Tendon injuries are common musculoskeletal system disorders in clinical, but the regeneration ability of tendon is limited. Tendon stem cells (TSCs) have shown promising effect on tissue engineering and been used for the treatment of tendon injury. Exosomes that serve as genetic information carriers have been implicated in many diseases and physiological processes, but effect of exosomes from TSCs on tendon injury repair is unclear. The aim of this study is to make clear that the effect of exosomes from TSCs on tendon injury healing. Exosomes were harvested from conditioned culture media of TSCs by a sequential centrifugation process. Rat Achilles tendon tendinopathy model was established by collagenase‐I injection. This was followed by intra‐Achilles‐tendon injection with TSCs or exosomes. Tendon healing and matrix degradation were evaluated by histology analysis and biomechanical test at the post‐injury 5 weeks. In vitro, TSCs treated with interleukin 1 beta were added by conditioned medium including exosomes or not, or by exosomes or not. Tendon matrix related markers and tenogenesis related markers were measured by immunostaining and western blot. We found that TSCs injection and exosomes injection significantly decreased matrix metalloproteinases (MMP)‐3 expression, increased expression of tissue inhibitor of metalloproteinase‐3 (TIMP‐3) and Col‐1a1, and increased biomechanical properties of the ultimate stress and maximum loading. In vitro, conditioned medium with exosomes and exosomes also significantly decreased MMP‐3, and increased expression of tenomodulin, Col‐1a1 and TIMP‐3. Exosomes from TSCs could be an ideal therapeutic strategy in tendon injury healing for its balancing tendon extracellular matrix and promoting the tenogenesis of TSCs.

Objectively: Tendinopathy is a common problem in sports medicine which can lead to severe morbidity. Aspirin, as the classical representative of non-steroidal anti-inflammatory drugs (NSAIDs) for its anti-inflammatory and analgesic actions, has been commonly used in treating tendinopathy. While its treatment effects on injury tendon healing are lacking, illuminating the underlying mechanism may provide scientific basis for clinical treatment. Materials and methods:Firstly, we used immunohistochemistry and qRT-PCR to detect changes in CD14, CD206, iNOS, IL-6, IL-10, MMP-3, TIMP-3, Col-1a1, biglycan, Comp, Fibronectin, TGF-β1，ACAN，EGR-1 and FMOD. Next, Western blot was used to measure the protein levels (IL-6, IL-10, TGF-β1, COMP, TIMP-3, STAT-3/P-STAT-3 and JNK/P-JNK) in TSCs. Then, migration and proliferation of TSCs were measured through wound healing test and BrdU staining. Finally, the mechanical properties of injury tendon were detected. Results:After aspirin treatment, the inflammation and scar formation in injury tendon were significantly inhibited by aspirin. Still, tendon's ECM was positively balanced.Increasing migration and proliferation ability of TSCs induced by IL-1β were significantly reversed. JNK/STAT-3 signalling pathway participated in the process above.In addition, biomechanical properties of injury tendon were significantly improved. Conclusions:Taken together, the findings suggested that aspirin inhibited inflammation and scar formation via regulation of JNK/STAT-3 signalling and decreased rerupture risk of injury tendon. Aspirin could be an ideal therapeutic strategy in tendon injury healing.

Pediatric high-grade gliomas (pHGGs) are aggressive brain tumors affecting children, and outcomes have remained dismal, even with access to new multimodal therapies. In this study, we compared the miRNomes and transcriptomes of pediatric low- (pLGGs) and high-grade gliomas (pHGGs) using small RNA sequencing (smRNA-Seq) and gene expression microarray, respectively. Through integrated bioinformatics analyses and experimental validation, we identified miR-137 and miR-6500-3p as significantly downregulated in pHGGs. miR-137 or miR-6500-3p overexpression reduced cell proliferation in two pHGG cell lines, SF188 and UW479. CENPE, KIF14 and NCAPG levels were significantly higher in pHGGs than pLGGs, and were direct targets of miR-137 or miR-6500-3p. Furthermore, knockdown of CENPE, KIF14 or NCAPG combined with temozolomide treatment resulted in a combined suppressive effect on pHGG cell proliferation. In summary, our results identify novel mRNA/miRNA interactions that contribute to pediatric glioma malignancy and represent potential targets for the development of new therapeutic strategies.

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Background: Haglund syndrome is a common disease that causes posterior heel pain. This study compared the clinical outcomes of dorsal closing wedge calcaneal osteotomy (DCWCO) and posterosuperior prominence resection (PPR) for the treatment of Haglund syndrome. Methods: This retrospective study included 12 patients who underwent DCWCO and 32 patients who underwent PPR from January 2010 to August 2016. Patients were evaluated using the American Orthopedic Foot Ankle Society ankle-hindfoot scale (AOFAS), Victorian Institute of Sport Assessment Scale for Achilles tendinopathy (VISA-A), Fowler-Philip angle, Bohler's angle, and calcaneal pitch angle preoperatively and postoperatively (at 3 months, 6 months, 1 year, and the latest follow-up). Results: Both groups exhibited a significant increase in their AOFAS and VISA-A scores after surgery. The DCWCO group had lower AOFAS scores than the PPR group at 6 months (77.6 ± 5.1 vs. 82.8 ± 7.8; P = 0.037) but had higher scores at the latest follow-up (98.2 ± 2.3 vs. 93.4 ± 6.1; P = 0.030). The DCWCO group had lower VISA-A scores at 3 months (56.9 ± 13.9 vs. 65.2 ± 11.0; P = 0.044) but higher scores at the latest follow-up (98.2 ± 2.6 vs. 94.3 ± 5.0; P = 0.010) than the PPR group. Both groups exhibited significant changes in the Fowler-Philip angle and Bohler's angle after surgery. The postoperative Fowler-Philip angle of the DCWCO group was greater than that of the PPR group (35.9°± 4.9°vs. 31.4°± 6.2°; P = 0.026). However, there was no statistically significant difference in any other angle of the two groups postoperatively. Conclusions: Compared to the PPR group, the DCWCO group had poorer short-term clinical outcomes but provide better long-term function and symptom remission. This method can be a good option for those patients with higher functional expectations.

Background/Aims: In this study, we examined whether the combination of hyperbaric oxygen (HBO) and diltiazem therapy provided a cardioprotective effect on myocardial ischemia-reperfusion injury (MIRI) rat model. Methods: Sixty healthy Sprague-Dawley rats were randomly divided into sham, IR, diltiazem (5 mg/kg), HBO (0.25 MPa, 60 min) and combination therapy (HBO plus diltiazem) groups. MIRI model was established by ligating the left anterior descending for 30 min, followed by 60 min of reperfusion. Results: The results show that HBO and diltiazem preconditioning significantly improves cardiac function and myocardial infarction area, increases nitric oxide, endothelial nitric oxide synthase and ATPase (Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase) activity and decreases levels of oxygen stress, myocardial enzymes and endothelin-1. Notably, HBO and diltiazem preconditioning significantly increased Bcl-2 protein expression and decreased Bax protein and caspase-3 mRNA expression. Conclusions: These data indicate that combination therapy protected against heart MIRI by reducing oxygen stress damage, correcting energy metabolism, improving endothelial function and inhibiting cell apoptosis.

This study examined the effects of a bout of low-intensity, prolonged downhill exercise on sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity, Ca(2+) uptake and release in rat red vastus muscle. Ionophore stimulation was determined to assess vesicle integrity by measuring the ratio of Ca(2+)-ATPase activities in the presence and absence of A23187. Observations of the muscle ultrastructure were made to evaluate muscle damage at the level of the myofibrils and SR. Adult male Sprague-Dawley rats (weight, 395 +/- 5.9 g) were either assigned as non-exercise controls or subjected to 90 min of downhill treadmill exercise (-16 deg; 15 m min(-1)), and then killed immediately, 4, 24, 48, 72 or 144 h after exercise (n = 7). Calcium uptake was significantly lower (P < 0.05) compared with control values (19.25 +/- 1.38 nmol min(-1) (mg protein)(-1)), by 29 and 36% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Calcium release was also significantly lower (P < 0.05) compared with control values (31.06 +/- 2.36 nmol min(-1) (mg protein)(-1)), by 37 and 39% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Ca(2+)-ATPase activity measured with ionophore was 31% lower (P < 0.05) 4 h postexercise, and remained lower (P < 0.05) 24 h postexercise. The ratio of Ca(2+)-ATPase activities in the presence and absence of A23187 was not significantly changed after exercise, indicating that membrane integrity was not altered by the exercise. Focal dilatations of the SR were observed immediately and 4 h following exercise, implying that SR may be susceptible to damage in the localized regions of overstretched sarcomeres. The results demonstrate that a bout of low-intensity, prolonged downhill exercise results in a long-lasting depression of SR function that is not fully restored after 2 days of recovery, which may underlie some functional impairments induced by eccentric exercise.

Tendon-derived stem cells (TDSCs) are multipotent adult stem cells with potential applications in tendon and tendon-bone junction repair. However, cellular characteristics change during in vitro passaging. Therefore, elucidation of the molecular and cellular mechanisms of tendon aging will be essential for the development of TDSC-based therapies. The aim of this study is to investigate the effect of CITED2, a nuclear regulator and transforming growth factor β2 (TGFβ2) on TDSC proliferation and senescence by comparing cells derived from Achilles tendon biopsies of young individuals (Y-TDSC) with those of older patients (O-TDSC). Our results showed that CITED2 mRNA and protein expression levels were significantly higher in Y-TDSCs than in O-TDSCs and O-TDSCs displayed decreased proliferation and increased senescence compared with Y-TDSCs. Furthermore, high levels of CITED2 protein expression in Y-TDSCs correlated with the downregulation of SP1 and p21 and the upregulation of MYC, potentially indicating the mechanism by which CITED2 upregulates TDSC proliferation. TGFβ2 was found to downregulate the expression of the CITED2 gene and knockdown of CITED2 abolished the effect of TGFβ2 on TDSC proliferation and senescence. Thus, the downregulation of CITED2 contributes to TGFβ-mediated senescence providing an insight into the molecular and cellular mechanisms that contribute to tendon aging and degeneration. Our findings may aid the development of cell-based therapies for tendon repair.