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SCIENCE OF THE TOTAL ENVIRONMENT · 2021 · IF 7.963

Carboxylesterases from bacterial enrichment culture degrade strobilurin fungicides

Weijun Wang,Zixi Zhao,Hai Yan,Haiyang Zhang,Qing X. Li,Xiaolu Liu

Strobilurin fungicides are a class of persistent fungicides frequently detected in the environment. Microbes can effectively degrade strobilurins, but the mechanisms are complex and diverse. Compared with isolated strains, bacterial consortia are more robust in terms of the degradation of multiple pollutants. The enrichment culture XS19 is a group of bacterial strains enriched from soil and degrades six strobilurins at 50 mg/L within 8 d, including azoxystrobin , picoxystrobin, trifloxystrobin, kresoxim-methyl, pyraclostrobin and enestroburin. LC-Q-TOF-MS analysis confirmed that XS19 can demethylate these strobilurins via hydrolysis of the methyl ester group. Analysis of the bacterial communities suggested that Pseudomonas (69.8%), Sphingobacterium (21.2%), Delftia (6.3%), and Achromobacter (1.6%) spp. were highly associated with the removal of strobilurins in the system. Metagenomics-based comprehensive analysis of XS19 suggested that carboxylesterases in Pseudomonas and Sphingobacterium play a central role in the catabolism of strobilurins. Moreover, the carboxylesterase inhibitor bis- p -nitrophenyl phosphate inhibited the degradation activity of strobilurins in XS19. This work proved that XS19 or carboxylesterases can effectively hydrolyze strobilurins, providing a reliable bioremediation paradigm.

研究领域: 环境科学 · 微生物学
✓ 已验证 DOI 高影响因子
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TOXICOLOGY AND APPLIED PHARMACOLOGY · 2017 · IF 3.791

Assessment of the inhibitory effects of pyrethroids against human carboxylesterases

Wei Lei,Dan-Dan Wang,Tong-Yi Dou,Jie Hou,Liang Feng,Heng Yin,Qun Luo,Jie Sun,Guang-Bo Ge,Ling Yang

Pyrethroids are broad-spectrum insecticides that widely used in many countries, while humans may be exposed to these toxins by drinking or eating pesticide-contaminated foods. This study aimed to investigate the inhibitory effects of six commonly used pyrethroids against two major human carboxylesterases (CES) including CES1 and CES2. Three optical probe substrates for CES1 (DME, BMBT and DMCB) and a fluorescent probe substrate for CES2 (DDAB) were used to characterize the inhibitory effects of these pyrethroids. The results demonstrated that most of the tested pyrethroids showed moderate to weak inhibitory effects against both CES1 and CES2, but deltamethrin displayed strong inhibition towards CES1. The IC 50 values of deltamethrin against CES1-mediated BMBT , DME, and DMCB hydrolysis were determined as 1.58   μM, 2.39   μM, and 3.3   μM, respectively. Moreover, deltamethrin was cell membrane permeable and capable of inhibition endogenous CES1 in living cells. Further investigation revealed that deltamethrin inhibited CES1-mediated BMBT hydrolysis via competitive manner but noncompetitively inhibited DME or DMCB hydrolysis. The inhibition behaviors of deltamethrin against CES1 were also studied by molecular docking simulation . The results demonstrated that CES1 had at least two different ligand-binding sites, one was the DME site and another was the BMBT site which was identical to the binding site of deltamethrin. In summary, deltamethrin was a strong reversible inhibitor against CES1 and it could tightly bind on CES1 at the same ligand-binding site as BMBT. These findings are helpful for the deep understanding of the interactions between xenobiotics and CES1.

研究领域: 毒理学 · 药理学 · 生物化学
✓ 已验证 DOI 高影响因子
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Developing a photoacoustic probe for in vivo imaging of carboxylesterase in lipid metabolic disorders

Kai Wang,Miao-Yan Wang,Chen-Xi Cao,Yu-Shun Yang,Ai-Guo Zhang,Ping-Gui Li,Chen-Yang Han,Hao-Xiang Jiang

Recent investigations have revealed the tight connections between carboxylesterase (CE) and the lipid metabolism-associated disorders. In this work, based on the previous reports, a photoacoustic (PA) probe Hcy-CE was developed for the in vivo imaging of CE in two lipid metabolism disorders. The reaction with CE led to the departure of the carbamate quencher together with the linkage, thus to release of the reporter Hcy to exhibit the turn-on signals of PA reporting accompanied with the absorbance and fluorescence modes. The responses in all three modes showed high consistency. In the PA mode, the linear correlation range was CE level 0–10 U/L, while the limit of detection value was 0.52 U/mL. The optical performance of the probe Hcy-CE in the solution system was practical with high steadiness and selectivity. Moreover, Hcy-CE exhibited potential capability of monitoring the CE level in the induced foam cells. In particular, Hcy-CE realized the in vivo imaging of the CE level from multiple views and continuous cross-sections in the model mice of different groups. The combination of the PA imaging with the blood biochemical tests and immunohistochemically staining methods might help distinguish the three statuses of different mice from each other. This work provided meaningful information for the accurate diagnosis and regulation of the lipid metabolism-related disorders.

研究领域: 生物医学工程 · 分子生物学 · 成像科学
✓ 已验证 DOI 高影响因子
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JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY · 2023 · IF 2.8

Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate Mofetil

Qingfeng Xie,Zhuo Cao,Weiling You,Xiaoping Cai,Mei Shen,Zhangyong Yin,Yiwei Jiang,Xin Wang,Siyu Ye

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.

研究领域: 肿瘤学 · 药理学 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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