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  • Busk posted an update 7 months, 1 week ago

    Platelets not COLC-preincubated served as controls. Seven patients were pre-selected as clopidogrel non-responders. COLC significantly reduced TRAP-induced platelet aggregation in clopidogrel responders and non-responders. Interestingly, COLC inhibited ADP-induced platelet aggregation in clopidogrel non-responders in which ADP still caused activation despite DAPT. We demonstrate that COLC inhibits platelet aggregation in clopidogrel non-responders with HPR despite DAPT with this ADP receptor-inhibitor. Further in vivo studies should be designed to evaluate the opportunity to prescribe colchicine after ACS/CCS to overcome the clopidogrel limitations in the DAPT therapy.This study investigated the impact and non-impact sports on bone mineral density accrual in adolescents over 18 months. The impact sports were beneficial for bone health (accrual of bone density). In contrast, swimmers had similar or lower bone mineral density compared with the control group depending on the skeletal site. PURPOSE To investigate the impact and non-impact sports on bone mineral density (BMD) accrual in adolescents over a period of 18 months METHODS The sample was composed of 71 adolescents, avarage age of 12.7 (± 1.7) years old at baseline. Bone outcomes were compared according to the loading of the sports practiced (impact sports, n = 33 [basketball, karate, and judo], non-impact sport, n = 18 [swimming], and control group, n = 20). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) and bone mineral apparent density (BMAD) estimated through equation. The results were compared between the groups using analysis of variance and analysis of covariance. RESULTS Adjusted aBMD at lower limbs, whole body less head (WBLH), and adjusted WBLH BMAD were significantly greater in the impact sport group than the non-impact sport group at all time points. Adjusted upper limbs aBMD was significantly higher at the impact sports group compared to the non-impact sport group at 9 months and 18 months, besides compared to the control group at baseline and 18 months. Non-impact sport group presented a significant lower adjusted aBMD compared with control group at lower limbs and WBLH at 9 months, and at 9 months and 18 months in WBLH BMAD. There was a significant interaction (time × sport group) at upper limbs (p = 0.042) and WBLH aBMD (p = 0.006), and WBLH BMAD (p  less then  0.001). CONCLUSION Impact sports were more beneficial on accumulating aBMD and BMAD over a period of 18 months, while non-impact group (swimmers) had similar and lower aBMD and BMAD compared with the control group.Tendon and ligament injuries are not uncommon in clinics and have poor self-healing capacity due to their bloodless and slow-proliferative nature. Promoting the repair or reconstruction of an injured structure is an urgent problem. While Scleraxis (Scx) is a highly specific tendon cell marker, its function has not been explored to a large extent. Hence, Recombinant adenovirus was used to study the influence of Scx overexpression on directional differentiation of human amniotic mesenchymal stem cells (hMSCAs). hAMSCs modified with Scx could dramatically enhance the gene expression of tendon-related molecules, containing Scx, collagens I and III, Tenascin-C, fibronectin, matrix metalloproteinase-2 (MMP-2), lysyl oxidase-1 (LOX-1) and Tenomodulin at all-time points (P  0.05). Immunofluorescence staining showed the cobweb-like fusion of collagen I and fibronectin in the AdScx group on day 7, with higher average fluorescence intensity than the control (P  less then  0.05). After mixing with Matrigel, transplants were subcutaneously implanted in nude mice, obvious inflammation and rejection of immune response were not observed and HE staining showed a histological feature of swirl of fibers is closely linked in parallel in hAMSCs modified with Scx. On the contrary, in the control group, an unorganized connective structure with cell distributed randomly was spotted. The results of promoted directional differentiation of stem cells and the spatial structure of the normal tendon tissue in three-dimensional space manifested that Scx can be used as a specific marker for tendon cells, and as a positive regulator for directional differentiation of hAMSCs, which is possible to be applied to novel therapeutics for clinical tendon and ligament injury by hAMSCs modified with Scx.Following the transection of peripheral sympathetic preganglionic axons comprising the cervical sympathetic trunk (CST), we observe robust glial and neuronal plasticity at 1 week post-injury in the rat spinal cord intermediolateral cell column (IML), which houses the injured parent neuronal cell bodies. This plasticity contributes to neuroprotection, as no neuronal loss in the IML is present at 16 weeks post-injury. Here, we administered the antibiotic minocycline or vehicle (VEH) daily for 1 week after CST transection to investigate the role of activated microglia in IML glial and neuronal plasticity and subsequent neuronal survival. At 1 week post-injury, minocycline treatment did not alter microglia number in the IML, but led to a dampened microglia activation state. Xevinapant molecular weight In addition, the increases in oligodendrocyte (OL) lineage cells and activated astrocytes following injury in VEH rats were attenuated in the minocycline-treated rats. Further, the normal downregulation of choline acetyltransferase (ChAT) in the injured neurons was blunted. At 16 weeks post-injury, fewer ChAT+ neurons were present in the minocycline-treated rats, suggesting that activated microglia together with the glial and neuronal plasticity at 1 week post-injury contribute to the long-term survival of the injured neurons. These results provide evidence for beneficial crosstalk between activated microglia and neurons as well as other glial cells in the cord following peripheral axon injury, which ultimately leads to neuroprotection. The influences of microglia activation in promoting neuronal survival should be considered when developing therapies to administer minocycline for the treatment of neurological pathologies.

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