Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

Concurrently bioprinted scaffolds with autologous bone and allogeneic BMSCs promote bone regeneration through native BMSC recruitment

Autologous bone marrow-derived mesenchymal stem cells(BMSCs)have been shown to promote osteogenesis;however,the effects of allogeneic BMSCs(allo-BMSCs)on bone regeneration remain unclear.Therefore,we explored the bone regeneration promotion effect of allo-BMSCs in 3D-printed autologous bone particle(ABP)scaffolds.First,we concurrently printed scaffolds with polycaprolactone,ABPs,and allo-BMSCs for appropriate support,providing bioactive factors and seed cells to promote osteogenesis.In vitro studies showed that ABP scaffolds promoted allo-BMSC osteogenic differentiation.In vivo studies revealed that the implantation of scaffolds loaded with ABPs and allo-BMSCs into canine skull defects for nine months promoted osteogenesis.Further experiments suggested that only a small portion of implanted allo-BMSCs survived and differentiated into vascular endothelial cells,chondrocytes,and osteocytes.The implanted allo-BMSCs released stromal cell-derived factor 1 through paracrine signaling to recruit native BMSCs into the defect,promoting bone regeneration.This study contributes to our understanding of allo-BMSCs,providing information relevant to their future application.