TY  - JOUR
AB  - Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.
AU  - Zeng, R.*
AU  - Lv, B.*
AU  - Lin, Z.*
AU  - Chu, X.*
AU  - Xiong, Y.*
AU  - Knoedler, S.
AU  - Cao, F.*
AU  - Lin, C.*
AU  - Chen, L.*
AU  - Yu, C.*
AU  - Liao, J.M.*
AU  - Zhou, W.*
AU  - Dai, G.*
AU  - Shahbazi, M.A.*
AU  - Mi, B.*
AU  - Liu, G.*
C1  - 69734
C2  - 55199
CY  - 16 Donghuangchenggen North St, Building 5, Room 411, Beijing, Dongcheng District 100009, Peoples R China
SP  - 366-380
TI  - Neddylation suppression by a macrophage membrane-coated nanoparticle promotes dual immunomodulatory repair of diabetic wounds.
JO  - Bioact. Mater.
VL  - 34
PB  - Keai Publishing Ltd
PY  - 2024
SN  - 2452-199X
ER  - 

TY  - JOUR
AB  - Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.
AU  - Wu, Y.*
AU  - Huang, X.*
AU  - Tan, Z.*
AU  - Zang, J.*
AU  - Peng, M.*
AU  - He, N.*
AU  - Zhang, T.*
AU  - Mai, H.
AU  - Xu, A.*
AU  - Lu, D.*
C1  - 67956
C2  - 54434
CY  - 16 Donghuangchenggen North St, Building 5, Room 411, Beijing, Dongcheng District 100009, Peoples R China
SP  - 196-213
TI  - FUS-mediated HypEVs: Neuroprotective effects against ischemic stroke.
JO  - Bioact. Mater.
VL  - 29
PB  - Keai Publishing Ltd
PY  - 2023
SN  - 2452-199X
ER  -