| 1 | Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation显示文摘Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases.However,effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases.Herein we report a novel strategy for engineering inflammationaccumulation nanoparticles via phenolic functionalization.Different phenol-functionalized nanoparticles were first developed,which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment.Phenolic compound-decorated poly(lactide-co-glycolide)nanoparticles,in particular tyramine(Tyr)-coated nanoparticles,showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis,acute liver injury,and acute lung injury,mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species.By combining a cyclodextrin-derived bioactive material with Tyr decoration,a multifunctional nanotherapy(TTN)was further developed,which displayed enhanced cellular uptake,antiinflammatory activities,and inflammatory tissue accumulation,thereby affording amplified therapeutic effects in mice with colitis or acute liver injury.Moreover,TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration,leading to considerably potentiated in vivo efficacies.Preliminary studies also revealed good safety of orally delivered TTN.Consequently,Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies. | Qiang Nie Chenwen Li Yu Wang Yi Hu Wendan Pu Qixiong Zhang Jiajun Cai Yongyao Lin Gang Li Chenping Wang Lanlan Li Yin Dou Jianxiang Zhang | 2023 | Acta Pharmaceutica Sinica B2023,13,1: | 1 |
| 2 | Prohibitin Protein Expression During Spermatogenesis in the Large Yellow Croaker, Larimichthys crocea显示文摘Mitochondria are important for animals’fertility,and their morphologies and functions during spermatogenesis are un-der investigation.However,the molecular mechanism that regulates the mitochondrial dynamic during spermatogenesis is still un-known.In this study,the cytological features of spermatogenesis were investigated in Larimichthys crocea.In addition,the structure and function of prohibitin(PHB),which is associated with mitochondrial structure and dynamic,was also investigated.The full-length cDNA and protein(Lc-PHB)from the L.crocea phb gene(Lc-phb)contained 1625 base pairs and 271 amino acids,respec-tively.Lc-PHB had a conserved primary structure that resulted in a transmembrane,SPFH(the analogous region of proteins stomat-ins,prohibitins,flotillins and HflK/C),and coiled-coil domains.It was detected at high levels in the muscle,liver,and heart,and at intermediate levels in the testis,gill,and brain.Lc-phb mRNA expression was detected in spermatogenic cells by fluorescence in situ hybridization.An immunofluorescence assay revealed that PHB protein was localized in the mitochondria during spermatogenesis.Specifically,PHB expression was detected in the perinuclear cytoplasm of spermatogonia,spermatocytes,and spermatids in the early developmental stage,and mainly localized on one side of the nuclei in the cytoplasm of spermatids in a middle developmental stage,and finally on the sperm midpiece.Western blotting showed that PHB was located in the extracted mitochondria protein fraction but not in the cytoplasm protein fraction of testes.Conclusively,these results indicated that PHB was expressed in the mitochondria dur-ing spermatogenesis.In addition,the study explained the mitochondrial dynamic during fish spermatogenesis and proposed a possi-ble relationship among PHB,spermatogenesis,and male fertility. | LIN Chenwen GAO Xinming NI Jie ZHANG Shengshuo LIU Cheng LUO Shengyu DU Chen ZHENG Xuebin HOU Congcong TANG Daojun ZHANG Chundan ZHU Junquan | 2022 | Journal of Ocean University of China2022,21,5: | 0 |