Background: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, right ventricular hypertrophy and failure. So far no effective treatment exists for this disease; hence, novel approaches are urgently needed. The aim of the present research was to observe the treatment effect of mesenchymal stromal cell derived exosomes and reveal the mechanism. Methods: Monocrotaline (MCT)-induced PH in rats and hypoxia-induced cell damage model were established, respectively. Exosomes derived from the supernatant of human umbilical cord mesenchymal stem cells (MSC-exo) were injected into MCT-PH model rat or added into the cells cultured medium. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods were used in vivo and vitro. Results: The results showed that MSC-exo could significantly attenuate right ventricular (RV) hypertrophy and pulmonary vascular remodelling in MCT-PH rats. In the cell culture experiments, we found that MSC-exo could significantly inhibit hypoxia-induced pulmonary arterial endothelial cell (PAEC) apoptosis and pulmonary arterial smooth muscle cells (PASMC) proliferation. Furthermore, the pulmonary arterioles endothelial-to-mesenchymal transition (EndMT) was obviously suppressed. Moreover, the present study suggest that MSC-exo can significantly upregulate the expression of Wnt5a in MCT-PH rats and hypoxic pulmonary vascular cells. Furthermore, with Wnt5a gene silencing, the therapeutic effect of MSC-exo against hypoxia injury was restrained. Conclusions: Synthetically, our data provide a strong evidence for the therapeutic of MSC-exo on PH, more importantly, we confirmed that the mechanism was associated with up-regulation of the expression of Wnt5a. These results offer a theoretical basis for clinical prevention and treatment of PH.

Background: The aim of this study was to explore the inhibitory effect of baicalin on myocardial apoptosis induced by ischemia-reperfusion (I/R). Methods: Sprague Dawley rats heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 μmol/l baicalin was administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Post-operation, the left ventricular (LV) end-diastolic pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin V-FITC/PI and tunel staining, and the apoptosis gene and protein was detected by RT-PCR and western blot. Furthermore, the protein expression of calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2- acetoxymethyl ester. Moreover, primary rats cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to culture medium. The cells survival rate, vitality and the apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively. Results: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulation the protein expression of CaSR, but up-regulation the protein expression of ERK1/2. Furthermore, when the cells were pretreatment with ERK1/2 inhibitor PD98059, the cells survival rate was significantly decreased, but LDH activity and apoptosis were significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could been inhibited by ERK1/2 inhibitor. Conclusion: In conclusion, our data suggested that baicalin attenuate I/R-induced myocardial injury maybe through suppression CaSR/ERK1/2 signaling pathway.

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The bionic joints composed of pneumatic muscles (PMs) can simulate the motion of biological joints. However, the PMs themselves have non-linear characteristics such as hysteresis and creep, which make it difficult to achieve high-precision trajectory tracking control of PM-driven robots. In order to effectively suppress the adverse effects of nonlinearity on control performance and improve the dynamic performance of PM-driven legged robot, this study designs a double closed-loop control structure based on neural network. First, according to the motion model of the bionic joint, a mapping model between PM contraction force and joint torque is proposed. Second, a control strategy is designed for the inner loop of PM contraction force and the outer loop of bionic joint angle. In the inner control loop, a feedforward neuron Proportional-Integral-Derivative controller is designed based on the PM three-element model. In the control outer loop, a sliding mode robust controller with local model approximation is designed by using the radial basis function neural network approximation capability. Finally, it is verified by simulation and physical experiments that the designed control strategy is suitable for humanoid motion control of antagonistic PM joints, and it can satisfy the requirements of reliability, flexibility, and bionics during human-robot collaboration.

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a systemic inflammatory disorder characterized by uncontrolled histiocytic proliferation, hemophagocytosis, macrophage activation, and up-regulation of inflammatory cytokines (Grom AA., Current opinion in rheumatology 2003; 15: 587–590). HLH is usually divided into two types: primary (familial) HLH and secondary (reactive) HLH. Primary HLH is associated with primary immune deficiencies in which specific gene mutations play an important role, such as perforin defects.