SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
·
IF 10.753
Fangwei Yang,Yixuan Li,Yunfei Xie,Weirong Yao,Fazheng Ren
Plenty of population epidemiology and cohort studies have found dialkyl phosphates (DAPs) in the urine were related to endocrine hormone disorders. However, we did not know whether these effects were caused by parent organophosphorus pesticides (OPs) or metabolite DAPs, especially the non-specific metabolite diethyl phosphate (DEP), which was the metabolic end product of most widely used diethyl OPs. In this study, animal experiments ( in vivo ), cell experiments ( in vitro ), small molecule-protein binding interaction experiments and computer molecular simulations ( in silico ) were used to explore the disturbing effects and molecular mechanisms of DEP on the hypothalamic-pituitary-adrenal (HPA) axis endocrine hormones. The animal experiments showed that chronic DEP exposure significantly disturbed the serum contents of HPA axis hormones in adult male rats. The target genes of glucocorticoid receptor (GR) in rat liver, including 11β-hsd1 and Pepck1 and PEPCK protein expressions, were down-regulated. Moreover, the gluconeogenic abilities of rats were impaired. However, it did not affect the expression of GR in the rat hypothalamus. These results indicated that the physiological functions of glucocorticoids and GR were damaged. Furthermore, spectroscopy experiments, cell experiments, molecular docking and molecular dynamics simulations also suggested that DEP can bind to nuclear receptors GR and Nur77, affecting their transcription factor functions, and the transcriptional expression levels of their downstream target genes were reduced. The biosynthesis and secretion of adrenocorticotropic hormone and glucocorticoids were blocked. Therefore, DEP can inhibit the production and physiological functions of HPA axis endocrine hormones by disrupting these related proteins and antagonizing nuclear receptors. These results were considered to provide a theoretical basis for strictly controlling the residue limits of OPs and their metabolites in foods, agricultural products and the environment. They also revealed new targets for evaluating the toxicities and risks of pesticide metabolites.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Chemistry
·
2023
·
IF 3
Yan Li,Yuqing Wang,Zhiqiang Zhao,Yunxia Li,Cheng Peng,Jianming Wu
A preliminary study has shown that 3, 8-Di-O-methylellagic acid 2-O-glucoside (DMAG), an ellagic tannin from Sanguisorba officinalis L., has the potential in relieving thrombocytopenia. However, there is a lack of information on the pharmacokinetics of DMAG in thrombocytopenia rats. Therefore, we aimed to establish a simple, rapid, and sensitive UHPLC-MS/MS method for quantifying DMAG and study its pharmacokinetic behavior in this study. DMAG and hispidulin (internal standard, IS) were separated on an Acquity Shim-pack GIST column using 0.1% formic acid in water and acetonitrile as the mobile phase with a total run time of 5 min and gradient elution at a flow rate of 0.3 mL/min. The recovery and matrix effects of DMAG were within 94.85%–100.40% and 94.55%–102.46%, respectively. The intraday RSD and interday RSD were between 3.31% and 13.19%, accuracy RE was ≤6.69%, and stability RSD changes were 3.38%–8.78%. As for intragastric administration, with shortened Tmax (3.00 vs. 2.16 h), Cmax (25.67 vs. 35.38 ng/mL) was added for a 2 mg/kg dose after the establishment of the thrombocytopenia rat model. Relative to normal rats treated with 4 mg/kg, in thrombocytopenia rats treated with the same dose, Cmax (49.13 vs. 67.78 ng/mL), AUC(0–t) (234.60 vs. 318.17 ng·h/mL), and AUC(0–∞) (322.74 vs. 498.57 ng h/mL) increased, MRT (18.15 vs. 26.32 h) prolonged, Tmax (3.00 vs. 2.33 h) shortened, and CL/F (12746.50 vs. 8093.50 mL/h/kg) reduced. As for intravenous administration, Cmax (1679.54 ng/mL), AUC(0–t) (589.02 g·h/mL), and AUC(0–∞) (605.58 g·h/mL) were significantly increased in thrombocytopenia rats than that in normal rats (743.76 ng/mL for Cmax, 242.46 g·h/mL for AUC(0–t), and 245.19 g·h/mL for AUC(0–∞)). Vz/F and CL/F were remarkably decreased from 343196.86 to 194659.43 mL/kg for Vz/F and 8236.18 to 3326.01 mL/h/kg for CL/F with the model establishment, respectively. Overall, we successfully developed a reliable UHPLC-MS/MS method for determining DMAG levels in rat plasma. The pharmacokinetic difference could be attributed to the pathological state of the thrombocytopenia rats, which may affect the absorption, distribution, metabolism, and excretion of DMAG. These findings lay the foundation for further evaluating the clinical efficiency and safety of DMAG in the treatment of thrombocytopenia.
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Wei Wang,Chao Liu,Zheng Luo,Xiaocao Wan,Liang Fang
The aim of present study was to develop an oxybutynin (OXY) transdermal patch with good permeation behavior and mechanical property. Special attention was paid to the effect of chemical enhancer on the molecular mobility of pressure sensitive adhesive (PSA) at molecular level. PSAs and permeation enhancers were investigated through in vitro experiment using rat skin. The optimized formulation was evaluated through pharmacokinetic study using rat. In addition, the molecular mechanism of sorbitan monooleate (Span® 80) in the improvement of PSA molecular mobility was investigated using FT-IR, molecular dynamics simulation, DSC and rheological study. As a result, the optimized formulation using amide PSA demonstrated good adhesion property. And the AUC 0-t and C max of optimized patch were 6435.8 ± 747.8 h ∗ ng/mL and 127.8 ± 18.0 ng/mL, respectively, which had no significant difference with commercial product. Furthermore, the improvement of the PSA mobility by Span® 80 rather than the decrease of interaction between drug and PSA was the main factor that enhanced the release of OXY from patch. In conclusion, a drug-in-adhesive OXY patch was developed, and the effect of PSA molecular mobility increase on the enhancement of drug skin permeation was proposed at molecular level.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2013
·
IF 3.498
Junling Zhang,Gang Chen,Miaomiao Tian,Ruigang Li,Xinjun Quan,Qiong Jia
γ-Alumina nanoparticles (γ-Al 2 O 3 ) were introduced to the conventional poly(methacrylic acid- co -ethylene glycol dimethacrylate) (MAA- co -EGDMA) monolith to prepare a novel organic-inorganic hybrid monolith, poly(MAA- co -EGDMA)-Al 2 O 3 monolith. The polymerization was induced in-situ with UV irradiation in an ultraviolet transparent polymethyl methacrylate (PMMA) microfluidic chip. The monolith-based solid phase microextraction system was used for the on-line determination of 2-amino-4-chlorophenol (ACP) in chlorzoxazone tablets coupled with an optical fiber spectrophotometer. Several parameters affecting the adsorption/desorption, including sample pH value, sample flow rate , sampling time, eluent flow rate, and eluting time, were investigated in detail. Under the optimized conditions, limit of detection (LOD) and limit of quantification (LOQ) of the method were calculated to be 2.8 and 9.1 µg L −1 , respectively, with the relative standard deviation (RSD) of 3.1%.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Rong-Xin Song,Xiao-Yi Ma,Ting-Ting Zhou,Zhi-Fang Yu,Jun Wang,Bao-Dong Li,Yu-Mo Jing,Han Wang,Yue Fu,Rui-Zhao Lv,Shi-Yan Jia,Xiao-Ming Li,Li-Min Zhang
Objective Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H 2 S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl- d -Aspartate (NMDA) receptor function. Methods Mice were immediately administered dl -propargylglycine (PAG) intragastrically as an H 2 S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. Results Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H 2 S-induced intestinal and cerebral injury. Conclusion This experimental data suggests that H 2 S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Minerals Metallurgy and Materials
·
2024
·Vol. 31
·期 4
·665-677
·
IF 5.6
Mweene Levie,Hong Gilsang,Jeong Hee-Eun,Kang Hee-won,Kim Hyunjung
Comparative experiments and theoretical analysis of the surface chemistry changes of goethite (GT) and goethite containing Ni (GTN) in the lattice in the presence of salicylhydroxamic acid (SA) were performed. It was revealed that in the presence of 100 g·t −1 of SA, the flotation recovery of GTN and GT increased with increasing pH, achieving a maximum recovery of 98.9% for both minerals at pH 8.3 and decreasing beyond that pH, with GTN having a slightly higher recovery than GT, except at pH 8.3. This was further confirmed by the higher complexation energies of GTN⋯SA (−883.87 kJ·mol −1 ) compared with GT⋯SA (−604.23 kJ·mol −1 ) resulting from covalent, closed-shell, and conventional hydrogen bonding. The higher adsorption of SA onto GTN relative to GT was due to the formation of a π-hole in GTN, thereby promoting a higher interaction of the collector with the mineral. Thus, the presence of Ni in the GT lattice improves and decreases the adsorption and desorption of SA onto and from the mineral, respectively, compared with those onto and from GT.
✓ 已验证
产品关联
DOI
高影响因子
ENERGY & FUELS
·
2024
·
IF 5.2
Zhuo-Yi Huang,Chun-Gang Xu,Xiao-Sen Li,Yun-Hao Li,Yi Wang,Zhao-Yang Chen
Hydrate-based carbon dioxide (CO2) sequestration in the deep sea or marine strata is an important process in achieving carbon emission reduction. However, the micro mechanism of gas hydrate formation in a seawater system has not yet reached consensus, which restricts the development of the hydrate-based CO2 sequestration. The basic process of water conversion into hydrates is the transformation from disordered water molecules to a structurally ordered state under specific conditions. The influence mechanism of CO2 hydrate formation in seawater in the presence of solid promoters with or without chemical functional group modification was systematically investigated by combining in situ Raman analysis with macroscopic experiments. The results indicate that the hydrate formation is determined by the transformation from weak hydrogen bonds to strong hydrogen bonds; hydroxyl groups help improve the promoting effect, and the acidity of the solution increases due to the retention of CO2 in the solution, which inhibits the secondary formation of CO2 hydrates.
✓ 已验证
产品关联
DOI
高影响因子
GREEN CHEMISTRY
·
2024
·Vol. 26
·期 4
·2011-2020
·
IF 9.3
Lixia Wang,Xinran Hu,Huatong Li,Zhiyang Huang,Jia Huang,Tayirjan Taylor Isimjan,Xiulin Yang
Deliberate engineering of built-in electric fields (BEFs) can facilitate electron transfer and promote asymmetrical charge distribution, thereby regulating the adsorption/desorption of reaction intermediates. Herein, an oxygen-deficiency-rich MnO-CeO2 is synthetized supported on a carbon sphere (MnO-CeO2@Cs), adeptly crafted with a prominent work function difference (ΔΦ) and robust BEF, targeting the electrocatalytic oxygen reduction reaction (ORR). Empirical and theoretical results substantiate that the BEF triggers interfacial charge redistribution, fine-tuning the adsorption energy of oxygen intermediates and hastening reaction kinetics. Consequently, the MnO-CeO2@Cs showcases commendable performance (E1/2 = 0.80 V and jL = 5.5 mA cm−2), outshining its single-component counterparts. Impressively, the MnO-CeO2@Cs-based zinc–air batteries (ZABs) boast an exemplary power density of 202.7 mW cm−2 and enduring stability of 297 h. Additionally, the solid-state ZAB commands a peak power density of 67.4 mW cm−2, underscoring its potential in flexible ZAB applications. This work delineates a strategic avenue to harness interfacial charge redistribution, aiming to enhance the catalytic performance and longevity of energy conversion/storage apparatuses.
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jingyi Zheng,Lixin Ding,Junjie Yi,Linyan Zhou,Lei Zhao,Shengbao Cai
This study investigated the effects of oil phases on the encapsulation rate, storage stability, and bioavailability of astaxanthin (ASTA) in Pickering emulsions (PEs). Results showed PEs of mixed oils (olive oil/edible tea oil) had excellent encapsulation efficiency (about 96.0%) and storage stability of ASTA. In vitro simulated gastrointestinal digestion results showed the mixed oil PE with a smaller interfacial area and higher monounsaturated fatty acid content may play a better role in improving ASTA retention and bioaccessibility. In vivo absorption results confirmed the mixed oil PE with an olive oil/edible tea oil of 7:3 was more favorable for ASTA absorption. Molecular dynamics simulation showed ASTA bound more strongly and stably to fatty acid molecules in the system of olive oil/edible tea oil of 7:3; and van der Waals force was the main binding force. NMR further proved there really were interactions between ASTA and four main fatty acids.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT DRUG METABOLISM
·
2025
·Vol. 26
·期 1
·55-71
·
IF 1.8
Aichun Gao,Hongjin Wang,Xiaoge Cheng,Caihong Li,Lixin Sun
BackgroundVincosamide, an indole alkaloid extracted from Nauclea officinalis, exhibits a range of pharmacological activities, such as anti-tumor, antibacterial, and anti-inflammatory properties. However, despite its promising therapeutic applications, there is a notable gap in research focused on the metabolic pathways of vincosamide.ObjectivesThis study aims to investigate the metabolism of vincosamide both in vitro and in vivo in rats, and to elucidate its metabolic pathways.MethodsSamples of liver microsomal incubation, plasma, bile, urine, and feces following vincosamide administration were analyzed by ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap-high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap HRMS). The collected data were analyzed using Compound Discovery 3.2 software and the molecular network method. The metabolites identified through these methodologies were subsequently validated using Xcalibur 4.1 software, which provided information on retention times, parent ions, and characteristic fragment ions.ResultsA total of 37 metabolites were identified, including 8 in vitro and 32 in vivo (3 in plasma, 7 in bile, 22 in urine, and 17 in feces). While the metabolism of vincosamide differs in vitro and in vivo in rats, the type of metabolic reaction that occurs is well-defined. The predominant metabolic pathways are oxidation, reduction, deglycosylation, hydration, glucuronidation, methylation, sulfation, glycine conjugation, cysteine conjugation, taurine conjugation, and complex reactions.ConclusionThis study elucidates the metabolism of vincosamide in vitro and in vivo in rats, thereby expanding the metabolite profile of vincosamide. These findings provide a foundation for the potential development of new drugs based on vincosamide.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2018
·
IF 4.61
Nan You,Hui Yao,Yun Wang,Hong-Tao Fan,Chang-Song Wang,Ting Sun
The pollution of antibiotics, including tetracyclines (TCs), in aquatic environments has become an issue of concern in recent years. Herein, an in situ sampling of TCs in pig breeding wastewater that utilizes the technique of diffusive gradients in thin films (DGT), based on commercial nanosized ZnO (nanoZnO) particles as the potential effective binding agent and a polyethersulfone (PES) membrane as the diffusion layer, was developed. The diffusion coefficients of tetracycline (TC), oxytetracycline (OTC) and chlortetracycline (CTC) in a PES membrane at 25 °C were (1.37 ± 0.06) × 10 −6 cm 2 s −1 , (1.29 ± 0.05) × 10 −6 cm 2 s −1 and (1.94 ± 0.07) × 10 −6 cm 2 s −1 , respectively. The results showed that the adsorption capacities of a gel disc containing 2.5 g L −1 of nanoZnO particles were as high as 3.93 ± 0.20 mg disc −1 for TC, 3.21 ± 0.20 mg disc −1 for OTC and 4.62 ± 0.22 mg disc −1 for CTC. Both a solution pH in the range of 5–9 and an ionic strength (as pNaCl) in the range of 1–3 had an insignificant influence on the TCs uptake by nanoZnO−DGT samplers. There was no significant influence of fulvic acid or tannic acid on the TC uptake by nanoZnO−DGT samplers at the tested mass ratios. For all spiked freshwater samples, there was no notable interference of matrices on the performance of the nanoZnO−DGT samplers, suggesting that the nanoZnO−DGT samplers yielded satisfactory results for the uptake of TCs at concentrations existing in the spiked freshwater samples. Field deployment of the nanoZnO−DGT samplers in pig breeding wastewater also exhibited excellent precision and accuracy, indicating that the nanoZnO−DGT samplers could be used as a promising method for the in situ sampling of TC antibiotics in aquatic environments.
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2017
·
IF 3.756
Enfang Shan,Zhu Zhu,Shuangcheng He,Dongbao Chu,Dinghao Ge,Yunran Zhan,Wei Liu,Jian Yang,Jing Xiong
Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e. In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro. In results, metformin suppresses the expression and activity of Ces1d and Ces1e in a dose- and time-dependent manner. The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin. Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125 . It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin. The findings deserve further elucidation including clinical trials and have a potential to make contribution for the rational medication in the treatment of T2D patients.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）