Search Results (124)

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

Background: Muscle injuries pose a significant challenge in sports, leading to decreased performance and shortened career longevity. Individuals homozygous for the nonsense X allele of the ACTN3 rs1815739 (R577X) polymorphism, characterized by a complete absence of α-actinin-3, have been associated with reduced power performance and may have an increased injury risk. This study aimed to investigate the association between the ACTN3 R577X polymorphism and both volleyball player status and the risk of non-contact musculoskeletal injuries in female volleyball players. Methods: The study included 5382 Turkish and Russian subjects of European descent (187 professional volleyball players and 5195 controls), of whom 50 female players provided injury data. Sport-related injury information was obtained from medical records maintained by team physicians and physiotherapists. Results: A pooled analysis of the two cohorts demonstrated that the frequency of the ACTN3 X allele was significantly lower in volleyball players than in controls, with an odds ratio of 0.763 (95% CI: 0.61–0.95, p = 0.02). In the pre-specified recessive contrast (XX vs. RR + RX) among 50 players, exact methods indicated higher injury odds for the XX genotype (OR = 7.87, 95% CI: 0.94–374.58; p = 0.0366), which was classified as borderline/exploratory. Penalized (Firth) regression produced estimates of a similar magnitude after adjustment for age and playing position (adjusted OR = 5.92, 95% CI: 1.12–60.98), although confidence intervals remained wide. Conclusions: The ACTN3 X allele is underrepresented in professional volleyball players, and it is associated with an increased risk of muscle injury in female players. Full article

This research was carried out to assess the impact of daidzein supplementation on production performance, serum biochemical indexes, meat quality, and the transcriptome of the longissimus dorsi (LM) muscle in heat-stressed Jinjiang cattle. Twenty 20-month-old Jinjiang cattle (initial mean ± SE: 438 ± 34.6 kg of body weight) were randomly divided into two treatment groups (n = 10 per treatment): control treatment and daidzein treatment (1000 mg/kg concentrate). After a 100-day feeding trial (consisting of a 10-day adaptation period and a 90-day daidzein feeding period), blood and LM muscle samples were collected on day 100. Daidzein significantly increased the average daily dry matter intake (ADMI), the concentration of free fatty acid (FFA) and glutamic-pyruvic transaminase (ALT) in serum, and the marbling score of the LM muscle. Additionally, daidzein significantly decreased the concentration of total cholesterol (TC) and leptin in serum, along with the shear force and L* value of LM in heat-stressed Jinjiang cattle. The transcriptome analysis demonstrated that 238 differentially expressed genes (DEGs) were identified through differential expression analysis, among which 168 genes were downregulated and 70 genes were upregulated. The results of KEGG pathways showed that these DEGs were significantly enriched in pathways related to beef tenderness, including the FoxO signaling pathway, Notch signaling pathway, and regulation of the actin cytoskeleton. Daidzein significantly affected the candidate genes (FOSL1, DGKH, Gadd45G, GAL, SEMA3, TOB, FABP8, TRIB2, Nech1, and GSTA3) involved in adipocyte differentiation, as well as genes (CSTB and ACTN) related to connective tissue structure in heat-stressed Jinjiang cattle. Daidzein plays a positive role in relieving heat stress and improving beef quality in heat-stressed Jinjiang cattle. Full article

Background/Objectives: This meta-analytical review assesses the relationship between effect size and replication success in genetic studies of athletic performance, focusing on the ACTN3 and ACE polymorphisms across power- and endurance-based sports. The analysis revealed substantial heterogeneity in reported effect sizes (overall I² = 72.3%), indicating considerable variability between studies, likely influenced by differences in population genetics, study design, and sample size. Methods: For ACTN3, the pooled effect sizes were 1.40 (95% CI: 1.18–1.65) for power sports and 1.35 (95% CI: 1.12–1.58) for endurance sports. Although the difference between these estimates is small, it reached statistical significance (p = 0.0237), reflecting the large sample size, but it remains of limited practical and clinical significance. For the ACE polymorphism, effect sizes were similar in both endurance (ES = 1.22, 95% CI: 1.05–1.41) and power sports (ES = 1.20, 95% CI: 1.03–1.43), with overlapping confidence intervals, indicating no meaningful difference in association strength between sport types. Effect sizes were calculated as odds ratios (OR) with 95% confidence intervals for case–control designs, with standardized conversion protocols applied for alternative study designs reporting standardized mean differences or regression coefficients. Results: Publication bias was detected, particularly in smaller studies on ACTN3 and power sports (Egger’s test p = 0.007). The pooled effect of ACTN3 in power sports (OR 1.40, 95% CI: 1.18–1.65, 95% PI: 0.89–2.20) was adjusted to OR 1.32 (95% CI: 1.15–1.51) following trim-and-fill publication bias correction. The high degree of heterogeneity (I² = 72.3%) cautions against overgeneralization of the pooled results and highlights the need for careful interpretation, robust replication studies, and standardized methodologies. Conclusions: The findings emphasize that, while genetic markers such as ACTN3 and ACE are statistically associated with athletic performance, the magnitude of these associations is modest and should be interpreted conservatively. Methodological differences and publication bias continue to limit the reliability of the evidence. Future research should prioritize large, well-powered, and methodologically consistent studies—ideally genome-wide approaches—to better account for the polygenic and multifactorial nature of elite athletic ability. Full article

Exercise addiction is described in the literature as a compulsive behavior associated with adverse health symptoms. Currently, knowledge about the biological and social factors that trigger the development of this behavior is still lacking, and there are no published studies on genetic variants associated with the disorder. Because of this, we genotyped specific polymorphisms in the genes DRD1 (rs265981), DRD2 (rs1800497), BDNF (rs6265), HFE (rs1799945), ACTN3 (rs1815739), PPARA (rs4253778), PPARGC1A (rs8192678), and AMPD1 (rs17602729) to investigate whether they were associated with exercise addiction. In total, 469 men and women, comprising athletes and non-athletes between the ages of 18 and 50, were enrolled in the study. Each participant provided an oral swab sample for genetic analysis and completed the Negative Addiction Scale questionnaire that tests for physical exercise addiction. For the DRD2 polymorphism, there was a significant association of the GG genotype with asymptomatic participants and of the AA genotype with participants symptomatic for exercise addiction. Additionally, for the BDNF polymorphism, the CC genotype was associated with symptomatic participants, and the T allele was associated with asymptomatic individuals. However, all associations were found by evaluating the SNP individually, and this demonstrates the difficulty in studying variables related to behavioral phenotypes. Full article