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1.
Sci Total Environ ; 893: 164881, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37321500

RESUMO

Increasing and widely detected contaminants of emerging concern (CECs) pose a threat to drinking water safety. Compared with traditional methods, the exposure-activity ratio (EAR) method based on the ToxCast database may have unique advantages in risk assessment of drinking water sources because it provides massive multi-target high-throughput screening toxicity effect data assessment for chemicals with missing traditional toxicity data. In this study, 112 CECs at 52 sampling sites in drinking water sources in Zhejiang Province of eastern China were investigated. Based on EARs and occurrence, priority chemicals were identified as difenoconazole (priority level 1), dimethomorph (priority level 2), acetochlor, caffeine, carbamazepine, carbendazim, paclobutrazol and pyrimethanil (priority level 3). Different from single observable biological effect in traditional methods, a variety of observable biological effects caused by high-risk targets were explored through adverse outcomes pathways (AOPs), revealing ecological risks as well as human health risks, for example, hepatocellular adenomas and carcinomas. Furthermore, the difference between the maximum EAR for a given chemical in a sample (EARmax) and the toxicity quotient (TQ) in priority screening of CECs was compared. The results show that screening priority CECs based on the EAR method is acceptable and more sensitive, suggesting the difference between in vitro and in vivo toxic effects and the necessity of incorporating the harm degree of biological effects into the EAR method to screen priority chemicals in the future.


Assuntos
Rotas de Resultados Adversos , Água Potável , Poluentes Químicos da Água , Humanos , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Medição de Risco/métodos
2.
J Nanobiotechnology ; 20(1): 364, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933359

RESUMO

BACKGROUND: Magnetosomes (BMPs) are organelles of magnetotactic bacteria (MTB) that are responsible for mineralizing iron to form magnetite. In addition, BMP is an ideal biomaterial that is widely used in bio- and nano-technological applications, such as drug delivery, tumor detection and therapy, and immunodetection. The use of BMPs to create multifunctional nanocomposites would further expand the range of their applications. RESULTS: In this study, we firstly demonstrate that the extracted BMP can remineralize in vitro when it is exposed to AgNO3 solution, the silver ions (Ag+) were transported into the BMP biomembrane (MM) and mineralized into a silver crystal on one crystal plane of Fe3O4. Resulting in the rapid synthesis of an Ag-Fe3O4 hybrid BMP (BMP-Ag). The synergy between the biomembrane, Fe3O4 crystal, and unmineralized iron enabled the remineralization of BMPs at an Ag+ concentration ≥ 1.0 mg mL-1. The BMP-Ag displayed good biocompatibility and antibacterial activity. At a concentration of 2.0 mg/mL, the BMP-Ag and biomembrane removed Ag-Fe3O4 NPs inhibited the growth of gram-negative and gram-positive bacteria. Thus using BMP-Ag as a wound dressing can effectively enhance the contraction of infected wounds. CONCLUSIONS: This study represents the first successful attempt to remineralize organelles ex vivo, realizing the biosynthesis of hybrid BMP and providing an important advancement in the synthesis technology of multifunctional biological nanocomposites.


Assuntos
Magnetossomos , Óxido Ferroso-Férrico/química , Bactérias Gram-Negativas , Ferro/química , Magnetossomos/química , Prata/química
3.
Int J Nanomedicine ; 17: 665-680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185331

RESUMO

PURPOSE: Nanoparticles (NPs) decorated with functional ligands are promising candidates for cancer diagnosis and treatment. However, numerous studies have shown that chemically coupled targeting moieties on NPs lose their targeting capability in the biological milieu because they are shielded or covered by a "protein corona". Herein, we construct a functional magnetosome that recognizes and targets cancer cells even in the presence of protein corona. METHODS: Magnetosomes (BMPs) were extracted from magnetotactic bacteria, M. gryphiswaldense (MSR-1), and decorated with trastuzumab (TZ) via affibody (RA) and glutaraldehyde (GA). The engineered BMPs are referred to as BMP-RA-TZ and BMP-GA-TZ. Their capacities to combine HER2 were detected by ELISA, the quantity of plasma corona proteins was analyzed using LC-MS. The efficiencies of targeting SK-BR-3 were demonstrated by confocal laser scanning microscopy and flow cytometry. RESULTS: Both engineered BMPs contain up to ~0.2 mg TZ per mg of BMP, while the quantity of HER2 binding to BMP-RA-TZ is three times higher than that binding to BMP-GA-TZ. After incubation with normal human plasma or IgG-supplemented plasma, GA-TZ-containing BMPs have larger hydrated radii and more surface proteins in comparison with RA-TZ-containing BMPs. The TZ-containing BMPs all can be targeted to and internalized in the HER2-overexpressing breast cancer cell line SK-BR-3; however, their targeting efficiencies vary considerably: 50-75% for RA-TZ-containing BMPs and 9-19% for GA-TZ-containing BMPs. BMPs were incubated with plasma (100%) and cancer cells to simulate human in vivo environment. In this milieu, BMP-RA-TZ uptake efficiency of SK-BR-3 reaches nearly 80% (slightly lower than for direct interaction with BMP-RA-TZ), whereas the BMP-GA-TZ uptake efficiency is <17%. CONCLUSION: Application of the RA scaffold promotes and orients the arrangement of targeting ligands and reduces the shielding effect of corona proteins. This strategy improves the targeting capability and drug delivery of NP in a simulated in vivo milieu.


Assuntos
Magnetossomos , Preparações Farmacêuticas , Coroa de Proteína , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Magnetossomos/metabolismo , Coroa de Proteína/metabolismo , Receptor ErbB-2/metabolismo , Trastuzumab/farmacologia
4.
Biotechnol Appl Biochem ; 64(4): 549-554, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27301870

RESUMO

Gene doping can be easily concealed since its product is similar to endogenous protein, making its effective detection very challenging. In this study, we selected insulin-like growth factor I (IGF-I) exogenous gene for gene doping detection. First, the synthetic IGF-I gene was subcloned to recombinant adeno-associated virus (rAAV) plasmid to produce recombinant rAAV2/IGF-I-GFP vectors. Second, in an animal model, rAAV2/IGF-I-GFP vectors were injected into the thigh muscle tissue of mice, and then muscle and blood specimens were sampled at different time points for total DNA isolation. Finally, real-time quantitative PCR was employed to detect the exogenous gene doping of IGF-I. In view of the characteristics of endogenous IGF-I gene sequences, a TaqMan probe was designed at the junction of exons 2 and 3 of IGF-I gene to distinguish it from the exogenous IGF-I gene. In addition, an internal reference control plasmid and its probe were used in PCR to rule out false-positive results through comparison of their threshold cycle (Ct) values. Thus, an accurate exogenous IGF-I gene detection approach was developed in this study.


Assuntos
Fator de Crescimento Insulin-Like I/genética , Reação em Cadeia da Polimerase em Tempo Real , Animais , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos/genética , Humanos , Camundongos , Camundongos Endogâmicos ICR
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