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To explore whether the potential instability of the cervical spine and cervical muscle degeneration in patients with cervical spondylotic radiculopathy (CSR) affect the efficacy of cervical traction, and whether cervical traction can aggravate the potential instability of the cervical spine. We divided the 113 recruited CRS patients into three groups based on the differences in horizontal displacement and abnormal angle, and measured the degree of cervical muscle degeneration in the patients through MRI. Considering functional scores, VAS, NDI and PCS scores of the three groups post-treatment were significantly improved. Through the intergroup analysis, we found that the improvement in functional scores in the mild and moderate instability trend groups was better than that in the severe group. Through MRI measurements, we found that the degree of cervical muscle degeneration was significantly increased in the severe instability trend group. Regarding the changes in X-Ray imaging parameters pre- and post-treatment, no significant differences were observed pre- and post-treatment. For patients with CSR, the more serious their predisposition for cervical instability was, the more severe the degree of cervical muscle degeneration was, which means the worse the curative effect was, but cervical traction did not aggravate the potential degree of cervical instability.
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Vértebras Cervicais , Imageamento por Ressonância Magnética , Radiculopatia , Espondilose , Tração , Humanos , Masculino , Feminino , Espondilose/diagnóstico por imagem , Espondilose/patologia , Pessoa de Meia-Idade , Tração/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Radiculopatia/diagnóstico por imagem , Radiculopatia/etiologia , Adulto , Idoso , Resultado do Tratamento , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/terapiaRESUMO
INTRODUCTION: The natural history of rotator cuff tears often involves progressive pain development, tear enlargement, and advancing muscle fatty degeneration. Both surgery and conservative management have proven to be effective treatments. Our study purpose was to compare the short to mid-term effects of rotator cuff repair on shoulder function, progression of tear size, and muscle degeneration compared to controls with asymptomatic tears that developed pain and were managed nonoperatively. METHODS: This comparative study consists of two separate longitudinal study arms. The control group consisted of asymptomatic degenerative cuff tears followed until pain development and then managed nonoperatively with continued surveillance. The surgical group consisted of subjects with degenerative tears that failed nonoperative treatment and underwent surgical intervention with a minimum of 2 years follow-up. Outcomes included VAS pain, ASES, AROM, strength, and ultrasonography. RESULTS: There were 83 controls and 65 surgical shoulders. The surgical group was younger at enrollment (58.9±5.3 yr vs. 61.2±7.8 yr, p=0.04). The median follow-up for control subjects after pain development was 5.1 years (IQR 3.6) and the median postoperative follow-up for the surgical group was 3.0 years (IQR 0.2). Baseline tear widths (median 14 mm, IQR 9 vs. 13 mm, IQR 8; p=0.45) and tear lengths (median 14 mm, IQR 13 vs. median 11 mm, IQR 8; p=0.06) were similar between the surgical group and controls. There were no differences in the baseline prevalence of fatty degeneration of the supraspinatus or infraspinatus muscles between groups (p=0.43 and p=0.58, respectively). At final follow-up, the surgical group demonstrated significantly lower VAS pain (0 [IQR 2] vs. 3.5 [IQR 4], p=0.0002), higher composite ASES (95 [IQR 13] vs. 65.8 [IQR 32], p=0.0002) and ADL scores (29 [IQR 4] vs. 22 [IQR 8], p=0.0002), greater abduction strength (69.6 N [SD 29] vs. 35.9 N [SD 29], p=0.0002), greater active forward elevation (155Ë [SD 8] vs. 142Ë [SD 28], p=0.002), greater active external rotation in abduction (mean 98.5Ë, SD 12 vs. mean 78.2Ë, SD 20; p=0.0002) compared to controls. Additionally, the prevalence of fatty muscle degeneration was lower in the surgical group for the supraspinatus and infraspinatus (25% vs. 41%, p=0.05; 17% vs. 34%, p=0.03; respectively). CONCLUSION: This prospective longitudinal study comparing a surgical cohort undergoing rotator cuff repair with a control group treated nonoperatively supports the notion that surgical intervention has the potential to alter the early natural history of degenerative rotator cuff disease. Patients in the surgical group demonstrated clinically relevant differences in pain and functional outcomes. Surgical intervention was protective against progressive muscle degeneration compared to nonoperative treatment.
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To explore the favorable factors that help slow the progression of disease in patients with mild Cervical Spondylotic Myelopathy (CSM). A retrospective analysis was conducted, involving the enrollment of 115 CSM patients. The categorization of patients into two groups was based on the duration of symptoms, assessments using the mJOA scale and Health Transition (HT) scores: mild-slow group and severe-rapid group. We found that the patients in both groups had similar degrees of spinal cord compression, but mild-slow group were older and had smaller C2-C7 cobb angle (Flexion) (CL(F)), C2-C7 cobb angle (Range of motion) (CL(ROM)), Transverse area (TA), Normal-TA, Compressive spinal canal area (CSCA), Normal-Spinal canal area (Normal-SCA) and lower Spinal cord increased signal intensity (ISI) Grade than the severe-rapid group. A binary logistic regression analysis showed that CL(ROM) and Normal-TA are favorable factors to help slow the progression of disease patients with mild CSM. Through ROC curves, we found that when CL(ROM) < 39.1° and Normal-TA < 80.5mm2, the progression of disease in CSM patients may be slower. Meanwhile, we obtained a prediction formula by introducing joint prediction factor: L = CL(ROM) + 2.175 * Normal-TA. And found that when L < 213.0, the disease progression of patients may be slower which was superior to calculate CL(ROM) and Normal-TA separately.
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Vértebras Cervicais , Progressão da Doença , Espondilose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Espondilose/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Estudos Retrospectivos , Idoso , Compressão da Medula Espinal/patologia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/patologia , Amplitude de Movimento Articular , Curva ROC , Adulto , Índice de Gravidade de DoençaRESUMO
[This corrects the article DOI: 10.3389/fendo.2024.1391970.].
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Objective: To measure the paraspinal muscle parameters, explore the characteristics of paraspinal muscles, and investigate the influence factors of paraspinal muscle degeneration in healthy people. Methods: Eighty-two healthy Chinese people were prospectively recruited between February 2020 and November 2020, including 36 males and 46 females. The age ranged from 21 to 75 years, with a mean of 48.0 years. The height ranged from 150 to 183 cm, with a mean of 165.6 cm. The body mass ranged from 43 to 100 kg, with a mean of 65.4 kg. The body mass index (BMI) ranged from 16.7 to 32.4 kg/m 2, with a mean of 23.7 kg/m 2. Parameters of the paraspinal muscles (multifidus muscle, erector spinae muscle, and psoas major muscle) at L 3, L 4, and L 5 levels were measured by MRI, including the relative total cross-sectional area (rtCSA), relative fatty cross-sectional area (rfCSA), relative signal intensity (rSI), and fatty infiltration (FI). The differences of paraspinal muscle parameters at different genders and different measurement levels were compared; Pearson or Spearman correlation analysis was used to explore the relationship between paraspinal muscle parameters and age, height, body mass, BMI. Results: From L 3 to L 5 level, the rtCSA and rfCSA of multifidus muscle and psoas major muscle as well as the rfCSA of erector spinae muscle increased, while rtCSA of erector spinae muscle decreased. The FI and rSI of paraspinal muscles increased gradually. The parameters of paraspinal muscles at L 4 and L 5 levels were significantly different from those at L 3 levels ( P<0.05). There were significant differences in rtCSA and rfCSA of multifidus muscle, rtCSA, FI, and rSI of erector spinae muscle as well as rtCSA, rfCSA, and FI of psoas major muscle between L 4 and L 5 levels ( P<0.05). Compared with males, the rfCSA and FI of multifidus muscle, FI of erector spinae muscle, and FI of psoas major muscle were significantly higher in females, while the rtCSA of psoas major muscle was significantly lower ( P<0.05). Age was significantly negatively correlated with rtCSA of paraspinal muscles ( P<0.05), but significantly positively correlated with FI of paraspinal muscles, rfCSA and rSI of multifidus and erector spinae muscles ( P<0.05). Height was significantly negatively correlated with rfCSA and FI of paraspinal muscles ( P<0.05). Conclusion: The degree of paraspinal muscle degeneration increases gradually along the spine axis from head to tail. Paraspinal muscle degeneration is related to age, height, and gender. The relationship between the body mass, BMI and paraspinal muscle degeneration needs further study.
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Índice de Massa Corporal , Imageamento por Ressonância Magnética , Músculos Paraespinais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Idoso , Imageamento por Ressonância Magnética/métodos , Adulto Jovem , Estudos Prospectivos , Vértebras Lombares/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/patologia , Tecido Adiposo/diagnóstico por imagemRESUMO
Objective: To investigate the relationship between degeneration of cervical intervertebral disc and degeneration of paravertebral muscles[multifidus (MF), cervical semispinalis (SCer), semispinalis capitis (SCap) and splenius capitis (SPL)]. Methods: 82 patients with chronic neck pain were randomly selected, including 43 males and 39 females, with 50.73 0.7.51 years old. All patients were scanned by 3.0T MRI Philips Ingenia performed conventional MRI sequence scanning and fat measurement sequence mDIXON-Quant scanning of cervical. Fat infiltration (FI) and cross-sectional area (CSA) of cervical paravertebral muscle (MF, SCer, SCap and SPL) at central level of C5-6 disc were measured by Philips 3.0T MRI image post-processing workstation. According to Pfirrmann grading system, there was no grade I in the included cases. The number of grade IIr IV cases were n=16, 40, 19 and 7 respectively. CSA and FI of cervical paravertebral muscles were compared with t test or one-way ANOVA, Spearman correlation analysis was used to evaluate the correlation between age, disc degeneration, and CSA, FI of cervical paravertebral muscles, and multiple linear regression analysis was used to analyze the independent influencing factors of CSA and FI. Results: CSA of cervical paravertebral muscles in male patients was significantly higher than that in female patients (all P<0.001), but there was no significant difference in FI (all P>0.05). Age was weakly correlated with CSA of MF+SCer, moderately correlated with CSA of SCap and SPL (r=-0.256, -0.355 and -0.361, P<0.05), weakly correlated with FI of SCap and SPL (r= 0.182 and 0.264, P<0.001), moderately correlated with FI of MF+SCer (r=0.408, P<0.001). There were significant differences in FI with disc degeneration (P<0.001, P=0.028 and P=0.005). Further correlation analysis showed that disc degeneration was strongly correlated with FI of MF+SCer (r=0.629, P<0.001), and moderately correlated with FI of SCap and SPL (r=0.363, P=0.001; r=0.345, P=0.002). Multiple linear regression analysis showed that sex and age were the influencing factors of CSA of SCap and SPL, sex was the independent influencing factor of CSA of MF+SCer, and disc degeneration was the independent influencing factor of FI. Conclusions: Age is negatively correlated with CSA and positively correlated with FI. Disc degeneration was correlated with FI of paravertebral muscles, especially with FI of MF and SCer. Sex and age were the influencing factors of CSA, while disc degeneration was the independent influencing factor of FI.
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Vértebras Cervicais , Degeneração do Disco Intervertebral , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/patologia , Pessoa de Meia-Idade , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Cervicalgia/diagnóstico por imagem , Cervicalgia/patologia , IdosoRESUMO
Low back pain (LBP) is a worldwide problem with public health. Paravertebral muscle degeneration (PMD) is believed to be associated with LBP. Increasing evidence has demonstrated that microRNA (miRNA)-mRNA signaling networks have been implicated in the pathophysiology of diseases. Research suggests that cell death, oxidative stress, inflammatory and immune response, and extracellular matrix (ECM) metabolism are the pathogenesis of PMD; however, the miRNA-mRNA mediated the pathological process of PMD remains elusive. RNA sequencing (RNA-seq) and single cell RNA-seq (scRNA-seq) are invaluable tools for uncovering the functional biology underlying these miRNA and gene expression changes. Using scRNA-seq, we show that multiple immunocytes are presented during PMD, revealing that they may have been implicated with PMD. Additionally, using RNA-seq, we identified 76 differentially expressed genes (DEGs) and 106 differentially expressed miRNAs (DEMs), among which IL-24 and CCDC63 were the top upregulated and downregulated genes in PMD. Comprehensive bioinformatics analyses, including Venn diagrams, differential expression, functional enrichment, and protein-protein interaction analysis, were then conducted to identify six ferroptosis-related DEGs, two oxidative stress-related DEGs, eleven immunity-related DEGs, five ECM-related DEGs, among which AKR1C2/AKR1C3/SIRT1/ALB/IL-24 belong to inflammatory genes. Furthermore, 67 DEMs were predicted to be upstream miRNAs of 25 key DEGs by merging RNA-seq, TargetScan, and mirDIP databases. Finally, a miRNA-gene network was constructed using Cytoscape software and an alluvial plot. ROC curve analysis unveiled multiple key DEGs with the high clinical diagnostic value, providing novel approaches for diagnosing and treating PMD diseases.
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INTRODUCTION: Skeletal muscle degeneration is a common effect of chronic muscle injuries, including fibrosis and fatty infiltration, which is the replacement of preexisting parenchymal tissue by extracellular matrix proteins and abnormal invasive growth of fibroblasts and adipocytes. METHOD: This remodeling limits muscle function and strength, eventually leading to reduced quality of life for those affected. Chemokines play a major role in the regulation of immunocyte migration, inflammation, and tissue remodeling and are implicated in various fibrotic and degenerative diseases. In this study, we aimed to investigate the role of the B-cell chemokine CXCL13 in the gastrocnemius muscle of the Achilles tendon rupture model mouse. We hypothesize that CXCL13 may promote fibrosis and aggravate skeletal muscle degeneration. We performed RNA sequencing and bioinformatics analysis of gastrocnemius muscle from normal and model mice to identify differentially expressed genes and signal pathways related to skeletal muscle degeneration and fibrosis. RESULTS: Our results show that CXCL13 is highly expressed in chronically degenerating skeletal muscle. Furthermore, CXCL13-neutralising antibodies with therapeutic potential were observed to inhibit fibrosis and adipogenesis in vivo and in vitro. CONCLUSION: Our study reveals the underlying therapeutic implications of CXCL13 inhibition for clinical intervention in skeletal muscle degeneration, thereby improving patient prognosis.
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BACKGROUND: Muscle edema formation and inflammatory processes are early manifestations of acute rotator cuff lesions in sheep. Histological analysis of affected muscles revealed edema formation, inflammatory changes, and muscle tissue disruption in MRs. HYPOTHESIS: Edema contributes to inflammatory reactions and early muscle fiber degeneration before the onset of fatty infiltration. STUDY DESIGN: Controlled laboratory study. METHODS: Osteotomy of the greater tuberosity, including the insertion of the infraspinatus tendon, was performed on 14 sheep. These experimental animal models were divided into 2 groups: a nontrauma group with surgical muscle release alone (7 sheep) and a trauma group with standardized application of additional trauma to the musculotendinous unit (7 sheep). Excisional biopsy specimens of the infraspinatus muscle were taken at 0, 3, and 4 weeks. RESULTS: Edema formation was histologically demonstrated in both groups and peaked at 3 weeks. At 3 weeks, signs of muscle fiber degeneration were observed. At 4 weeks, ingrowth of loose alveolar and fibrotic tissue between fibers was detected. Fatty tissue was absent. The diameter of muscle fibers increased in both groups, albeit to a lesser degree in the trauma group, and practically normalized at 4 weeks. Immunohistology revealed an increase in macrophage types 1 and 2, as well as inflammatory mediators such as prostaglandin E2 and nuclear factor kappa-light-chain-enhancer of activated B cells. CONCLUSION: Early muscle edema and concomitant inflammation precede muscle fiber degeneration and fibrosis. Edema formation results from tendon release alone and is only slightly intensified by additional trauma. CLINICAL RELEVANCE: This study illustrates that early edema formation and inflammation elicit muscle fiber degeneration that precedes fatty infiltration. Should this phenomenon be applicable to human traumatic rotator cuff tears, then surgery should be performed as soon as possible, ideally within the first 21 days after injury.
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Lesões do Manguito Rotador , Traumatismos dos Tendões , Humanos , Animais , Ovinos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Traumatismos dos Tendões/cirurgia , Modelos Teóricos , Inflamação/patologia , Tecido Adiposo/patologiaRESUMO
Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.
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A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.
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Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Atrofia Muscular , Lesões do Manguito Rotador , Tenotomia , Animais , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Atrofia Muscular/etiologia , Manguito Rotador/cirurgia , Manguito Rotador/patologia , Manguito Rotador/inervação , Masculino , CamundongosRESUMO
BACKGROUND: Patients treated for symptomatic rotator cuff tear (RCT) on one shoulder seem to have a higher prevalence of RCT on the contralateral shoulder. PURPOSE: To compare the supraspinatus (SSP) tendon and RC muscle properties on the contralateral shoulder in patients after repair surgery to those healthy individuals using quantitative magnetic resonance imaging (MRI). MATERIAL AND METHODS: A total of 23 patients treated for RCT (group A) and 23 healthy controls (group B) were recruited. Constant score, visual analog scale score (VAS), and MRI examinations were conducted. The SSP tendon structural status was graded based on the Zlatkin classification and quantified on ultrashort echo time (UTE)-T2* mapping images. Fatty degeneration of RC muscles was classified according to the Goutallier classification and quantified on T2 mapping. RESULTS: The Constant and VAS scores were comparable between groups A and B (all P >0.05). No significant differences were observed in tendon structural status between the two groups (P >0.05). However, significant differences were established in UTE-T2* values of the SSP tendon on the distal subregion between groups A and B (16.4 ± 2.4â ms vs. 14.8 ± 1.2â ms; P = 0.01). Regarding muscle degeneration, no significant differences were displayed in T2 values and Goutallier classification of RC muscles (all P >0.05). CONCLUSION: Patients with a treated RCT demonstrated inferior SSP tendon in the distal subregion on the contralateral shoulders one year postoperatively compared to that of healthy controls based on quantitative MRI data.
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Imageamento por Ressonância Magnética , Lesões do Manguito Rotador , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Pessoa de Meia-Idade , Idoso , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Estudos de Casos e Controles , AdultoRESUMO
The muscle is the principal tissue that is capable to transform potential energy into kinetic energy. This process is due to the transformation of chemical energy into mechanical energy to enhance the movements and all the daily activities. However, muscular tissues can be affected by some pathologies associated with genetic alterations that affect the expression of proteins. As the muscle is a highly organized structure in which most of the signaling pathways and proteins are related to one another, pathologies may overlap. Duchenne muscular dystrophy (DMD) is one of the most severe muscle pathologies triggering degeneration and muscle necrosis. Several mathematical models have been developed to predict muscle response to different scenarios and pathologies. The aim of this review is to describe DMD and Becker muscular dystrophy in terms of cellular behavior and molecular disorders and to present an overview of the computational models implemented to understand muscle behavior with the aim of improving regenerative therapy.
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Distrofia Muscular de Duchenne , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Animais , Simulação por Computador , Modelos BiológicosRESUMO
Glossectomy is a surgical procedure performed to remove all or part of the tongue in patients with cancer. The removal of a significant part of the tongue has a marked effect on speech and swallowing function, as patients may lose not only the tongue muscles but also the median lingual septum (MLS). Therefore, to achieve successful tongue regeneration, it is necessary to investigate the developmental processes of not only the tongue muscles but also the MLS. This study was conducted to clarify the mutual development of the tongue muscles and the MLS in human fetuses. Serial or semi-serial histological sections from 37 embryos and fetuses (aged 5-39 weeks) as well as nine adults were analyzed. The MLS appeared at Carnegie stage 15 (CS15), and until 12 weeks of gestation, abundant fibers of the intrinsic transverse muscle crossed the septum in the entire tongue. However, in near-term fetuses and adults, the contralaterally extending muscles were restricted to the deepest layer just above the genioglossus muscle. This finding indicates that the crossing transverse muscle showed the highest density at mid-term. A thorough understanding of both the MLS and the tongue muscles is necessary for successful tongue regeneration.
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Feto , Língua , Adulto , Humanos , Língua/fisiologia , Músculos Faciais , Cadáver , Crescimento e DesenvolvimentoRESUMO
Fatty expansion is one of the features of muscle degeneration due to muscle injuries, and its presence interferes with muscle regeneration. Specifically, poor clinical outcomes have been linked to fatty expansion in rotator cuff tears and repairs. Our group recently found that fibroblast growth factor 8b (FGF-8b) inhibits adipogenic differentiation and promotes myofiber formation of mesenchymal stem cells in vitro. This led us to hypothesize that FGF-8b could similarly control the fate of muscle-specific cell populations derived from rotator cuff muscle involved in muscle repair following rotator cuff injury. In this study, we isolate fibro-adipogenic progenitor cells (FAPs) and satellite stem cells (SCs) from rat rotator cuff muscle tissue and analyzed the effects of FGF-8b supplementation. Utilizing a cell plating protocol, we successfully isolate FAPs-rich fibroblasts (FIBs) and SCs-rich muscle progenitor cells (MPCs). Subsequently, we demonstrate that FIB adipogenic differentiation can be inhibited by FGF-8b, while MPC myogenic differentiation can be enhanced by FGF-8b. We further demonstrate that phosphorylated ERK due to FGF-8b leads to the inhibition of adipogenesis in FIBs and SCs maintenance and myofiber formation in MPCs. Together, these findings demonstrate the powerful potential of FGF-8b for rotator cuff repair by altering the fate of muscle undergoing degeneration.
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Lesões do Manguito Rotador , Manguito Rotador , Ratos , Animais , Manguito Rotador/cirurgia , Adipogenia , Fator 8 de Crescimento de Fibroblasto , Lesões do Manguito Rotador/cirurgia , Células Musculares , Desenvolvimento MuscularRESUMO
Rotator cuff tears are a prevalent musculoskeletal problem that affect many individuals and may result in substantial social and health-related expenses. Moreover, the muscular fat infiltration and dystrophy associated with rotator cuff tears have been persistent challenges in rotator cuff surgical repair and postoperative rehabilitation. In this study, an in situ-formed injectable sodium alginate (SA) and bioglass (BG) hydrogel consisting of poly (lactic-co-glycolic acid) (PLGA) microspheres containing metformin (SA/BG-PLGA-Met) was developed for the prevention of muscular fat infiltration and dystrophy. Metformin and silicon ions were slowly released by the combined hydrogel, resulting in long-term biological effects. Moreover, the hydrogel displayed excellent degradability and biocompatibility. Extracts of SA/BG-PLGA-Met inhibited the adipogenesis of 3T3-L1 cells and stimulated the myogenic differentiation of C2C12 cells in vitro. In a mouse model of rotator cuff degeneration, the SA/BG-PLGA-Met hydrogel inhibited fat infiltration and dystrophy of the supraspinatus muscle. Overall, the SA/BG-PLGA-Met hydrogel, as a novel biomaterial, has great clinical potential for preventing rotator cuff muscle fat infiltration and atrophy.
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Duchenne muscular dystrophy (DMD) is an inherited disorder with mutations in the dystrophin gene characterized by progressive muscle degeneration and weakness. Therapy such as administration of glucocorticoids, exon skipping of mutant genes and introduction of dystrophin mini-genes have been tried, but there is no radical therapy for DMD. In this study, we used C. elegans carrying mutations in the dys-1 gene as a model of DMD to examine the effects of febuxostat (FBX). We applied FBX to dys-1 mutant animals harboring a marker for muscle nuclei and mitochondria, and found that FBX ameliorates the muscle loss. We next used a severer model dys-1; unc-22 double mutant and found the dys-1 mutation causes a weakened muscle contraction. We applied FBX and other compounds to the double mutant animals and assayed the movement. We found that the administration of FBX in combination of uric acid has the best effects on the DMD model.
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Proteínas de Caenorhabditis elegans , Transtornos dos Movimentos , Animais , Distrofina/genética , Caenorhabditis elegans/genética , Febuxostat/farmacologia , Proteínas de Caenorhabditis elegans/genética , Músculos/patologia , Transtornos dos Movimentos/patologia , Atrofia Muscular/patologiaRESUMO
(1) Background: Paraspinal muscle degeneration affects the quality of life in patients with degenerative lumbar scoliosis (DLS) and lumbar spinal stenosis (LSS). We aimed to describe the characteristics and differences in the paraspinal muscle parameters between patients with DLS and LSS and investigate their correlation with health-related quality of life (HRQOL). (2) Methods: There were forty-four participants in each group, namely the DLS, LSS, and healthy groups, who were matched at a ratio of 1:1 according to age, sex, and BMI. Differences in paraspinal muscle parameters among the three groups were compared using analysis of variance or the Mann-Whitney U test, and paraspinal muscle degeneration and HRQOL were analyzed using Spearman's correlation analysis. (3) Results: In the upper lumbar, the psoas (PS), quadratus lumborum (QL), and multifidus (MF) cross-sectional area (CSA) in the DLS group were smaller than those in the other groups. In the lower lumbar region, the CSA of the PS, QL, erector spinae (ES), and gross CSA (GCSA) of the MF in the DLS group were not significantly different from those in the LSS group. These values were lower than those observed in the healthy group. The lean muscle fat index (LMFI) of the MF and ES groups was higher than those of the other groups. Regarding HRQOL, we found that PS and MF CSA were strongly associated with HRQOL in healthy individuals; however, only MF was associated with HRQOL in the LSS group. (4): Conclusion: PS in the upper lumbar region and MF degeneration were more severe in patients with DLS than in those with LSS. ES degeneration was similar between the LSS and DLS groups. MF muscle atrophy in patients with LSS and asymmetric changes in the MF in DLS are associated with quality of life.
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Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant epigenetic disorder with highly variable muscle involvement and disease progression. Ongoing clinical trials, aimed at counteracting muscle degeneration and disease progression in FSHD patients, increase the need for reliable biomarkers. Muscle magnetic resonance imaging (MRI) studies showed that the appearance of STIR-positive (STIR+) lesions in FSHD muscles represents an initial stage of muscle damage, preceding irreversible adipose changes. Our study aimed to investigate fibrosis, a parameter of muscle degeneration undetectable by MRI, in relation to disease activity and progression of FSHD muscles. We histologically evaluated collagen in FSHD1 patients' (STIR+ n = 27, STIR- n = 28) and healthy volunteers' (n = 12) muscles by picrosirius red staining. All patients (n = 55) performed muscle MRI before biopsy, 45 patients also after 1 year and 36 patients also after 2 years. Fat content (T1 signal) and oedema/inflammation (STIR signal) were evaluated at baseline and at 1- and 2-year MRI follow-up. STIR+ muscles showed significantly higher collagen compared to both STIR- (p = 0.001) and healthy muscles (p < 0.0001). STIR- muscles showed a higher collagen content compared to healthy muscles (p = 0.0194). FSHD muscles with a worsening in fatty infiltration during 1- (P = 0.007) and 2-year (P < 0.0001) MRI follow-up showed a collagen content of 3.6- and 3.7-fold higher compared to FSHD muscles with no sign of progression. Moreover, the fibrosis was significantly higher in STIR+ muscles who showed a worsening in fatty infiltration in a timeframe of 2 years compared to both STIR- (P = 0.0006) and STIR+ muscles with no sign of progression (P = 0.02). Fibrosis is a sign of muscle degeneration undetectable at MRI never deeply investigated in FSHD patients. Our data show that 23/27 of STIR+ and 12/28 STIR- muscles have a higher amount of collagen deposition compared to healthy muscles. Fibrosis is higher in FSHD muscles with a worsening in fatty infiltration thus suggesting that its evaluation with innovative non-invasive techniques could be a candidate prognostic biomarker for FSHD, to be used to stratify patients and to evaluate the efficacy of therapeutic treatments.
Assuntos
Distrofia Muscular Facioescapuloumeral , Humanos , Distrofia Muscular Facioescapuloumeral/diagnóstico , Distrofia Muscular Facioescapuloumeral/patologia , Músculo Esquelético/patologia , Prognóstico , Estudos Retrospectivos , Biomarcadores , Imageamento por Ressonância Magnética/métodos , Progressão da Doença , ColágenoRESUMO
Toxicity caused by chronic hyperglycemia is a significant factor affecting skeletal muscle myogenesis, resulting in diabetic myopathy. Chronic and persistent hyperglycemia causes activation of the atrophy-related pathways in the skeletal muscles, which eventually results in inflammation and muscle degeneration. To counteract this process, various bioactive compound has been studied for their reversal or hypertrophic effect. In this study, we explored the molecular mechanisms associated with reversing glucotoxicity's effect in C2C12 cells by arachidonic acid (AA). We found a substantial increase in the pro-inflammatory cytokines and ROS production in hyperglycemic conditions, mitigated by AA supplementation. We found that AA supplementation restored protein synthesis that was downregulated under glucotoxicity conditions. AA enhanced myogenesis by suppressing high glucose induced inflammation and ROS production and enhancing protein synthesis. These results imply that AA has cytoprotective actions against hyperglycemia-induced cytotoxicity.