Search Results (75)

Pelvic organ prolapse (POP) is a common pelvic floor disorder with substantial impact on women’s quality of life, necessitating accurate and reproducible diagnostic methods. This study investigates the use of three-dimensional (3D) transperineal ultrasound, integrated with artificial intelligence (AI), to evaluate pelvic floor biomechanics and identify correlations between biometric parameters and prolapse severity. Thirty-seven female patients diagnosed with genital prolapse (mean age: 65.3 ± 10.6 years; mean BMI: 29.5 ± 3.8) were enrolled. All participants underwent standardized 3D transperineal ultrasound using the Mindray Smart Pelvic system, an AI-assisted imaging platform. Key biometric parameters—anteroposterior diameter, laterolateral diameter, and genital hiatus area—were measured under three functional states: rest, maximal Valsalva maneuver, and voluntary pelvic floor contraction. Additionally, two functional indices were derived: the distensibility index (ratio of Valsalva to rest) and the contractility index (ratio of contraction to rest), reflecting pelvic floor elasticity and muscular function, respectively. Statistical analysis included descriptive statistics and univariate correlation analysis using Pelvic Organ Prolapse Quantification (POP-Q) system scores. Results revealed a significant correlation between laterolateral diameter and prolapse severity across multiple compartments and functional states. In apical prolapse, the laterolateral diameter measured at rest and during both Valsalva and contraction showed positive correlations with POP-Q point C, indicating increasing transverse pelvic dimensions with more advanced prolapse (e.g., r = 0.42 to 0.58; p < 0.05). In anterior compartment prolapse, the same parameter measured during Valsalva and contraction correlated significantly with POP-Q point AA (e.g., r = 0.45 to 0.61; p < 0.05). Anteroposterior diameters and genital hiatus area were also analyzed but showed weaker or inconsistent correlations. AI integration facilitated real-time image segmentation and automated measurement, reducing operator dependency and increasing reproducibility. These findings highlight the laterolateral diameter as a strong, reproducible anatomical marker for POP severity, particularly when assessed dynamically. The combined use of AI-enhanced imaging and functional indices provides a novel, standardized, and objective approach for assessing pelvic floor dysfunction. This methodology supports more accurate diagnosis, individualized management planning, and long-term monitoring of pelvic floor disorders. Full article

Background: Gallbladder hypomotility is a key pathogenic factor in cholelithiasis. Non-invasive interventions to enhance gallbladder contractility remain limited. Ultrasound therapy has shown promise in various muscular disorders, but its effects on gallbladder function are unexplored. Methods: This study employed low-intensity pulsed ultrasound (LIPUS) at a 3 MHz frequency and 0.8 W/cm² intensity with a 20% duty cycle to irradiate the gallbladder region of fasting guinea pigs. Gallbladder contractile function was evaluated through multiple complementary approaches: in vivo assessment via two-dimensional/three-dimensional ultrasound imaging to monitor volumetric changes; quantitative functional evaluation using nuclear medicine scintigraphy (^99mTc-HIDA); and ex vivo experiments including isolated gallbladder muscle strip tension measurements, histopathological analysis, α-smooth muscle actin (α-SMA) immunohistochemistry, and intracellular calcium fluorescence imaging. Results: Ultrasound significantly enhanced gallbladder emptying, evidenced by the volume reduction and increased ejection fraction. Scintigraphy confirmed accelerated bile transport in treated animals. Ex vivo analyses demonstrated augmented contractile force, amplitude, and frequency in ultrasound-treated smooth muscle. Histological examination revealed smooth muscle hypertrophy, α-SMA upregulation, and elevated intracellular calcium levels. Extended ultrasound exposure produced sustained functional improvements without tissue damage. Conclusions: Ultrasound effectively enhances gallbladder contractile function through mechanisms involving smooth muscle structural modification and calcium signaling modulation. These findings establish the experimental foundation for ultrasound as a promising non-invasive therapeutic approach to improve gallbladder motility and potentially prevent gallstone formation. Full article

Recent studies on myogenic satellite cells (SCs) in Duchenne muscular dystrophy (DMD) documented altered division capacities and impaired regeneration potential of SCs in DMD patients and animal models. It remains unknown, however, if SC-intrinsic effects trigger these deficiencies at pre-contractile stages of myogenesis rather than resulting from the pathologic environment. In this study, we isolated SCs from a porcine DMD model and age-matched wild-type (WT) piglets for comprehensive analysis. Using immunofluorescence, differentiation assays, traction force microscopy (TFM), RNA-seq, and label-free proteomic measurements, SCs behavior was characterized, and molecular changes were investigated. TFM revealed significantly higher average traction forces in DMD than WT SCs (90.4 ± 10.5 Pa vs. 66.9 ± 8.9 Pa; p = 0.0018). We identified 1390 differentially expressed genes and 1261 proteins with altered abundance in DMD vs. WT SCs. Dysregulated pathways uncovered by gene ontology (GO) enrichment analysis included sarcomere organization, focal adhesion, and response to hypoxia. Multi-omics factor analysis (MOFA) integrating transcriptomic and proteomic data, identified five factors accounting for the observed variance with an overall higher contribution of the transcriptomic data. Our findings suggest that SC impairments result from their inherent genetic abnormality rather than from environmental influences. The observed biological changes are intrinsic and not reactive to the pathological surrounding of DMD muscle. Full article

Rabbit meat constitutes a high-protein, low-fat nutritional resource demonstrating rising consumption, particularly within the Asia-Pacific region. Consequently, muscle growth and developmental pattern in meat rabbits represent critical economic considerations. To elucidate the primary signaling pathways governing muscle development, we first performed comparative body weight analyses between two rabbit breeds exhibiting divergent growth rates: the fast-growing Checkered Giant (Ju) and slow-growing Sichuan Ma rabbit. Subsequent, post-natal qualities of thigh and longissimus dorsi muscle fiber were quantified across three developmental phases (28, 56, and 84 days post-natal). The results showed the body weight of Ju rabbit was significantly higher than that of Ma rabbit beyond 3 weeks post-natal (p < 0.05), while Ma rabbit exhibited larger muscle fiber areas in both tissues at 56 days (p < 0.05). The transcriptome analysis showed that 284 and 305 differentially expressed genes (DEGs) (|log2FC| > 1, padj < 0.05) were identified in thigh muscle and longissimus dorsi muscle, respectively. GO (Gene Ontology) analysis of DEGs indicated DEGs in the thigh muscle were enriched in these terms related to biological processes of muscle cell migration and smooth muscle cell migration, cellular components of sarcomere, myofibril, and actin filament bundle, while DEGs in longissimus dorsi muscle were enriched in these terms associated with biological processes of muscle cell migration, smooth muscle cell migration and muscle structure development, cellular component of actin cytoskeleton, contractile fiber, myofibril, myosin complex and molecular function of actin filament binding. Integrated GO, KEGG and PPI analyses of co-expressive DEGs implicated the HIF-1 signaling pathway and Glycolysis/Gluconeogenesis in muscular development. Different expression of energy metabolism hub-genes might be the primary reason for interbreed muscle developmental disparities. Full article

Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates the possibility to form functional and reproducible 3D SkMOs, to investigate on potential patient-related phenotypic differences. Methods: In this study, we employed fibrin-based 3D skeletal muscle organoids derived from immortalized myogenic precursors of DMD patients carrying either a stop codon mutation in exon 59 or a 48–50 deletion. We compared dystrophic lines with a healthy wild-type control (HWT) by assessing microtissue formation ability, contractile function at multiple timepoints along with intracellular calcium dynamics via calcium imaging, as well as expression of myogenic markers. Results: We found patient-specific structural and functional differences in the early stages of 3D SkMO development. Contractile force, measured as both single twitch and tetanic responses, was significantly lower in dystrophic 3D SkMOs compared to HWT, with the most pronounced differences observed at day 7 of differentiation. However, these disparities diminished over time under similar culturing conditions and in the absence of continuous nerve-like stimulation, suggesting that the primary deficit lies in delayed myogenic maturation, as also supported by gene expression analysis. Conclusions: Our results underline that, despite the initial maturation delay, DMD muscle precursors retain the capacity to form functional 3D SkMOs once this intrinsic lag is overcome. This suggests a critical role of dystrophin in early myogenic development, while contraction-induced stress and/or an inflammatory microenvironment are essential to fully recapitulate dystrophic phenotypes in 3D SkMOs. Full article

Background/Objectives: Studies of the effects of anchor schemes (perceived intensity vs. relative intensity) on muscular performance have reported mixed findings. Therefore, the present study examined the effects of different anchor schemes on time-to-task failure (TTF), muscular performance, neuromuscular responses, and potentiated twitch torque (PTT). Methods: On separate days, 15 men (age = 21.5 ± 2.3 yrs) performed forearm flexion maximal voluntary isometric contractions (MVICs) before and after sustained tasks anchored to a rating of perceived exertion of 6 (RPEFT) and with the torque at RPE = 6 (TRQFT). Electromyographic amplitude (EMG AMP) and mean power frequency (EMG MPF) were recorded from the biceps brachii (BB). Supramaximal stimuli were delivered to the motor nerve of the BB following the MVICs to quantify the PTT. Repeated measures ANOVAs assessed the mean differences between anchor schemes for MVIC, neuromuscular, and PTT responses. Paired t-tests compared the magnitude of percent changes for the dependent variables. Results: The TTF for the RPEFT was longer (p < 0.001) than the TRQFT, but the MVIC decreased similarly (12.7 ± 9.5% vs. 20.3 ± 7.9%, p = 0.054). Electromyographic AMP did not change (p = 0.288), while EMG MPF decreased (15.7 ± 10.2%, p < 0.011) for the TRQFT only. Mean decreases in PTT were comparable for both tasks (p < 0.003), although the percent change was greater for the TRQFT (49.6 ± 16.1%, p < 0.001). Conclusions: The differences in TTF, but similar decreases in MVIC suggested that participants reached a sensory tolerance limit. Based on EMG MPF and PTT, the TRQFT caused greater peripheral perturbations to contractile function than the RPEFT. Full article

Background/Objectives: Cesarean birth (CB) is linked to nonspecific low back pain (NSLBP). Different properties of the muscular tissue, including contractile, biomechanical, and viscous properties, may reflect its physiological or pathological condition. This study aimed to measure these properties of lumbar paravertebral muscles (LPVMs) and their relationship with post-CB mothers with moderate-severity NSLBP and match their measurements to those of the controls. Methods: Sixty women were included in this case–control research. They were divided into two equal groups: Group (A) representing cases, consisted of 30 females who experienced CB and complained of moderate-severity NSLBP, and Group (B) representing controls, consisted of 30 healthy females who had never experienced pregnancy with no or mild-severity NSLBP. Results: The statistical analysis between the two groups yielded significant differences in the right and left LPVMs’ tone (p = 0.002 and 0.015), relaxation time (p = 0.002 and 0.022), and creep (p = 0.013 and 0.008), respectively. On the other side, there were non-significant differences in the right and left LPVMs’ stiffness (p = 0.055 and 0.367) and elasticity (p = 0.115 and 0.231), respectively. The regression analysis’s final model indicated a strong overall performance (Nagelkerke: 1.00). Conclusions: The LPVMs of post-CB mothers with moderate-severity NSLBP showed remarkable changes in both contractile and viscous properties: muscle tone notably decreased, while viscosity increased. However, biomechanical properties like stiffness and elasticity showed negligible changes. This fitted regression analysis illustrated the holistic strong effect of LPVMs’ properties as risk factors contributing to post-CB NSLBP, emphasizing their consideration in diagnosis and intervention strategies for such cases. Full article

Muscular strength and explosiveness are generally known as factors that affect physical performance. Physical ability modeling has a profound connection with long-term athlete development and talent identification. The purpose of the current study was to investigate differences in contractile characteristics (maximal isometric force and maximal rate of force development) among various muscle groups in youth elite female team handball players (n = 35, 16.6 ± 1.1 years) compared to a control group (n = 28, 16.7 ± 1.1 years). The following tests were performed: isometric non-dominant hand grip, isometric dominant hand grip, isometric deadlift, isometric standing leg extension, and isometric bilateral ankle extension. For each subject, the maximal isometric force and maximal rate of force development were derived from the isometric strength tests. The research analyzed a total of twenty-four variables, presented in both absolute and relative values. Statistical analysis revealed significant differences among all pairs of variables in the absolute values of maximal isometric force (Λ = 0.531, F = 10.07, p = 0.000) and maximal rate of force development (Λ = 0.692, F = 5.08, p = 0.001) between the two groups. The most significant difference was found in the grip of the dominant hand, where the impact of the difference was 43.6% and 37.0% for the absolute values of force and explosiveness. Conversely, no differences were observed between the pairs of variables representing the relative values across the two subject groups, except for the dominant hand grip relative force (p = 0.006). The results provide information about the contractile potentials of important muscle groups in the game of handball, which could help in adapting strength training according to the specifics of the strength and explosivity development of young female handball players. Full article

Spinal muscular atrophy (SMA) is caused by a deficiency of the ubiquitously expressed survival motor neuron (SMN) protein. The main pathological hallmark of SMA is the degeneration of lower motor neurons (MNs) with subsequent denervation and atrophy of skeletal muscle. However, increasing evidence indicates that low SMN levels not only are detrimental to the central nervous system (CNS) but also directly affect other peripheral tissues and organs, including skeletal muscle. To better understand the potential primary impact of SMN deficiency in muscle, we explored the cellular, ultrastructural, and molecular basis of SMA myopathy in the SMNΔ7 mouse model of severe SMA at an early postnatal period (P0-7) prior to muscle denervation and MN loss (preneurodegenerative [PND] stage). This period contrasts with the neurodegenerative (ND) stage (P8-14), in which MN loss and muscle atrophy occur. At the PND stage, we found that SMN∆7 mice displayed early signs of motor dysfunction with overt myofiber alterations in the absence of atrophy. We provide essential new ultrastructural data on focal and segmental lesions in the myofibrillar contractile apparatus. These lesions were observed in association with specific myonuclear domains and included abnormal accumulations of actin-thin myofilaments, sarcomere disruption, and the formation of minisarcomeres. The sarcoplasmic reticulum and triads also exhibited ultrastructural alterations, suggesting decoupling during the excitation–contraction process. Finally, changes in intermyofibrillar mitochondrial organization and dynamics, indicative of mitochondrial biogenesis overactivation, were also found. Overall, our results demonstrated that SMN deficiency induces early and MN loss-independent alterations in myofibers that essentially contribute to SMA myopathy. This strongly supports the growing body of evidence indicating the existence of intrinsic alterations in the skeletal muscle in SMA and further reinforces the relevance of this peripheral tissue as a key therapeutic target for the disease. Full article

Background: Prokinetic agents are effective in increasing gastrointestinal (GI) contractility and alleviating constipation, often caused by slow intestinal motility. Lubiprostone (LUB), known for activating CLC-2 chloride channels, increases the chloride ion concentration in the GI tract, supporting water retention and stool movement. Despite its therapeutic efficacy, the exact mechanisms underlying its pharmacological action are poorly understood. Here, we investigated whether LUB activates the canonical transient receptor potential cation channel type 4 (TRPC4) through stimulation with E-type prostaglandin receptor (EP) type 3. Methods: Using isotonic tension recordings on mouse colon strips, we examined LUB-induced contractility in both proximal and distal colon segments. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine mRNA levels of EP1-4 receptor subtypes in distal colonic muscular strips and isolated myocytes. The effects of a TRPC4 blocker and EP3 antagonist on LUB-stimulated contractions were also evaluated. Results: LUB showed significant contraction in the distal segment compared to the proximal segment. EP3 receptor mRNA levels were highly expressed in the distal colon tissue, which correlated with the observed enhanced contraction. Furthermore, LUB-induced spontaneous contractions in distal colon muscles were reduced by a TRPC4 blocker or EP3 antagonist, indicating that LUB-stimulated EP3 receptor activation may lead to TRPC4 activation and increased intracellular calcium in colonic smooth muscle. Conclusions: These findings suggest that LUB improves mass movement through indirect activation of the TRPC4 channel in the distal colon. The segment-specific action of prokinetic agents like LUB provides compelling evidence for a personalized approach to symptom management, supporting the defecation reflex. Full article

Background: A knee injury in an athlete leads to periods of forced exercise interruption. Myocardial work (MW) assessed by echocardiographic and cardiopulmonary exercise testing (CPET) are two essential methods for evaluating athletes during the period following injury. However, compared to pre-surgery evaluations, the variations in cardiovascular parameters and functional capacity assessed by these methods after surgery remain unclear. Methods: We evaluated 22 non-professional athletes aged 18–52, involved in prevalently aerobic or alternate aerobic/anaerobic sports activities, who were affected by a knee pathology requiring surgical treatment. The evaluation was performed at rest using transthoracic echocardiography, including MW assessment, and during exercise using CPET. Each athlete underwent the following two evaluations: the first before surgery and the second after surgery (specifically at the end of the deconditioning period). Results: Resting heart rate (HR) increased significantly (from 63.3 ± 10.85 to 71.2 ± 12.52 beats per minute, p = 0.041), while resting diastolic and systolic blood pressure, forced vital capacity, and forced expiratory volume in the first second did not show significant changes. Regarding the echocardiographic data, global longitudinal strain decreased from −18.9 ± 1.8 to −19.3 ± 1.75; however, this reduction was not statistically significant (p = 0.161). However, the global work efficiency (GWE) increased significantly (from 93.0% ± 2.9 to 94.8% ± 2.6, p = 0.006) and global wasted work (GWW) reduced significantly (from 141.4 ± 74.07 to 98.0 ± 50.9, p = 0.007). Additionally, the patients were able to perform maximal CPET at both pre- and post-surgery evaluations, as demonstrated by the peak respiratory exchange ratio and HR. However, the improved myocardial contractility (increased GWE and decreased GWW) observed at rest did not translate into significant changes in exercise parameters, such as peak oxygen consumption and the mean ventilation/carbon dioxide slope. Conclusions: After surgery, the athletes were more deconditioned (as indicated by a higher resting HR) but exhibited better resting myocardial contractility (increased GWE and reduced GWW). Interestingly, no significant changes in exercise capacity parameters, as evaluated by CPET, were found after surgery, suggesting that the improved myocardial contractility was offset by a greater degree of muscular deconditioning. Full article

Pericytes are a distinct type of cells interacting with endothelial cells in blood vessels and contributing to endothelial barrier integrity. Furthermore, pericytes show mesenchymal stem cell properties. Muscle-derived pericytes can demonstrate both angiogenic and myogenic capabilities. It is well known that regenerative abilities and muscle stem cell potential decline during aging, leading to sarcopenia. Therefore, this study aimed to investigate the potential of pericytes in supporting muscle differentiation and angiogenesis in elderly individuals and in patients affected by Ullrich congenital muscular dystrophy or by Bethlem myopathy, two inherited conditions caused by mutations in collagen VI genes and sharing similarities with the progressive skeletal muscle changes observed during aging. The study characterized pericytes from different age groups and from individuals with collagen VI deficiency by mass spectrometry-based proteomic and bioinformatic analyses. The findings revealed that aged pericytes display metabolic changes comparable to those seen in aging skeletal muscle, as well as a decline in their stem potential, reduced protein synthesis, and alterations in focal adhesion and contractility, pointing to a decrease in their ability to form blood vessels. Strikingly, pericytes from young patients with collagen VI deficiency showed similar characteristics to aged pericytes, but were found to still handle oxidative stress effectively together with an enhanced angiogenic capacity. Full article

Skeletal muscle is a complex organ essential for locomotion, posture, and metabolic health. This review explores our current knowledge of Mustn1, particularly in the development and function of skeletal muscle. Mustn1 expression originates from Pax7-positive satellite cells in skeletal muscle, peaks during around the third postnatal month, and is crucial for muscle fiber differentiation, fusion, growth, and regeneration. Clinically, Mustn1 expression is potentially linked to muscle-wasting conditions such as muscular dystrophies. Studies have illustrated that Mustn1 responds dynamically to injury and exercise. Notably, ablation of Mustn1 in skeletal muscle affects a broad spectrum of physiological aspects, including glucose metabolism, grip strength, gait, peak contractile strength, and myofiber composition. This review summarizes our current knowledge of Mustn1’s role in skeletal muscle and proposes future research directions, with a goal of elucidating the molecular function of this regulatory gene. Full article

The diaphragm muscle is essential for breathing, and its dysfunctions can be fatal. Many disorders affect the diaphragm, including muscular dystrophies. Despite the clinical relevance of targeting the diaphragm, there have been few studies evaluating diaphragm function following a given experimental treatment, with most of these involving anti-inflammatory drugs or gene therapy. Cell-based therapeutic approaches have shown success promoting muscle regeneration in several mouse models of muscular dystrophy, but these have focused mainly on limb muscles. Here we show that transplantation of as few as 5000 satellite cells directly into the diaphragm results in consistent and robust myofiber engraftment in dystrophin- and fukutin-related protein-mutant dystrophic mice. Transplanted cells also seed the stem cell reservoir, as shown by the presence of donor-derived satellite cells. Force measurements showed enhanced diaphragm strength in engrafted muscles. These findings demonstrate the feasibility of cell transplantation to target the diseased diaphragm and improve its contractility. Full article

Muscle function reflects muscular mitochondrial status, which, in turn, is an adaptive response to physical activity, representing improvements in energy production for de novo biosynthesis or metabolic efficiency. Differences in muscle performance are manifestations of the expression of distinct contractile-protein isoforms and of mitochondrial-energy substrate utilization. Powerful contractures require immediate energy production from carbohydrates outside the mitochondria that exhaust rapidly. Sustained muscle contractions require aerobic energy production from fatty acids by the mitochondria that is slower and produces less force. These two patterns of muscle force generation are broadly classified as glycolytic or oxidative, respectively, and require disparate levels of increased contractile or mitochondrial protein production, respectively, to be effectively executed. Glycolytic muscle, hence, tends towards fibre hypertrophy, whereas oxidative fibres are more disposed towards increased mitochondrial content and efficiency, rather than hypertrophy. Although developmentally predetermined muscle classes exist, a degree of functional plasticity persists across all muscles post-birth that can be modulated by exercise and generally results in an increase in the oxidative character of muscle. Oxidative muscle is most strongly correlated with organismal metabolic balance and longevity because of the propensity of oxidative muscle for fatty-acid oxidation and associated anti-inflammatory ramifications which occur at the expense of glycolytic-muscle development and hypertrophy. This muscle-class size disparity is often at odds with common expectations that muscle mass should scale positively with improved health and longevity. Brief magnetic-field activation of the muscle mitochondrial pool has been shown to recapitulate key aspects of the oxidative-muscle phenotype with similar metabolic hallmarks. This review discusses the common genetic cascades invoked by endurance exercise and magnetic-field therapy and the potential physiological differences with regards to human health and longevity. Future human studies examining the physiological consequences of magnetic-field therapy are warranted. Full article