The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Tanshinone IIA promotes the proliferation and differentiation ability of primary muscle stem cells via MAPK and Akt signaling.

Salvia miltiorrhiza Bunge is a widely-used traditional Chinese medicine to treat a variety of diseases including muscle disorders. The underlying pharmacological mechanisms of which active component and how it functions are still unknown. Tanshinone IIA (Tan IIA) is the main active lipophilic compound in Salvia miltiorrhiza Bunge. Muscle stem cells (MuSCs) play a crucial role in maintaining healthy physiological function of skeletal muscle. For the purpose of this study, we investigated the effects of Tan IIA on primary MuSCs as well as mechanism. The EdU staining, cell counts assay and RT-qPCR results of proliferative genes revealed increased proliferation ability of MuSCs after Tan IIA treatment. Immunofluorescent staining of MyHC and RT-qPCR results of myogenic genes found Tan IIA contributed to promoting differentiation of MuSCs. In addition, enrichment analysis of RNA-seq data and Western blot assay results demonstrated activated MAPK and Akt signaling after treatment of Tan IIA during proliferation and differentiation. The above proliferative and differentiative phonotypes could be suppressed by the combination of MAPK inhibitor U0126 and Akt inhibitor Akti 1/2, respectively. Furthermore, HE staining found significantly improved myofiber regeneration of injured muscle after Tan IIA treatment, which also contributed to muscle force and running performance recovery. Thus, Tan IIA could promote proliferation and differentiation ability of MuSCs through activating MAPK and Akt signaling, respectively. These beneficial effects also significantly contributed to muscle regeneration and muscle function recovery after muscle injury.

Traditional Chinese Medicine for Topical Treatment of Skeletal Muscle Injury.

Muscle injuries are common musculoskeletal problems, but the pharmaceutical agent for muscle repair and healing is insufficient. Traditional Chinese Medicine (TCM) frequently uses topical treatments to treat muscle injuries, although scientific evidence supporting their efficacy is scarce. In this study, an in vitro assay was used to test the cytotoxicity of a topical TCM formula containing Carthami Flos, Dipsaci Radix, and Rhei Rhizoma (CDR). Then, a muscle contusion rat model was developed to investigate the in vivo effect and basic mechanisms underlying CDR on muscle regeneration. The in vitro assay illustrated that CDR was non-cytotoxic to immortalized rat myoblast culture and increased cell viability. Histological results demonstrated that the CDR treatment facilitated muscle repair by increasing the number of new muscle fibers and promoting muscle integrity. The CDR treatment also upregulated the expression of Pax7, MyoD and myogenin, as evidenced by an immunohistochemical study. A gene expression analysis indicated that the CDR treatment accelerated the regeneration and remodeling phases during muscle repair. This study demonstrated that topical CDR treatment was effective at facilitating muscle injury repair.

Investigation of the biochemical and histopathological effects of vitamin C, selenium, and therapeutic ultrasound on muscle damage in rats.

Muscle injury is a common type of soft tissue injury. Increased oxidative damage has been reported after muscle injuries. Therapeutic ultrasound is commonly used for such injuries. This study compared the efficacy of therapeutic ultrasound treatment and various antioxidant agents in experimental muscle injuries. For this purpose, some serum enzymes, oxidative stress, and inflammatory markers were evaluated together with histopathological examinations. Six groups were formed with 6 male Wistar albino rats in each group. These groups were control, only injury (OI), ultrasound (U), vitamin C (Vit C), selenium (S), and mixture (M). Muscle injury was caused by a laceration of the gastrocnemius muscle in all groups except the control group. No treatment was performed in the OI group. At the end of the 6-day application, all rats were sacrificed. As for serum enzymes, CK, ALT, and AST levels returned to control values in almost all treatment groups. Total oxidative status (TOS) and oxidative stress index (OSI) increased in the OI group, while they decreased in the S and M groups. In addition, the decrease in MPO activity in the blood tissue of the Vit C group was statistically significant. There were no significant changes between groups in terms of serum inflammatory markers and histological findings. This study has shown that the ingestion of vitamin C and selenium may contribute to the treatment of muscle injury in addition to therapeutic ultrasound treatment. However, further studies are needed to support these results.

Orthobiologic Interventions for Muscle Injuries.

Muscle injuries represent a common problem in active populations. Orthobiologics continue to be studied for their ability to improve muscle healing. To date, the basic science research for treating muscle injuries with platelet-rich plasma or stem cell remains novel. Furthermore, there are even fewer clinical studies on these topics, and their findings are inconclusive. Reviewing the literature, muscle injuries treated with ultrasound-guided leukocyte-rich PRP injections appear to have the strongest evidence. Scar formation remains a major barrier in muscle injury healing, and there is optimism for future orthobiologic treatments that target the downregulation of TGF-B, resulting in decreased scar development.

[Effect of electroacupuncture of "Weizhong" (BL40) on iron metabolism disorder in rats with lumbar multifidus muscle injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Weizhong" (BL40) on the disorder of iron metabolism and the level of oxidative stress after lumbar multifidus muscle injury (LMMI), so as to explore its mechanisms underlying promoting the repair of LMMI. METHODS: Male SD rats were randomly divided into normal, model and EA groups (6 rats in each group). The LMMI model was established by injecting 0.5% bupivacaine (BPVC) solution (400 µL) into the lumbar multifidus muscle with the syringe-needle close to the spinous process (L4-L5). Twenty-four hours after successful establishment of the model, EA (2 Hz/15 Hz, 2 mA) was applied to bilateral BL40 for 30 min, once a day for 2 days. Histopathological changes of the multifid muscle were observed under microscope after H.E. staining, and the iron granules in the multifid muscle tissue observed after Prussian blue staining. The expression of glutathione synthase (GSS) was detected by Western blot, and the expressions of iron regulatory protein 1 (IRP1), ferroportin (Fpn), ferritin heavy chain 1 (FTH1, iron metabolism-related proteins) and gluta-thione peroxidase 4 (GPX4, functions in protecting cells against detrimental lipid peroxidation and governing a novel form of regulated necrotic cell death, called ferroptosis) mRNAs were detected by quantitative real-time PCR. The contents of glutathione (GSH) and malondialdehyde (MDA) were measured by biochemical methods. RESULTS: H.E. staining showed large areas of necrosis and breakage of muscle fibers, disordered arrangement of muscle fibers, widened muscle cell space, accompanying with a large number of inflammatory cell infiltration in the multifidus muscle tissue of the model group, which was relatively milder in the EA group. Outcomes of Prussian blue staining showed that compared with the normal group, there were more iron particles in the multifidus muscle tissue and enlarged muscle fiber gaps, which was also milder in the EA group. Compared with the normal group, the expression level of IRP1 mRNA and content of MDA were significantly increased (P<0.001), the expression levels of Fpn, FTH1 and GPX4 mRNAs and GSS protein, and the content of GSH were considerably decreased (P<0.001) in the model group. In comparison with the model group, the increase of IRP1 mRNA expression and MDA content, as well as the decrease of Fpn, FTH1 and GPX4 mRNAs expressions and GSH content were reversed in the EA group (P<0.001,P<0.05,P<0.01). CONCLUSION: EA of BL40 has a protect effect in BPVC-induced injury of lumbar multifidus muscle in rats, which may be related to its functions in improving iron metabolism to reduce oxidative damage by regulating expression of IRP1, Fpn and FTH1.

Acute Obturator Externus Injury in Professional Soccer Players: A Case Series.

When patients present with hip or groin pain, proximal quadriceps or adductor injuries are often initially suspected. In this case report, however, we present three cases of professional soccer players who were found to have obturator externus injury. A 30-year-old player and a 24-year-old player complained of pain in the left side after long distance shooting during an in-season training session and a match, respectively. Another 24-year-old player complained of pain in the right side after long distance passing during a preseason training session. On physical examination, active hip external rotation and passive hip internal rotation and extension elicited pain in all three players. All three players underwent magnetic resonance imaging (MRI) which found obturator externus grade II injuries for two players and grade I injury for one player. Rehabilitation protocols included relative rest, cryotherapy, and electrotherapy over a period of one week. All patients were able to return to play after 10 days. Correct identification of obturator externus injury afforded our players a favorable prognosis and a relatively quick return-to-sport compared with quadricep or adductor injury.

Influence of Heat Treatment on Muscle Recovery after Skeletal Muscle Injury in Rats: Histological and Immunohistochemical Studies.

Background: Muscle injuries represent a great part of athletic injuries. The repairing of skeletal muscle after injury is highly influenced by its regenerative response that may be affected by thermotherapy. Aim: This research examined the consequence of heat therapy on muscle recovery after skeletal muscle injury in rats. Materials and Methods: Forty-five male adult albino rats were classified into three groups: control, cardiotoxin-injected without heat (nonheating group), and cardiotoxin-injected with heat (heating group). Muscle injury was caused by the injection of cardiotoxin intramuscularly into the tibialis anterior muscles. Heating treatment (40°C for 20 min) was started immediately after the injury. Subsequent observations were performed at day 1, 3, and 7 after injury, including histological imaging and vimentin immunostaining expression. Results: In the heating group, the regenerating myotubes, having two or more central nuclei, first looked at 3 days after muscle injury, while in the nonheating group, the regenerating fibers were first observed at 7 days after muscle injury. Immunohistochemically, the vimentin reactions were absent in control muscle fibers but were identified in regenerating muscle fiber of the heating group earlier than in the nonheating group. Conclusion: Starting of heat treatment immediately after muscle injury promoted the regeneration of muscle fibers.

A Comparative Study on Relieving Exercise-Induced Fatigue by Inhalation of Different Citrus Essential Oils.

Citrus essential oils (CEOs) possess physiological functions due to diverse aroma components. However, evidence for the effects of CEOs on exercise performance and exercise-induced fatigue is limited. The CEOs with discrepancies in components may exert different effects on the amelioration of exercise-induced fatigue. In this study, sweet orange (Citrus sinensis L.) essential oil (SEO), lemon (Citrus limon Osbeck) essential oil (LEO), and bergamot (Citrus bergamia Risso and Poit) essential oil (BEO) were chosen to explore the effect on amelioration of exercise-induced fatigue. Our results demonstrated that SEO and LEO increased the swimming time by 276% and 46.5%, while BEO did not. Moreover, the three CEOs exerted varying effects on mitigating exercise-induced fatigue via inhibiting oxidative stress, protecting muscle injury, and promoting glucose-dependent energy supply. Accordingly, BEO showed the best efficiency. Moreover, the GC-MS and Pearson correlation analysis of BEO showed that the contents of the major components, such as (±)-limonene (32.9%), linalyl butyrate (17.8%), and linalool (7.7%), were significantly positively correlated with relieving exercise-induced fatigue.

Histological and biochemical effects of preventive and therapeutic vascular photobiomodulation on rat muscle injury.

The intravascular or transcutaneous application of photobiomodulation (PBM) over blood vessels (vascular photobiomodulation, VPBM) has been used for the treatment of inflammatory and chronic conditions with promising systemic results. This study evaluated the VPBM effects on a model of muscle regeneration after acute injury and compared the outcomes of preventive and therapeutic VPBM. Transcutaneous VPBM was administered over the rat's main tail vein. Serum levels of creatine kinase (CK), aspartate aminotransferase (AST), and lactate were evaluated and muscles were processed for macroscopic and microscopic analysis. Preventive and therapeutic VPBM led to decreased inflammatory infiltrate, edema, and myonecrosis but with an increase in immature muscle fibers. CK, AST, and lactate levels were lower in the groups treated with VPBM (lowest concentrations in preventive VPBM application). Preventive and therapeutic VPBM were capable of exerting a positive effect on acute muscle injury repair, with more accentuated results when preventive VPBM was administered.

Reliability and discriminative validity of real-time ultrasound elastography in the assessment of tissue stiffness after calf muscle injury.

OBJECTIVE: To investigate the reliability and discriminative validity of real-time ultrasound elastography (RTE) measures of soft-tissue elasticity after calf muscle tear. DESIGN: Cross-sectional, intra/inter-examiner reliability and comparative validity study. SETTING: Department of Physical Therapy. PARTICIPANTS: Twenty-one recreational athletes were included and examined 6 weeks after sustaining a grade I-II calf musculature tear. MAIN OUTCOME MEASURES: Soft-tissue elasticity was measured by two experienced assessors using RTE assessments in both the longitudinal and transverse planes of the athletes' injured and uninjured calf muscles. Elasticity was estimated by using the strain ratio (SR), which was calculated by dividing the strain (displacement) value taken at the medial gastrocnemius-soleus myotendinous junction (reference) by the strain value taken at the centre of the injury (index) as visualized on B-mode sonogram. Intra- and inter-observer reliability was estimated calculating intra-class correlation coefficients (ICCs) and standard error of measurement (SEM). Differences in elasticity between injured and healthy legs were assessed using t-tests or Wilcoxon tests for repeated measures. RESULTS: All RTE assessments in both planes showed ICC values ranging from 0.77 to 0.95 and SEM values ranging from 0.72 to 0.99. Additionally, RTE enabled both assessors to determine differences in elastic properties between injured and control legs (p < 0.001). CONCLUSION: RTE measures of calf muscles demonstrated good reliability and were able to differentiate injured from non-injured muscle tissue. RTE may provide a fast and objective measure in sports medicine to improve the detection of risk factors for muscle injury related to alterations of the mechanical behaviour of soft tissues during healing process.

[Effect of electroacupuncture at "Weizhong" (BL40) on expression of muscular PDGF-CC, PDGFR-α and MMP-1 in rats with lumbar multifidus muscle injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Weizhong" (BL40) on the expression of platelet-derived growth factor (PDGF)-CC, PDGF receptor (PDGFR)α and matrix metalloproteinase-1 (MMP-1) in rats with lumbar multifidus muscle injury (LMMI) so as to study its mechanisms underlying improvement of skeletal muscle injury. METHODS: Fifty-four male SD rats were randomly divided into normal group (n=6), model group (n=24) and EA group (n=24), and the latter two groups were further divided into four subgroups (1, 3, 5 and 7 days), with 6 rats in each group. The LMMI model was established by injection of 0.5% bupivacaine (BPVC, 100 µL×4) into the multifidus along the L4 and L5 spinous process. EA (2 Hz/50 Hz, 1 mA) was applied to bilateral "Weizhong"(BL40) for 20 min, once daily for 1, 3, 5 and 7 days respectively, from the first day on after modeling. Histopathological changes of the left multifidus muscle were observed after H.E. staining, and the expression of PDGF-CC, PDGFR-α and MMP-1 proteins in the right multifidus was observed by Western blot. RESULTS: Compared with the normal group, the expression levels of PDGF-CC protein in the model subgroup 1 d, 3 d and 7 d were significantly decreased (P<0.05), and those of PDGFR-α and MMP-1 proteins in the model subgroup 5 d and 7 d, and PDGF-CC protein in the model subgroup 5 d significantly increased (P<0.05). In comparison with the model subgroups, the expression levels of PDGF-CC in the EA subgroup 3 d, 5 d and 7 d, PDGFR-α in the EA subgroup 5 d, and MMP-1 in the EA group 3 d and 5 d were significantly increased or significantly further increased (P<0.05). H.E. staining showed different shapes and uneven sizes, with large area of damage, enlarged muscle space and inflammatory cell infiltration in the model group, which was relatively milder in the EA subgroups particularly in subgroup 5 d and 7 d. CONCLUSION: EA stimulation of BL40 for about 5 days has a positive effect in promoting the repair of the injured multifidus muscle in LMMI rats, which may be related to its function in up-regulating the expression of muscular PDGF-CC, PDGFR-α and MMP-1 proteins.

Evaluation of the Efficacy of Supplementation with Planox® Lemon Verbena Extract in Improving Oxidative Stress and Muscle Damage: A Randomized Double-Blind Controlled Trial.

Excessive exercise load can cause muscle soreness and fatigue, as well as inflammation and oxidative stress. Lemon verbena (Aloysia triphylla; Lippia citriodora) is often used as a spice in tea or beverages. Its leaves are rich in polyphenols, which have antioxidant and anti-inflammatory bioactivities. In the present study, we investigated whether supplementation with Planox® lemon verbena extract (LVE) could improve muscle damage and biochemical indicators after exhaustive exercise challenge. All subjects (30 males and 30 females) underwent a double-blind trial and were randomly divided into a placebo group (0 mg/human/day) and an LVE supplement group (400 mg/human/day), with gender-equal distribution. All subjects started supplementation 10 days before exhaustive exercise and continued it until all tests were completed. Before the intervention, after the exhaustive exercise, and on the following 3 days, the participants underwent 12-minute Cooper running/walking; blood collection; assessments of pain, muscle stiffness, maximum jump heights, and isometric maximum muscle strength. The results showed that supplementation with LVE effectively increased GPx and reduced CK, IL-6, 8-OHdG and muscle pain after the exhaustive exercise, but it had significant effect on strength recovery. In summary, LVE is a safe and edible natural plant extract that can reduce muscle damage and soreness after exercise. This trial was registered at clinicaltrials.gov as NCT04742244.

Exertional rhabdomyolysis in newly enrolled cadets of a military academy.

INTRODUCTION/AIMS: Exertional rhabdomyolysis (ER) often occurs during prolonged intense exercise in hot environments, posing a threat to the health of military personnel. In this study we aimed to investigate possible risk factors for ER and provide further empirical data for prevention and clinical treatment strategies. METHODS: A retrospective investigation of 116 concurrent ER cases was conducted. Conditional logistic regression analyses were performed to assess the association between each potential risk (or protective) factor and ER. The clinical characteristics of the 71 hospitalized patients were analyzed descriptively. RESULTS: After screening, the following variables significantly increased the risk of ER: shorter length of service (recruits; odds ratios [OR], 7.49; 95% confidence interval [CI], 2.58-21.75); higher body mass index (BMI; OR, 1.14, 95% CI, 1.03-1.26); lack of physical exercise in the last half year (less than once per month; OR, 3.20; 95% CI, 1.08-9.44); and previous heat injury (OR, 2.94; 95% CI, 1.26-6.89). Frequent fruit consumption (OR, 0.57; 95% CI, 0.33-0.99), active hydration habit (OR, 0.37; 95% CI, 0.20-0.67), water replenishment of more than 2 L on the training day (OR, 0.15; 95% CI, 0.05-0.45), and water replenishment of at least 500 mL within 1 hour before training (OR, 0.33; 95% CI, 0.12-0.88) significantly decreased the risk of ER. Of the 71 hospitalized patients, 41 (57.7%) were diagnosed with hypokalemia on admission. DISCUSSION: In military training, emphasis should be placed on incremental adaptation training before more intense training, and close attention should be given to overweight and previously sedentary recruits. Fluid replenishment before exercise, increased fruit intake, and proper potassium supplementation may help prevent ER.

Urinary Titin N-Fragment Evaluation in a Randomized Controlled Trial of Beta-Hydroxy-Beta-Methylbutyrate for Acute Mild Trauma in Older Adults.

The effects of beta-hydroxy-beta-methylbutyrate (HMB) complex administration and the significance of titin, a biomarker of muscle injury, in elderly minor trauma patients in acute phase has not been established. In this single-center, randomized controlled study, trauma patients aged ≥ 70 years with an injury severity score < 16 were included. Titin values on days 1 and 3 were measured and the intervention group received HMB complex (2.4 g of HMB + 14 g of glutamine + 14 g of arginine) and the control group received glutamine complex (7.2 g of protein including 6 g of glutamine). The cross-sectional area of the rectus femoris (RFCSA) on ultrasound, grip strength, and the Barthel Index were assessed on the first day of rehabilitation and after 2 weeks. We analyzed 24 HMB and 25 control participants. Titin values on day 3 correlated with grip strength (r = -0.34, p = 0.03) and the Barthel Index (r = -0.39, p = 0.01) at follow-up. HMB complex supplementation had no effect on the RFCSA (2.41 vs. 2.45 cm2, p = 0.887), grip strength (13.3 vs. 13.1 kg, p = 0.946), or the Barthel Index (20.0 vs. 50.0, p = 0.404) at follow-up. Titin values might associate with subsequent physical function. Short-term HMB complex supplementation from acute phase did not ameliorate muscle injury.

Alterations in Systemic Inflammatory Response Following a Half-Marathon Race with a Combined Curcumin and Pomegranate Supplement: A Feasibility Study.

Endurance running training can lead to gradual accumulation of inflammation and soreness ultimately resulting in overuse injuries. Management of soreness and inflammation with pharmaceuticals (i.e. non-prescription pain relievers) during long-term training is not a suitable solution due to known side effects (e.g. gastrointestinal complications, etc.). Dietary polyphenols (i.e. curcumin, pomegranate, etc.) have been purported to reduce inflammation and muscle soreness, without these negative side effects making them ideal for use in an exercise model. The purpose of the present feasibility study was to explore the combined effect of optimized curcumin and pomegranate extract supplementation prior to (PRE) and after (4H and 24H) an organized half-marathon race on blood inflammatory proteins and inflammation-associated RNA. Daily supplementation (1000 mg/d) started 26 days before a half-marathon which doubled on days 27-31. Data were analyzed with R software and Welch t-test, significance set at p < 0.05. At both 4H and 24H, supplementation was associated with alterations in protein (IL-10, IL-13, IL-4, ITAC, MIP-1alpha, MIP-3alpha, BDNF, sIL-2Ralpha, and TNF-alpha; p < 0.05) and RNA (CCL22, GUSB, IL-6, LINC00305, NKILA, PTGES, THRIL, TRAF6, ARG2, CD1A, CD55, CFI, CSF2, CXC3CL1, CX3CR1, EDNRB, GATA3, LILRB5, THY1, CD3D, MRC1, GPR183, HAMP, MBL2, CASP3, B2M, KLRF2, PDCD1LG2, IL-10, PTGS2, TLR2, IL-6R, IL-8, IL-7R, MASP1, MYD88, TNFRSF1B, TNFRSF1A, and TIRAP; p < 0.05) biomarkers compared to control. Pathway classification of these biomarkers indicated supplementation may be associated with a more favorable muscle recovery profile. Our findings support the notion that combined curcumin and pomegranate supplementation may represent a useful addition to a comprehensive exercise training plan.

Needling on trigger point promotes muscle regeneration after bupivacaine injection induced injury.

Dry needling treatment has a promising relieving effect on Myofascial Pain Syndrome (MPS). In China, acupuncture practitioners use acupuncture needle instead to insert the "A-Shi" acupoint to treat MPS which is defined as the same as the trigger point of dry needling. This method has been applied for thousands of years in China. In this study, bupivacaine injection induced gastrocnemius muscle injury in mice. We applied the clinical improved needling method on animal model by making the angle between the skin and needle less than 30 degree. Animals got needling treatment 24 h later at the point where the bupivacaine was injected. Results of muscle H.E. staining showed that, compared to bupivacaine injection group without needling, acupuncture treatment group showed more intact muscle fibers, less inflammatory cell infiltration and fractured muscle fibers. By RNA sequencing analysis, our work firstly demonstrated that the physical stimulation of needling changed the gene expression of muscle tissue to accelerate the muscular regeneration process. Therefore, our study proved that simple needling at "A-Shi" acupoint promoted muscle regeneration and revealed underlying mechanisms of the beneficial effects of acupuncture and dry needle treatments.

An injectable liposome for sustained release of tanshinone IIA to the treatment of acute blunt muscle injury by augmenting autophagy and alleviating oxidative stress.

Acute blunt skeletal muscle injury occurs frequently in sports and traffic accidents, and even leads to muscle necrosis and impaired functionality. Current treatment options for muscle injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscles. Tanshinone IIA is extracted from Salvia Miltiorrhizae, which is effective in the treatment of injury repair. But the clinical application of tanshinone IIA is limited due to its low water solubility, low permeability to biofilm and low bioavailability. In this study, tanshinone IIA liposomes were prepared to improve the bioavailability and sustained release of tanshinone IIA. The particle size, dispersion coefficient, zeta potential, encapsulation efficiency (EE) and drug loading (DL) of tanshinone IIA liposomes were 150.67 ± 27.23 nm, 0.20 ± 0.015, -8.73 ± 2.28 mV, 70.32 ± 4.04% and 15.63%, respectively. The results of quantitative real-time polymerase chain reaction (QRT-PCR) showed that tanshinone IIA liposome significantly promoted the expression of vimentin and reduce MHCIIB expression compared with other groups (P < 0.05). Western blotting showed that tanshinone IIA liposome could effectively promote the expression of autophagy-related proteins (VPS34, Beclin 1 and CTSD) and decrease p62 expression levels to treat injured muscle. Through HE, immunohistochemistry, ELISA and serological tests, we found that tanshinone IIA liposome not only effectively promoted the expression of desmin, but also reduced the expression of collagen-I and inhibited the production of pro-inflammatory factors, such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) (P < 0.05). In addition, tanshinone IIA liposome therapy significantly reduced the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD) after muscle injury compared with other groups (P < 0.05). In conclusion, tanshinone IIA liposome possesses an effective therapeutic effect on acute blunt muscle injury in rats by augmenting autophagy and alleviating oxidative stress. The continuous release of tanshinone IIA encapsulated by liposomes for disease treatment provide a new idea for the efficient and safe use of drugs with low lipid solubility and bioavailability for the treatment of acute blunt muscle injury and repair of other injuries.

Intramuscular Injection of Combined Calf Blood Compound (CFC) and Homeopathic Drug Tr14 Accelerates Muscle Regeneration In Vivo.

Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.

The Effects of Bioavailable Curcumin (Cureit) on Delayed Onset Muscle Soreness Induced By Eccentric Continuous Exercise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study.

Delayed onset muscle soreness (DOMS) is a multifactorial progression related to muscle pain, swelling, stiffness, tenderness, altered joint kinematics, muscle fiber disruption, decreased strength and power, and acute tissue damage. Curcumin, a natural phytonutrient, could manage DOMS induced by eccentric continuous exercise due to its wide range of biological activities. This study was a randomized, placebo-controlled, double-blind clinical study to assess the efficacy of Cureit™-a bioavailable form of curcumin that may decrease damage from inflammation and oxidative stress associated with severe muscle damage induced by continuous eccentric exercise. The results of the study showed that oral consumption of Cureit significantly reduced DOMS, slightly reduced creatinine kinase concentrations, and slightly increased VO2 max value compared with placebo, and found safe for administration. The consumption of Cureit led to improved recovery and reduction of DOMS without any side effects due to the enhancement of bioavailable form of curcumin.