Search Results (2,993)

Yaks are uniquely adapted to survive in the harsh environment of the Qinghai-Tibetan Plateau, where oxygen is scarce, temperatures are freezing, and food availability changes drastically with seasons. Understanding how these animals cope with such extreme conditions is crucial for both conservation and agriculture. This review explores the hidden biological mechanisms behind the yak’s remarkable resilience, focusing on a special type of genetic material called non-coding RNAs (ncRNAs). Unlike regular genes, these molecules act like master switches, controlling how the yak’s body responds to stress and builds important tissues. We examined how these genetic switches influence the animal’s ability to store fat and muscle, produce milk, develop reproductive organs, and withstand low oxygen levels in the heart and lungs. Our findings reveal that these ncRNAs regulate key biological pathways related to energy usage, cell protection, and tissue structure. By mapping out these genetic controls, this study provides valuable insights that can help scientists breed healthier yaks and better understand how large animals adapt to extreme climates. Full article

Although praziquantel (PZQ) is the main antischistosomal drug currently in use, concerns remain regarding incomplete reversal of schistosomiasis-induced pathology and the emergence of drug resistance. This study evaluates the combined effect of PZQ with safranal, a bioactive saffron constituent, on Schistosoma mansoni-induced pathology in mice. Male CD1 Swiss albino mice were exposed to 60 S. mansoni cercariae and, at week 9 post-infection, were treated with PZQ (500 mg/kg orally for two consecutive days), safranal (50 mg/kg/day), or both, for three weeks. The animals were sacrificed at week 11 post-infection. Worm and egg burdens, liver histopathology, fibrotic markers, oxidative stress, and inflammatory cytokines were assessed. Combined PZQ + safranal therapy significantly reduced adult worm counts and hepatic and intestinal egg loads compared to PZQ alone. All treatments decreased liver index (hepatomegaly), with the combination treatment providing the best intervention. Histological analyses revealed significantly reduced granuloma size and hepatic necrosis post-treatment, particularly in the combination group. The levels of proinflammatory cytokines (TNF-α, IL-1β) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were significantly lowered in treated mice, most notably with the combination treatment. Oxidative stress was also markedly attenuated, and infected mice exhibited elevated malondialdehyde and depleted antioxidant enzymes (SOD, CAT, GSH). Interestingly, PZQ and/or safranal restored antioxidant status and reduced lipid peroxidation, with the combination being most effective. Furthermore, collagen deposition and expression of hepatic fibrotic markers α-smooth muscle actin (α-SMA), TGF-β1, and matrix metalloproteinase-9 were most effectively suppressed by combined therapy. To conclude, safranal enhances PZQ’s antischistosomal efficacy and confers additive protection against Schistosoma-induced liver fibrosis. Full article

Mandibular angle fractures pose a significant clinical challenge in maxillofacial surgery, and conventional fixation systems often show merely adequate biomechanical performance. This study presents a new mini-plate geometric configuration and outlines its rigorous verification and a preliminary validation procedure. The proposed ‘U’-shaped grade 4 titanium mini-plate with self-tapping screws was developed specifically for the stable fixation of mandibular angle fractures. A three-dimensional mandible model incorporating an angular fracture gap exceeding 1 mm was constructed and analyzed using SolidWorks. Finite Element Analysis (FEA) was employed as a verification tool to evaluate stress, strain, and displacement distributions in the mandibular ramus, plate, and screws under bilateral masticatory muscle loading, with material integrity assessed against yield-strength thresholds using von Mises’ stress theory. Rapid and functional prototypes were subsequently fabricated to physically validate the proposed mini-plate. The maximum stress across the entire model was 446.8 MPa, localized at the middle lower screw, while the maximum stress at the designed plate was 110 MPa, which remains well within the safe limits and is approximately 60.7% lower than the reported maximum stress values for conventional fixation systems. The new mini-plate exhibited robust biomechanical performance, offering a more favorable mechanical environment conducive to bone healing. Full article

As global populations grow and technology advances, daily life is increasingly shaped by digital systems such as computers and smart devices. However, prolonged device use has contributed to increasing physical and mental health concerns, particularly those associated with poor sitting posture. Posture-related strain is frequently overlooked and contributes to musculoskeletal discomfort, including back, neck, shoulder, and wrist pain, and may also be associated with sleep disturbances and elevated stress levels. To the best of our knowledge and based on the existing literature, this is the first study to introduce a machine learning-based framework for advanced muscle strain severity classification using Internet of Things (IoT) devices that integrates posture monitoring and muscle strain detection into a unified low-cost framework ($23 hardware cost). The primary objective of this work is accurate classification of muscle strain severity, while real-time alerts serve as a secondary ergonomic feedback mechanism. Specifically, this study makes four major contributions. First, we created a novel dataset through real-time acquisition of electromyography (EMG) and posture signals from participants in hospital and industrial environments, capturing diverse muscle strain patterns validated against clinical assessment procedures. Second, we designed a two-part hardware architecture consisting of posture detection (PD) and strain detection (SD) modules using a NodeMCU ESP8266, HC-SR04 ultrasonic sensor, EMG sensor, and buzzer for real-time physiological monitoring, incorporating EMG-specific preprocessing including band-pass filtering, rectification, and RMS smoothing. Third, we proposed and evaluated a hybrid machine learning framework integrating Vision Transformer (ViT) and XGBoost to classify strain severity into three study-specific categories: baseline (EMG RMS < 40 µV), compensatory strain (40–59 µV), and overload (≥60 µV). These categories were used as reproducible severity proxies for machine learning annotation and should not be interpreted as universal biomarkers of structural tissue damage. Finally, the proposed framework achieved a classification accuracy of 99.0% (95% CI: 98.5–99.5%) with an inference latency of 15.2 ms. Full article

High-intensity 5 km running offers an ideal framework to analyze the organism’s multidimensional responses. Since previous research primarily analyzed isolated aspects of fatigue, this study aimed to examine the integrated acute neuromuscular, metabolic, and perceptual responses to a 5 km run. Twenty-one recreational male runners participated. Pre- and post-race assessments included body composition, blood lactate, m. rectus femoris ultrasound thickness, quadriceps maximal voluntary isometric contraction (MVIC), heart rate, perceived exertion (Borg CR10), and 5 km finish time. Statistical analysis was performed in the Jamovi software, utilizing descriptive statistics, the Shapiro–Wilk test of normality, the Wilcoxon signed-rank test with effect size calculation, and Spearman’s correlation coefficient, at a significance level of p < 0.05. Post-race measurements revealed a significant decrease in quadriceps MVIC (pre: 305 ± 99 N vs. post: 259 ± 88 N; p = 0.002) and an increase in blood lactate (pre: 0.8 ± 0.4 vs. post: 6.9 ± 1.4 mmol/L; p < 0.001), alongside high average heart rates (165 ± 16 bpm). However, ultrasound-assessed muscle architecture remained unchanged. The 5 km run induced pronounced neuromuscular and metabolic fatigue. Unchanged muscle architecture suggests that acute strength decline is primarily mediated by metabolic and neural mechanisms, rather than immediate structural–morphological factors. These findings highlight the value of an integrated assessment approach for understanding acute fatigue responses following high-intensity 5 km running and may contribute to more precise training-load prescription and recovery monitoring in recreational runners. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Coronary artery vasospasm (CAV) is a transient, reversible constriction of the epicardial coronary arteries that reduces coronary blood flow and may cause myocardial ischemia. Despite its clinical significance, CAV remains underdiagnosed and can present as chest pain, acute coronary syndrome, malignant arrhythmias or sudden cardiac death. Vasospasm may occur in both angiographically normal coronary arteries and at sites of pre-existing atherosclerotic stenosis. The pathophysiology of CAV is multifactorial and involves vascular smooth muscle cells (VSMCs) hyperreactivity, endothelial dysfunction, chronic inflammation and autonomic dysregulation. VSMCs contraction is mediated by phosphorylation of the myosin light chain (MLC) through calcium (Ca²⁺)/calmodulin-dependent myosin light chain kinase (MLCK), while relaxation is regulated by myosin light chain phosphatase (MLCP). Increased intracellular Ca²⁺ levels and enhanced Ca²⁺ sensitivity contribute to excessive vasoconstriction. Rho-kinase (ROCK) plays a pivotal role in sustained vasospasm by inhibiting MLCP, thereby promoting prolonged smooth muscle contraction. Endothelial dysfunction contributes to CAV by disrupting normal vascular tone regulation, largely as a result of decreased nitric oxide (NO) mediated vasodilation. Chronic low-grade inflammation and oxidative stress exacerbate both endothelial dysfunction and VSMCs contraction. Understanding these molecular mechanisms is essential for identifying novel therapeutic targets. Emerging treatment strategies, including ROCK inhibitors, endothelin receptor antagonists and anti-inflammatory agents, may improve outcomes in patients with refractory CAV. Full article

Type 2 diabetes mellitus (T2DM) is a highly prevalent and devastating chronic metabolic disease worldwide, with pathogenesis centrally characterized by insulin resistance and pancreatic β-cell dysfunction. Accumulating evidence has demonstrated that glucose metabolic reprogramming represents an adaptive metabolic shift from oxidative phosphorylation to aerobic glycolysis in cells in response to a hyperglycemic microenvironment. This shift acts as an upstream important event driving the initiation and progression of T2DM. This review summarizes the characteristics of glucose metabolic reprogramming in insulin-sensitive target organs under T2DM conditions, including the liver, skeletal muscle, adipose tissue and pancreatic β-cells. It also discusses four major downstream effector mechanisms: mitochondrial energy metabolism disturbance, augmented oxidative stress, disruption of mitochondria-associated endoplasmic reticulum membranes (MAMs) coupled with calcium homeostasis imbalance, and systemic inflammatory response. On this basis, we summarize the intervention strategies targeting the above signaling pathways, including antioxidant therapy, restoration of MAMs integrity and calcium homeostasis, systemic anti-inflammatory intervention, and multi-target regulatory effects of traditional Chinese medicine. Current studies indicate that early intervention in downstream stress events is induced by glucose metabolic reprogramming. This is particularly true for the preservation of MAMs’ integrity; restoration of calcium homeostasis; and inhibition of NLRP3 inflammasome activation, the latter of which is expected to block or delay the progression from prediabetes to clinical T2DM. Nevertheless, substantial gaps still remain in the understanding of the dynamic regulatory mechanisms of MAMs, tissue-specific therapeutic targets, and relevant clinical translational research. Future integration of multi-omics technologies will provide novel therapeutic strategies and theoretical foundations for the early prevention and treatment of T2DM. Full article

Chronic coronary syndromes (CCSs) are increasingly recognized as complex immunometabolic vascular disorders in which coronary microvascular dysfunction (CMD), persistent low-grade inflammation, oxidative stress, and maladaptive cellular remodeling contribute to ischemic symptoms and adverse outcomes beyond epicardial stenosis. CMD represents a heterogeneous condition comprising both functional and structural endotypes and constitutes a major determinant of myocardial ischemia, heart failure progression, and adverse cardiovascular outcomes, even in the absence of obstructive coronary artery disease. Emerging evidence indicates that immunometabolic reprogramming of endothelial cells, vascular smooth muscle cells, and immune cells sustains microvascular dysfunction in CCSs. Metabolic shifts toward glycolysis, mitochondrial dysfunction, redox imbalance, and dysregulated lipid metabolism promote chronic inflammatory activation within the coronary microenvironment. Convergent mitochondrial stress (including NAD⁺ decline) and redox injury promote endothelial senescence and increase susceptibility to regulated cell death, progressively limiting vasodilatory reserve and predisposing to microvascular rarefaction. Pyroptosis and ferroptosis-like lipid peroxidation further exacerbate endothelial barrier disruption and inflammatory amplification. In parallel, inflammasome activation, iron-dependent lipid peroxidation, impaired autophagy, and endoplasmic reticulum stress form interconnected molecular networks that amplify vascular injury through self-reinforcing mechanisms. This narrative review integrates mechanistic and translational evidence linking immunometabolic dysregulation, mitochondrial stress, thromboinflammatory signaling, endothelial senescence, and regulated cell death to distinct CMD endotypes. We propose a systems-level framework in which coronary microvascular dysfunction is conceptualized as an immunometabolic vascular network disorder, with reduced coronary flow reserve (CFR)—often termed myocardial flow reserve (MFR) in PET studies—emerging as the integrative functional endpoint of these interacting molecular perturbations and a robust predictor of major cardiovascular events. Full article

Burn wound healing is a complex and dynamic process involving coordinated regulation of inflammation, oxidative stress, angiogenesis, and tissue remodeling. Polygonum cuspidatum, a traditional Chinese medicinal herb widely used for trauma- and inflammation-related disorders, represents an important source of bioactive compounds for tissue repair. Piceatannol (PIC), a naturally occurring stilbene constituent of P. cuspidatum, possesses potent anti-inflammatory and antioxidant activities; however, its therapeutic potential in burn wound healing remains insufficiently understood. In the present study, the therapeutic effects and underlying mechanisms of topical PIC were investigated using a murine deep second-degree burn model combined with multiple skin-related cellular models, including keratinocytes, fibroblasts, endothelial cells, and macrophages. PIC markedly accelerated wound closure and improved histological architecture, as evidenced by reduced inflammatory infiltration, enhanced collagen organization, and increased neovascularization. Mechanistically, PIC suppressed NF-κB activation and modulated KEAP1/NRF2-associated redox signaling, thereby alleviating inflammation–oxidative stress crosstalk during wound healing. In keratinocyte–fibroblast co-culture systems, PIC inhibited fibroblast-to-myofibroblast transition, reduced α-smooth muscle actin (α-SMA) expression, and attenuated excessive collagen deposition, suggesting anti-fibrotic activity. In addition, PIC promoted endothelial tube formation through activation of the STAT3–VEGF signaling axis. Collectively, these findings demonstrate that PIC facilitates burn wound repair through coordinated anti-inflammatory, antioxidative, pro-angiogenic, and anti-fibrotic effects. This study provides pharmacological support for the therapeutic potential of P. cuspidatum-derived compounds in burn management and highlights PIC as a promising candidate for topical treatment of burn injuries. Full article

Background/Objectives: The transcription factor carbohydrate response element-binding protein (ChREBP) is a key glucose-sensing regulator that governs glucose and lipid metabolic homeostasis. However, its specific functions in skeletal muscle remain insufficiently clarified. The present study aimed to investigate the roles of ChREBP in skeletal muscle exercise capacity, energy metabolism, and adaptive remodeling, as well as muscle regeneration. Methods: We generated a skeletal muscle-specific ChREBP knockout mouse model, and assessed their exercise performance, energy metabolism, skeletal muscle fiber composition, and injury repair capacity. Additionally, hypoxia and high-fructose diet models were established to analyze the function of ChREBP in skeletal muscle adaptive remodeling. C2C12 myoblasts and primary muscle satellite cells were used to explore its effects on myogenic differentiation. Results: Genetic deletion of ChREBP induced no detectable alterations in myofiber composition, overall metabolic status, or muscle adaptive remodeling triggered by hypoxia and high-fructose diet. In vitro assays demonstrated that ChREBP overexpression facilitates C2C12 myogenic differentiation. Adeno-associated virus-mediated ChREBP overexpression enhanced histological markers of regeneration, including desmin-positive regenerative area and the cross-sectional area of newly formed myofibers after cardiotoxin-induced injury. Conclusions: Collectively, our experimental data indicate that ChREBP is largely dispensable for maintaining basal skeletal muscle homeostasis and stress-induced adaptive remodeling. Meanwhile, this study identifies a previously unrecognized regulatory role of ChREBP in the processes of skeletal muscle damage repair and post-injury regeneration. Full article

Background: Lepidium meyenii Walp (L. meyenii), traditionally known as maca, is widely recognized for its health-promoting properties, including potential protection against exercise-induced muscle damage (EIMD). However, its precise effect on post-exercise blood biomarkers remains unclear. Objective: This study aimed to qualitatively review research published until April 2026 examining L. meyenii supplementation to reduce blood markers of muscle damage and protein degradation post-exertion in animal studies. Specifically, the effect size (ES) of L. meyenii supplementation on post-exercise levels of creatine kinase (CK), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) was estimated. Methods: This systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. The certainty of the evidence was assessed using the GRADE framework. Relevant studies were identified through Web of Science, Scopus, SPORTDiscus, PubMed, and MEDLINE. Eligible studies included in vivo experiments in animals with controlled designs and pre-/post-intervention assessments. Methodological quality and risk of bias were evaluated using the CAMARADES tool. Statistical analysis involved standardized mean differences (SMD) using Hedges’ g with 95% confidence intervals. Results: 15 studies were included in the systematic review, and 14 studies in animals in the meta-analysis. The CAMARADES scores ranged from 5 to 7 points, indicating moderate methodological quality. Supplementation with L. meyenii was not associated with statistically significant changes in LDH (SMD = −1.37; 95% CI −3.34 to 0.59), BUN (SMD = −0.37; 95% CI −2.16 to 1.42) nor CK (SMD = 0.29; 95% CI −5.45 to 6.03), with very high heterogeneity (I² > 97%). Exploratory subgroup analyses and meta-regression analyses by formulation type and dose did not identify any moderators that could robustly explain this heterogeneity. Conclusions: The available evidence does not support a robust overall effect of L. meyenii supplementation on blood biomarkers of muscle damage or protein catabolism in animals subjected to physical stress. The high degree of heterogeneity could not be robustly explained by either the type of formulation or the dose. These findings, which are exploratory and hypothesis-generating in nature, highlight the need for standardized, well-characterized formulations and trials with adequate statistical power. Full article

Background/Objectives: Diabetic cardiomyopathy (DCM) is largely driven by severe oxidative stress and calcium dyshomeostasis. We examined the targeted antioxidant and therapeutic effects of zinc sulfate (ZnSO₄) on contractile dynamics, oxidative damage, calcium turnover, and apoptosis/fibrosis in aged female rats with type 2 diabetes. Methods: Thirty-two aged female Wistar rats were divided into Control, Control + ZnSO₄, Diabetes (DM), and DM + ZnSO₄ groups. DM was induced via high-fat diet and 30 mg/kg streptozotocin. After a 4-week complication period, treatment groups received 10 mg/kg/day ZnSO₄ (i.p.) for 6 weeks. Left ventricular papillary muscle contraction, oxidative/antioxidant markers (MDA/GSH), and gene expressions (SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, PLN) were evaluated. Myocardial architecture, fibrosis, and apoptosis were analyzed immunohistochemically. In DM rats, contractile force (CF) and velocities (±dF/dtmax) significantly declined. Results: Concurrently, SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, and antioxidant GSH decreased, while oxidative lipid damage (MDA), PLN, Caspase-3 activity, Collagen I, and fibrosis increased (p < 0.001). ZnSO₄ treatment in diabetic rats acted as a potent antioxidant modulator; it restored redox balance, activated the SIRT1/GLUT4 pathway, protected calcium-handling proteins from oxidative degradation, and significantly improved contractile dynamics. It also preserved myocardial architecture by reducing apoptosis and fibrosis. In healthy rats, ZnSO₄ caused mild stress and early fibrosis. Conclusions: In conclusion, while inducing mild stress in healthy myocardium, zinc supplementation provides robust antioxidant protection in diabetic hearts. It activates SIRT1, suppresses oxidative damage, maintains calcium homeostasis, and restores contractile dynamics, demonstrating strong antioxidant therapeutic potential against DCM. Full article

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies. Full article