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Xuehan Wang,Mingxuan Li,Liwei Liu,Rui Mou,Xiuming Zhang,Yanling Bai,Haijin Xu,Mingqiang Qiao 한국미생물학회 2012 The journal of microbiology Vol.50 No.6
A Pseudomonas aeruginosa mutant strain M122 was isolated from a Mu transposon insertion mutant library. In our prophase research, we have found that PA0058, a novel gene encodes a 234-residue conserved protein, was disrupted in the M122 mutant. In this study, the bacteriostatic experiment in vitro indicates that M122 has abnormally high aminoglycoside resistance. We expressed PA0058 in E. coli and found that PA0058 oxidizes and reduces disulfide. This biochemical characterization suggests that PA0058 is a novel disulfide oxidoreductase. Hence, the protein was designated as DsbM. Microarray analysis of the M122 mutant showed its unusual phenotype might be related to the bacterial antioxidant defense system mediated by the oxyR regulon. Meanwhile, we detected –SH content in the periplasm of M122 and wild strain and found a lower –SH/S–S ratio in M122. Therefore, we consider that the loss of dsbM function decreased the –SH/S–S ratio, which then prolongs the OxyR-regulated response, thereby conferring high aminoglycoside resistance to the M122 mutant strain. Our findings have important implications for understanding the mechanisms underlying aminoglycoside resistance in P. aeruginosa.
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Sang Xuehan,Zhao Xiuhong,Yan Lianqi,Jin Xing,Wang Xin,Wang Jianjian,Yin Zhenglu,Zhang Yuxin,Meng Zhaoxiang 한국조직공학과 재생의학회 2022 조직공학과 재생의학 Vol.19 No.3
BACKGROUND: Intra-articular injection is a classic strategy for the treatment of early osteoarthritis (OA). However, the local delivery of traditional therapeutic agents has limited benefits for alleviating OA. Exosomes, an important type of extracellular nanovesicle, show great potential for suppressing cartilage destruction in OA to replace drugs and stem cellbased administration. METHODS: In this study, we developed a thermosensitive, injectable hydrogel by in situ crosslinking of Pluronic F-127 and hyaluronic acid, which can be used as a slow-release carrier to durably retain primary chondrocyte-derived exosomes at damaged cartilage sites to effectively magnify their reparative effect. RESULTS: It was found that the hydrogel can sustainedly release exosomes, positively regulate chondrocytes on the proliferation, migration and differentiation, as well as efficiently induce polarization of M1 to M2 macrophages. Intraarticular injection of this exosomes-incorporated hydrogel significantly prevented cartilage destruction by promoting cartilage matrix formation. This strategy also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163? regenerative M2 macrophages over CD86? M1 macrophages in synovial and chondral tissue, with a concomitant reduction in pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and increase in anti-inflammatory cytokine (IL-10) in synovial fluid. CONCLUSION: Our results demonstrated that local sustained-release primary chondrocyte-derived exosomes may relieve OA by promoting the phenotypic transformation of macrophages from M1 to M2, which suggesting a great potential for the application in OA.
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