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Elevated angiogenesis was reported in twelve eligible studies through multiple signaling pathways such as PI3K/Akt, MAPK/ERK, and JAK/STAT. The well-known signaling pathway to inhibit scar formation was TGF-β2/SMAD2. However, all included studies were not blinded enough which may have introduced bias. Therefore, the transition of EV’s efficacy into the clinics is deeply rooted in the following important factors 1) pre-clinical studies with a lower risk of bias and longer follow-up time, and 2) consistent, reproducible, and feasible manufacturing of EVs production in a large-scale commercial program.

Accumulating evidence has reported the role of microRNA (miR) on atherosclerosis (AS), while it is unclear about the relationship between microRNA-125b-5p (miR-125b-5p) and AS. Thus, the object of this study was to investigate the impact of exosomal miR-125b-5p targeting mitogen-activated protein 4 kinase 4 (Map4k4) on AS plaque formation.

The AS model was established using a high fat diet in ApoE

mice. Mouse bone marrow-derived mesenchymal stem cells (BMSCs) were selected and BMSC-exosomes (BMSC-EXO) were extracted and then identified. The targeted relationship between miR-125b-5p and Map4k4 was tested. BMSC-EXO were modified with miR-125b-5p- and Map4k4-related sequences to interfere with AS mice. MiR-125b-5p and Map4k4 expression in AS tissues were tested. The inflammation-related indices, blood lipid, plaque area, apoptosis index, MMP-9 and α-SMA expression in mice with AS were measured.

BMSCs and BMSC-EXO were successfully isolated. MiR-125b-5p was down-regulated and Map4k4 was up-regulated in aorta tissues from ApoE

mice after AS modeling, verses those from C57BL/6 mice without modeling. MiR-125b-5p targeted Map4k4. BMSC-EXO increased miR-125b-5p expression and decreased Map4k4 expression. BMSC-EXO/up-regulated miR-125b-5p and down-regulated Map4k4 in exosomes decreased inflammatory reaction, blood lipid, plaque area, MMP-9 expression and increased α-SMA expression, as well as inhibited apoptosis index of AS mice.

Functional studies revealed that exosomal miR-125b-5p from BMSCs suppresses atherosclerotic plaque formation via inhibiting Map4k4 expression.

Functional studies revealed that exosomal miR-125b-5p from BMSCs suppresses atherosclerotic plaque formation via inhibiting Map4k4 expression.Our previous work revealed the protective effect of Qiliqiangxin (QLQX) on cardiac microvascular endothelial cells (CMECs), but the underlying mechanisms remain unclear. We aimed to investigate whether QLQX exerts its protective effect against high-concentration angiotensin II (Ang II)-induced CMEC apoptosis through the autophagy machinery. CMECs were cultured in high-concentration Ang II (1 μM) medium in the presence or absence of QLQX for 48 h. We found that QLQX obviously inhibited Ang II-triggered autophagosome synthesis and apoptosis in cultured CMECs. QLQX-mediated protection against Ang II-induced CMEC apoptosis was reversed by the autophagy activator rapamycin. Specifically, deletion of ATG7 in cultured CMECs indicated a detrimental role of autophagy in Ang II-induced CMEC apoptosis. QLQX reversed Ang II-mediated ErbB2 phosphorylation impairment. click here Furthermore, inhibition of ErbB2 phosphorylation with lapatinib in CMECs revealed that QLQX-induced downregulation of Ang II-activated autophagy and apoptosis was ErbB2 phosphorylation-dependent via the AKT-FoxO3a axis. Activation of ErbB2 phosphorylation by Neuregulin-1β achieved a similar CMEC-protective effect as QLQX in high-concentration Ang II medium, and this effect was also abolished by autophagy activation. These results show that the CMEC-protective effect of QLQX under high-concentration Ang II conditions could be partly attributable to QLQX-mediated ErbB2 phosphorylation-dependent downregulation of autophagy via the AKT-FoxO3a axis.Repetitive acute intermittent hypoxia (AIH – brief, episodes of low inspired oxygen) elicits spinal motor plasticity, resulting in sustained improvements of respiratory and non-respiratory motor function in both animal models and humans with chronic spinal cord injury (SCI). We previously demonstrated that 7 days of AIH combined with task-specific training improves performance on a skilled locomotor task for at least 3 weeks post-treatment in rats with incomplete SCI. Here we investigated the effect of repetitive AIH administered for 12 wks on a forelimb reach-to-grasp task in a rat model of chronic, incomplete cervical SCI. In a replicated, sham-controlled, randomized and blinded study, male Spraque-Dawley rats were subject to partial hemisection at the 3rd cervical spinal segment, and exposed to daily AIH (10, 5 min episodes of 11% inspired O2; 5 min intervals of 21% O2) or sham normoxia (continuous 21% O2) for 7 days beginning 8 weeks post-injury. Treatments were then reduced to 4 daily treatments per week, and continued for 11 weeks. Performance on 2 pre-conditioned motor tasks, single pellet reaching and horizontal ladder walking, was recorded each week for up to 12 weeks after initiating treatment; performance on spontaneous adhesive removal was also tested. SCI significantly impaired reach-to-grasp task performance 8 weeks post-injury (pre-treatment). Daily AIH improved reaching success by the first week of treatment versus sham controls, and this difference was maintained at 12 weeks (p less then 0.0001). Daily AIH did not affect step asymmetry or stride length during ladder walking or adhesive removal time. Thus, prolonged AIH combined with task-specific training improved forelimb reach-to-grasp function in rats with a chronic cervical hemisection, but not off-target motor tasks. This study further supports the idea that daily AIH improves limb function when combined with task-specific training.Leptin, an adipokine sharing structural characteristics of the long-chain helical cytokine family with the crucial role as a regulator in energy homeostasis, has been paid more and more attention to its immunoregulatory function. Emerging evidence has indicated the roles of leptin on autoimmune diseases such as systemic lupus erythematous (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA) and psoriasis, implying that leptin may be involved in autoimmune disorders. It is very definite that there exists immunocyte dysfunction in RA patients. Growing data has manifested that leptin is increased in both serum and synovial fluid of RA patients compared to healthy controls, suggesting leptin probably takes part in the pathogenesis of RA. The aim of this review is to discuss about what we currently know with regard to the role of leptin in immune system and its effects on RA crucial cells. To clarify the role of leptin in the pathogenesis of RA is beneficial to both the treatment and medical study.