NEUROTOXICOLOGY
·
2015
·
IF 3.379
Lihua Hu,Chuanyang Su,Xiufang Song,Qiong Shi,Juanli Fu,Xiaomin Xia,Demei Xu,Erqun Song,Yang Song
Although there are few studies suggested PCP exposure induced developmental and behavioral disorders, however, the occurrence of neurotoxicity and PCP has not been firmly established. Tetrachlorobenzoquinone (TCBQ) is a reactive metabolite of environmental pollutant pentachlorophenol (PCP). To the best of our knowledge, there has no information regarding to the neurological toxic effect of TCBQ available. Here, we demonstrated that TCBQ induces cytotoxicity in pheochromocytoma PC12 cell line, and the mode-of-action analysis indicated the involvement of apoptotic signalings, such as the activation of caspase family proteins, the increased expressions of Fas and Fas-associated death domain (FADD), the loss of mitochondrial membrane potential (MMP), the release of cytochrome c (Cyt c ) and the cleavage of the caspase substrates poly(ADP-ribose) polymerase (PARP). BI-6C9, a specific BH3-interacting domain death agonist (Bid) inhibitor, repressed TCBQ-induced Bid truncation, along with the activation of caspase 3 and the release of Cyt c , suggested the cross-talk of extrinsic and intrinsic apoptotic signalings. Furthermore, the inhibition of caspase 8 impaired TCBQ-induced the activation of caspase 3, as well as the release of Cyt c and the cleavage of Bid, suggesting caspase 8 acting as the upstream molecule of Bid, and TCBQ-induced apoptosis is initiated via caspase 8, leads to the activation of caspase 9/3 through Bid-mediated amplification loop. Finally, the pretreatment of antioxidant NAC ameliorated Fas, FADD and caspase 8/3 expressions, which illustrated that TCBQ-induced apoptotic signaling is ROS dependent. Taken together, these results indicated that the cleavage of Bid may play an important role in TCBQ-induced neurotoxicity which promotes the cross-talk of extrinsic and intrinsic apoptotic signalings in PC12 cells.
研究领域:
毒理学
·
神经科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2022
·Vol. 33
·期 43
·435101
·
IF 3.953
Meng Lan,Zhaodi Kong,Fengjie Liu,Tengteng Zou,Lihong Li,Tiange Cai,Huaqin Tian,Yu Cai
Abnormal apoptosis can lead to uncontrolled cell growth, aberrant homeostasis or the accumulation of mutations. Therapeutic agents that re-establish the normal functions of apoptotic signaling pathways offer an attractive strategy for the treatment of breast cancer. Baicalin (BA) is one of the natural compounds with anti-proliferation and pro-apoptosis activities against numerous tumor cells. However, low bioavailability restricts the clinical application of BA. In order to improve its therapeutic efficacy and study the mechanism of actions, active targeting delivery systems were developed for targeting tumor environment and selective cell killing effects. It emphasized on the construction of folate-conjugated albumin nanoparticles loaded with baicalin (FA-BSANPs/BA) and mechanisms of which on the promotion of breast cancer apoptosis. The physicochemical properties and structural characteristics of FA-BSANPs/BA were investigated. Cell experiments were carried out to study the targeted anti-breast cancer effects of FA-BSANPs/BA and its mechanism. The results showed that FA-BSANPs/BA was successfully constructed with stable structural characteristics and sustained release effects. Cellular uptake and MTT showed that it increased targeted uptake efficiency and cytotoxicity. Flow cytometry and western blot confirmed that it promoted apoptosis by increasing the expression of caspase-8 and ROS, and decreasing the level of Bid. It is suggested that the pro-apoptotic mechanism of FA-BSANPs/BA is related to regulation of key proteins in extrinsic apoptotic pathway. In conclusion, FA-BSANPs/BA is a good delivery carrier and significantly inhibits the breast cancer growth compared with free BA. The mechanism of FA-BSANPs/BA promoting apoptosis of breast cancer may be due to its action on the caspase-8/Bid/ROS pathway.
研究领域:
肿瘤学
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药理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Buildings
·
2021
·Vol. 11
·期 8
·363
·
IF 2.648
Liang Xiao,Kunhui Ye,Junhong Zhou,Xiaoting Ye,Ramadhani Said Tekka
Collusive bidding has been an insidious issue in the construction industry. Bidders initiate collusive networks of various sizes to win market shares. The popularity of collusive bidding networks affects market fairness and erodes the interests of market players. Although considerable research efforts were made to diagnose collusive bidding networks, there remains a gap in knowledge regarding the relationships bid riggers use to engage in the networks. Therefore, this study used the social network method, where two hundred sixteen collusion cases were collected from China to test these relationships. The results show that collusive bidding networks were characterized by sparseness, a small scale, a high concentration, and strong randomness. Three types of collusive bidding networks were also detected: contractual, spontaneous, and shadow. Furthermore, these collusive bidding networks had discrepancies regarding participants’ identities, forms of collusive bids, and the determination of bid winners. It was found that the proposed social network model of deliberating bid riggers’ relationships lays a solid foundation for the detection of collusive bidding in the construction sector.
研究领域:
管理科学
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建筑工程
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产业经济学
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反垄断监管
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社会治理
✓ 已验证
DOI
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2017
·Vol. 181
·期 1
·62-70
·
IF 2.399
Zhang Hui,Chang Zhenyu,Mehmood Khalid,Abbas Rao Zahid,Nabi Fazul,Rehman Mujeeb Ur,Wu Xiaoxing,Tian Xinxin,Yuan Xiaodan,Li Zhaoyang,Zhou Donghai
Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40–100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly ( P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.
研究领域:
细胞生物学
·
毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子