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Search Results (313)

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12 pages, 636 KB  
Article
AI-Based 3D-Segmentation Quantifies Sarcopenia in Multiple Myeloma Patients
by Thuy-Duong Do, Tobias Nonnenmacher, Marieke Burghardt, Stefanie Zschaebitz, Marina Hajiyianni, Elias Karl Mai, Marc-Steffen Raab, Carsten Müller-Tidow, Hans-Ulrich Kauczor, Hartmut Goldschmidt and Ulrike Dapunt
Diagnostics 2025, 15(19), 2466; https://doi.org/10.3390/diagnostics15192466 - 26 Sep 2025
Abstract
Background: Sarcopenia is characterized by a loss of muscle mass and strength, resulting in functional limitations and an increased risk of falls, injuries and fractures. The aim of this study was to obtain detailed information on skeletal muscle changes in patients with [...] Read more.
Background: Sarcopenia is characterized by a loss of muscle mass and strength, resulting in functional limitations and an increased risk of falls, injuries and fractures. The aim of this study was to obtain detailed information on skeletal muscle changes in patients with multiple myeloma (MM) during treatment. Methods: A total of 51 patients diagnosed with MM who had undergone whole-body low-dose computed tomography acquisition prior to induction therapy (T1) and post autologous stem cell transplantation (T2) were examined retrospectively. Total volume (TV), muscle volume (MV) and intramuscular adipose tissue volume (IMAT) of the autochthonous back muscles, the iliopsoas muscle and the gluteal muscles were evaluated on the basis of the resulting masks of the BOA tool with the fully automated combination of TotalSegmentator and a body composition analysis. An in-house trained artificial intelligence network was used to obtain a fully automated three-dimensional segmentation assessment. Results: Patients’ median age was 58 years (IQR 52–66), 38 were male and follow-up CT-scans were performed after a mean of 11.8 months (SD ± 3). Changes in MV and IMAT correlated significantly with Body-Mass-Index (BMI) (r = 0.7, p < 0.0001). Patients (n = 28) with a decrease in BMI (mean −2.2 kg/m2) during therapy lost MV (T1: 3419 cm3, IQR 3176–4000 cm3 vs. T2: 3226 cm3, IQR 3014–3662 cm3, p < 0.0001) whereas patients (n = 20) with an increased BMI (mean +1.4 kg/m2) showed an increase in IMAT (T1: 122 cm3, IQR 96.8–202.8 cm3 vs. T2: 145.5 cm3, IQR 115–248 cm3, p = 0.0002). Loss of MV varied between different muscle groups and was most prominent in the iliopsoas muscle (−9.8%) > gluteus maximus (−9.1%) > gluteus medius (−5.8%) > autochthonous back muscles (−4.3%) > gluteus minimus (−1.5%). Increase in IMAT in patients who gained weight was similar between muscle groups. Conclusions: The artificial intelligence-based three-dimensional segmentation process is a reliable and time-saving method to acquire in-depth information on sarcopenia in MM patients. Loss of MV and increase in IMAT were reliably detectable and associated with changes in BMI. Loss of MV was highest in muscles with more type 2 muscle fibers (fast-twitch, high energy) whereas muscles with predominantly type 1 fibers (slow-twitch, postural control) were less affected. This study provides valuable insight into muscle changes of MM patients during treatment, which might aid in tailoring exercise interventions more precisely to patients’ needs. Full article
19 pages, 3168 KB  
Article
Estrogens and Antioxidants Prevent the Formation of Tubular Aggregates in Aging Male Mice
by Giorgia Rastelli, Matteo Serano, Barbara Girolami, Alice Brasile, Vincenzo Sorrentino, Laura Pietrangelo and Feliciano Protasi
Int. J. Mol. Sci. 2025, 26(18), 9122; https://doi.org/10.3390/ijms26189122 - 18 Sep 2025
Viewed by 169
Abstract
Tubular aggregates (TAs), ordered arrays of sarcoplasmic reticulum (SR) tubes, are the main morphological alteration found in muscle biopsies from patients affected by TA myopathy (TAM). TAM has been linked to mutations in the genes encoding for STIM1 and ORAI1, which are two [...] Read more.
Tubular aggregates (TAs), ordered arrays of sarcoplasmic reticulum (SR) tubes, are the main morphological alteration found in muscle biopsies from patients affected by TA myopathy (TAM). TAM has been linked to mutations in the genes encoding for STIM1 and ORAI1, which are two proteins that mediate Store-Operated Ca2+ entry (SOCE). SOCE is a mechanism that allows recovery of extracellular Ca2+ during fatigue, when the SR becomes depleted. As TAs also form in fast-twitch muscle fibers of aging male mice (not in females), we studied the effect of sex hormones on the aggregation of TAs during aging. We administered estrogen (ad libitum in drinking water) to male mice from 10 to 18 months of age and then evaluated the following: (a) the presence of TAs using histology and electron microscopy (EM); (b) oxidative stress, a mechanism that could underlie damage to proteins and membranes (and possibly their accumulation in TAs); and (c) SOCE function during ex vivo stimulation in the presence or absence of external Ca2+ or SOCE blocker (BTP-2). The results collected indicate that treatment with estrogen (a) significantly reduced the formation of TAs; (b) reduced oxidative stress, which was elevated in aging male mice; and (c) restored SOCE, i.e., the capability of aged EDL muscles to use external Ca2+ by promoting maintenance of Ca2+ Entry Units (CEUs, the intracellular junctions that mediate SOCE). Finally, we also show that formation of TAs is reduced by treatment of mice with N-acetilcysteine (NAC), a potent antioxidant also administered ad libitum in drinking water. Full article
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14 pages, 1761 KB  
Article
Muscle Fiber Recruitment Characteristics in Trained Older Adults: An EMG Frequency Analysis During Voluntary Contraction
by Tatsuhiko Matsumoto, Yutaka Takamaru, Chikao Nakayama, Shuji Sawada and Shuichi Machida
J. Funct. Morphol. Kinesiol. 2025, 10(3), 355; https://doi.org/10.3390/jfmk10030355 - 17 Sep 2025
Viewed by 478
Abstract
Background: Age-related declines in skeletal muscle quality and quantity contribute to frailty and sarcopenia, leading to physical dysfunction in older adults. In particular, the selective atrophy of fast-twitch fibers is closely linked to reduced lower limb strength and increased fall risk. This study [...] Read more.
Background: Age-related declines in skeletal muscle quality and quantity contribute to frailty and sarcopenia, leading to physical dysfunction in older adults. In particular, the selective atrophy of fast-twitch fibers is closely linked to reduced lower limb strength and increased fall risk. This study aimed to evaluate the effects of habitual body weight resistance training on muscle fiber recruitment patterns during maximal voluntary contraction (MVC) and squatting movements using spectral characteristics of surface electromyography (EMG). Methods: Fifty healthy community-dwelling older adults (28 males, 22 females; aged 64–84 years) were categorized into exercise and non-exercise groups based on training habits. Surface EMG signals were recorded from the rectus femoris muscle during MVC, normal squat, half-squat, and squat movements. Power spectral density (PSD) was analyzed using Welch’s method and divided into frequency bands: type I (20–60 Hz), type IIa(1) (60–115 Hz), type IIa(2) (115–170 Hz), and type IIx (170–350 Hz). Results: While statistical significance was limited, the exercise group tended to show higher ratio PSDs in type IIa and IIx bands, and lower PSDs in the type I band during MVC. During half-squats, the non-exercise group exhibited higher contributions above 60 Hz, suggesting inefficient fast-twitch fiber recruitment. Conclusions: Habitual body weight resistance training may influence muscle fiber recruitment patterns in older adults. EMG spectral analysis offers a non-invasive means to detect age- and training-related neuromuscular adaptations. Full article
(This article belongs to the Section Functional Anatomy and Musculoskeletal System)
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9 pages, 1405 KB  
Article
Time Course of a Single, 0.6 mg/kg Dose of Rocuronium Neuromuscular Block During Sevoflurane or Propofol Anesthesia in Infants—A Prospective, Randomized Trial
by Béla Fülesdi, Péter Luterán, Mena Boktor, László Asztalos, György Nagy, Sorin J. Brull and Csilla Molnár
J. Clin. Med. 2025, 14(18), 6459; https://doi.org/10.3390/jcm14186459 - 13 Sep 2025
Viewed by 373
Abstract
Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single [...] Read more.
Background: There is little data available in infants on the extent to which inhalational anesthetics prolong the effects of neuromuscular blocking agents compared with intravenous agents. Here, we assessed the differences between the neuromuscular blocking effects (duration and recovery time) of a single dose of rocuronium during propofol vs. sevoflurane anesthesia. Methods: The prospective study enrolled 20 infants (4–12 months of age) scheduled for craniosynostosis surgery, randomly assigned to receive general anesthesia maintenance with sevoflurane or propofol. All patients received 0.6 mg/kg rocuronium as a single bolus dose to facilitate tracheal intubation and surgery. Primary study endpoint was the clinical duration of rocuronium, from administration until spontaneous recovery to a train-of-four ratio (TOFR) > 0.90. Secondary endpoints were times for reappearance of the first, second, third, and fourth twitches of the TOF (T1, T2, T3 and T4, respectively) in the two patient groups. Results: There were no differences in the infants’ age (sevoflurane maintenance: 5.8 ± 2.4 months; propofol maintenance: 6.7 ± 3.1 months, p = 0.47) or weight (sevoflurane: 7722 ± 1644 g; propofol: 7433 ± 1782 g, p = 0.71). Rocuronium onset time was 101.0 ± 55.0 s in the sevoflurane group and 83.4 ± 47.9 s in the propofol group (p = 0.46). Total duration of anesthesia was comparable in the sevoflurane (122.0 ± 23.8 min) and propofol (107.7 ± 25.2 min, p = 0.18) groups. Rocuronium recovery to TOFR > 0.9 required 136 min (CI: 123.7–149.5 min) in the sevoflurane group and 61.5 min (CI: 58.0–101.0 min) in the propofol group (p < 0.001). Conclusions: In infants, sevoflurane maintenance enhances the neuromuscular blocking effect of a single, 0.6 mg/kg BW dose of rocuronium as compared to propofol maintenance. After discontinuation of sevoflurane, additional time is necessary to reach the acceptable TOFR >0.9 needed before tracheal extubation. The present study further underscores the importance of objective (quantitative) neuromuscular monitoring in infants to guide intraoperative management and prevent residual neuromuscular block. Full article
(This article belongs to the Special Issue Paediatric Anaesthesia: Clinical Updates and Perspectives)
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17 pages, 9712 KB  
Article
Super-Enhancer Drives THBS3 Expression to Regulate the Proliferation and Differentiation of Bovine Muscle Stem Cells
by Han Huang, Yongwang Zhang, Kehe Cen, Chaoxia Zou, Leyi Wang, Jiaqi Lu, Haiming Mai, Jinquan Ding, Junbo Pan, Zeyang Zhao, Junming Li, Yanfei Deng, Jingwei Wei, Deshun Shi, Yingming Wei and Ruimen Zhang
Animals 2025, 15(17), 2615; https://doi.org/10.3390/ani15172615 - 6 Sep 2025
Viewed by 508
Abstract
Skeletal muscle, the primary meat-producing tissue in bovines, is regulated by a complex transcriptional network during development. The role of Thrombospondin 3 (THBS3) and its associated super-enhancer (SE) in this process remains largely unknown. Here, by integrating multi-omics data, we identified [...] Read more.
Skeletal muscle, the primary meat-producing tissue in bovines, is regulated by a complex transcriptional network during development. The role of Thrombospondin 3 (THBS3) and its associated super-enhancer (SE) in this process remains largely unknown. Here, by integrating multi-omics data, we identified THBS3 as a novel core regulator of myogenesis, orchestrated by a cognate super-enhancer (THBS3-SE). Functional assays demonstrated that THBS3 knockdown significantly promoted the proliferation and myogenic differentiation of bovine muscle stem cells (MuSCs) and accelerated their commitment to a fast-twitch fiber fate. Transcriptomic analysis linked THBS3 function to key signaling pathways controlling muscle growth, especially the mechanistic target of rapamycin (mTOR) signaling pathway. Mechanistically, we found that distal enhancers within the THBS3-SE loop to the THBS3 promoter drive its transcription, and CRISPR-based interference of these enhancers recapitulated the pro-myogenic effects of THBS3 knockdown. Collectively, our findings unveiled a THBS3-SE-mediated regulatory axis that critically governed bovine MuSCs’ fate. Targeting this axis may offer a novel strategy for improving beef production efficiency. Full article
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10 pages, 807 KB  
Article
Behavioral Assessment of Equine Relaxation Following Manual Therapy: A Pilot Study
by Yavuzkan Paksoy, Kerem Ural, Hasan Erdoğan, Songül Erdoğan and Serdar Paşa
Vet. Sci. 2025, 12(9), 865; https://doi.org/10.3390/vetsci12090865 - 5 Sep 2025
Viewed by 663
Abstract
The aim of this pilot study was to evaluate the relaxation, stress reduction and behavioral changes observed after manual therapy applied to horses exposed to racing and physical training stimulus. This descriptive approach is aimed at veterinary clinicians to evaluate the therapy process [...] Read more.
The aim of this pilot study was to evaluate the relaxation, stress reduction and behavioral changes observed after manual therapy applied to horses exposed to racing and physical training stimulus. This descriptive approach is aimed at veterinary clinicians to evaluate the therapy process more effectively with behavioral feedback. For this purpose, the study was conducted in two different equestrian clubs in Adana (Adana Mediterranean and Suvari Equestrian Clubs) between 2023 and 2024. A total of 32 racehorses (16 Thoroughbred, 16 Arabian; 16 female, 16 male) of different ages, genders and breeds were included in the study. Five minutes of manual therapy was applied for each of 7 different muscle groups. After the massage, behavioral observations were made for 10 min by moving 2 m away from the animals, and no separate baseline assessment was performed prior to the intervention. The application was carried out by a veterinarian with 15 years of experience. Importantly, no separate baseline assessment or control group was performed, and only behavioral responses were evaluated, which represents a major limitation of this pilot study. Among the observed behaviors in all horses, blinking, muscle twitching, respiratory changes, lip relaxation, licking and chewing were recorded for all horses. Relaxation signs such as head dropping (78.1%), yawning (34.4%), and ears falling to the side (62.5%) were frequently observed. Behaviors such as the appearance of the third eyelid (3.1%), grunting (12.5%) and sneezing (15.6%) were observed at a low percentage. Individual variables such as gender and breed did not have a statistically significant effect on the percentage of behavior (Chi-square test, p > 0.05). In conclusion, these preliminary findings suggest that manual therapy applications might be effective in reducing stress by triggering relaxation behaviors in riding horses, as these behaviors have been previously reported in the literature as reliable indicators of relaxation. Evaluation of behavioral responses after massage could be an important tool in determining physiotherapeutic effects. The fact that the application is performed by experienced people is an important factor that increases the success of the therapy and shows that manual therapy provides relaxation regardless of individual differences. Future controlled studies integrating physiological stress biomarkers are warranted to confirm these observations. Full article
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26 pages, 2348 KB  
Article
Voluntary Wheel Running Mitigates Disease in an Orai1 Gain-of-Function Mouse Model of Tubular Aggregate Myopathy
by Thomas N. O’Connor, Nan Zhao, Haley M. Orciuoli, Sundeep Malik, Alice Brasile, Laura Pietrangelo, Miao He, Linda Groom, Jennifer Leigh, Zahra Mahamed, Chen Liang, Feliciano Protasi and Robert T. Dirksen
Cells 2025, 14(17), 1383; https://doi.org/10.3390/cells14171383 - 4 Sep 2025
Viewed by 694
Abstract
Tubular aggregate myopathy (TAM) is an inherited skeletal muscle disease associated with progressive muscle weakness, cramps, and myalgia. Tubular aggregates (TAs) are regular arrays of highly ordered and densely packed straight-tubules observed in muscle biopsies; the extensive presence of TAs represent a key [...] Read more.
Tubular aggregate myopathy (TAM) is an inherited skeletal muscle disease associated with progressive muscle weakness, cramps, and myalgia. Tubular aggregates (TAs) are regular arrays of highly ordered and densely packed straight-tubules observed in muscle biopsies; the extensive presence of TAs represent a key histopathological hallmark of this disease in TAM patients. TAM is caused by gain-of-function mutations in proteins that coordinate store-operated Ca2+ entry (SOCE): STIM1 Ca2+ sensor proteins in the sarcoplasmic reticulum (SR) and Ca2+-permeable ORAI1 channels in the surface membrane. Here, we assessed the therapeutic potential of endurance exercise in the form of voluntary wheel running (VWR) in mitigating TAs and muscle weakness in Orai1G100S/+ (GS) mice harboring a gain-of-function mutation in the ORAI1 pore. Six months of VWR exercise significantly increased specific force production, upregulated biosynthetic and protein translation pathways, and normalized both mitochondrial protein expression and morphology in the soleus of GS mice. VWR also restored Ca2+ store content, reduced the incidence of TAs, and normalized pathways involving the formation of supramolecular complexes in fast twitch muscles of GS mice. In summary, sustained voluntary endurance exercise improved multiple skeletal muscle phenotypes observed in the GS mouse model of TAM. Full article
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23 pages, 28830 KB  
Article
Micro-Expression-Based Facial Analysis for Automated Pain Recognition in Dairy Cattle: An Early-Stage Evaluation
by Shuqiang Zhang, Kashfia Sailunaz and Suresh Neethirajan
AI 2025, 6(9), 199; https://doi.org/10.3390/ai6090199 - 22 Aug 2025
Viewed by 795
Abstract
Timely, objective pain recognition in dairy cattle is essential for welfare assurance, productivity, and ethical husbandry yet remains elusive because evolutionary pressure renders bovine distress signals brief and inconspicuous. Without verbal self-reporting, cows suppress overt cues, so automated vision is indispensable for on-farm [...] Read more.
Timely, objective pain recognition in dairy cattle is essential for welfare assurance, productivity, and ethical husbandry yet remains elusive because evolutionary pressure renders bovine distress signals brief and inconspicuous. Without verbal self-reporting, cows suppress overt cues, so automated vision is indispensable for on-farm triage. Although earlier systems tracked whole-body posture or static grimace scales, frame-level detection of facial micro-expressions has not been explored fully in livestock. We translate micro-expression analytics from automotive driver monitoring to the barn, linking modern computer vision with veterinary ethology. Our two-stage pipeline first detects faces and 30 landmarks using a custom You Only Look Once (YOLO) version 8-Pose network, achieving a 96.9% mean average precision (mAP) at an Intersection over the Union (IoU) threshold of 0.50 for detection and 83.8% Object Keypoint Similarity (OKS) for keypoint placement. Cropped eye, ear, and muzzle patches are encoded using a pretrained MobileNetV2, generating 3840-dimensional descriptors that capture millisecond muscle twitches. Sequences of five consecutive frames are fed into a 128-unit Long Short-Term Memory (LSTM) classifier that outputs pain probabilities. On a held-out validation set of 1700 frames, the system records 99.65% accuracy and an F1-score of 0.997, with only three false positives and three false negatives. Tested on 14 unseen barn videos, it attains 64.3% clip-level accuracy (i.e., overall accuracy for the whole video clip) and 83% precision for the pain class, using a hybrid aggregation rule that combines a 30% mean probability threshold with micro-burst counting to temper false alarms. As an early exploration from our proof-of-concept study on a subset of our custom dairy farm datasets, these results show that micro-expression mining can deliver scalable, non-invasive pain surveillance across variations in illumination, camera angle, background, and individual morphology. Future work will explore attention-based temporal pooling, curriculum learning for variable window lengths, domain-adaptive fine-tuning, and multimodal fusion with accelerometry on the complete datasets to elevate the performance toward clinical deployment. Full article
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20 pages, 757 KB  
Article
Exploring Twitch Viewers’ Donation Intentions from a Dual Perspective: Uses and Gratifications Theory and the Practice of Freedom
by José Magano, Manuel Au-Yong-Oliveira and Antonio Sánchez-Bayón
Information 2025, 16(8), 708; https://doi.org/10.3390/info16080708 - 19 Aug 2025
Viewed by 1041
Abstract
This study examines the factors that motivate viewers to financially support streamers on the Twitch digital platform. It proposes a conceptual framework that combines the uses and gratifications theory (UGT) with Michel Foucault’s concept of the practice of freedom (PF). Using a cross-sectional [...] Read more.
This study examines the factors that motivate viewers to financially support streamers on the Twitch digital platform. It proposes a conceptual framework that combines the uses and gratifications theory (UGT) with Michel Foucault’s concept of the practice of freedom (PF). Using a cross-sectional quantitative survey of 560 Portuguese Twitch users, the model investigates how three core constructs from UGT—entertainment, socialization, and informativeness—affect the intention to donate, with PF acting as a mediating variable. Structural equation modeling confirms that all three UGT-based motivations significantly influence donation intentions, with socialization exhibiting the strongest mediated effect through PF. The findings reveal that Twitch donations go beyond mere instrumental or playful actions; they serve as performative expressions of identity, autonomy, and ethical subjectivity. By framing PF as a link between interpersonal engagement and financial support, this study provides a contribution to media motivation research. The theoretical integration enhances our understanding of pro-social behavior in live streaming environments, challenging simplistic, transactional interpretations of viewer contributions vis-à-vis more political ones and the desire to freely dispose of what is ours to give. Additionally, this study may lay the groundwork for future inquiries into how ethical self-formation is intertwined with monetized online participation, offering useful insights for academics, platform designers, and content creators seeking to promote meaningful digital interactions. Full article
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15 pages, 1214 KB  
Article
Sodium p-Perfluorous Nonenoxybenzene Sulfonate (OBS) Induces Developmental Toxicity Through Apoptosis in Developing Zebrafish Embryos: A Comparison with Perfluorooctane Sulfonate
by Yilong Zou, Xueping Huang, Xianglian Wang, Manqing Xu and Yong Sun
Water 2025, 17(16), 2450; https://doi.org/10.3390/w17162450 - 19 Aug 2025
Viewed by 581
Abstract
Perfluorooctane sulfonate (PFOS) is a representative persistent organic pollutant that exerts toxic effects on aquatic organisms. As an alternative to PFOS, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been frequently detected in aquatic environments and human tissues in recent years. However, its toxic [...] Read more.
Perfluorooctane sulfonate (PFOS) is a representative persistent organic pollutant that exerts toxic effects on aquatic organisms. As an alternative to PFOS, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been frequently detected in aquatic environments and human tissues in recent years. However, its toxic effects on aquatic organisms and potential health risks to humans remain unclear. Zebrafish embryos are transparent and amenable to in vivo manipulation and observation. Therefore, in the present study, we investigated its developmental toxicity in zebrafish embryos, with PFOS as the positive control. We exposed zebrafish embryos to different concentrations of OBS (15, 20, and 25 mg/L) and PFOS (15 mg/L) for 2–168 h post fertilization (hpf) and then examined physiological and gene expression changes. At 24 hpf, spontaneous twitches in the 25 mg/L OBS group decreased to (5 ± 0.34)/min. By 48 hpf, the 20 mg/L OBS group’s hatching rate was (47.78 ± 2.22)%, significantly lower than the control. At 72 hpf, heart rates in both the PFOS and OBS groups were elevated, at 82 ± 0.6, 84.5 ± 0.5, 89.4 ± 0.3, and 93.7 ± 0.4, respectively. Similarly to PFOS, OBS induced developmental toxicity in zebrafish embryos. In addition, both OBS and PFOS exposure downregulated the expression level of anti-apoptotic Bcl-2 in zebrafish embryos, with a notable 0.53-fold decrease observed in the 25 mg/L OBS group. Conversely, they upregulated the expression levels of pro-apoptotic Bax, Caspase-3, and Caspase-9, with Caspase-3 expression increasing 1.14-, 1.5-, and 1.7-fold in the 15 mg/L PFOS, 20 mg/L OBS, and 25 mg/L OBS groups, respectively. These OBS- and PFOS-induced changes in gene expression increased apoptosis, suggesting that OBS can induce developmental toxicity in zebrafish embryos, and that its effect is comparable to that of PFOS. Therefore, considering its aquatic toxicity, measures aimed at limiting or remediating OBS pollution in the environment are necessary. Full article
(This article belongs to the Section Biodiversity and Functionality of Aquatic Ecosystems)
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20 pages, 4912 KB  
Article
Klotho Deficiency Promotes Skeletal Muscle Weakness and Is Associated with Impaired Motor Unit Connectivity
by Linda A. Bean, Connor Thomas, Juan F. Villa, Alexander J. Fitt, Areli Jannes S. Javier, Akanksha Agrawal, Hanna Whitney, Guilherme Nascimento Dos Santos, Kenneth E. White, Joshua R. Huot and Steven S. Welc
Int. J. Mol. Sci. 2025, 26(16), 7986; https://doi.org/10.3390/ijms26167986 - 19 Aug 2025
Viewed by 495
Abstract
Muscle wasting and weakness are critical clinical problems that limit mobility and independence, reduce health span, and increase the risk of physical disability. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, [...] Read more.
Muscle wasting and weakness are critical clinical problems that limit mobility and independence, reduce health span, and increase the risk of physical disability. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, including aging, chronic kidney disease, and myopathy. The objective of this study was to investigate a mechanistic role for Klotho in regulating muscle wasting and weakness. Body weight, lean mass, muscle mass, and myofiber caliber were reduced in Klotho-deficient mice. In the tibialis anterior muscle of Klotho-null mice, type IIa myofibers were resistant to changes in size, and muscle composition differed with a higher concentration of type IIb fibers to the detriment of type IIx fibers. Glycolytic GPDH enzymatic activity also increased. Klotho-deficient mice showed impaired muscle contractility, with reduced twitch force, torque, and contraction–relaxation rates. RNA sequencing revealed upregulation of synaptic and fetal sarcomeric genes, prompting us to examine muscle innervation. Klotho deficiency led to neuromuscular junction remodeling, myofiber denervation, and functional motor unit loss. Loss of motor units correlated with absolute torque. Collectively, these findings reveal a novel mechanism through which systemic Klotho deficiency disrupts muscle synapses and motor unit connectivity, potentially contributing to muscle wasting and weakness. Full article
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22 pages, 1122 KB  
Review
Muscle Aging Heterogeneity: Genetic and Structural Basis of Sarcopenia Resistance
by Angelina Titova, Airat Bilyalov, Nikita Filatov, Stepan Perepechenov, Darya Kupriyanova, Sergei Brovkin, Dmitrii Shestakov, Natalia Bodunova and Oleg Gusev
Genes 2025, 16(8), 948; https://doi.org/10.3390/genes16080948 - 11 Aug 2025
Cited by 1 | Viewed by 1625
Abstract
Sarcopenia, the progressive loss of skeletal muscle mass and function with age, significantly contributes to frailty and mortality in older adults. Notably, muscles do not age uniformly—some retain structure and strength well into old age. This review explores the mechanisms underlying differential resistance [...] Read more.
Sarcopenia, the progressive loss of skeletal muscle mass and function with age, significantly contributes to frailty and mortality in older adults. Notably, muscles do not age uniformly—some retain structure and strength well into old age. This review explores the mechanisms underlying differential resistance to muscle aging, with a focus on sarcopenia-resistant muscles. We analyzed current literature across molecular biology, genetics, and physiology to identify key regulators of muscle preservation during aging. Special attention was given to muscle fiber types, mitochondrial function, neuromuscular junctions, and satellite cell activity. Muscles dominated by slow-twitch (type I) fibers—such as the soleus, diaphragm, and extraocular muscles—demonstrate enhanced resistance to sarcopenia. This resilience is linked to sustained oxidative metabolism, high mitochondrial density, robust antioxidant defenses, and preserved regenerative capacity. Key molecular pathways include mTOR, PGC-1α, and SIRT1/6, while genetic variants in ACTN3, MSTN, and FOXO3 contribute to interindividual differences. In contrast, fast-twitch muscles are more vulnerable due to lower oxidative capacity and satellite cell depletion. Unique innervation patterns and neurotrophic support further protect muscles like extraocular muscles from age-related atrophy. Resistance to sarcopenia is driven by a complex interplay of intrinsic and extrinsic factors. Understanding why specific muscles age more slowly provides insights into muscle resilience and suggests novel strategies for targeted prevention and therapy. Expanding research beyond traditionally studied muscles is essential to develop comprehensive interventions to preserve mobility and independence in aging populations. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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20 pages, 7049 KB  
Article
Coupled Bone–Muscle Degeneration in Chronic Pancreatitis: A Juvenile Porcine Model of Secondary Osteosarcopenia
by Siemowit Muszyński, Michał Świetlicki, Dorota Wojtysiak, Agnieszka Grzegorzewska, Piotr Dobrowolski, Małgorzata Świątkiewicz, Marcin B. Arciszewski, Iwona Puzio, Joanna Bonior, Agnieszka Tomczyk-Warunek, Maria Mielnik-Błaszczak and Ewa Tomaszewska
Int. J. Mol. Sci. 2025, 26(16), 7690; https://doi.org/10.3390/ijms26167690 - 8 Aug 2025
Viewed by 439
Abstract
Osteosarcopenia, characterized by concurrent bone loss and muscle wasting, significantly impacts mobility and quality of life. While age-related primary osteosarcopenia is well-studied, secondary osteosarcopenia (SOS) caused by chronic diseases remains poorly understood, particularly in young individuals. The present study aimed to comprehensively characterize [...] Read more.
Osteosarcopenia, characterized by concurrent bone loss and muscle wasting, significantly impacts mobility and quality of life. While age-related primary osteosarcopenia is well-studied, secondary osteosarcopenia (SOS) caused by chronic diseases remains poorly understood, particularly in young individuals. The present study aimed to comprehensively characterize musculoskeletal alterations associated with SOS using a juvenile porcine model of cerulein-induced chronic pancreatitis. Femoral bone analysis included densitometry, mechanical testing, histomorphometry, and serum bone turnover markers. The quadriceps femoris muscle was evaluated through histological analysis and gene expression profiling of antioxidant enzymes and apoptotic regulators. Animals with SOS showed significantly reduced femoral BMD compared to controls, with altered cortical geometry and compromised mechanical properties. Trabecular bone analysis revealed classic osteoporotic changes with decreased bone volume fraction. Negative changes were also observed in the growth plate morphology, indicating impaired endochondral ossification. Bone turnover markers indicated elevated bone resorption and altered formation. Muscle analysis demonstrated sarcopenic changes with selective atrophy of fast-twitch type II fibers and increased fiber density. At the molecular level, SOS muscles exhibited downregulated expression of CAT and CASP3, suggesting muscle atrophy predominantly mediated by oxidative stress and caspase-independent proteolysis rather than classical apoptosis. In conclusion, chronic pancreatitis in young pigs induces coupled bone and muscle degeneration consistent with secondary osteosarcopenia, demonstrating that muscle–bone crosstalk dysfunction occurs early in chronic inflammatory disease. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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31 pages, 4843 KB  
Review
Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets
by Uttapol Permpoon, Jiyeong Moon, Chul Young Kim and Tae-gyu Nam
Int. J. Mol. Sci. 2025, 26(15), 7616; https://doi.org/10.3390/ijms26157616 - 6 Aug 2025
Cited by 1 | Viewed by 2075
Abstract
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose [...] Read more.
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
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Article
Evaluation of Cervical Myoclonus in Dogs with Spinal Diseases: 113 Cases (2014–2023)
by Ana Martinez, Emili Alcoverro, Edward Ives and Lisa Alves
Animals 2025, 15(15), 2298; https://doi.org/10.3390/ani15152298 - 6 Aug 2025
Viewed by 631
Abstract
Cervical myoclonus (CM) has been associated with intervertebral disc extrusion (IVDE), with a higher prevalence in French Bulldogs. The presence of CM in other breeds and with other aetiologies has not been reported. The purpose of this study was to describe the signalment, [...] Read more.
Cervical myoclonus (CM) has been associated with intervertebral disc extrusion (IVDE), with a higher prevalence in French Bulldogs. The presence of CM in other breeds and with other aetiologies has not been reported. The purpose of this study was to describe the signalment, neurological examination, neuroanatomical localisation and grade, imaging findings, diagnosis, treatment, follow-up and resolution of CM in dogs. An observational multicentred retrospective analysis identified 173 dogs with CM; of those, 113 met the inclusion criteria. French Bulldogs (n = 52/113, 46%), Beagles (n = 8/113, 7.1%), Chihuahuas and Shih-Tzus (n = 6/113 for each, 5.31%) were the most affected breeds. Apparent cervical pain was the most common finding on neurologic examination (n = 70/113, 62%). Magnetic resonance imaging (MRI) was consistent with nerve root impingement in 17% (n = 19/113) of the dogs. The most frequently diagnosed conditions were degenerative (n = 100/113, 88.5%), inflammatory (n = 8/113, 7.1%), neoplastic (n = 3/113, 2.7%), vascular (n = 1/113, 0.9%) and congenital (n = 1/113, 0.9%) in origin. Dogs with a neoplastic aetiology tended to be older than those with other causes. Follow-up was recorded in 77 dogs, and 75 of these (n = 75/77, 97.4%) had resolution of the CM. The results supported that cervical myoclonus can be caused by various underlying conditions and can affect different dog breeds. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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