Search Results (128)

Background: Anterior cruciate ligament (ACL) rupture, Achilles tendinopathy, and stress fracture are common sports injuries with significant long-term effects on performance and health. Despite similar exposure, injury susceptibility varies among athletes, suggesting a genetic component. Variants in COL1A1, COL5A1, ACTN3, MMP3, and GDF5 genes influence collagen integrity, muscle performance, and extracellular matrix remodelling, making them potential risk factors. Objective: To systematically review associations between five selected genes and musculoskeletal injury risk. Methods: Following PRISMA 2020 guidelines, PubMed, EMBASE, SPORTDiscus, and Web of Science were searched for studies examining these genes in relation to sports injuries. Data were extracted using Covidence and assessed for quality via the Newcastle–Ottawa Scale (NOS). Results: Twenty-six studies (n > 7000) were included. COL1A1 rs1800012 showed a protective effect against ACL rupture; COL5A1 rs1272 and rs13946 increased risk for ACL rupture and Achilles tendinopathy. MMP3 variants (rs679620, 5A/6A) showed variable associations, particularly in combination with COL5A1. ACTN3 R577X was linked to higher muscle and soft tissue injury risk in XX genotype carriers. Evidence for GDF5 rs143383 was limited but suggested a possible association with stress fractures. Conclusions: Genetic variants in COL1A1, COL5A1, MMP3, ACTN3, and GDF5 may influence susceptibility to ACL rupture, Achilles tendinopathy, and stress fractures. Larger, multi-ethnic studies are needed to validate these findings and inform personalised injury prevention strategies. Full article

Objective: Resistance exercise can induce muscle damage that impairs sports performance and cellular repair. Myokines, particularly mitochondrial myokines, play an important role in regulating energy metabolism and muscle recovery. The ACTN3 R577X polymorphism, which alters the expression of α-actinin-3 in muscle fibers, may influence myokine responses by modulating exercise adaptation and recovery. Methods: Seventy-five amateur runners (30–55 years) from the São Paulo International Marathon were evaluated. Plasma levels of mitochondrial myokines (BDNF, FGF-21, FSTL, IL-6, apelin, IL-15, musclin, and myostatin) were measured before and after the race and correlated with ACTN3 R577X genotypes. Results: In this study, the genotypic frequencies of the ACTN3 R577X polymorphism were 36% (RR), 39% (RX), and 14% (XX). Plasma concentrations of BDNF, FSTL, FGF-21, and IL-6 increased immediately after running across all genotypes, with no significant differences observed between genotypes. In contrast, plasma levels of myostatin, musclin, IL-15, and apelin decreased during the recovery period only among runners carrying the R allele. Conclusions: Mitochondrial myokine responses to resistance exercise were not substantially different among genotypes of the ACTN3 R577X polymorphism. However, myokines associated with protein breakdown and bioenergetic adaptation were reduced during the recovery period in runners carrying the R allele, which may impact muscle repair and bioenergetic adaptation. Full article

Whole-genome bisulfite sequencing (WGBS) was employed in this article to map blood DNA methylation profiles at single-base resolution in Yili horses before a 5000 m speed race, with comparative analysis of epigenetic differences between the ‘elite group’ and ‘ordinary group’ across six four-year-old stallions. The overall methylation level in the elite group was generally higher than that in the ordinary groups, with a minority of regions showing hypomethylation. For instance, the promoter regions of key metabolic and neuro-related genes exhibited significant hypomethylation. The article identified over 10,000 CG differential methylation regions (DMRs), predominantly enriched in promoter and CpG island regions, anchoring 7221 differentially methylated genes (DMGs). These DMGs were significantly enriched in key biological processes including oxidative phosphorylation, protein binding, axon guidance, glutamatergic synapses, and the Hedgehog signalling pathway. Among these, six genes—ACTN3, MSTN, FOXO1, PPARGC1A, ND1, and ND2—were selected as core candidate genes closely associated with muscle strength, energy metabolism, and stress adaptation. The study confirms that the differences in athletic ability among Yili horses have a significant epigenetic basis, with DNA methylation participating in the epigenetic regulation of athletic traits by modulating the expression of genes related to energy metabolism and neuroplasticity. The constructed “promoter hypomethylated DMR panel” holds promise for translation into non-invasive blood-based epigenetic markers for early performance evaluation and targeted breeding in racehorses. This provides a theoretical basis and molecular targets for improving equine athletic phenotypes and optimising training strategies. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Background: Sarcopenia and sarcopenic obesity are increasingly recognized in kidney transplant recipients (KTRs), yet their molecular underpinnings remain poorly defined. We sought to synthesize current evidence on biomarker associations with muscle loss and function in the post renal transplant setting. Methods: A comprehensive search of PubMed/MEDLINE and Cochrane databases was conducted according to PRISMA guidelines. Studies evaluating biomarkers related to sarcopenia or sarcopenic obesity in adult and pediatric KTRs were included. Quality assessment was performed with the NHLBI tool. Results: Seven studies were included, encompassing 548 KTRs. Myostatin levels predicted sarcopenia in KTRs (cut-off: 390 pg/mL) and inversely correlated with Metabolic equivalent of Tasks (METs), handgrip strength (HGS), and graft performance. Although adiponectin was negatively correlated with body fat, its high-molecular-weight isoform was linked to lower muscle mass and long-term graft decline. Leptin was associated with sarcopenic obesity and lower estimated Glomerular Filtration Rate (eGFR). Insulin like Growth Factor-1 (IGF-1) independently predicted HGS but not muscle mass. Brain-derived neurotrophic factor (BDNF) levels predicted sarcopenia (cut off: 17.8 ng/mL) and reflected physical activity levels. Visfatin showed no association with sarcopenia but it was positively correlated with eGFR. Lastly, certain polymorphisms of Alpha-actinin-3 (ACTN3) were shown to genetically predispose to post-transplant sarcopenia. Conclusions: These emerging candidate biomarkers provide promising mechanistic insight into post-transplant muscle decline and may ultimately support more personalized risk assessment. Further validation is needed, and functional measures remain the most reliable clinical tools at present. Full article

Background: The aim of this study is to investigate the pathophysiology of cataract by analyzing signaling pathways in three sample types obtained from four different lens groups: age-related (ARC), diabetic (DC), post-vitrectomy cataract (PVC) and clear control lenses. Methods: Three sample types—the aqueous humor, the anterior capsule and the phaco cassette content—were collected during cataract surgery from 39 participants (ARC = 12, DC = 11, PVC = 7 and control = 9). The samples were prepared based on Sp3 protocol. The recognition and quantification of proteins were performed with liquid chromatography online with tandem mass spectrometry using the DIA-NN software. Perseus software (v1.6.15.0) was used for statistical analysis. Data are available via ProteomeXchange with identifiers PXD045547, PXD045554, PXD045557, and PXD069667. Results: In total, 1986 proteins were identified in the aqueous humor, 2804 in the anterior capsule, and 3337 in the phaco cassette samples. Proteins involved in actin and microtubule cytoskeleton organization, including ACTN4, were downregulated in all three cataract groups compared to controls. Proteins involved in glycolipid metabolic process, including GAL3ST1, GAL3ST4, and GLA, were upregulated in ARC compared to controls. Proteins involved in the non-canonical Wnt receptor signaling pathway, including FRZB, SFRP1, SFRP2, SFRP5, WNT5A, and WNT7A, were upregulated in ARC compared to DC, PVC, and controls. Conclusions: Comprehensive proteomic profiles were generated using DIA proteomics by comparing ARC, DC, and PVC versus controls. This is the first study to use phaco cassette contents to investigate cataract formation in comparison to controls. Our findings significantly enhance the current understanding of human cataract pathophysiology and provide novel insights into the mechanisms underlying cataract formation. Full article

Artistic gymnastics is one of the most physically demanding sports, characterized by a high incidence of both acute and chronic injuries. Although previous research has primarily focused on biomechanical and training-related factors, the multifactorial etiology of injuries—including molecular and genetic aspects—remains insufficiently explored. This systematic review aimed to synthesize current evidence on the causes, mechanisms, and prevention of injuries in artistic gymnastics, with particular emphasis on biomechanical, molecular, and genetic determinants of injury risk and athletic performance. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and was registered in the PROSPERO database (Registration No: CRD420251167521). Electronic databases (PubMed, KoBSON, and Google Scholar) were searched for studies published between 2015 and 2025 using the keywords “gymnastics injuries,” “overuse injuries,” “injury prevention,” “biomechanics,” “IL-6,” “TNF-α,” and “miRNA biomarkers.” Nineteen studies met the inclusion criteria and were analyzed based on injury incidence, localization, mechanisms, and molecular and genetic associations. The majority of injuries were localized in the joints of both upper and lower extremities, particularly during puberty and at higher competitive levels. Repetitive loading, improper technique, and insufficient recovery were identified as the main etiological factors. Molecular biomarkers such as IL-6, TNF-α, and miRNAs (miR-155, miR-146a) were found to play key roles in inflammatory responses, while genetic polymorphisms including ACTN3 R577X, ESR1 rs2234693, and CYP19A1 rs936306 were associated with flexibility, explosive strength, and susceptibility to injury. Injury prevention in artistic gymnastics requires a personalized and multidisciplinary approach that integrates biomechanical, clinical, molecular, and genetic data. Incorporating molecular and genetic profiling into training and rehabilitation programs may enhance early detection of overuse conditions and optimize both health and performance outcomes in gymnasts. Full article

Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk. Full article

Heat stress (HS) severely significantly reduces milk yield and causes substantial economic losses of dairy cows. TMT-based proteomes and an untargeted metabolomics approach were used to conduct the proteomics and metabolomics in heat-stressed (HS, n = 6) and heat-resistant (HR, n = 6) Chinese Holstein. The proteomics showed that 29 differentially expressed proteins (DEPs), with SERPINA3-7, ACTN4, and PLOD1 up-regulated, and GSN down-regulated in HR cows. The metabolomics showed that 168 differential positive metabolites and 170 differential negative metabolites were identified, with HR cows exhibiting lower levels of anti-inflammatory compounds, such as N6-Acetyl-L-lysine. In addition, 29 DEPs and 338 metabolites revealed four key pathways, including the lysine degradation (ko00310) and metabolic pathway (ko01100) with underlying protein–metabolite interactions, where up-regulated PLOD1 and ACTN4 and down-regulated EXT1 and GSN were observed to be interacting with the down-regulated N6-Acetyl-L-lysine, citric acid, 4-Pyridoxic acid, uracil, and uric acid, and the up-regulated arachidonic acid was enriched, which could be used for rapid and noninvasive screening of heat-tolerant cows. Functional validation through cell experiments, qPCR, and Western blot analyses showed that the interference of the ACTN4 gene could induce dairy cow mammary epithelial cell apoptosis, which could be regarded as a potential biomarker for HS in Chinese Holstein. Our results facilitate a better understanding of the molecular mechanism underlying the HS issue in dairy cows and provide a crucial insight into the alternative strategies to enhance animal welfare and productivity under high-temperature conditions. Full article

Mutations in the ACTN1 gene, which encodes the cytoskeletal protein α-actinin-1, have been implicated in the etiology of autosomal dominant congenital macrothrombocytopenia. α-Actinin-1 is a member of the spectrin superfamily and is essential for key physiological processes in megakaryocytes and platelets. The pathophysiological mechanisms by which α-actinin-1 mutations lead to macrothrombocytopenia have been attributed to alterations in actin organization, increased binding affinity of α-actinin-1 to actin filaments, and modulation of integrin αIIbβ3 signaling. In previous studies, we utilized megakaryocyte-specific α-actinin-1 knockout (PF4-ACTN1^−/−) mice to explore the influence of α-actinin-1 on megakaryocyte and platelet function. Despite these efforts, the precise mechanisms remain inadequately understood. To advance our understanding and clarify the role of α-actinin-1 in thrombopoiesis, we first delineated the functions of α-actinin-1 in megakaryocytes and platelets, followed by a comprehensive overview of the proteins known to interact with α-actinin-1. As a pivotal scaffold protein, α-actinin-1 interacts with a complex network of partners, including integrin αIIbβ3, and actin filaments, to modulate cytoskeletal dynamics, megakaryocyte maturation, and proplatelet formation. In addition to its well-documented proteins that interact with α-actinin-1 within megakaryocytes and platelets, α-actinin-1 also associates with proteins outside the megakaryocytic lineage, such as cytohesin-2 and MOB1, which have been predominantly examined in other cellular contexts. These varied interactions imply that α-actinin-1 may influence megakaryocyte and platelet functions through multiple mechanisms. This review provides a comprehensive synthesis of current knowledge regarding the structure, binding partners of α-actinin-1, and essential roles of α-actinin-1 in thrombopoiesis. Full article

Background: Physical conditioning is essential to meet the operational demands of military environments. However, high-intensity exercise provokes muscle microinjuries resulting in exercise-induced muscle damage. This condition is typically monitored using serum biomarkers such as creatine kinase (CK), myoglobin (MYO), and lactate dehydrogenase (LDH). Nevertheless, individual variability and genetic factors complicate the interpretation. In this context, the rs1815739 variant (ACTN3), the most common variant related to exercise phenotypes, hypothetically could interfere with the muscle physiological response. This study aimed to evaluate the kinetics of serum biomarkers during a high-intensity activity and their potential association with rs1815739 polymorphism. Materials and Methods: 32 male cadets were selected during the Army Paratrooper Course. Serum was obtained at six distinct moments while they performed regular course tests and recovery time. Borg scale was assessed in 2 moments (~11 and ~17). Results: Serum levels of CK, CK-MB, MYO, and LDH significantly increase after exercise, proportionally to Borg’s level, following the applicability of longitudinal studies to understand biomarker levels in response to exercise. R allele carriers (ACTN3) were only slightly associated with greater levels of MYO and CK, mainly in relative kinetic levels, and especially at moments of greater physical demand/recovery. Although the ACTN3 was slightly related to different biomarker levels in our investigation, the success or healthiness in military activities is multifactorial and does not depend only on interindividual variability or physical capacity. Conclusions: Monitoring biomarkers and multiple genomic regions can generate more efficient exercise-related phenotype interventions. Full article

Podocytopathy, characterized by proteinuria, contributes significantly to kidney diseases, with hypertension playing a key role in damaging podocytes and the glomerular filtration barrier (GFB). The lack of functional in vitro models, however, impedes research and treatment development for hypertensive podocytopathy. We established a novel constant pressure-driven podocyte-on-chip model, utilizing our previously developed dynamic staining self-assembly cell array chip (SACA chip) and 3D printing. This platform features a differentiated podocyte monolayer under controlled hydrostatic pressures, mimicking the epithelial side of the GFB. Using this platform, we investigated mechanical force-dependent permeability to three sizes of fluorescent dextran under varying hydrostatic pressures, comparing the results with a puromycin aminonucleoside (PAN)-induced injury model. We observed that external pressures induced size-dependent permeability changes and altered cell morphology. Higher pressures led to greater macromolecule infiltration, especially for larger dextran (70 kDa, 500 kDa). Mature podocytes exhibited immediate, pressure-dependent cytoskeleton rearrangements, with better recovery at lower pressures (20 mmHg) but irreversible injury at higher pressures (40, 60 mmHg). These morphological changes were also corroborated by dynamic mRNA expression of cytoskeleton-associated proteins, Synaptopodin and ACTN4. This platform offers a promising in vitro tool for investigating the pathomechanisms of hypertension-induced podocytopathy, performing on-chip studies of the GFB, and conducting potential drug screening. Full article

Skeletal muscles, accounting for 40% of mammalian body mass, exhibit pronounced heterogeneity due to their distinct anatomical locations. Animal husbandry has focused excessively on longissimus dorsi (LDM) development while neglecting other muscles. In this study, we integrated Bulk RNA Sequencing (bulk RNA-seq) and Liquid Chromatography–Mass Spectrometry (LC-MS) analyses of Soleus (SOL), Gastrocnemius (GAS), and Psoas major muscles (PMM) across three key stages in Duroc pigs. We identified nine critical genes (S100A1, MBOAT2, CA3, GYG2, ACTN3, ENO3, SLC3A2, SLC16A10, and GAPDH) and eight metabolites potentially involved in regulating both skeletal muscle development and fiber-type transformation. The heterogeneity between SOL and GAS was low at birth but increased gradually during development. In contrast, PMM exhibited higher heterogeneity than SOL and GAS from birth. Notably, expression levels of MYH7, MYH1, and MYH4 displayed stage-specific and muscle type-dependent variations. Moreover, we observed a developmental shift from the MAPK signaling pathway (1–21 d) to the regulation of the actin cytoskeleton (21–120 d). Pairwise comparisons between the SOL, GAS, and PMM revealed that the signaling pathways were enriched in muscle fiber-type switching. Collectively, through the integration of bulk RNA-seq and LC-MS data, this study provides novel molecular breeding strategies for the genetic improvement of meat-producing animals. Full article

The TT genotype of the ACTN-3 polymorphism (rs1815739) has been previously associated with lower sprinting and jumping performance, higher frequency and severity of muscle injuries and eccentric muscle damage in professional football players. This study examined the influence of rs1815739 polymorphism on maximal running speed (MRS) during official matches in elite football players. MRS was collected, using a Global Position System (GPS) at high sampling frequencies (50 Hz), from 45 footballers of the same team during 26 official matches (707 match observations). A buccal swab was used to extract genomic DNA, and an RFLP PCR technique was used to determine the ACTN-3 genotype. The main finding of the present study was that CC players showed significantly higher MRS than TT players (CC = 33.1 ± 1.3 km·h⁻¹; CT = 32.7 ± 1.6 km·h⁻¹; TT = 31.5 ± 1.9 km·h⁻¹, p = 0.041). Moreover, the players harboring a copy of the C allele showed a trend toward higher MRS than TT genotype (CC + CT = 32.9 ± 1.5 km·h⁻¹ vs. TT = 31.5 ± 1.9 km·h⁻¹, p = 0.06). We found, for the first time, an association between the ACTN-3 polymorphism and match-play MRS in elite football players. Our results bring new knowledge to the literature regarding the advantage conferred by the C allele (CC and CT genotypes) of the ACTN-3 polymorphism on sprint performance in football providing perspectives for modulating the speed training program in relation to ACTN-3 genotypes, enhancing performance avoiding muscle lesions. Full article

Background/Objectives: This systematic review aimed to gather the most recent evidence regarding the link between genetic polymorphisms and physical performance in team sports, with a focus on the practical utility of this information for athlete selection, training personalization, and injury prevention. Methods: Sixteen studies published between 2018 and 2025 were analyzed and selected from six international databases, in accordance with the PRISMA guideline. Only English-language studies were included, which evaluated active athletes in team sports and investigated associations between genetic variations, such as Actinin Alpha 3 (ACTN3 R577X), Angiotensin I Converting Enzyme (ACE I/D), Peroxisome Proliferator-Activated Receptor Alpha (PPARA), Interleukin 6 (IL6), and Nitric Oxide Synthase 3 (NOS3), and physical performance parameters. The methodological quality of the studies was assessed using the Q-Genie tool, with all studies scoring over 45 across all 11 items, indicating high quality. Results: The ACTN3 and ACE genes stood out due to their consistent association with traits such as strength, speed, endurance, and recovery capacity. Other genes, such as PPARA, Fatty Acid Amide Hydrolase (FAAH), Angiotensinogen (AGT), and NOS3, complemented this genetic profile by being involved in the regulation of energy metabolism and injury predisposition. An increasing number of studies have begun to adopt cumulative genotype scores, suggesting a shift from a monogenic approach to complex predictive models. Conclusions: The integration of genetic profiling into the evaluation and management of athletes in team sports is becoming increasingly relevant. Although current evidence supports the applicability of these markers, robust future research conducted under standardized conditions is necessary to validate their use in sports practice and to ensure sound ethical standards. Full article