作者：
Li Xiao-Xiao;Ding Shu-Mao;Yang Xu;Yuan Jun-Lin*
期刊：
分析化学,2018年46(1):27-32 ISSN：0253-3820
通讯作者：
Yuan Jun-Lin
作者机构：
[Ding Shu-Mao; Yuan Jun-Lin; Yang Xu; Li Xiao-Xiao] Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Yuan Jun-Lin] C;Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
摘要：
Diisodecyl phthalate (DIDP) is extensively used as an environmentally friendly plasticizer. However, little is known about the adverse effects and the underlying mechanisms of DIDP exposure on immunological diseases. We aimed to determine the role and mechanisms of DIDP exposure in allergic contact dermatitis-like skin lesions. We show that oral DIDP exposure can aggravate allergic dermatitis in mice. Moreover, an increase of ROS, total serum IgE and IL-4 levels were concomitant with this deterioration. We detected the expression of Thymic stromal lymphopoietin (TSLP) and the activation of STATs and NF-kappa B signal pathways. The data indicated that DIDP in combination with FITC triggers TSLP production. Our results also suggested that DIDP exacerbated the activation of NF-kappa B signal pathways, with an enhancement in TSLP expression, which potentiated the activation of STATs and the degranulation of mast cells in the skin, and finally exacerbated allergic dermatitis. The study also suggested that melatonin enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic dermatitis. The results demonstrated that DIDP exacerbated allergic dermatitis through oxidative stress and enhanced TSLP production. (C) 2016 Elsevier Ltd. All rights reserved.
作者机构：
[Chen, Mingqing; Yang, Xu; Kang, Jun] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Ding, Yong; Li, Baizhan; Liu, Hong] Chongqing Univ, Key Lab Gorges Reservoir Reg Ecoenvironm 3, Minist Educ, Chongqing 400045, Peoples R China.
通讯机构：
[Chen, Mingqing] C;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
摘要：
The possible pathogenic role and mechanism of Di-iso-nonyl phthalate (DINP) in allergic dermatitis is still controversial. This work has shown that oral exposure to DINP exacerbated allergic dermatitis tissue lesions in FITC-sensitized mice. The lesions was accompanied by an enhancement of TRPA1 expression and an increase in IgG1, IL-6 and IL-13 levels. This work also found that blocking TRPA1 by HC030031 effectively prevented the development of allergic dermatitis resulting from oral exposure to DINP and/or FITC-sensitized mice. This result is marked by the down regulation of IgG1 levels, a reduction in mast cell degranulation and a decrease in IL-6 and IL-13 levels. We also showed that blocking NF-κB inhibited TRPA1 expression, and that blocking TRPA1 had no significant effect on the activation of NF-κB or TSLP expression. This study helps in understanding the role DINP exposure plays in the development of allergic dermatitis and provides new insight into the mechanisms behind the DINP-induced adjuvant effect.
作者机构：
[卢美玲; 李睿; 赵云; 朱雨晴; Ge, Jing; 江清英; 杨旭; 郭晴] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China
通讯机构：
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
摘要：
Mono-butyl phthalate (MBP) has reproductive toxicity but the related mechanisms have not been fully elucidated in vivo. We exposed male Balb/c mice to MBP by gavage at doses of 0, 25, 50, 100, 200 mg/kg for 14 days, and then evaluated the testicular alterations at the histological and molecular levels. MBP reduced mouse sperm count along with sperm malformation and seminiferous tubule degeneration in a dose-dependent manner. MBP dosed at 200 mg/kg significantly increased reactive oxygen species and malondialdehyde content in mouse testes. High doses of MBP (200 mg/kg) also significantly reduced mRNA expressions of testis growth and function related genes (Sox9 and Dazl). Our findings suggest that oxidative stress and down-regulated expression of Sox9 and Dazl may play important roles in MBP-induced testis injury.
作者机构：
[Li, Jinquan; Chen, Hanqing; Chai, Zhifang; Wang, Bing; Feng, Weiyue; Cai, Chengxu] Chinese Acad Sci, Inst High Energy Phys, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China.;[Li, Jinquan; Yang, Xu] Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Sect Environm Biomed, Wuhan 430079, Peoples R China.;[Cai, Chengxu] Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China.
通讯机构：
[Feng, Weiyue; Yang, Xu] C;Chinese Acad Sci, Inst High Energy Phys, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China.;Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Sect Environm Biomed, Wuhan 430079, Peoples R China.
摘要：
Inflammatory bowel diseases (IBD) are widespread inflammatory diseases that cause debilitating health problems including cancer. In this study, we show that ZnO nanoparticle (ZnONP) treatment has markedly dose-dependent effects on the remission of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We demonstrate the mechanism involves the antioxidant and anti-inflammatory abilities of ZnONPs to suppress ROS and malondialdehyde (MDA) production; increase GSH level; suppress proinflammatory cytokines IL-1β and TNF-α and myeloperoxidase (MPO). The ZnONP treatment is able to activate the Nrf2 pathway in the cellular antioxidant defense system. The novel finding is that ZnONP combined with mesalazine (5-ASA) can enhance the therapeutic efficacy of 5-ASA in the treatment of DSS-induced colitis. Lastly, we found that ZnONP treatment can restore the changes in special colonic bacteria of DSS-mice while the drug 5-ASA cannot. These results indicate that ZnONPs can act as a medical additive for the therapy of IBD.
作者机构：
[Wu, Yang; Li, Yan; Wang, Peng-Cheng; Gong, Zhi-Yong] Wuhan Polytech Univ, Coll Food Sci & Engn, Minist Educ, Key Lab Deep Proc Major Grain & Oil, Wuhan 430023, Hubei, Peoples R China.;[Yang, Xu] Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.;[Pi, Qing-Meng] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;[Li, Yan] Yale Univ, Sch Engn & Appl Sci, Dept Biomed Engn, New Haven, CT 06520 USA.;[Pi, Qing-Meng] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Orthoped Surg, Shanghai 200233, Peoples R China.
通讯机构：
[Wu, Yang] W;[Yang, Xu] C;Wuhan Polytech Univ, Coll Food Sci & Engn, Minist Educ, Key Lab Deep Proc Major Grain & Oil, Wuhan 430023, Hubei, Peoples R China.;Cent China Normal Univ, Coll Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
摘要：
Exposure to ambient fine particulate matter (FPM) has been thought to be associated with cardiovascular disease. However, the pathogenesis remains largely unknown. Animal models have been widely used in toxicological research, but species difference makes it impossible to directly translate discoveries from animals to humans. In this study, we developed a 3D functional human microvascular network in a microfluidic device. The established model enables endothelial cells to form vessel-like microtissues and have physiological functions which are closer to cells in human blood vessels. The perfusable microvasculature allows the delivery of nutrients, and oxygen, as well as flow-induced mechanical stimuli into the luminal space of the endothelium. The microflow effectively mimic the blood flow in human vessels. FPMs were introduced into this physiologically human vessel-like microenvironment following the fluid flow. The vascular toxicity was evaluated based on this organotypic 3D microvessel model. Our results demonstrated that intravascular accumulation of FPM could enhance ROS generation which may further cause endothelial dysfunction by oxidative stress. This is expressed in disorder of NO expression and IL-6 up-regulation. These are expected to enhance endothelial inflammation which might in turn accelerate coagulation that is associated with thrombosis. Human organotypic 3D microvessel models provide a possible bridge for how the research outcomes translate to humans. These models could partly simulate the physiological responses of human vessels to FPM stimulation. This simple and versatile platform can be used for a wide range of applications in vascular physiology studies of particulate matter in the context of cardiovascular disease.
期刊：
Toxicology and Applied Pharmacology,2017年324(2):36-44 ISSN：0041-008X
通讯作者：
Xiang, Shuanglin;Yang, Xu
作者机构：
[Chen, Mouying; Wei, Chenxi; Qiu, Feng; Xiang, Shuanglin] Hunan Normal Univ, Sch Life Sci, Key Lab Ecol Safety Monitoring & Evaluat, Changsha 410081, Hunan, Peoples R China.;[Wei, Chenxi; Yuan, Junlin; You, Huihui; Wen, Huaxiao; Yang, Xu] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Sect Environm Biomed, Wuhan 430079, Hubei, Peoples R China.;[Yang, Xu] Cent China Normal Univ, Sch Life Sci, 152 Luo Yu Rd, Wuhan 430079, Hubei, Peoples R China.;[Xiang, Shuanglin] Hunan Normal Univ, Sch Life Sci, 36 Lu Shan Rd, Changsha 410081, Hunan, Peoples R China.
通讯机构：
[Xiang, Shuanglin] H;[Yang, Xu] C;Hunan Normal Univ, Sch Life Sci, 36 Lu Shan Rd, Changsha 410081, Hunan, Peoples R China.;Cent China Normal Univ, Sch Life Sci, 152 Luo Yu Rd, Wuhan 430079, Hubei, Peoples R China.
摘要：
Formaldehyde (FA) is a human leukemogen. Since there is a latency period between initial FA exposure and the development of leukemia, the subsequent impact of FA on hematopoietic stem or progenitor cells (HSCs/HPCs) in post-exposure stage is crucial for a deep understanding of FA-induced hematotoxicity. BALB/c mice were exposed to 3 mg/m(3) FA for 2 weeks, mimicking occupational exposure, and were monitored for another 7 days post-exposure. Meanwhile, we included benzene (BZ) as a positive control, separately and together with FA because co-exposure occurs frequently. After 7-day recovery, colonies of progenitors for CFU-GM and BFU-E, and nucleated bone marrow cells in FA-exposed mice were comparable to controls, although they were significantly reduced during exposure. Levels of reactive oxygen species (ROS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in CFU-GM and BFU-E from FA-exposed mice were higher than controls, although the increase in 8-OHdG was not significant. Granulocyte-macrophage colony stimulating factor (GM-CSF) level in the FA group was lower than controls, but the expression level for the receptor was not upregulated. It suggests that HSCs/HPCs in FA-exposed mice respond to a small amount of GM-CSF and proliferate rapidly, which may cause a possible risk of expansion of abnormal stem/progenitor cell clones. FA co-exposure with BZ was more potent for promoting CFU-GM formation and inducing ROS in BFU-E and 8-OHdG in CFU-GM during the post-exposure period. The compensation of myeloid progenitors with elevated ROS and 8-OHdG may lead to a risk of transforming normal HSCs/HPCs to leukemic stem/progenitor cells. Thus, co-exposure may pose a greater leukemia risk. (C) 2017 Elsevier Inc. All rights reserved.
