Search Results (1,943)

Chronic kidney disease, acute kidney injury and cardiorenal syndrome are major determinants of cardiovascular morbidity and mortality, yet conventional renal assessment based on serum creatinine, estimated glomerular filtration rate and urine output often fails to detect early structural injury or pathway-specific cardiorenal risk. This narrative review synthesized recent evidence on emerging renal and cardiorenal biomarkers with potential value for cardiovascular risk stratification beyond creatinine. Literature published between 2015 and April 2026 was reviewed, focusing on biomarkers of tubular injury, functional renal impairment, fibrosis/remodeling and mineral metabolism. NGAL and KIM-1 may detect tubular stress and proximal tubular injury before overt functional decline and have shown relevance in heart failure, acute coronary syndromes and post-cardiac surgery settings. Cystatin C and pro-enkephalin refine functional renal assessment and may improve prognostic classification when creatinine is confounded by frailty, muscle mass or acute hemodynamic changes. Soluble ST2 and galectin-3 reflect inflammation, fibrosis and cardiorenal remodeling, while FGF-23 links kidney dysfunction to cardiovascular risk through phosphate imbalance, vascular calcification and myocardial hypertrophy. Multi-biomarker panels may help identify dominant cardiorenal phenotypes and personalize monitoring intensity. However, routine implementation requires standardized assays, validated thresholds, cost-effectiveness data and prospective evidence that biomarker-guided management improves clinical outcomes. Full article

Background: Continuous-flow left ventricular assist devices (LVADs) and heart transplantation (HTX) improve survival and quality of life in advanced heart failure. However, restoration of central hemodynamics does not consistently normalize exercise capacity, physical performance, or body composition. Persistent skeletal muscle dysfunction, endothelial abnormalities, metabolic disturbances, and adverse body composition changes frequently limit functional recovery. Methods: This narrative review examines determinants of rehabilitation outcomes across the transition from advanced heart failure to LVAD support and subsequent HTX. Particular emphasis is placed on restoration of pulsatile circulation, vascular and microcirculatory adaptation, immunosuppressive therapy, body composition remodeling, and emerging immunometabolic mechanisms. Results: Rehabilitation outcomes appear to be increasingly determined by peripheral rather than central cardiovascular factors. Continuous-flow LVAD support induces vascular, endothelial, autonomic, and microcirculatory adaptations that may persist after transplantation. Although HTX restores physiological pulsatile circulation and cardiac output, recovery is often limited by skeletal muscle dysfunction, impaired mitochondrial capacity, chronotropic abnormalities, and adverse body composition changes. Immunosuppressive therapies further influence muscle plasticity, adipose tissue distribution, insulin sensitivity, endothelial function, and exercise adaptation, contributing to phenotypes such as sarcopenia, myosteatosis, and sarcopenic obesity. Conclusions: Functional recovery after LVAD support and HTX is a multidimensional process extending beyond restoration of cardiac function. We propose a hemodynamic–immunometabolic framework in which vascular adaptation, skeletal muscle biology, body composition remodeling, and immunosuppressive therapy interact to determine rehabilitation success and may inform personalized rehabilitation strategies. Full article

Weekend cyclists are individuals who engage in vigorous physical activity only on weekends, as opposed to those who exercise regularly during the week. Research suggests that concentrating physical training on one or two days may benefit heart health and metabolism, similar to exercising regularly. However, it remains unclear whether weekend cyclists exhibit similar adaptations in metabolic, performance, and muscle oxygenation markers. The aim of this study is to compare cardiorespiratory fitness, body composition, cardiometabolic risk markers, muscle strength, and muscle oxygenation between cyclists who concentrated training on weekends and cyclists who distributed training across three or more days per week. In this study, we used an analytical, observational, non-experimental design that recruited 28 cyclists, divided into weekend cyclists (n = 14) and regular cyclists (n = 14). Body composition, blood tests, lower body strength, aerobic capacity, and muscle oxygen saturation were assessed. Results: Weekend cyclists exhibited lower VO₂max (36.7 ± 3.9 vs. 48.9 ± 6.3 mL·kg⁻¹·min⁻¹), lower knee extension strength (3.16 ± 0.57 vs. 4.42 ± 0.83 Nm·kg⁻¹), and reduced ΔSmO₂ responses during exercise compared with regular cyclists (all p < 0.05). In addition, weekend cyclists presented higher body fat percentage (25.9 ± 3.8 vs. 17.2 ± 4.2%), greater waist circumference (90.5 ± 4.3 vs. 83.6 ± 5.1 cm), and lower HDL cholesterol levels (54.2 ± 8.4 vs. 64.1 ± 11.0 mg/dL). In conclusion, weekend cyclists have lower cardiorespiratory fitness, muscular strength, and reduced ΔSmO₂ responses during incremental exercise, along with higher levels of visceral fat and triglycerides, compared to those who train three or more days a week. The distribution and frequency of training within their workout plans were associated with differences in cardiorespiratory fitness and cardiometabolic markers. Full article

Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-β) superfamily, thereby regulating diverse physiological processes, including regulation of skeletal muscle, adipose, and bone homeostasis. FST also promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles and metabolic health in mice. Given the emerging association between brown adipose tissue (BAT) activation and reduced atherosclerosis, we investigated the anti-atherogenic potential of FST. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area and positively correlated with the expression of multiple adipose browning-associated genes. Adeno-associated viral delivery of Fst (AAV1-FST344) in Ldlr^−/− mice significantly reduced aortic lesion area, improved plasma lipid profiles, and decreased expression of adhesion (VCAM1) and inflammatory (iNOS, TNF-α) markers in white adipose tissue (WAT), liver, and heart. Fst gene delivery also markedly increased uncoupling protein 1 (UCP1) expression in WAT, consistent with WAT browning. Integrated correlation analyses of Fst expression with tissue metabolites, together with plasma metabolite–lesion associations identified in the HMDP, implicated the arginase 1 (Arg1)-mediated metabolic pathway as a key regulator of atherogenesis. Consistent with these findings, Arg1 expression was significantly elevated in WAT, liver, and heart of AAV1-FST344-treated mice and in wild-type versus Fst-knockout mouse embryonic fibroblasts (MEFs). Immunostaining localized Arg1 predominantly to CD68⁺ macrophages in heart and liver. Given recent evidence identifying Arg1 as a novel mediator of efferocytosis, these findings suggest that Arg1 may promote macrophage metabolic reprogramming and resolution of inflammation by enhancing the clearance of apoptotic cells. Furthermore, Fst gene delivery increased the expression of fibroblast growth factor 21 (Fgf21) and adiponectin (AdipoQ) in WAT. Collectively, these findings identify Fst as a novel anti-atherogenic regulator that protects against vascular disease by promoting adipose browning, improving lipid metabolism, and activating Arg1-mediated metabolic pathways. Full article

Background: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication driven by inflammatory cascades. Current genetic studies are restricted to single-trait analyses that cannot capture the shared genetic architecture spanning from immune dysregulation to structural myocardial damage. Methods: We applied genomic structural equation modeling to integrate genome-wide association study (GWAS) summary statistics for six phenotypes—sepsis, cardiac troponin I, left ventricular ejection fraction (LVEF), left ventricular diastolic strain rate, right ventricular peak ejection rate, and heart failure—constructing a latent factor for the shared genetic basis of SICM-related phenotypes. Downstream analyses included multivariate GWAS, fine-mapping (SuSiE/FINEMAP), sparse canonical correlation analysis-based transcriptome-wide association study (sCCA-TWAS) with FOCUS prioritization, MAGMA gene-set enrichment, cell-type enrichment (CELLECT), spatial transcriptomic mapping (gsMap), and stratified LD score regression (S-LDSC). Results: The model showed adequate fit (CFI = 0.936), with left ventricular diastolic strain rate and LVEF anchoring the factor most strongly (λ = 0.811 and 0.636, respectively). Multivariate GWAS identified 4220 lead variants, of which 4197 did not reach genome-wide significance in any constituent single-trait GWAS. Cross-referencing sCCA-TWAS with FOCUS fine-mapping prioritized 39 genes spanning inflammatory transduction, gap junction remodeling, proteostatic defense, and energy sensing. AMPK signaling was recurrently captured across fine-mapping and transcriptome-wide analyses. CELLECT identified cardiac muscle cells as the sole significant cell type. Conclusions: This study provides the first integrative multi-trait genetic framework for the shared genetic basis of SICM-related phenotypes, identifying AMPK as a recurrently captured pleiotropic hub at the inflammation–metabolism intersection and providing a foundation for future biomarker and mechanistic investigations. Full article

Background and Objectives: Cachexia is a systemic wasting syndrome associated with poor outcomes in chronic diseases, including heart failure (HF). Although the cachexia index (CXI), which integrates skeletal muscle mass, serum albumin, and the neutrophil-to-lymphocyte ratio, has shown prognostic value in oncology, its clinical significance in HF remains poorly defined. Materials and Methods: This retrospective single-center cohort study evaluated a selected subgroup of adults hospitalized with decompensated heart failure between January 2020 and January 2025 who had undergone abdominal computed tomography within the preceding 6 months, enabling CT-based body composition assessment. Skeletal muscle index was measured at the L3 vertebral level, and CXI was calculated as (SMI × serum albumin)/neutrophil-to-lymphocyte ratio. Patients were followed for all-cause mortality and HF-related rehospitalizations. Results: A total of 127 patients were included (mean age 70.45 ± 12.73 years; 51.2% male). CXI showed excellent discrimination for mortality (AUC 0.951; 95% CI 0.905–0.996), with an optimal cut-off value of <20.87. Patients with low CXI had significantly higher all-cause mortality (80.5% vs. 4.7%, p < 0.001) and more HF-related hospitalizations [4 (3–5) vs. 0.5 (0–1), p < 0.001] than those with high CXI. Conclusions: In patients hospitalized with decompensated HF, low CXI was strongly associated with all-cause mortality and recurrent hospitalization, suggesting that CXI may serve as an integrative prognostic marker in this population. Full article

Yaks have long inhabited the Qinghai-Tibetan Plateau. This region features low-oxygen, frigid temperatures and pronounced seasonal variation in nutrient availability. They have evolved adaptive phenotypes centered on energy metabolism reprogramming, tissue structure remodeling, and stress homeostasis maintenance. In recent years, non-coding RNAs (ncRNAs) have been confirmed as an important component of the yak’s post-transcriptional regulatory network. They play a key bridging role between environmental stress perception and phenotypic output through mechanisms such as influencing RNA splicing, stability, translation activity, and constructing competitive endogenous RNA (ceRNA) networks. This article systematically reviews the biogenesis pathways and core regulatory patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). It focuses on summarizing the expression profile characteristics and dynamic spatiotemporal changes of these three types of ncRNAs in physiological contexts such as muscle and fat deposition, mammary gland lactation, testicular development, and hypoxia response in the heart, lungs, and vascular system of yaks. Current research evidence indicates that the regulatory network of yaks ncRNAs shows significant convergence on multiple key signaling pathways, mainly concentrating on lipid metabolism (PPAR/AMPK), nutrition and growth signals (PI3K-Akt/MAPK/mTOR), extracellular matrix remodeling (ECM-receptor interaction, Wnt/TGF-β), and cell stress fate determination (apoptosis, oxidative stress/ferroptosis) modules. Among them, some core circRNA and lncRNA-miRNA-mRNA regulatory axes have been functionally validated in vitro. Despite the phased progress, current research on ncRNA in yaks still faces bottlenecks: the multi-omics molecular atlases (encompassing genomics, transcriptomics, proteomics, and metabolomics) of key high-altitude adaptive organs remain incomplete, analysis processes lack sufficient standardization, and most studies stay at the association network level with limited causal mechanism validation. To address these limitations, future research should focus on building a standardized evidence chain, integrating multi-omics and single-cell/spatial transcriptome technologies, and conducting mechanism verification for traits in independent populations, thereby providing a solid theoretical basis for understanding the extreme environmental adaptation mechanisms of yaks and molecular breeding improvement. 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

Genetic cardiomyopathies (GCMs) are chronic heart muscle disorders requiring lifelong monitoring and treatment. Although quality of life (QoL) and health-related quality of life (HRQoL) are increasingly recognized as important outcomes in cardiomyopathy care, their conceptualization and measurement remain inconsistent. This scoping review aims to (a) identify the tools most commonly used to assess QoL and HRQoL in adults with genetic cardiomyopathies and (b) map the thematic areas of existing studies, including symptom burden, psychological distress, diagnostic challenges, and the impact of medical and psychological interventions. PubMed, Scopus, and PsycINFO were systematically searched, and the final search was completed in November 2025. Seventeen peer-reviewed studies met the inclusion criteria and were included in this scoping review. The review followed the PRISMA extension for Scoping Reviews and included both quantitative, qualitative and mixed-methods designs. Most studies employed standardized tools such as EQ-5D (N = 5), SF-36/SF36v2 (N = 5), and the Kansas City Cardiomyopathy Questionnaire (N = 3), while others included the Minnesota Living with Heart Failure Questionnaire (N = 2) and disease-specific or ad hoc measures. The most frequently investigated themes included impairments in physical functioning, emotional well-being, symptom burden, psychological distress, and social participation. Several studies showed that patients’ perceived QoL was more closely associated with symptom burden and psychological adjustment than with objective clinical indicators alone. Clinical interventions showed mixed or limited effects on QoL and HRQoL outcomes, even when clinical parameters improved. Qualitative research further emphasized the lived experiences of patients and families, highlighting unmet needs in care. Less commonly addressed findings concerned caregiver perspectives, patient–provider communication, treatment adherence, socioeconomic disadvantage, healthcare costs, productivity loss, and the experiences of patients with rarer cardiomyopathy-related conditions. The results highlight how QoL and HRQoL are central but still inconsistently assessed outcomes in cardiomyopathy research. This review calls for greater conceptual clarity between QoL and HRQoL, greater standardization in measurement tools, broader inclusion of psychosocial variables, and more patient-centred research approaches to better support individuals living with cardiomyopathies. Full article

Although considerable research has investigated non-motorized treadmills (NMTs), most studies have focused on healthy adults or athletes. This study aimed to compare trunk and lower limb muscle activation during walking on an NMT and flat ground (FG) at different exercise intensities in patients with stroke. Eighteen patients with stroke participated in this within-subject, repeated-measures experimental study conducted at a single hospital. Participants performed walking trials under six randomized conditions, comprising both NMT and FG walking at intensities of 20%, 40%, and 60% of heart rate reserve (HRR). Muscle activation of the affected-side erector spinae, internal oblique, gluteus medius, gluteus maximus, vastus medialis oblique, biceps femoris, and lateral gastrocnemius was assessed. Walking on the NMT resulted in significantly greater overall muscle activation than walking on FG (p < 0.05). In addition, significant differences in trunk and lower limb muscle activation were observed across HRR levels during both NMT and FG walking (p < 0.05), indicating that exercise intensity influenced neuromuscular responses. These findings suggest that NMT walking, particularly at higher intensities, acutely increases neuromuscular demands, providing preliminary evidence for its potential application as a demanding walking condition for stroke rehabilitation. Full article

Lactate was traditionally considered a metabolic by-product of anaerobic glycolysis, mainly associated with tissue hypoxia and muscle fatigue. However, increasing evidence has redefined lactate as a multifunctional metabolic intermediate and signaling molecule involved in exercise-induced systemic adaptations. During physical activity, circulating lactate levels rise markedly when skeletal muscle production exceeds systemic clearance, allowing lactate to act as an exercise-responsive metabolite, or exerkine, and as a mediator of cardiometabolic adaptation. In the cardiovascular system, lactate serves not only as an efficient substrate for myocardial energy production but also as a regulator of vascular tone, endothelial function, angiogenesis, inflammation, and cardiac remodeling. These effects occur through receptor-dependent and receptor-independent mechanisms, including activation of hydroxycarboxylic acid receptor 1 (HCAR1/GPR81), modulation of intracellular redox balance, and histone or non-histone protein lactylation. This review summarizes current evidence on lactate in cardiovascular physiology and disease, focusing on myocardial lactate metabolism, HCAR1/GPR81 signaling, protein lactylation, extracellular vesicle communication, gut microbiota interactions, and therapeutic implications in heart failure, atherosclerosis, and diabetic cardiomyopathy. Although lactate is also produced under resting, postprandial, and pathological conditions, exercise is characterized by the amplitude and kinetics of lactatemia, coordinated hormonal and hemodynamic responses, and transient high-concentration signaling. These features support exercise-derived lactate as a context-dependent cardiovascular exerkine. Full article

Aging is a systemic degenerative process that can lead to functional decline in multiple organs, such as skeletal muscles and the heart, and accelerates the overall aging process through organ-to-organ interactions mediated by metabolites such as short-chain fatty acids (SCFAs). SCFAs serve as a crucial link connecting intestinal health and anti-aging, and their levels and functions undergo significant changes with aging. However, current research lacks understanding of the downstream molecular mechanisms of SCFAs, and intervention methods are mostly limited to simple regulation. This article clarifies the intrinsic relationship between SCFAs and aging from a systemic perspective, analyzes their regulatory mechanisms through key signaling pathways, examines their roles in tissue barrier protection, the improvement of metabolic disorders, and immune regulation, and summarizes their therapeutic potential and diversified intervention strategies in aging-related diseases. The detailed molecular mechanisms by which SCFAs regulate aging are still unclear, and there are no precise intervention plans for different aging stages and organ damage. In the future, we need to utilize techniques such as single-cell sequencing and organ models to explore the regulation of aging cell fates, providing support for the development of metabolite-mediated personalized anti-aging intervention measures. Full article

Background/Objectives: Implant-associated infections are challenging conditions in orthopedic surgery. This experimental study aimed to evaluate phage localization within infected tissues following different routes of administration. Methods: An implant-related infection model was created using methicillin-resistant Staphylococcus aureus (MRSA) in twenty-four rats. Subjects were randomly divided into four groups depending on the bacteriophage administration route. Three rats were designated as the control group. Phage suspension was applied intraperitoneally, intravenously, orally and locally at 0.1 mL/day of 1 × 10⁸ PFU/mL suspension for three consecutive days. In the control group, intravenous, intraperitoneal and oral phage suspensions were administered separately at the same dose for 3 days. After completion of the experiment, tibia samples were taken in the experimental group. Additionally, liver, kidney, stomach, brain, heart muscle and striated muscle tissue samples were taken from the three subjects in the control group. Results: In the control group, unconfirmed phage-like structures were incidentally observed in some mitochondria of renal proximal tubular epithelial cells on transmission electron microscopy. In the experimental group, there was a strong positive linear relationship between the total number of bacteria and the number of bacteriophage clusters, independent of the groups. Conclusions: Bacteriophage clusters were detected in infected tibial tissues after all administration routes, suggesting phage localization at the infection site. Unexpected phage-like clusters were observed within mitochondria of proximal tubular epithelial cells in the control animals. This finding should be regarded as an unconfirmed incidental finding requiring further validation. 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

Pulmonary hypertension (PH) is a progressive, multifactorial syndrome characterized by elevated pulmonary arterial pressure and right heart dysfunction, associated with significant morbidity, impaired quality of life, and poor prognosis. Advances in classification, hemodynamic definitions, and targeted pharmacotherapies have improved understanding and management, yet therapeutic challenges persist across the five World Health Organization groups of PH. Historically, exercise was discouraged due to concerns about adverse hemodynamic effects, but growing evidence has suggested that structured, supervised training is safe and beneficial. Randomized trials and meta-analyses show improvements in six-minute walk distance, peak oxygen uptake, right ventricular function, ventilatory efficiency, and health-related quality of life, with a low incidence of adverse events. Physiological adaptations include favorable cardiac remodeling, enhanced endothelial function, improved skeletal and respiratory muscle performance, and improved neurohormonal activity. Despite this evidence, barriers such as patient fears, limited clinical expertise, and restricted access to specialized rehabilitation programs hinder widespread implementation. Current guidelines recommend supervised exercise as part of pulmonary rehabilitation for patients with stable PH, supporting its role as an adjunct to pharmacotherapy. This descriptive review briefly summarizes the pathophysiology of PH, phenotype-related differences and current therapeutic approaches, and the beneficial adaptations to exercise training, with the aim of informing exercise specialists and supporting safer, more effective integration of exercise-based rehabilitation into patient care. Full article