Diabetic nephropathy (DN) remains one of the severe complications associated with diabetes mellitus. It is worthwhile to uncover the underlying mechanisms of clinical benefits of human urine‐derived stem cells (hUSCs) in the treatment of DN. At present, the clinical benefits associated with hUSCs in the treatment of DN remains unclear. Hence, our study aims to investigate protective effect of hUSC exosome along with microRNA‐16‐5p (miR‐16‐5p) on podocytes in DN via vascular endothelial growth factor A (VEGFA). Initially, miR‐16‐5p was predicated to target VEGFA based on data retrieved from several bioinformatics databases. Notably, dual‐luciferase report gene assay provided further verification confirming the prediction. Moreover, our results demonstrated that high glucose (HG) stimulation could inhibit miR‐16‐5p and promote VEGFA in human podocytes (HPDCs). miR‐16‐5p in hUSCs was transferred through the exosome pathway to HG‐treated HPDCs. The viability and apoptosis rate of podocytes after HG treatment together with expression of the related factors were subsequently determined. The results indicated that miR‐16‐5p secreted by hUSCs could improve podocyte injury induced by HG. In addition, VEGA silencing could also ameliorate HG‐induced podocyte injury. Finally, hUSC exosomes containing overexpressed miR‐16‐5p were injected into diabetic rats via tail vein, followed by qualification of miR‐16‐5p and observation on the changes of podocytes, which revealed that overexpressed miR‐16‐5p in hUSCs conferred protective effects on HPDCs in diabetic rats. Taken together, the present study revealed that overexpressed miR‐16‐5p in hUSC exosomes could protect HPDCs induced by HG and suppress VEGFA expression and podocytic apoptosis, providing fresh insights for novel treatment of DN.

Diabetic nephropathy (DN) is a complication of diabetes that is increasing in prevalence in China. Extracellular vesicles (EVs) carrying microRNAs (miRs) may represent a useful tool in the development of therapies for DN. Here, we report that EVs released by adipose-derived mesenchymal stem cells (ADSCs) during DN contain a microRNA (miR), miR-26a-5p, that suppresses DN. Using bioinformatic analyses, we identified differentially expressed miRs in EVs from ADSCs and in DN and predicted downstream regulatory target genes. We isolated mesenchymal stem cells (MSCs) from adipose tissues, and collected EVs from the ADSCs. We exposed mouse glomerular podocytes and MP5 cells to high glucose (HG), ADSCs-derived EVs, miR-26a-5p inhibitor/antagomir, Toll-like receptors 4 (TLR4) plasmids, or the NF-κB pathway activator (phorbol-12-myristate-13-acetate, PMA). We used the CCK-8 assay and flow cytometry to investigate the impact of miR-26a-5p on cell viability and apoptosis and validated the results of these assays with in vivo experiments in nude mice. We found that in DN, miR-26a-5p is expressed at very low levels, whereas TLR4 is highly expressed. Of note, EVs from ADSCs ameliorated the pathological symptoms of DN in diabetic mice, and transferred miR-26a-5p to HG-induced MP5 cells, improving viability while suppressing apoptosis of MP5 cells. We also found that miR-26a-5p protects HG-induced MP5 cells from injury by targeting TLR4, inactivating the NF-κB pathway and down-regulating vascular endothelial growth factor A (VEGFA). Moreover, ADSCs-derived EVs transferred miR-26a-5p to mouse glomerular podocytes, which ameliorated DN pathology. These findings suggest that miR-26a-5p from ADSC-derived EVs protects against DN.

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BackgroundNephropathy, a chronic progressive kidney disease often characterized by glomeruli scarring and sclerosis, is a major complication of diabetes mellitus. Development of nephropathologic lesions has been shown to be associated with suppressed AKT phosphorylation and elevated level of apoptosis. Moreover, it has been established that the TRB3 gene is capable of inhibiting AKT phosphorylation and promoting apoptosis.Material/MethodsIn this study, we injected TRB3 siRNA into Wistar rats with type 1 diabetes, and monitored development of nephropathy in the rats. Urinary albumin excretion and serum creatinine were used as primary indicators, and nephritic histology was also examined. We also measured the serum level of pro-inflammatory cytokines collagen expression, and phosphorylation of PI3K and AKT proteins in the kidneys.ResultsBy silencing the TRB3 gene with siRNA, diabetic-induced nephropathy symptoms were alleviated, such as increased serum creatinine level and urinary albumin secretion. Additionally, histological examination showed lower levels of nephropathic lesions, and samples of the kidneys showed less accumulation of collagen proteins. Levels of serum cytokines, including TNF-α, IL-1β, and IL-6, were also lowered, whereas phosphorylation levels of PI3K and AKT were increased. In summary, TRB3 silencing in diabetic rats had a significant ameliorative effect on their nephropathy.ConclusionsSilencing of TRB3 has a significant ameliorative effect on diabetic nephropathy in rats.

For space robots, it is difficult to track continuous time-varying manifolds on SE(3) by using traditional closed-loop control strategies, which are designed to track the position and the attitude separately. Therefore, the dynamics model should be rebuilt, and the corresponding control strategy should be redesigned. Firstly, the dynamics equations for a space robot in the joint space and workspace are established separately in the framework of Lie group SE(3) and screw theory based on the Lagrange principle. Secondly, based on the proposed feedback form, a PD (proportional derivative) control law of output force on the end-effector is designed, and a closed-loop continuous tracking control strategy is proposed using the force Jacobian matrix and the kinematic model. The simulation results show that the control scheme has good performance when the system state changes gently. Furthermore, a robust sliding mode tracking control scheme is designed. The simulation results show that the proposed robust control law has better accuracy than the PD control law because the system state changes wildly. Finally, a robust fuzzy sliding mode tracking control scheme is designed to deal with the chattering phenomenon. The simulation results show that the proposed robust fuzzy control law can eliminate the chattering well and decrease the joint control torque significantly. The robustness of the proposed robust fuzzy control law is also verified by numerical simulation.