responses. Hypophosphatemia-induced hyperventilation manifests as unexplained tachypnea and respiratory alkalosis, often misdiagnosed as anxiety or pain, while hyperventilation-induced hypophosphatemia contributes to diaphragmatic dysfunction and poor ventilatory performance. Common precipitating factors include refeeding syndrome, diabetic ketoacidosis, continuous renal replacement therapy, and malnutrition. Complications extend beyond respiratory dysfunction to include cardiac depression, immune dysfunction, prolonged ICU stays, and increased healthcare costs. Current diagnostic approaches rely on serum phosphate measurements, which poorly reflect total body stores due to significant intracellular shifts. Emerging biomarkers such as fibroblast growth factor 23 (FGF23) and advanced monitoring technologies, including continuous phosphate tracking, may enhance recognition. Treatment strategies emphasize targeted phosphate repletion based on severity, with intravenous supplementation and ventilatory support tailored to minimize complications. Preventive measures, including risk stratification, prophylactic supplementation, and ventilator management, are critical for high-risk populations. Despite advances, knowledge gaps persist in optimizing monitoring and repletion protocols, understanding genetic variations, and identifying ideal phosphate targets for improved respiratory outcomes. This review provides a comprehensive framework for recognizing and managing hypophosphatemia’s impact on respiratory dysfunction in critically ill patients. Adopting evidence-based interventions and leveraging emerging technologies can significantly improve clinical outcomes, reduce ICU complications, and enhance recovery in this vulnerable population. Full article

Background: The TWNK gene encodes a protein that colocalizes with mitochondrial DNA (mtDNA) in mitochondrial nucleoids. It acts as mtDNA helicase during replication, thus playing a pivotal role in the replication and maintenance of mtDNA stability. TWNK mutations are associated with a wide spectrum of clinical phenotypes and a marked heterogeneity. However, heterozygous nonsense variants in the gene have never been described in association with disease. Methods: We analyzed a next-generation sequencing (NGS) targeted gene panel in a cohort including 40 patients with high clinical suspicion of mitochondrial disorders. Selected patients underwent a complete neurological examination, electrophysiology tests, and muscle biopsy. Segregation analysis was performed in available family members. The 3D structure of twinkle was visualized and analyzed using Swiss Model and Pymol version 3.1.6.1. Results: We found four TWNK-mutated subjects from two unrelated families. They exhibited a variable clinical spectrum, ranging from asymptomatic individuals to subjects with psychiatric disorder, chronic progressive external ophthalmoplegia (CPEO), and CPEO-plus. All the subjects shared the heterozygous TWNK p.Glu665Ter variant. Discussion and Conclusions: We describe the clinical phenotype and muscle biopsy findings associated with the first reported heterozygous nonsense TWNK variant, thus expanding the current knowledge of Twinkle-related disorders. Our findings are in line with the high intrafamilial clinical variability associated with TWNK mutations. Although PEO and skeletal muscle involvement remain hallmarks of the disease, extra-muscular features should be carefully assessed. Full article

With the growing availability of strength training information through online platforms and social media, there is an increasing need to ensure that individuals possess sufficient knowledge to train safely and effectively. Nonetheless, previous studies on strength training literacy have primarily focused on university students and have not adequately examined differences in knowledge across age groups or the roles of training experience and instruction. This study aimed to assess the knowledge of (a) targeted muscle groups and (b) proper form and movement among adults aged 20–69 years and to explore how this knowledge varies by age, sex, and experience in training and professional instruction. A total of 1000 adults (100 males and 100 females in each decade from their 20s to 60s) participated in an online survey. The participants were categorized into three groups according to their training and instructional experience. Knowledge was assessed using 10 items pertaining to targeted muscles and 18 items related to exercise form and movement. Three-way analysis of variance was conducted to analyze the associations between age, sex, and experience. Overall, 75.5% of the participants reported strength training experience, whereas 29.3% had received instruction. Knowledge of the targeted muscle groups was significantly higher in participants in their 60s than in those in their 20s (p = 0.014); however, the overall accuracy remained below 60%. No significant effect of instruction on anatomical knowledge was observed. In contrast, both training and instructional experience were positively associated with knowledge of form and movement, although the accuracy remained modest among all groups (50–60%). Sex differences in instructional experience varied by age, with older females reporting higher rates than their male counterparts. In conclusion, knowledge of strength training among adults remains insufficient, particularly regarding anatomical targets. Although instruction enhances the understanding of form and movement, it does not guarantee anatomical literacy. To improve training outcomes and safety, instructional strategies should integrate clear, structured, and pedagogically informed approaches that emphasize movement execution and muscle engagement. Full article

Background/Objectives: Lack of objective evidence exists regarding changes in physical function and impact on daily functioning in paediatric post-COVID-19 condition (PPCC). This study aimed to assess exercise capacity, fatigue, and peripheral and respiratory muscle strength in PPCC patients compared with healthy controls. Additionally, the impact of PPCC on domains of daily life was evaluated. Methods: A cross-sectional study was performed. Study variables: exercise capacity (6 min walk test, 6MWT), inspiratory muscle strength (maximal inspiratory pressure, PImax), handgrip strength (handheld dynamometer, HHD), quadriceps femoris muscle thickness (QF MT), rectus femoris muscle thickness (RF MT), rectus femoris cross-sectional area (RF CSA), rectus femoris echo-intensity (RF EI), fatigue (Paediatric Functional Assessment of Chronic Illness Therapy-Fatigue, pedsFACIT-F), and physical activity (Assessment of Physical Activity Levels Questionnaire, APALQ). Results: A total of 115 PPCC patients and 227 healthy controls were included. The PPCC group had lower 6MWT (509.00 ± 86.12, p < 0.001), PImax (68.71 ± 26.23, p < 0.001), HHD (82.84 ± 29.09, p < 0.001), APALQ (7.94 ± 3.14, p < 0.001), pedsFACIT-F (24.51 ± 11.01, p < 0.001), QF MT mid-thigh (33.21 ± 7.99, p = 0.011), and higher RF EI (p < 0.001) vs. controls. Only 37.63% of the PPCC group resumed previous sports, 43.48% were unable to attend school full-time and 28.7% could not participate in after-school activities. Conclusions: Paediatric post-COVID-19 condition patients exhibited significant impairments in terms of physical function, with a high impact on daily functioning. This knowledge is necessary to provide targeted therapeutic interventions. Full article

Background and Clinical Significance: Triosephosphate isomerase (TPI) deficiency is a rare autosomal recessive metabolic disorder caused by a pathogenic variant in the TPI1 gene. It is characterised by chronic haemolytic anaemia, progressive neuromuscular dysfunction, and reduced life expectancy. Patients typically present with symptoms in the first few months of life, including muscle weakness, ataxia, and recurrent respiratory infections. Diagnosis is confirmed by genetic testing, and management is generally symptomatic as no treatment is available. Case Presentation: We describe the case of an infant diagnosed with TPI deficiency in the context of haemolytic anaemia with progressive neurological deterioration and respiratory failure. Conclusions: This case illustrates the complexity of the disease and highlights the importance of early diagnosis and contributes to the limited literature by providing a detailed clinical description and highlighting the diagnostic challenges associated with this condition. Beyond its clinical relevance, this report emphasises the potential role of personalised medicine in the management of TPI deficiency. Early identification of specific genotypes may inform prognosis and guide individualised supportive strategies. As knowledge of the molecular underpinnings of TPI deficiency expands, opportunities may emerge for targeted therapeutic approaches tailored to patient-specific characteristics. Full article

Obesity (lipotoxicity) results from a chronic imbalance between energy intake and expenditure. It is strongly associated with type 2 diabetes mellitus (T2DM, glucotoxicity) and considered a major risk factor for the development of metabolic complications. Their convergence constitutes “diabesity”, representing a major challenge for public health worldwide. Limited treatment efficacy highlights the need for novel, multi-targeted therapies. Non-shivering thermogenesis (NST), mediated by brown and beige adipose tissue and skeletal muscle, has emerged as a promising therapy due to its capacity to increase energy expenditure and improve metabolic health. Also, skeletal muscle plays a central role in glucose uptake and lipid oxidation, further highlighting its relevance in diabesity. This review explores current and emerging knowledge on physiological stimuli, including cold exposure, physical activity, and fasting, as well as bioactive ingredients and drugs that stimulate NST in thermogenic tissues. Special emphasis is placed on melatonin as a potential regulator of mitochondrial function and energy balance. The literature search was conducted using MEDLINE and Web of Science. Studies were selected based on scientific relevance, novelty, and mechanistic insight; prioritizing human and high-quality rodent research published in peer-reviewed journals. Evidence shows that multiple interventions enhance NST, leading to improved glucose metabolism, reduced fat accumulation, and increased energy expenditure in humans and/or rodents. Melatonin, in particular, shows promise in modulating thermogenesis through organelle-molecular pathways and mitochondrial protective effects. In conclusion, a multi-target approach through the activation of NST by physiological, nutritional, and pharmacological agents offers an effective and safe treatment for diabesity. Further research is needed to confirm these effects in clinical practice and support their use as effective therapeutic strategies. Full article

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, especially in older adults where frailty complicates treatment outcomes. Multimodal prehabilitation—comprising nutritional support, physical exercise, and psychological interventions—has emerged as a promising strategy to enhance patients’ resilience before CRC surgery. Clinical studies demonstrate that prehabilitation significantly reduces postoperative complications, shortens hospital stays, and improves functional recovery. Nutritional interventions focus on counteracting malnutrition and sarcopenia through tailored dietary counseling, protein supplementation, and immunonutrients like arginine and glutamine. Physical exercise enhances cardiorespiratory fitness and muscle strength while modulating immune and metabolic pathways critical for surgical recovery. Psychological support reduces anxiety and depression, promoting mental resilience that correlates with better postoperative outcomes. Despite clear clinical benefits, the molecular mechanisms underlying prehabilitation’s effects—such as inflammation modulation, immune activation, and metabolic rewiring—remain poorly understood. This review addresses this knowledge gap by exploring potential biological pathways influenced by prehabilitation, aiming to guide more targeted, personalized approaches in CRC patient management. Advancing molecular insights may optimize prehabilitation protocols and improve survival and quality of life for CRC patients undergoing surgery. Full article

Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors. Full article