HUCMSCs transplantation combined with ultrashort wave therapy attenuates neuroinflammation in spinal cord injury through NUR77/ NF-κB pathway.

AIMS: Spinal cord injury (SCI) is a major cause of long-term physical impairment. Currently, treatment for SCI is limited to supportive measures, which can lead to permanent disability, representing a serious social burden. The present study aimed to evaluate the inflammatory microenvironment effects of human umbilical cord mesenchymal stem cells (HUCMSCs)+ Ultrashort Wave (USW) therapy on SCI and reveal possible mechanisms. MAIN METHODS: Low-dose USW was treated one day after SCI, and HUCMSCs suspension was transferred to the lesion using a micro-syringe 7 days after SCI. The functional effects of HUCMSCs and USW, separately and combinedly, were measured, together with the infiltration of CD3+ cells, formation of A1 astrocytes and activation of NUR77/ NF-κB pathway. KEY FINDINGS: Our results showed that HUCMSCs+USW therapy improved motor function of SCI rat, together with decreased infiltration of CD3+ T cells, and decreased induction of microglia and A1 astrocytes. And also USW treatment played a very important role on decreasing the infiltration of CD3+ T cells and IBA-1+ cells. Reduced production of pro-inflammatory cytokines IL-1ß and IL-6 was also observed in rats receiving HUCMSCs+USW therapy, medicated by NUR77/NF-κB pathway. SIGNIFICANCE: These findings indicated that HUCMSCs+USW therapy could attenuate inflammatory microenvironment through NUR77/NF-κB signaling pathway, which might contribute to its better outcome.

miR-150 inhibitor ameliorates adriamycin-induced focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome in USA. Its mechanisms remain unclear and the effective treatment lacks. We previously reported that upregulation of microRNA (miR)-150 in human podocytes increases profibrotic proteins and decreases anti-fibrotic suppressor of cytokine signaling 1 (SOCS1). We aimed to clarify whether miR-150 inhibitor can ameliorate glomerular injury and to identify its corresponding mechanisms in adriamycin-induced FSGS mice. We found that renal miR-150 increased in adriamycin-induced FSGS mice and FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) was absorbed by the animal kidneys 6 h after subcutaneous injection. The administration of LNA-anti-miR-150 (2 mg/kg BW twice weekly for 6 w) inhibited renal miR-150 levels without systemic toxicity. With renal miR-150 inhibition, proteinuria, hypoalbuminemia, and hyperlipemia were ameliorated in FSGS mice compared to the scrambled LNA. Meanwhile, the elevated profibrotic proteins and proinflammatory cytokines, decreased antifibrotic SOCS1, and the filtration of T cells in FSGS mice were reverted by LNA-anti-miR-150. Finally, we found that miR-150 most located on podocytes in renal biopsies of FSGS patients. We conclude that LNA-anti-miR-150 might be a novel promising therapeutic agent for FSGS. The renal protective mechanisms might be mediated by anti-fibrosis and anti-inflammation as well as reducing infiltration of T cells in the kidney.

Co-occurrence of PLA2R-positive membranous nephropathy without crescents, and PR3-positive eosinophilic granulomatosis with polyangiitis
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Primary membranous nephropathy (PMN) is a common cause of adult nephrotic syndrome, most commonly associated with autoantibodies against M-type phospholipase A2 receptor (PLA2R). Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a rare disorder characterized by asthma, eosinophilia, and multiorgan vasculitis. Here, we report the case of an adult who presented with typical nephrotic syndrome. Renal biopsy revealed PLA2R-positive PMN without crescents. He had a history of asthma, eczema, and eosinophilia, and testing revealed positive serological proteinase 3 (PR3) and antineutrophil cytoplasmic antibody (ANCA). Further skin and bone marrow biopsy revealed histologic eosinophilic infiltration, and a diagnosis of EGPA was made. The renal biopsy revealed a few eosinophils in glomerular capillary lumen and tubulointerstitial. Treatment with a glucocorticoid and cyclophosphamide was initiated. At 32 months after completing therapy, the patient was in complete clinical remission, and the PR3-ANCA result was negative.