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BACKGROUND:Mesenchymal stem cells are multipotent stromal cells isolated from bone marrow,fat,umbilical cord and other tissues.It can differentiate into different cell types and secrete a variety of proteins with therapeutic potential,which has a good application prospect in the repair of muscle tissue. OBJECTIVE:To review the research progress of mesenchymal stem cells in promoting muscle tissue repair and provide a theoretical basis for further clinical application. METHODS:Relevant articles published from inception to 2022 were retrieved from CNKI,VIP,WanFang,PubMed,Embase and Web of Science databases.The keywords were"mesenchymal stem cells,muscle tissue,muscle injury,muscle atrophy,exosomes,scaffolds"in Chinese and English.The literature about mesenchymal stem cell migration promoting muscle fiber proliferation and repair was screened.Finally,98 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The related mechanisms of mesenchymal stem cell migration promoting muscle fiber proliferation and repair are complex,mostly by anti-inflammatory,inhibiting interstitial fibrosis,inhibiting the fat formation and other ways to promote muscle fiber proliferation and repair.(2)The related biological scaffolds and cell co-culture based on mesenchymal stem cells can significantly compensate for the low survival rate of mesenchymal stem cells after colonization.(3)At present,mesenchymal stem cell therapy still has apparent limitations.In the future,mesenchymal stem cells combined with other therapies should become the primary development trend.
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BACKGROUND:Vitamin C,as an essential nutrient,has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia.Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia. OBJECTIVE:To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia,and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence. METHODS:The first author performed a computer search of PubMed,Web of Science,CNKI and other databases for relevant studies involving vitamin C in sarcopenia.The search keywords were"vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle"in English and Chinese,respectively.The search period was from each database inception to July 2023.After screening,85 articles were included for further review. RESULTS AND CONCLUSION:Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia.In addition,vitamin C supplementation is also useful for improving skeletal muscle mass,strength and physical function with potential synergistic effects in exercise strategies for sarcopenia.The effects of vitamin C on sarcopenia may be via the following biological mechanisms:vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle,thus positively regulating protein metabolic homeostasis,and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function.In addition,vitamin C affects myoblast proliferation,differentiation and myotube size,mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways,which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue.The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors,such as the choice of supplementation dose and duration,the design of exercise prescription when vitamin C is combined with an exercise intervention,and the assessment of the redox status of the individual.It is recommended that future studies should be conducted in older patients with sarcopenia(<50 μmol/L)with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1 000 mg/d vitamin C(for 6 months or longer)with at least two or more types of multi-type combined exercise,with supplementation timed to take place at 1 hour after the end of the exercise,and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored.In conclusion,the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more,while the appropriate design of exercise prescriptions(especially the type and intensity of exercise)needs to be further determined.
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BACKGROUND:Rotator cuff muscle degeneration(muscle atrophy,fibrosis and fatty infiltration)is a common condition after rotator cuff tears,which seriously affects shoulder function and surgical outcomes.Ginsenoside Rg1 has biological effects such as anti-oxidation,anti-apoptosis and lipid-lowering.However,the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE:To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS:Sixty C57BL/6J mice were randomly divided into sham group,model group,ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group,with 15 mice in each group.The skin of the right shoulder of mice in the sham group was cut and sutured.Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups.Supraspinatus tendon and suprascapular nerve compression were administrated.Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation,while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively,once a day,for 6 weeks.Mice were assessed for limb function by gait analysis the day after the last injection.After euthanasia,the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility.Muscle tissue was stained with oil red O and Masson.RT-PCR was used to detect the expression of atrophy,fibrosis,and fatty infiltration related genes. RESULTS AND CONCLUSION:Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased paw print area and step length(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility(P<0.05),and significantly decreased wet muscle mass reduction ratio,fatty infiltration area ratio,and collagen fiber area ratio(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy,fibrosis,and fatty infiltration related genes(P<0.05).There was no significant difference in paw print area,supraspinatus muscle contractility,and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups(P>0.05),and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group(P<0.05).To conclude,ginsenoside Rg1 could significantly reduce muscle atrophy,fibrosis and fatty infiltration following massive rotator cuff tear in mice,which is beneficial to improve muscle strength and limb function.
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BACKGROUND:Obesity has become a global health issue,often accompanied by complications including obesity-related muscle atrophy.While exercise has been reported to improve various obesity-related diseases,there is limited research focusing on exercise modes. OBJECTIVE:To compare the effects of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on obesity-related muscle atrophy in mice under the premise of the same exercise distance,providing a scientific basis for exercise interventions for obesity-related muscle atrophy. METHODS:Seventy-two male C57BL/6 mice were divided into six groups(n=12 per group):standard chow diet,standard chow diet+MICT,standard chow diet+HIIT,high-fat diet,high-fat diet+MICT,and high-fat diet+HIIT.The study evaluated the effects of 8-week treadmill training with different exercise modes on long-term high-fat diet-induced muscle atrophy by detecting muscle mass,muscle index,muscle fiber cross-sectional area,muscle lipid deposition,and the expression of muscle atrophy marker genes Murf-1 and Atrogin-1 in the gastrocnemius muscle of mice exposed to long-term high-fat diet. RESULTS AND CONCLUSION:Compared to the high-fat diet group,both MICT and HIIT improved the decrease in gastrocnemius muscle index(MICT+18.8%vs.HIIT+17.6%,not significant between the two modes),muscle fiber atrophy(MICT+15.5%vs.HIIT+13.7%,not significant between the two modes),and muscle lipid deposition(MICT-19.8%vs.HIIT-17.1%,not significant between the two modes).At the gene level,compared with the high-fat diet group,both MICT and HIIT could significantly down-regulate the expression of Murf-1(MICT-62.4%vs.HIIT-52.6%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01)and Atrogin-1(MICT-43.3%vs.HIIT-29.8%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01).Based on exercise mode comfort and genetic evidence,MICT mode might be more suitable for exercise interventions in obesity-related muscle atrophy.
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【Objective】 To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease (KBD) in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion (ROM) with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients. 【Methods】 To investigate the registered KBD patients from KBD areas in Shaanxi Province, we measured the general demographic data of the patients were collected and the ROM of the knee joint (flexion and extension), the ankle joint (dorsiflexion and plantar flexion), and the muscle atrophy related indexes such as the upper arm circumference, thigh circumference, calf circumference and grip strength. According to the population characteristics, i.e., gender, age, body mass index (BMI) and KBD grade, the median and quartile of joint ROM and muscle atrophy of KBD patients were reported, and then the differences in each index among different groups were analyzed. Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender, age and BMI. 【Results】 A total of 480 patients with KBD were investigated in this study, who consisted of 249 (51.9%) males and 231 (48.1%) females, with an average age of (63.10±7.32) years and an average BMI of (23.49±8.90) kg/m2. The knee flexion ROM, knee extension ROM, ankle dorsiflexion ROM and ankle plantar flexion ROM were [105.0 (95.0, 120.0)] °, [0.0 (-15.0, 0.0)] °, [5.0 (0.0, 15.0)] ° and [20.0 (15.0, 30.0)] °, respectively, in KBD patients in Shaanxi Province. The left thigh circumference, right thigh circumference, left calf circumference, right calf circumference, and upper arm circumference were [43.0 (40.0, 47.0)] cm, [43.0 (39.0, 47.0)] cm, [29.0 (27.0, 32.0)] cm, [29.5 (27.0, 32.0)] cm, [27.0 (25.0, 30.0)] cm, respectively. The left hand grip strength and right hand grip strength were [13.4 (9.5, 18.4)] kg and [13.9 (9.8, 18.2)] kg, respectively. With the increase of age, the extension range of the left and right knee joints of KBD patients showed a decreasing trend (H=31.499, 31.847; all P<0.001). The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group, with statistically significant differences (H=7.753, 12.333; P=0.021, 0.002). The knee flexion, thigh circumference, and calf circumference of the left and right sides showed a decreasing trend under different KBD grades (H=14.345, 17.256, 8.000, 8.462, 8.558, 9.633; all P<0.05). Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference, calf circumference, and grip strength in patients with KBD (all P<0.05). There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD (P<0.01). 【Conclusion】 The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province, and there is a correlation between joint motion and muscle atrophy.
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Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.
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Exosomes/physiology , Muscle, Skeletal/metabolism , Cell Communication , HomeostasisABSTRACT
OBJECTIVE To investigate the improvement effects and mechanism of imperatorin on cachexia model mice. METHODS Fifteen male C57BL/6J mice were randomly divided into blank control group， model group and imperatorin group， with 5 mice in each group. Except for blank control group， the remaining mice were inoculated with LLC cell suspension subcutaneously on the dorsal surface， and the drug was administered by gavage daily from the 7th day of inoculation. The imperatorin group was gavaged with imperatorin suspension （0.5% sodium carboxymethylcellulose solution as solvent） at 60 mg/kg； blank control group and model group were given an equal volume of 0.5% sodium carboxymethylcellulose solution， for 13 d of continuous administration. During the administration period， food intake and body mass of mice were recorded daily and regularly， tumor long and short diameters were measured every two days， and tumor volume was calculated. The skeletal muscle mass and tumor mass of each group were weighed and the tumor-free body weight was calculated； the pathological changes of skeletal muscle were observed and the cross-sectional area of skeletal muscle fibers was calculated； the phosphorylation levels of signal transduction and activator of transcription 3 （STAT3） （measured as p-STAT3/STAT3 ratio）， muscle atrophy box F gene （MAFbx）， myostatin （Myog）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， Caspase3 protein and mRNA expression were all detected. RESULTS Compared with blank control group， body mass and skeletal muscle mass of model group were decreased significantly （P＜0.05）， and reduced food intake， loose arrangement of skeletal muscle， large cell space were observed； the cross-sectional area of skeletal muscle fiber was significantly reduced， while p-STAT3/STAT3 ratio， protein and mRNA expressions of MAFbx， Bax and Caspase3 were somo_amour@163.com increased significantly （P＜0.05）. The protein and mRNA expressions of Myog and Bcl-2 were significantly reduced （P＜ 0.05）. Compared with model group， body weight， tumor-free weight and skeletal muscle weight were increased significantly in imperatorin group （P＜0.05）； food intake increased， while the expressions of tumor weight and volume were decreased significantly （P＜0.05）； the expressions of above proteins and genes were improved significantly （P＜0.05）. CONCLUSIONS Imperatorin can improve the tumor cachexia state， the mechanism of which may be related to the regulation of ubiquitin-proteasome pathway and anti-apoptosis.
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The peripheral vestibular organs are sensors for linear acceleration (gravity and head tilt) and rotation,and turn them into nerve signals that travel to the central nervous system to regulate physiological functions, which play an important role in regulating body stability, ocular movement, autonomic nerve activity, arterial pressure, body temperature, as well as muscle and bone metabolism. The effect of gravity on these functions can be attributed to high plasticity of the vestibular system. In this review, changes in vestibular-related physiological functions induced by the hypergravity and microgravity were introduced, including arterial pressure,muscle and bone metabolism, feeding behavior and body temperature, with the aim to better understand the physiological function of vestibular in adaption to special gravity environment.
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OBJECTIVES@#To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1).@*METHODS@#A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected.@*RESULTS@#After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05).@*CONCLUSIONS@#Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
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Animals , Female , Male , Rabbits , Electroacupuncture , Muscle, Skeletal , Muscular Atrophy/therapy , NF-kappa B/genetics , Peripheral Nerve Injuries , Rats, Sprague-Dawley , Sciatic NerveABSTRACT
Skeletal muscle is a vital tissue not only for maintaining posture and body movements but also for energy metabolism in human body. Skeletal muscle is highly plastic in response to various stimuli, resistance exercise or anabolic hormones can increase muscle mass, which is termed “muscle hypertrophy”. Contrary, immobility, aging and severe illness can reduce muscle mass, which is termed “muscle atrophy”. Loss of skeletal muscle mass is associated with loss of independent living, the morbidity of a variety of diseases and mortality throughout life. Therefore, understanding mechanisms that regulate skeletal muscle mass is essential for improving the quality of life. Recent studies reported microRNAs (miRNAs), which is a class of non-coding RNAs, play a crucial role in the regulation of muscle mass. This review provides a current understanding of the function of miRNAs in regulation of skeletal muscle mass.
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Objective:To identify the feasibility of inferior vena cava variability (ΔDIVC) combined with rectus femoris atrophy fraction in predicting the outcome of weaning from invasive mechanical ventilation (IMV).Methods:From January to December 2021, the patients with the need for IMV admitted to the Affiliated Yixing Hospital of Jiangsu University were recruited into prospective case-control study. The patients who met the withdrawal criteria were treated with a 2-h spontaneous breathing trial (SBT) and then extubated immediately. Patients with stable spontaneous breathing after extubation for more than 48 h were classified as successful weaning group, and on the contrary, the other patients were classified as failed weaning group. The clinical data and withdrawal indexes of the two groups were evaluated. The correlation between ΔD IVC and rectus femoris atrophy fraction was assessed. The influencing factors of weaning outcome were observed. The diagnostic value of ΔD IVC, rectus femoris atrophy fraction and the combination of two indexes in predicting weaning success were calculated by a plotting receiver operating characteristic (ROC) curve. Results:Sixty IMV patients were included in this study, including 38 cases of successful weaning and 22 cases of failed weaning. The two groups were comparable with regard to clinical data (all P>0.05). The rectus femoris cross-sectional area in the two groups diminished gradually with the length of ICU stay ( F=3.266, 3.625, both P<0.05). The rectus femoris cross-sectional area at the first SBT was significantly lower than that on the first day of admission in both groups [the successful weaning group: (2.54±0.88) cm 2vs. (3.08±0.98) cm 2; the failed weaning group: (2.22±0.87) cm 2vs. (3.02±1.10) cm 2, both P<0.05], but there was no significant difference between the two groups (all P>0.05). Patients in the successful weaning group had higher ΔD IVC and higher rectus femoris atrophy fraction than those in the weaning failure group [ΔD IVC: (25.02±4.65)% vs. (20.30±3.16)%; rectus femoris atrophy fraction: (81.89±5.09)% vs. (72.68±8.98)%, both P<0.05]. There was a positive correlation between ΔD IVC and rectus femoris atrophy fraction ( r=0.346, P=0.007). Both ΔD IVC and rectus femoris atrophy fraction played an important role in affecting weaning success (all P<0.05). The area under the curve (AUC) of ΔD IVC combined with rectus femoris atrophy fraction for predicting the weaning success was 0.880, which was significantly higher than that of ΔD IVC (AUC=0.791) or rectus femoris atrophy fraction (AUC=0.826). Conclusions:The predictive value of ΔD IVC combined with rectus femoris atrophy fraction for successful weaning of patients undergoing IMV is relatively accurate, which can be used to guide weaning.
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SUMMARY OBJECTIVE: The aim of this study was to compare the pressure pain threshold and the thickness of the cervical muscles in patients with tension-type headache versus healthy participants. METHODS: An observational, retrospective, cross-sectional study was conducted at the Universidad Europea de Madrid between May and June 2022. Adults aged 18-65 years with tension-type headache diagnosed for more than 6 months were compared to healthy controls. B-mode ultrasound imaging was employed to measure the thickness of the neck stabilizing muscles, longus colli, and multifidus at the C5 and C6 levels, respectively. pressure pain threshold measurements were assessed bilaterally in the following regions: upper trapezius, masseter, temporalis, anterior tibialis, and median nerve. RESULTS: A total of 40 participants (90% females; 36.3±12.9 years, BMI 24.2±3.7 kg/m2) participated in the study. Compared with the control group (n=20), participants in the tension-type headache group (n=20) presented statistically significant lower values in all pressure pain threshold measures. Additionally, the tension-type headache group presented statistically significant lower values in the thickness of the following muscles: right multifidus at rest (1.0±0.2 cm versus 1.3±0.2 cm; p<0.001), left multifidus at rest (1.1±0.1 cm versus 1.3±0.1 cm; p<0.001) and during contraction (1.2±0.1 cm versus 1.5±0.2 cm; p<0.001), left longus colli at rest (1.0±0.2 cm versus 1.2±0.1 cm; p=0.01) and during contraction (1.2±0.2 cm versus 1.4±0.1 cm; p<0.001), and right longus colli during contraction (1.2±0.2 cm versus 1.4±0.2 cm; p=0.02). CONCLUSION: This study concluded that patients with tension-type headache showed lower thickness and lower pressure pain threshold of cervical muscles compared to healthy controls.
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ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3（STAT3）/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group， a model group， a Liu Junzitang group， an inhibitor group （stattic group），and a Liu Junzitang + inhibitor group （combination group）， with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation， the mice in the corresponding groups received Liu Junzitang （9.56 g·kg-1·d-1） by gavage and intraperitoneal injection of stattic ［25 mg·kg-1·（2 d）-1］. After three weeks of drug intervention， the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin （HE） staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 （p-STAT3）， STAT3， muscle atrophy F-box （MAFbx）， and muscle RING finger protein 1 （MuRF1） in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT3， MAFbx， and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group， the model group showed lightened body and the gastrocnemius muscle， reduced cross-sectional area of gastrocnemius muscle fibers， and increased protein expression of p-STAT3， STAT3， MAFbx， and MuRF1 and mRNA expression of STAT3， MuRF1， and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the model group， the Liu Junzitang group showed increased body weight， gastrocnemius muscle weight， and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and decreased protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and reduced protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the combination group showed increased body weight and gastrocnemius muscle weight （P<0.05），and decreased protein expression of p-STAT3， STAT3， MuRF1， and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the Liu Junzitang group， the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle （P<0.05）. ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia， and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
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Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.
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@#Objective To perform a visualized analysis of the current status, hotspots and frontiers of research on denervated muscle atrophy in the past five years.Methods The Web of Science core database was used to retrieve relevant documents in the field of denervated muscle atrophy, and visualized analysis was performed on CiteSpace 5.8.R3 in terms of annual number of published papers, frequency of citations, countries, institutions, authors, keywords and references.Results A total of 516 articles were retrieved from 2017 to 2021. The annual number of published papers was on the rise, and the number of citations was increasing year by year. The United States, Canada and England were high-influence countries, the University of Padua in Italy was the leading institution. The author SUN Hualin published the most articles. The authors Bodine S C and Sandri M were the main influencers. Physiological and pathological mechanisms based on cytology, molecular biology and tissue morphology, as well as prevention and treatment measures based on physical factor therapy, drugs and exercise were the research hotspots in this field. It might be coming that taking reactive oxygen species as the target and looking for multi-targeted proteolytic system drugs as the goal for prevention and treatment.Conclusion This visualized analysis has comprehensively summarized the trends and development of denervated muscle atrophy research, and identified the potential research frontiers and hot directions in the near future.
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Objective:To observe any effect of supplementing treadmill training with applications of the traditional Chinese Songchi ointment in the rehabilitation of gastrocnemius muscles atrophied through disuse.Methods:Forty-five Wistar rats were randomly divided into a normal control group ( n=8) and a model group ( n=37). The rats in the model group had their left hind limbs immobilized by the Nagai method to induce disused muscle atrophy (DMA). That group was then randomly subdivided into a model control (MC) group, a treadmill training group (the EX group), a Songchi ointment group (SC group) and a comprehensive rehabilitation group (the CR group), each of 8. The EX and SC groups were given treadmill training at 18m/min or topical application of Songchi ointment once a day, 6 days a week for 6 weeks. The CR group was given both treatments. After the 6 weeks, hematoxylin and eosin staining was used to evaluate the pathological changes in the gastrocnemius of each rat′s left hind limb. Serum levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assays. PI3K, Akt and mTOR mRNA and protein were assayed using real-time quantitative PCR and western blotting. Results:The arrangement of muscle fibers in the MC group was disordered and there was a large number of infiltrated inflammatory cells. Such conditions were significantly relieved in the CR group. After the intervention the levels of inflammatory factors TNF-α and IL-1β in the CR group were, on average, significantly lower than those observed in the MC group, the EX group or the SC group, while the level of anti-inflammatory factor IL-10 was significantly higher. The average PI3K, Akt and mTOR mRNA and protein levels of group CR were significantly higher than those of the MC and EX groups.Conclusions:The traditional Chinese Songchi ointment can usefully supplement treadmill training to relieve DMA. It upregulates IL-10, activates the PI3K Akt/mTOR signaling pathway and promotes the synthesis of muscle fiber protein while down-regulating TNF-α and IL-1β and muscle fiber inflammatory response.
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O'Sullivan-Mcleod syndrome is a very rare variant of MND with a good prognosis. Its clinical feature is distal lower motor neuron syndrome of both upper limbs, and there is no effective treatment at present. We reported a case of O'Sullivan-Mcleod syndrome in this paper.The patient exhibited with middle-aged progressive distal muscle weakness and atrophy of both upper limbs, without sensory, cognitive or behavioral impairment and without pyramidal tract sign. Laboratory examination, imaging and genetic tests showed no obvious abnormalities. EMG revealed neurogenic damage to the small muscles of both hands. Now we retrospectively analyzed the clinical features of a patient with O'Sullivan-McLeod syndrome, and data from 18 cases for comparative analysis, in order to improve its understanding by clinicians.
ABSTRACT
Objective:The incidence rate of cancer cachexia is high in late stage of cancer， which is characterized by skeletal muscle atrophy and rapid reduction of adipose tissue and systemic inflammation. Cachexia is highly related to a variety of tumors， and causes a large proportion of cancer deaths. Cancer cachexia can lead to serious complications in patients with cancer， then， the quality of life of patients decreases， the psychological state becomes negative， and the state of illness is further worsened. At present， there is no effective intervention means to completely reverse cachexia. The combined use of multiple targets and effective components of traditional Chinese medicine（TCM）， as well as the treatment based on syndrome differentiation and the theory of TCM play an important role in the prevention and treatment of cancer cachexia. Therefore， exploring the pathogenesis of cancer cachexia and prevention and treatment with TCM is helpful for basic study and clinical application. Method:In this paper， cancer cachexia and TCM in China national knowledge infrastructure （CNKI） and Public Medline （PubMed） databases were retrieved， and 98 Chinese and English literatures were included through summarization to elaborate the pathogenesis of cancer cachexia and the prevention and treatment of TCM. Result:Emphasis was given to the important role of inflammatory reaction， skeletal muscle atrophy， energy metabolism abnormality and multiple signal joint regulation in occurrence of cancer cachexia， and the unique advantages and significant role of TCM in treatment of cancer cachexia under different treatment principles. Conclusion:Inflammatory reaction， skeletal muscle atrophy， abnormal energy metabolism make the pathogenesis of cancer cachexia complex and diverse. TCM prescriptions， Chinese herbal medicine and their effective ingredients have the natural advantages of targeting multiple pathways， controlling multiple signal pathways and inhibiting various inflammatory factors in the prevention and treatment of cancer cachexia， and are safe and effective in improving diet， prolonging the survival period of patients and keeping weight.
ABSTRACT
Objective:To compare the effects of intermittent feeding and continuous feeding on muscle atrophy, nutritional status and nutritional intolerance of critically ill patients, and to provide a reference for critically ill patients to select more suitable nutritional support in clinic.Methods:An observational study was conducted. The clinical data of 59 critically ill patients who received enteral nutrition admitted to anesthesia intensive care unit (ICU) of the Second Affiliated Hospital of Air Force Military Medical University of the Chinese People's Liberation Army from January 2019 to December 2020 were analyzed. According to different feeding methods, the patients were divided into intermittent feeding group ( n = 32, 200-250 mL nutrient solution was pumped each time, 4-5 times a day, 5-6 hours interval each time) and continuous feeding group ( n = 27, nutrient solution was pumped continuously and evenly). The changes of related indexes before and 7 days after enteral nutrition in ICU were recorded, including rectus femoris thickness and cross-sectional area, nutritional status related indexes [hemoglobin (Hb), albumin (ALB), prealbumin (PA) and blood glucose], incidence of aspiration, diarrhea, constipation, vomiting, abnormal gastric residue volume (gastric residue volume > 250 mL), other nutritional intolerance and the length of ICU stay. Results:After nutritional support for 7 days, the thickness and cross-sectional area of rectus femoris decreased in both groups, indicating muscle atrophy occurred in both groups, and there was no significant difference in change value of thickness or cross-sectional area of rectus femoris between intermittent feeding group and continuous feeding group [the change value of rectus femoris thickness (cm): -0.06±0.04 vs. -0.07±0.03, the change value of rectus femoris cross-sectional area (cm 2): -0.71±0.23 vs. -0.81±0.24, both P > 0.05]. There were no significant differences in nutritional status related indicators after nutritional support for 7 days between intermittent feeding group and continuous feeding group [Hb (g/L): 102.2±10.9 vs. 103.2±11.3, ALB (g/L): 34.1±3.6 vs. 32.9±4.0, PA (mg/L): 209.8±10.6 vs. 205.9±13.7, blood glucose (mmol/L): 6.34±1.91 vs. 6.93±3.54, all P > 0.05]. The patients in both groups had intestinal nutrition intolerance such as aspiration, diarrhea, constipation and vomiting. However, the incidence of abnormal gastric residual volume in intermittent feeding group was significantly lower than that in continuous feeding group [9.4% (3/32) vs. 33.3% (9/27), P < 0.05]. There was no significant difference in the length of ICU stay between intermittent feeding group and continuous feeding group (days: 21.03±11.51 vs. 21.41±9.74, P > 0.05). Conclusions:Compared with continuous feeding, intermittent feeding does not improve the muscle atrophy and nutritional status of critically ill patients, but reduce the symptoms of enteral nutrition intolerance caused by abnormal increase of gastric residual volume. It is an easy-to-implement, safe and feasible feeding method.
ABSTRACT
OBJECTIVE@#To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein.@*METHODS@#Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot.@*RESULTS@#In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (@*CONCLUSION@#Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.