Search Results (96)

Acute heart failure (AHF) causes abrupt hemodynamic disturbances, including reduced forward flow and venous congestion, which may extend beyond the heart and contribute to peripheral organ stress. Skeletal muscle may be particularly vulnerable to these changes, but the relationship between acute hemodynamic status and circulating markers of skeletal muscle stress and regulation remains unclear. We prospectively enrolled 35 men hospitalized with AHF and non-invasively assessed their cardiac index (CI) by impedance cardiography and right atrial pressure (RAP) by echocardiography. Plasma carbonic anhydrase III (CA3), creatine kinase-MM (CK-MM), lactate, myostatin, and follistatin were measured at admission, discharge, and 30 days after discharge. Patients were analyzed according to low CI, defined as CI < 2.2 L·min⁻¹·m⁻²; elevated RAP, defined as RAP ≥ 8 mmHg; and combined CI/RAP profiles. CA3 and CK-MM were higher in patients with low CI or elevated RAP and were highest in the low-CI/elevated-RAP profile. CA3 and lactate did not significantly change during follow-up, whereas CK-MM modestly increased at 30 days. Myostatin and follistatin were highest at admission and decreased after clinical stabilization. In this pilot cohort of men hospitalized with AHF, estimated lower perfusion and greater venous congestion were associated with higher circulating markers of skeletal muscle stress, while muscle regulatory myokines declined after stabilization. These findings suggest that skeletal muscle-related biomarkers may reflect peripheral consequences of acute hemodynamic disturbance in AHF and warrant further investigation in larger cohorts. Full article

Background: Bone remodeling depends on the dynamic balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Follistatin-like 1 (FSTL1) has been reported as an osteoclast-secreted protein that inhibits osteoclast differentiation, but its direct effects on osteoblast differentiation remain unclear. This study aimed to determine whether FSTL1 regulates osteoblast differentiation and mesenchymal stem cell migration and characterizes its role in osteoclast-osteoblast cellular cross-talk under in vitro conditions. Methods: Bone marrow-derived macrophages (BMMs) and stromal cells (BMSCs) from mice were used to induce osteoclast and osteoblast differentiation, respectively. Chemotaxis was assessed by Transwell migration, and osteoblast differentiation was evaluated in BMSC and MC3T3-E1 cells using staining, qRT-PCR, Western blotting, and proliferation assays. Results: FSTL1 significantly suppressed osteoclast differentiation and resorptive activity, confirmed by TRAP staining and pit assay, respectively. Expression of osteoclast markers such as NFATc1, TRAP, and DC-STAMP was reduced under FSTL1 treatment. In BMSCs, FSTL1 did not affect proliferation but significantly enhanced chemotaxis. Moreover, FSTL1 promoted osteogenic differentiation and mineralization, as demonstrated by increased ALP activity and Alizarin Red S staining. In MC3T3-E1 pre-osteoblasts, FSTL1 increased cell proliferation and mineralization by MTS and Alizarin Red staining. Key osteogenic markers, including Runx2 and osteocalcin, were also upregulated. Conclusions: Osteoclast-derived FSTL1 significantly suppresses osteoclastogenesis and promotes mesenchymal cell chemotaxis and osteogenic differentiation, indicating a role in regulating osteoclast–osteoblast cellular interactions in vitro. Targeting FSTL1 signaling may represent a promising therapeutic strategy for osteoporosis and other disorders of impaired bone remodeling. Full article

Objective: This study evaluated the effects of a 12-week High-Intensity Functional Training (HIFT) program combined with thylakoid supplementation on plasma adipo-myokine levels (Decorin, Myostatin, Follistatin, Activin A, and TGF-β1) in men with obesity. Secondary outcomes included anthropometric indices, lipid profiles, and insulin resistance markers. Methods: Sixty men with obesity (age: 27.6 ± 8.4 years; BMI: 32.6 ± 2.6 kg/m²) were randomly assigned to four groups (n = 15 per group): Placebo (PG), Supplement (SG), HIFT + placebo (TPG), and HIFT + supplement (TSG). To ensure robustness against the 27% attrition rate, statistical analyses included both per-protocol and intention-to-treat (ITT) models. HIFT was performed for 3 sessions/week (Borg scale: 15–17). Results: Following Bonferroni correction for multiple endpoints, repeated-measures ANOVA showed significant Time × Group interactions for most adipo-myokines and metabolic markers. Both training groups (TPG and TSG) demonstrated improvements in body composition and insulin sensitivity compared to PG (p < 0.05). While no significant differences were observed between TPG and TSG for systemic metabolic markers, preliminary data suggested that thylakoid supplementation might provide modest complementary modulations in specific myokines (e.g., decorin and follistatin). However, these observed trends did not reach clinical superiority over exercise alone in the broader metabolic profile. Conclusions: Twelve weeks of HIFT is an effective primary driver for modulating the adipo-myokine network in obese men. Although thylakoid supplementation showed potential for selective complementary effects on certain myokines, these findings are exploratory given the small sample size. The clinical significance and long-term complementary value of thylakoid-exercise interactions require further validation in larger, more diverse cohorts. Full article

Sarcopenia, defined as the progressive decline of muscle mass, strength, and function, severely compromises autonomy and quality of life in older adults. This systematic review evaluated synergistic effects of protein supplementation combined with resistance exercise on biochemical and functional biomarkers of sarcopenia. The search for scientific evidence was conducted in PubMed, Scopus, ScienceDirect, and Cochrane databases (2019–2025), applying explicit inclusion and exclusion criteria, like only randomized controlled trials in humans, published in English, Spanish, or French, were included to ensure high-quality evidence. After selection, the risk of bias of the articles was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Seven randomized controlled trials, with a total of 260 participants, met the eligibility criteria. Interventions combining resistance exercise three times per week at 60–80% of one-repetition maximum with daily protein supplementation of at least 15 g, mainly from dairy sources, showed synergistic effects. Improvements were observed in inflammatory and anabolic biomarkers, with reductions in myostatin, activin, and IL-6, and increases in IGF-1, follistatin, and IL-10. Functional outcomes included gains in muscle strength, fat-free mass, and muscle fiber cross-sectional area. Despite heterogeneity in duration and sample size, findings support this combined approach as a promising and clinically applicable strategy to prevent and treat sarcopenia. No external funding was received, and the review is registered in PROSPERO (CRD42025640989). Full article

Background/Objectives: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) represents one of the major contributors to morbidity and mortality in Rheumatoid arthritis (RA), yet its underlying molecular mechanisms remain incompletely defined. Activin A, a member of the transforming growth factor-β (TGF-β) superfamily, has emerged as a key regulator of inflammation, fibroblast activation, and tissue remodeling. However, its role in RA patients with interstitial lung disease (ILD) has not been fully elucidated. We aimed to investigate circulating levels of Activin A, Follistatin-Like Protein-1 (FSTL1), and Follistatin-Like Protein-3 (FSTL3) in patients with RA, RA-ILD, idiopathic pulmonary fibrosis (IPF), and healthy controls and explore their associations with disease activity and pulmonary function parameters. Methods: This cross-sectional study included 90 participants: healthy controls (n = 20), RA (n = 25), RA-ILD (n = 21), and IPF (n = 24). Serum biomarkers were quantified using validated enzyme-linked immunosorbent assays (ELISAs). Clinical characteristics, inflammatory markers, disease activity indices, and pulmonary function tests were recorded. Group comparisons and correlation analyses were performed using appropriate parametric and non-parametric statistical methods. Results: Circulating Activin A levels were progressively increased from controls to RA, RA-ILD, and IPF, with significantly higher concentrations in all disease groups relative to controls. FSTL1 levels were significantly reduced in RA-ILD patients compared with RA and controls, while FSTL3 levels were markedly elevated in IPF. Activin A did not correlate with disease activity indices or pulmonary function parameters, whereas FSTL1 correlated positively with diffusing capacity of the lungs for carbon monoxide and disease duration, and FSTL3 showed an inverse association with lactate dehydrogenase. Conclusions: Activin A may be associated with the fibroinflammatory burden in both RA-ILD and IPF. The observation of altered circulating levels of Follistatin-like proteins—key regulatory molecules with multifaceted biological functions—suggests that the underlying pathogenesis is complex and governed by tightly regulated, interconnected signaling pathways. Full article

Sarcopenia is a progressive, age-related loss of skeletal muscle mass, strength, and function, strongly associated with frailty, disability, and chronic disease. Its pathogenesis involves chronic low-grade inflammation, hormonal imbalance, and impaired anabolic signaling, making biomarkers essential for diagnosis, prognosis, and intervention monitoring. This review systematically analyzes randomized controlled trials (RCTs) evaluating the impact of physical exercise on biomarkers relevant to sarcopenia. Exercise modulates both pro-inflammatory markers (e.g., IL-6, TNF-α, CRP) and anti-inflammatory cytokines (e.g., IL-10, IL-15), while also affecting growth factors like IGF-1, myostatin, and follistatin. These changes support muscle anabolism, reduce catabolic signaling, and improve physical performance. In addition, we highlight a growing class of emerging exerkines, including irisin, apelin, beta-aminoisobutyric acid (BAIBA), decorin, brain-derived neurotrophic factor (BDNF), and meteorin-like factor (Metrnl). These molecules exhibit promising roles in mitochondrial health, lipid metabolism, muscle regeneration, and immune modulation, key processes in combating inflamm-aging and sarcopenic decline. Despite encouraging findings, biomarker responses remain heterogeneous across studies, limiting translational application. The integration of biomarker profiling with exercise prescription holds the potential to personalize interventions and guide precision medicine approaches in sarcopenia management. Future large-scale, standardized trials are needed to validate these biomarkers and optimize exercise protocols for aging populations. Full article

Duchenne muscular dystrophy (DMD), which results from mutations that disrupt the expression of dystrophin proteins, is characterized by progressive muscle fiber wasting and the development of skeletal muscle fibrosis. The severe pathology leads to loss of ambulation, respiratory insufficiency, cardiomyopathy, and early death in patients. Dystrophin-focused therapies based on adeno-associated viral (AAV) vector-mediated gene addition, antisense oligonucleotide-induced repair of the transcript reading frame, and chemically driven stop codon readthrough have been conditionally approved for use in subsets of patients. From trials, it is apparent that these therapies act to stabilize the disease phenotype rather than improve it significantly, meaning that early treatment results in better outcomes. AAV-mediated delivery of a form of utrophin, a structural and functional homolog of dystrophin, GALGT2, a sarcolemmal stabilizer, and Klotho, the anti-aging hormone that is silenced in a mouse model of DMD as a result of the disease pathology, have been explored in preclinical compensatory gene addition studies. Recombinant follistatin protein has been used to target the fibrosis seen. An all-in-one type of therapy is likely to provide a synergistic effect such that efficacy of the dystrophin restoration strategy would be improved. For this, CRISPRa could hold potential through the targeting of multiple relevant genes simultaneously. The suitability of targeting these genes will be discussed, as will the stages of the development of CRISPRa for DMD. A perspective on the future prospects of CRISPRa in relation to likely issues that would need addressing and how they may be overcame will be given. Full article

Muscle growth is a critical determinant of meat yield and quality in livestock. Although follistatin (FST) is recognized as a key regulator of skeletal muscle development and fat metabolism, its specific function in geese remains largely unexplored. In this study, we identified two transcript variants of goose FST (gFST) in Zhedong White geese: gFST-X1 (1125 bp), encoding a 343-amino acid protein with a 28-amino acid signal peptide and four conserved domains, and gFST-X2, which contains a 243 bp insertion within the gFST-X1 transcript. RT-qPCR analysis revealed that gFST mRNA expression varied across tissues from female embryos (25 days), adults (70 days), and laying geese (270 days), as well as in skeletal muscle satellite cells (SMSCs) at embryonic day 16 (E16d). Overexpression of gFST in SMSCs resulted in 3596 differentially expressed genes (DEGs), including 2247 upregulated and 1349 downregulated genes (padj < 0.01). Key stemness markers (PAX7, PAX3) and myogenic regulators (MYOG, MYOD, MYF5) were significantly downregulated, whereas genes associated with lipid metabolism (PPARG, FABP5, ACSL5) and myosin-related processes (MYO1D, MYO1F, MYO1E) were markedly upregulated (padj < 0.01). Functional enrichment analysis linked these DEGs to the TGF-β, PPAR signaling, fatty acid metabolism, and Notch signaling pathways. These transcriptomic findings were further validated by qRT-PCR. Collectively, our results demonstrate the dual regulatory role of gFST in skeletal muscle development and provide new mechanistic insights into muscle development in geese. Full article

In recent years, Meteorin-like protein (Metrnl/IL-41) and Follistatin-like 1 (FSTL1) have emerged as multifunctional molecules that play roles in immunity, metabolism and tissue remodeling. Although they demonstrate pleiotropic effects, they are promising candidates for biomarkers and possible therapeutic targets. The development of new, disease-specific biomarkers will enable clinicians to more effectively monitor inflammatory activity, more accurately assess disease severity, better predict survival, and select appropriate medical treatments. In this review, we present the role of Meteorin-Like Protein (Metrnl) and Follistatin-like 1 (FSTL1) in inflammation in autoimmune rheumatic diseases, as well as in other autoimmune pathologies, cardiovascular diseases, and metabolic diseases. Metrnl, widely expressed in different tissues and organs, is very important for inflammation, immune responses and metabolic disorders. FSTL1 also shows dynamic changes in its expression through various diseases, including cardiovascular conditions, cancer, asthma, and arthritis. Both proteins participate in multiple important signaling pathways, and understanding their diagnostic and therapeutic potential holds great scientific interest. Their complex nature requires careful evaluation of safety concerns and translation to clinical practice. Full article

Purpose: This study sets out to analyze the correlation of ET-1, a vasoactive peptide, along with various cytokines and vascular factors, with clinical parameters and OCT/OCT-A measurements in glaucoma participants. Methods: Eyes of participants with cataract (n = 30) or glaucoma (n = 87) were examined with optical coherence tomography (OCT) and OCT angiography (OCT-A). Aqueous humor (AqH) from the examined eye and plasma were sampled during cataract or glaucoma surgery and analyzed by means of ELISA and Luminex assay to determine their levels of ET-1 and 35 proteins deemed relevant for regulation of the AqH outflow pathway, ocular perfusion (OP), and glucose metabolism. Results: Glaucomatous eyes are characterized by reductions in RNFL thickness and OP, reflected by reduced vessel density. Furthermore, significantly elevated peripheral ET-1 levels were detected in participants with glaucoma. In addition, significantly elevated AqH levels of MMP-2, MMP-3, ET-1, sEMMPRIN, ZAG, sLOX-1, follistatin, cortisol, endostatin, sTIE-2, and PDGF-BB were detected in the glaucomatous eyes, with correlation to reduced VD for APN, C3a, MMP-3, resistin, sTIE-2, and ZAG. Multivariable analysis showed a correlation of AqH APN levels with the reduced VD in glaucomatous eyes. Conclusions: The peripheral ET-1 level and the intraocular levels of APN, C3a, MMP-3, resistin, sTIE-2, and ZAG are associated with impaired OP in glaucoma. Furthermore, elevated intraocular levels of MMP-3, ZAG, and APN were identified as biomarkers for impaired perfusion in glaucoma. Full article

The COVID-19 pandemic has revealed significant secondary complications affecting musculoskeletal (MSK) health, especially in patients with pre-existing conditions. This review synthesizes data from clinical and experimental studies on key MSK biomarkers, including cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), osteocalcin, alkaline phosphatase (ALP), procollagen type I N-terminal peptide (PINP), osteopontin (OPN), matrix metalloproteinases (MMP-3 and MMP-9), myostatin, IGF-1, follistatin, and creatine kinase. COVID-19 is associated with decreased COMP and osteocalcin levels, indicating cartilage degradation and impaired bone formation, alongside elevated HA, ALP, PINP, OPN, and MMPs, reflecting increased joint inflammation, bone remodeling, and tissue breakdown. Changes in myostatin, IGF-1, follistatin, and creatine kinase levels have been shown to be linked with COVID-19-related sarcopenia. These biomarker alterations provide insight into the underlying mechanisms of MSK damage in COVID-19 patients and highlight the potential for using these markers in early diagnosis and management of post-COVID musculoskeletal disorders. Further longitudinal research is essential to develop targeted therapies aimed at mitigating long-term MSK complications in affected individuals. Full article

Background: Pancreatic cystic lesions may be benign and require observation or cancerous, with high mortality, requiring risky surgery. Diagnosis is often difficult, and the search for biomarkers to differentiate pancreatic cancer from other lesions is ongoing. Methods: 60 consecutive patients, operated on due to histopathologically confirmed pancreatic cancer or due to pancreatic cystic lesions, were analyzed. The concentrations of 16 immunological factors (sHER-2neu, sEGFR, sIL-6Ra, follistatin, FGF-basic, sVEGFR-2, PECAM-1, PDGF-AB BB, prolactin, G-CSF, HGF, sTIE-2, SCF, sVEGFR-1, osteopontin, and leptin) were assessed in both serum and cystic fluid and compared between the groups. Results: Lower PDGF-AB/BB and leptin concentrations in serum, as well as lower sTIE-2, osteopontin, and leptin levels, were associated with cancer. In cystic tumors, for some factors, significant differences between cancerous and benign lesions were found when the differences in cystic fluid and serum concentrations were compared. Conclusions: PDGF-AB/BB, leptin, sTIE-2, and osteopontin, as well as the comparison of serum/cystic fluid concentrations of immunological factors, might be useful for pancreatic cystic tumor diagnosis. However, this requires confirmation in a larger study. Full article

Rheumatoid arthritis (RA) is a highly prevalent chronic inflammatory rheumatic disorder leading to functional impairment and sequels. The search for new biomarkers helping in detecting RA subjects of high risk of functional disability is required. Studies showing high follistatin levels in RA have been described; however, none of them have placed focus on the role of follistatin as marker of deteriorated functionality. We aim to identify whether follistatin concentrations could be a potential biomarker of physical disability and disease activity in RA patients. Fifty-seven female RA subjects and 20 age–gender-matched controls were included in a cross-sectional evaluation. An assessment of clinical characteristics, grip strength, gait speed, and muscle mass was conducted. In RA subjects, disability was assessed using HAQ-DI and active disease using the DAS28-ESR. Follistatin levels were measured by ELISA. We compared (a) RA + functional disability and (b) RA + preserved physical function. Serum follistatin levels were increased in RA subjects compared to controls (175 ± 119 vs. 133 ± 47; p = 0.030). Follistatin levels correlated with deteriorated physical function levels (r = 0.491; p < 0.001) and severe activity (r = 0.344; p = 0.009). The RA + functional disability group, as compared to the RA + preserved physical function group, had higher serum follistatin levels (218 ± 159 vs. 141 ± 59; p = 0.030), lower grip strength (7.9 ± 4.6 vs. 14.5 ± 5.1; p < 0.001), reduced gait speed (0.77 ± 0.20 vs. 0.92 ± 0.20; p = 0.010), as well as higher proportions of tender joints ≥4 (48% vs. 16%; p = 0.008), and higher disease activity scores (3.8 ± 1.5 vs. 2.8 ± 1.2; p = 0.008). We concluded that higher follistatin levels are associated with physical functional impairment and the severity of disease activity in women with RA. Future studies are required to evaluate whether these follistatin levels can be related to other outcomes such as labor disability, hospitalization, and falls. Full article

Cardiovascular diseases, which are among the most common diseases of the population and among the leading causes of death, are a constant topic of many research centers. A deeper understanding of their pathogenesis may contribute to the development of innovative diagnostic and therapeutic techniques. Recently, the role of myokines—a group of cytokines secreted mainly by muscle cells—has been increasingly emphasized in the development of these diseases. Both their excess and deficiency can cause undesirable effects that are involved in the pathomechanism of these diseases. In this review, we focus on the latest studies on the role of myonectin, irisin, musclin, follistatin-like1 (FSTL1), dermcidin, apelin, and myostatin in the pathogenesis of coronary artery disease, heart attack, heart failure, and hypertension. In particular, we look at myostatin and irisin in the context of the development of heart failure and decreased levels of apelin with higher cardiovascular risk in a group of patients with rheumatoid arthritis. Full article

Background/Objectives: To investigate associations between Follistatin (FST) gene polymorphisms (SNPs) and baseline musculoskeletal traits, and their interactions with 16-week exercise interventions. Methods: A cohort of 470 untrained Northern Han Chinese adults (208 males, 262 females), sourced from the “Research on Key Technologies for an Exercise and Fitness Expert Guidance System” project, was analyzed. These participants were previously randomly assigned to one of four exercise groups (Hill, Running, Cycling, Combined) or a non-exercising Control group, and completed their respective 16-week protocols. Body composition, bone mineral content (BMC), bone mineral density (BMD), and serum follistatin levels were all assessed pre- and post-intervention. Dual-energy X-ray absorptiometry (DXA) was utilized for the body composition, BMC, and BMD measurements. FST SNPs (rs3797296, rs3797297) were genotyped using matrix assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) or microarrays. To elucidate the biological mechanisms, we performed in silico functional analyses for rs3797296 and rs3797297. Results: Baseline: In females only, the rs3797297 T allele was associated with higher muscle mass (β = 1.159, 95% confidence interval (CI): 0.202–2.116, P_{_adj} = 0.034) and BMC (β = 0.127, 95% CI: 0.039–0.215, P_{_adj} = 0.009), with the BMC effect significantly mediated by muscle mass. Exercise Response: Interventions improved body composition, particularly in females. Gene-Exercise Interaction: A significant interaction occurred exclusively in women undertaking hill climbing: the rs3797296 G allele was associated with attenuated muscle mass gains (β = −1.126 kg, 95% CI: −1.767 to −0.485, P_{_adj} = 0.034). Baseline follistatin correlated with body composition (stronger in males) and increased post-exercise (primarily in males, Hill/Running groups) but did not mediate SNP effects on exercise adaptation. Functional annotation revealed that rs3797297 is a likely causal variant, acting as a skeletal muscle eQTL for the mitochondrial gene NDUFS4, suggesting a mechanism involving muscle bioenergetics. Conclusions: Findings indicate that FST polymorphisms associate with musculoskeletal traits in Northern Han Chinese. Mechanistic insights from functional annotation reveal potential pathways for these associations, highlighting the potential utility of these genetic markers for optimizing training program design. Full article