目的:研究正常小鼠妊娠第7 d子宫和淋巴结的淋巴细胞归巢分子[周围淋巴结地址素(PNAd)和血管细胞粘附分子-1(VCAM-1)]的分布。方法:应用免疫组化染色观察C57Bl/6小鼠妊娠第7 d PNAd和VCAM-1在子宫和淋巴结的表达。结果:在小鼠妊娠第7 d...目的:研究正常小鼠妊娠第7 d子宫和淋巴结的淋巴细胞归巢分子[周围淋巴结地址素(PNAd)和血管细胞粘附分子-1(VCAM-1)]的分布。方法:应用免疫组化染色观察C57Bl/6小鼠妊娠第7 d PNAd和VCAM-1在子宫和淋巴结的表达。结果:在小鼠妊娠第7 d中,PNAd强表达于外周淋巴结高内皮静脉血管的内皮细胞,但在子宫,仅弱表达于子宫内膜上皮;VCAM-1弱表达于淋巴结部分血管内皮、淋巴细胞,但广泛表达于子宫的各层血管内皮。结论:PNAd和VCAM-1在小鼠妊娠第7 d子宫和淋巴结有各自的分布特点,可能与妊娠期淋巴细胞的分布有关。展开更多
Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting...Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.展开更多
基金This work was partially supported by grants from the National Natural Science Foundation of China(Nos.31971302 and 82170532)the Natural Science Foundation of Guangdong Province of China(No.2019A1515011597)+2 种基金the talent young scientist supporting program of China Association for Science and Technology,the Educational Commission of Guangdong Province of China key Project(No.2020ZDZX2001)the joint grant between Guangzhou City and College(No.202102010106)Guangzhou Science and Technology Plan Project(No.202201011509).
文摘Patients with ulcerative colitis(UC)often loss responses over long term usage of conventional therapies.Tofacitinib,a pan-Janus kinases(JAK)inhibitor is approved for moderate to severe UC treatment,while dose-limiting systemic side effects including infections,cancers and lymphoma limit its popularity of clinical application.This study sought to construct an anti-mucosal vascular addressin cell-adhesion molecule-1(anti-MAdCAM-1)antibody modified reactive oxygen species(ROS)responsive human serum albumin-based nanomedicine denoted as THM,to improve the therapeutic efficacy of tofacitinib for UC treatment.THM has the drug releasing properties in response to ROS stimulation.In vitro studies show that THM selectively adhered to the endothelial cells and had obvious anti-inflammatory effect on macrophages.Meanwhile,the nanomedicine can inhibit the phenotypic switching of M1 macrophages and promote M2 polarization to produce anti-inflammatory medicators during wound healing.In addition,in vivo fluorescence imaging verified that THM exhibited enhanced preferential accumulation and extended retention in inflamed colon.Moreover,THM significantly reduced the production of proinflammatory cytokines in the colon and suppressed the homing of T cells to the gut in dextran sodium sulfate induced experimental colitis.This work elucidates that the inflamed colon-targeted delivery of tofacitinib by nanomedicine is promising for UC treatment and sheds light on addressing the unmet medical need.
