ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Di Ju,Youssef Dewer,Shipan Zhang,Chao Hu,Peirong Li,Xueqing Yang
The codling moth Cydia pomonella L. (Lepidoptera: Tortricidae) is one of the most notorious pests of pome fruits and walnuts worldwide, which has developed resistance to almost all classes of insecticides, including abamectin (ABM). ATP-binding cassette (ABC) transporters are thought to play a vital roles in insecticide detoxification by reducing the toxic concentrations of insecticides in an organism tissues. Despite the tremendous progress in understanding the detoxification mechanisms at the molecular level, the physiological functions of ABC transporters in insects have been poorly investigated. In this study, we found that the ABC inhibitor verapamil synergized significantly the toxicity of ABM, suggesting a potential role of ABC in detoxification. A total of 54 ABC genes were identified in the third-instar larvae of C. pomonella after treatment with sublethal doses (LD 10 and LD 30 ) of ABM. The expression profile of these genes in ABM-treated larvae at different time points (24, 48, 72 hr) using transcriptomic analysis (RNA-seq) was also investigated. The results showed that the expression of about 30 ABC genes was significantly co-upregulated after treatment. Several specific genes were up-regulated at 48 hr after treatment of larvae with LD 10 ABM. Among these up-regulated genes, we found that the relative expression level of the CPOM19553 was 29.7-fold and 16.0-fold higher when larvae were exposed to ABM at the LD 10 and LD 30 doses compared to control, respectively. Unlike other ABC genes, only CPOM08323 exhibited significant expression levels in the head and cuticle of the third-instar larvae of C. pomonella exposed to the two sublethal doses of ABM, with no expression was observed in the detoxification tissues such as midgut and Malpighian tubule. This study suggests that these up-regulated genes may be involved in ABM resistance in C. pomonella . Our findings will provide an additional information required for further analysis of ABC transporter genes associated with xenobiotic metabolism in C. pomonella .
研究领域:
昆虫学
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分子生物学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Nan Fang,Xueping Zhao,Yanjie Li,Yuqin Luo,Xiangyun Wang,Hongmei He,Changpeng Zhang,Jinhua Jiang
Novel pesticides broflanilide (BFI), afidopyropen (ADP), and flupyradifurone (FPO) have been widely used and become the new organic pollutants . However, uptake, translocation and residual distribution of BFI, ADP, and FPO in plants remain unclear. Therefore, residues distribution, uptake, and translocation of BFI, ADP, and FPO were investigated in mustard field trials and hydroponic experiments. The field results indicated that the residues of BFI, ADP, and FPO were 0.001–1.87 mg/kg at 0–21 d and dissipated fast in mustard (half-lives=5.2–11.3 d). More than 66.5 % of FPO residues were distributed in the cell-soluble fractions because of their high hydrophilicity, while hydrophobic BFI and ADP were primarily stored in the cell walls and organelles . The hydroponic data showed that the foliar uptake rates of BFI, ADP, and FPO were weak (bioconcentration factors<1), but the root uptake rate was strong (bioconcentration factors>1). The upward and downward translations of BFI, ADP, and FPO were limited (translation factor<1). BFI and ADP are uptake by roots via apoplast pathway, and FPO is uptake via symplastic pathway. This study contributes to the understanding of the formation of pesticide residues in plants and provides a reference for safe application and risk assessment of BFI, ADP, and FPO.
研究领域:
植物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 21
·3482
·
IF 5.561
Yongmei Li,Lu Li,Jinhong Tian,Fengxin Zheng,Hui Liao,Zean Zhao,Yanyu Chen,Jianxin Pang,Ting Wu
Hyperuricemia (HUA), characterized by abnormal serum uric acid (UA) levels, is recognized as an important risk factor for hyperuricemic nephropathy (HN), which is strongly linked to gut microbiota. This study investigated the protective effects and regulatory mechanisms of insoluble fiber from barley leaves (BL) against HN, induced by adenine (Ad) and potassium oxonate (PO). The results showed that BL dramatically reduced the levels of serum UA and creatinine (CR) and alleviated renal injury and fibrosis. Moreover, BL modulated oxidative stress and downregulated the expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidneys of mice with HN. In addition, the 16S rRNA sequence data showed that BL also increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, includingBacteroides,Alloprevotella, andEisenbergiella. Besides, BL treatment also increased SCFAs levels. Of interest, the application of SCFAs in hyperuricemic mice effectively reduced their serum UA. Furthermore, SCFAs dose-dependently inhibited URAT1 and GLUT9 in vitro and potently interacted with URAT1 and GLUT9 in the docking analysis. When taken together, our results indicate that BL and its metabolite SCFAs may be potential candidates for relieving HUA or HN.Keywords:barley leaf;hyperuricemic nephropathy;gut microbiota;SCFAs;URAT1;GLUT9
研究领域:
营养学
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药理学
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胃肠病学
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肾病学
✓ 已验证
DOI
PubMed
高影响因子
TREE PHYSIOLOGY
·
2024
·
IF 3.5
Liu Jian,Li Jing,Deng Chen,Liu Zhe,Yin Kexin,Zhang Ying,Zhao Ziyan,Zhao Rui,Zhao Nan,Zhou Xiaoyang,Chen Shaoliang
Nitrogen (N) plays an important role in mitigating salt stress in tree species. We investigate the genotypic differences in the uptake of ammonium (NH4+) and nitrate (NO3−) and the importance for salt tolerance in two contrasting poplars, salt-tolerant Populus euphratica and salt-sensitive P. popularis. Total N content, growth, and photosynthesis were significantly reduced in P. popularis after 7 days exposure to NaCl (100 mM) supplied with 1 mM NH4+ and 1 mM NO3−, while the salt effects were not pronounced in P. euphratica. The 15NH4+ trace and root flux profiles showed that salt-stressed poplars retained ammonium uptake, which was related to the up-regulation of ammonium transporters (AMTs) in roots, as two of the four AMTs tested significantly increased in salt-stressed P. euphratica (i.e., AMT1.2, 2.1) and P. popularis (i.e., AMT1.1, 1.6). It should be noted that P. euphratica differs from salt-sensitive poplar in the maintenance of NO3− under salinity. 15NO3− tracing and root flux profiles showed that P. euphratica maintained nitrate uptake and transport, while the capacity to uptake NO3− was limited in salt-sensitive P. popularis. Salt increased the transcription of nitrate transporters (NRTs), NRT1.1, 1.2, 2.4, 3.1, in P. euphratica, while P. popularis showed a decrease in the transcripts of NRT1.1, 2.4, 3.1 after 7 days of salt stress. Furthermore, salt-stimulated transcription of plasmalemma H+-ATPases (HAs), HA2, HA4 and HA11 contributed to H+-pump activation and NO3− uptake in P. euphratica. However, salt stimulation of HAs was less pronounced in P. popularis, where a decrease in HA2 transcripts was observed in the stressed roots. We conclude that the salinity-decreased transcripts of NRTs and HAs reduced the ability to uptake NO3− in P. popularis, resulting in limited nitrogen supply. In comparison, P. euphratica maintains NH4+ and NO3− supply, mitigating the negative effects of salt stress.
研究领域:
植物学
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植物生理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Hangyu Lin,Xiaodong Mao,Yanlin Wei,Songzhang Li,Jianguang Qin,Song Zhu,Shengqi Su,Tao He
Methylmercury (MeHg) readily accumulates in aquatic organisms while transferring and amplifying in the aquatic food chains. This study firstly explores the in vivo accumulation sites and metabolic regulation of MeHg in the rotifer Brachionus plicatilis by aggregation-induced emission fluorogen (AIEgen) and metabolomics. Fluorescent image analysis by AIEgen showed that MeHg in B . plicatilis mainly occured in the ciliary corona, esophagus, mastax, stomach and intestine in the direct absorption group. In the other group, where B . plicatilis were indirectly supplied with MeHg via food intake, the accumulation of MeHg in the rotifer occurred in the ciliary corona, various digestive organs, and the pedal gland. However, the MeHg accumulated in the rotifer is difficult to metabolize outside the body. Metabolomics analysis showed that the significant enrichment of ABC transporters was induced by the direct exposure of rotifers to dissolved MeHg. In contrast, exposure of rotifers to MeHg via food intake appeared to influence carbon, galactose , alanine , aspartate and glutamate metabolisms. Besides, the disturbed biological pathways such as histidine metabolism, beta-alanine metabolism and pantothenate and CoA biosynthesis in rotifers may be associated with L-aspartic acid upregulation in the feeding group. The significant enrichment of ABC transporters and carbon metabolism in rotifers may be related to the accumulation of MeHg in the intestine of rotifers. In both pathways of MeHg exposure, the arginine biosynthesis and metabolism of rotifers were disturbed, which may support the hypothesis that rotifers produce more energy to resist MeHg toxicity. This study provides new insight into the accumulation and toxicity mechanisms of MeHg on marine invertebrates from the macro and micro perspectives.
研究领域:
环境生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2014
·
IF 2.61
Jingze Duan,Yan Xie,Huilin Luo,Guowen Li,Tao Wu,Tong Zhang
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin’s permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added ( p < 0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin’s cellular transport and elaborates isorhamnetin’s absorption mechanisms to provide a foundation for further studies.
研究领域:
药理学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
PHYSIOLOGY AND MOLECULAR BIOLOGY OF PLANTS
·
2025
·
IF 3.3
Wu Mengyao,Wang Haiou,Wang Wenxuan,Ren Xiaoyu,Zhang Juming
Hydroponic experiments and computational simulations were conducted to investigate the changes in the gene expression, structure, and binding mode of the rice transporter protein OsTIL to OPEs by the presence of Cd 2+ and Zn 2+ . OPEs and Zn 2+ were observed to promote seedling growth and OPEs alleviated the suppressive effect of Cd 2+ on seedlings. Usually, Cd 2+ and Zn 2+ inhibited the accumulations of OPEs in plants accompanied by the decrease of RCF (root concentration factor) and TF (transport coefficient). In particular, Zn 2+ promoted TDCPP accumulation only in roots accompanied by the increase of RCF and the decrease of TF. Furthermore, Cd 2+ and Zn 2+ affected the gene expressions of OPEs transporter-OsTIL response in the accumulation of OPEs in both single and compound pollution. After molecular dynamics simulation analysis, RMSD of the protein backbone, binding pocket, and ligand only in TDCPP-OsTIL complex also were significantly affected by two metal ions. Furthermore, two metal ions can press the interaction of OPEs and OsTIL by reducing the stability of protein structure and the numbers of HB (hydrogen bonds) and enlarging the pocket. However, Zn 2+ extra supports an enlarged entrance for TDCPP, which could facilitate the entry of the coordination complex of Zn 2+ with TDCPP into the pocket and improve TDCPP capacity of OsTIL.
研究领域:
植物学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL BOTANY
·
2018
·Vol. 69
·期 10
·2595-2608
·
IF 5.354
Luo Huifeng,Dai Cheng,Li Yongping,Feng Jia,Liu Zhongchi,Kang Chunying
The red color of the foliage and fruit in strawberry comes from anthocyanins stored in the vacuole; however, how this anthocyanin accumulation is regulated remains unclear. A reduced anthocyanin in petioles (rap) mutant was identified in an N-ethyl-N-nitrosourea (ENU) mutagenized population of YW5AF7, a white-fruited variety of the wild strawberry Fragaria vesca. The causative mutation was identified to be a premature stop codon in a glutathione S-transferase (GST) gene. In addition to the foliage coloration, RAP also mediates fruit pigmentation and acts downstream of the fruit-specific transcription factor FvMYB10. Among all eight GST genes in the same subfamily, RAP is most abundantly expressed in the ripening fruit. Expression analysis and transient expression assays demonstrated that RAP is the principal transporter of anthocyanins among the paralogs. Moreover, domain-swap experiments showed that both the N- and C-terminals of RAP are essential for the binding capability of anthocyanins. In addition, transient knock-down of RAP resulted in reduced fruit coloration in cultivated strawberry. Collectively, our results demonstrate that RAP encodes the principal GST transporter of anthocyanins in the strawberry foliage and fruit, and it could be modified to alter the fruit color in strawberry.
研究领域:
植物学
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遗传学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Pharmacology Research & Perspectives
·
2022
·Vol. 10
·期 1
·e00928
·
IF 2.963
Siyuan Cao,Min Zhang,Minyan Yuan,Dan Yang,Mei Zhao,Shuo Zhang,Pengjiao Wang,Rongping Zhang,Xiuli Gao
The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert substances in clinical safety evaluations. However, a large number of studies have shown that pharmaceutical excipients regulate the metabolism and transport of drugs in the body and improve the bioavailability. The pharmaceutical excipient polyethylene glycol 400 (PEG400) as a good solubilizer and surfactant has the potential to improve the bioavailability of drugs. The combined action of UDP-glucuronosyltransferases (UGTs) and efflux transport proteins is responsible for the intestinal disposition and poor bioavailability of baicalein. Our aim is to study the effect of PEG400 on the absorption of baicalein on the Caco-2 monolayer, and confirm the interaction of PEG400 with UGTs (UGT1A8 and UGT1A9) and efflux transports. We initially found that baicalein in the Caco-2 monolayer would be metabolized into glucuronide conjugates BG and B6G under the action of UGT1A8 and UGT1A9 on the endoplasmic reticulum membrane, and then mainly excreted to different sides by acting of MRP and BCRP. The addition of PEG400 significantly accelerated the metabolism of B in Caco-2 cells and increased the penetration of BG and B6G. Furthermore, PEG400 also significantly decreased the efflux ratio of BG and B6G, which was the evidence of the interaction with the efflux transporters. In the in vitro intestinal microsome regeneration system, low concentration PEG400 decreased the K m value of UGT1A8 and UGT1A9 (key enzymes that mediate the production of BG and B6G); high concentration PEG400 enhanced the V max value of UGT1A8 and UGT1A9. In conclusion, our results determined that PEG400 interacted with some UGTs and efflux transporters, which were the main factors affecting the absorption of baicalein.
研究领域:
药学
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药理学
·
药物代谢
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Hongyan Zhang,Jiandong Yu,Lisha Ma,Yue Zhao,Shujun Xu,Jingbin Shi,Ke Qian,Mancang Gu,Hongsheng Tan,Li Xu,Yun Liu,Chaofeng Mu,Yang Xiong
Multi-drug resistance (MDR) in breast cancer poses a great threat to chemotherapy. The expression and function of the ATP binding cassette (ABC) transporter are the major cause of MDR. Herein, a linear polyethylene glycol (PEI) conjugated with dicyandiamide, which called polymeric metformin (PolyMet), was successfully synthesized as a simple and biocompatible polymer of metformin. PolyMet showed the potential to reverse MDR by inhibiting the efflux of the substrate of ATP-binding cassette (ABC) transporter from DOX resistant MCF-7 cells (MCF-7/DOX). To test its MDR reversing effect, PolyMet was combined with DOX to treat mice carrying MCF-7/DOX xenografts. In order to decrease the toxicities of DOX and delivery PolyMet and DOX to tumor at the same time, PolyMet was complexed with poly-γ-glutamic acid-doxorubicin (PGA-DOX) electrostatically at the optimal ratio of 2:3, which were further coated with lipid membrane to form lipid/PolyMet-(PGA-DOX) nanoparticles (LPPD). The particle size of LPPD was 165.8 nm, and the zeta potential was +36.5 mV. LPPD exhibited favorable cytotoxicity and cellular uptake in MCF-7/DOX. Meanwhile, the bioluminescence imaging and immunohistochemical analysis indicated that LPPD effectively conquered DOX-associated MDR by blocking ABC transporters (ABCB1 and ABCC1) via PolyMet. Remarkably, LPPD significantly inhibited the tumor growth and lowered the systemic toxicity in a murine MCF-7/DOX tumor model. This is the first time to reveal that PolyMet can enhance the anti-tumor efficacy of DOX by dampening ABC transporters and activating the AMPK/mTOR pathway, which is a promising strategy for drug-resistant breast cancer therapy.
研究领域:
肿瘤学
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药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Yaodong Yi,Liping Li,Feifeng Song,Ping Li,Mingyang Chen,Shixin Ni,Hengbin Zhang,Hui Zhou,Su Zeng,Huidi Jiang
Oxaliplatin (OXA) is a third-generation platinum drug; however, its application is greatly limited due to the severe peripheral neurotoxicity. This study aims to confirm the transport mechanism of OXA and to explore whether L-tetrahydropalmatine (L-THP) would alleviate OXA-induced peripheral neurotoxicity by selectively inhibiting these uptake transporters in vitro and in vivo . Our results revealed that organic cation transporter 2 (OCT2), organic cation/carnitine transporter 1 (OCTN1) and organic cation/carnitine transporter 2 (OCTN2) were involved in the uptake of OXA in dorsal root ganglion (DRG) neurons and mitochondria, respectively. L-THP (1−100 μM) reduced OXA (40 μM) induced cytotoxicity in MDCK-hOCT2 (Madin–Darby canine kidney, MDCK), MDCK-hOCTN1, MDCK-hOCTN2, and rat primary DRG cells, and decreased the accumulation of OXA in above cells and rat DRG mitochondria, but did not affect its efflux from MDCK-hMRP2 cells. Furthermore, Co-administration of L-THP (5–20 mg/kg for mice, 10–40 mg/kg for rats; twice a week, iv or ig ) attenuated OXA (8 mg/kg for mice, 4 mg/kg for rats; twice a week, iv ) induced peripheral neurotoxicity and reduced the platinum concentration in the DRG. Whereas, L-THP (1−100 μM for cells; 10–20 mg/kg for mice) did not impair the antitumour efficacy of OXA (40 μM for cells; 8 mg/kg for mice) in HT29 tumour-bearing nude mice nor in tumour cells (HT29 and SW620 cells). In conclusion, OCT2, OCTN1 and OCTN2 contribute to OXA uptake in the DRG and mitochondria. L-THP attenuates OXA-induced peripheral neurotoxicity via inhibiting OXA uptake but without impairing the antitumour efficacy of OXA. L-THP is a potential candidate drug to attenuate OXA-induced peripheral neurotoxicity.
研究领域:
药理学
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神经毒理学
·
癌症研究
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药物递送系统
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF APPLIED BIOLOGY
·
2024
·Vol. 185
·期 3
·360-370
·
IF 2.2
Huayang Xu,Hongzhen Zhang,Guoyu Wei,Yuling Jiang,Meto Yao Charles,Anlong Hu
Kasugamycin (KSM), an aminoglycoside antibiotic, has been widely used as a natural fungicide to control plant diseases, particularly for managing rice blast. However, its uptake mechanism and transport in rice remain to be explored. In this article, rice seedlings were treated by the foliar spraying method, and the content of KSM in rice leaves, stems and roots under different treatments was detected by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS), respectively. Results showed that leaf-applied KSM could be transported to the phloem and migrate to roots and stems after uptake by leaves. Concentration, temperature and pH had significant effects on the uptake of KSM. Compared with the control, the competitive inhibitors d -glucose and phlorizin both inhibited the uptake of KSM, demonstrating that sugar transporter proteins were involved in the uptake process. The energy inhibitors dinitrophenol (DNP) and carbonyl cyanide chlorophenylhydrazone (CCCP) also significantly inhibited the uptake of KSM, indicating that the uptake of KSM required energy consumption. Thus, the uptake of KSM by rice was an active process involving sugar transporter proteins, and it could migrate downward through the phloem. This study contributes to the promotion of the scientific application of antibiotics and the biological control of crop diseases. It will also provide a theoretical basis for the development of root-targeted pesticides and transport pesticides with phloem mobility.
研究领域:
植物生理学
·
农药科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）