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An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
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Humanos , Células Estrelladas Hepáticas/patología , Receptores de Calcitriol , Cirrosis Hepática/patología , Macrófagos/metabolismoRESUMEN
IL-6 is an important cytokine that plays an important role in the pathogenesis of rheumatoid arthritis. We summarized the clinical efficacy and safety of tocilizumab, the IL-6 receptor monoclonal antibody in rheumatoid arthritis, and compared tocilizumab with TNF-α blocking mAbs. The efficiency of tocilizuamb is equivalent to that of TNF-α blockers, and each of the drugs has its advantages and disadvantages. We also summarized the clinical trials of the mAbs blocking IL-6 pathway in development. According to the results of recent studies by several research teams including our research group, IL-6 is another key target for the treatment of rheumatoid arthritis after TNF-α. The listing of the IL-6 blockers provides more choices for personalized treatment of rheumatoid arthritis in the future.
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Objective To investigate the effect of aerobic exercise combined with routine rehabilitation therapy on cardiorespiratory exercise function and rehabilitation efficacy in stroke patients with hemiplegia.Methods Thirty consecutive stroke patients with the first-ever hemiplegia were enrolled prospectively.They were randomly assigned to an experimental group (n=13) or a control group (n=13) according to the random number table (n=15 in each group).Four patients withdrew,and finally 26 patients completed the study (n=13 in each group).The two groups of patients were given routine rehabilitation therapy.On the basis of routine rehabilitation therapy,the experimental group was also treated with aerobic exercise training,once a day,30 min each time for 4 weeks.The evaluations of cardiopulmonary exercise tests were performed on both groups before treatment and after 4 weeks of treatment (peak oxygen uptake [VO2peak]),anaerobic threshold [AT],peak minute ventilation [VEpeak]),and motor function (Fugl-Meyer assessment scale [FMA],activities of daily living (Barthel index [BI]) were performed.The differences between the two groups before and after treatment were compared.Results (1)Cardiopulmonary exercise test results:Compared with before treatment,VO2peak,AT,and VEpeak were increased significantly (16±4 ml/[kg·min] vs.13±3 ml/[kg·min],12.9±2.5 kg·min vs.10.0±2.7 ml/[kg·min],41±12 L/min vs.34±9 L/min,t=9.668,4.328,and 3.662,respectively,all P0.05).The differences in VO2peak,AT,and VEpeak in the patients of the control group before and after treatment were 0.4 (0.2,0.6),0.1 (-0.5,0.7 ml/kg·min) and 0 (-2.5,5.0 L/min),respectively.The differences of VO2peak,AT,and VEpeak in patients of the experimental group before and after treatment were 3.0 (2.2,3.9 ml/[kg·min],2.7 (1.8,5.3 ml/[kg·min],and 7.0 (1.0,13.0 L/min),respectively.There were significant differences in VO2peak,AT,and VEpeak before and after treatment between the two groups (Z=4.287,3.721,and 2.236,respectively,P0.05).Conclusion On the basis of routine rehabilitation therapy,stroke patients with hemiplegia increasing aerobic exercise training may improve their cardiopulmonary exercise function.
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The self—formulated modified“Blood—activating andQi—benefitting Decoction of Fructus Cirri Sarco-dactylis”with heavy dose of Radix Angelica Sinensiswas applied for the treatment of 50 cases of apoplexycomplicated with pseudo—Bulbar paralysis.The totaleffective rate of dysathria was 98% with a 58% abovemarked effect rate,while the total effective rate for-choking and coughing was 98%,with a 94% abovemarkedly effective rate.