osteoarthritis (oa) is one of the most prevalent joint disorders globally. Patients suffering from oa are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose-derived stem cells (adScs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient-derived primary cells. First, it was tested whether patient-derived adScs could differentiate into chondrogenic and osteogenic lineages. The adScs were then used as a source of exosomes. it was found that exosomes isolated from adScs, when co-cultured with activated synovial fibroblasts, downregulated the expression of pro-inflammatory markers interleukin (il)-6, nF-κB and tumor necrosis factor-α, while they upregulated the expression of the anti-inflammatory cytokine IL-10; without exosomes, the opposite observations were made. in addition, inflammation-inflicted oxidative stress was induced in vitro by stimulating chondrocytes with H 2 o 2 . Treatment with exosomes protected articular chondrocytes from H 2 o 2 -induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including collagen type ii and β-catenin; inhibition of Wnt/β-catenin, using the antagonist icG-001, prevented exosome-induced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microrna (mir)-145 and mir-221. The upregulation of mir-145 and mir-221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patient-derived exosomes, produced from adScs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.

We developed a novel and efficient method for the synthesis of various 3-alkylated quinoxalin-2(1H)-ones (32 examples, 70%-96% yields) through electron donor-acceptor complex enabled alkylation of quinoxalin-2(1H)-ones with N-hydroxyphthalimide esters as the alkyl source and Na 2 S as the catalytic electron donor under external photocatalyst-, oxidant-and additive-free conditions.

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Objective Recent studies found that exosomes (Exo) derived from mesenchymal stem cells (MSC) (MSC‐Exo) accelerated diabetic wound healing. However, the low yield during exosome extraction is still a major barrier to their clinical utility. Methods We constructed a method to produce umbilical cord MSC‐derived nanovesicles (UCMSC‐NV) by serial extrusion through filters and investigated the effects of UCMSC‐NV on wound healing in vivo and in vitro, as well as the potential mechanisms. Results We found that the characteristics of UCMSC‐NV were similar to those of exsome (UCMSC‐Exo) but with much higher production yields. Further analysis showed that UCMSC‐NV promoted the migration of fibroblasts and angiogenesis in vitro, and both UCMSC‐NV and UCMSC‐Exo showed similar therapeutic capacities for wound healing in vivo. Sequencing analysis revealed that UCMSC‐NV and UCMSC‐Exo had similar miRNA compositions, and the target genes of the differentially expressed miRNAs in UCMSC‐NV were enriched in pathways of inflammation and damage‐repair‐related functions. Mass spectrometry analysis showed that UCMSC‐NV encapsulated functional proteins that may achieve therapeutic effect equally as good as UCMSC‐Exo. Conclusions UCMSC‐NV are more efficacious and can be obtained at a higher yield than UCMSC‐Exo and are a promising therapeutic strategy to improve wound healing in diabetes patients.