FORENSIC SCIENCE INTERNATIONAL
·
2018
·
IF 1.974
Ting Wang,Baohua Shen,Hejian Wu,Jingying Hu,Huili Xu,Min Shen,Ping Xiang
Methamphetamine (MA) and amphetamine (AM) are widely abused drugs. These compounds contain a chiral center, and their enantiomers exhibit different pharmacologic, pharmacokinetic, and metabolic properties due to differences in binding affinities to their receptor sites. Until now, there was a lack of information on the decline in the concentration of drugs in hair after abstinence. A simple procedure for the chiral separation and determination of methamphetamine (MA) and its metabolite amphetamine (AM) enantiomers by LC–MS/MS in hair samples has been developed and fully validated. The LODs and LLOQs were 0.02 ng/mg and 0.05 ng/mg for all analytes, respectively. This method was successfully applied to both real hair specimens from chronic MA users and after the discontinuation of MA. The concentration of total MA, and total AM in fifty-eight authentic hair specimens ranged from 7.8 ng/mg to 521.0 ng/mg, and from 0.3 ng/mg to 84.0 ng/mg, respectively. Both enantiomers of MA and/or AM were detected in seven of fifty-eight authentic hair specimens. Hair specimens were from thirteen women with a known history of MA abuse, who went to a rehabilitation center and ceased consuming MA (for 4–5 months). The S -isomers of MA and AM were detected in all the 5–6 cm segments. Both enantiomers of MA were detected in nine of the 5–6 cm segments and the enantiomers of AM were found in only five of the nine samples. Assuming a hair growth rate of 1 cm/month, the mean hair elimination half-lives of S -MA, R -MA, S -AM, and R -AM were 0.64(95% CI, 0.46–0.96), 0.58(95% CI, 0.41–0.93), 0.62(0.49–0.88), and 0.50 months (95% CI, 0.42–0.56), respectively. With the developed method, R/S -MA and R/S -AM could be detected in the hair of former drug users for approximately 4 months after abstinence. S -MA is the most commonly found analyte in hair segments and is principally used by abusers. Our results suggest that to evaluate the discontinuation of MA abuse after a 6-month period of abstinence, a 3-cm proximal hair segment should be free of MA at the SOHT proposed cut-off level.
研究领域:
毒理学
·
分析化学
·
法医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2018
·
IF 3.118
Yan-dan Zhou,Jin-gang Hou,Wei Liu,Shen Ren,Ying-ping Wang,Rui Zhang,Chen Chen,Zi Wang,Wei Li
Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, the in vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20( R )-Ginsenoside Rg3 (20( R )-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway . Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20( R )-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20( R )-Rg3 pretreatment. Moreover, 20( R )-Rg3 pretreatment significantly alleviated APAP-induced apoptosis , necrosis, and inflammatory infiltration in liver tissues. Importantly, 20( R )-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20( R )-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2023
·
IF 3.8
Yushuang Liu,Hanshu Zhao,Nan Chen,Yuelong Li,Zeyang Zheng,Zhiyu Sun,Zhongling Zhang
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress occur in ischemic stroke. The disruption of these two organelles can directly lead to cell death through various signaling pathways. Thus, investigation of the associated molecular mechanisms in cerebral ischemia is a prerequisite for stroke treatment. Pleckstrin homology-like domain family A member 1 (PHLDA1) is a multifunctional protein that can modulate mitochondrial function and ER stress in cardiomyocyte and cancer cells. This work studied the role of PHLDA1 in cerebral ischemic/reperfusion (I/R) injury and explored the underlying mechanisms associated with mitochondrial functions and ER stress. Middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated neurons were used as I/R models in vivo and in vitro, respectively. PHLDA1 was upregulated in ischemic penumbra of MCAO/R-induced mice and OGD/R-exposed neurons. In vitro , PHLDA1 knockdown protected neurons from OGD/R-induced apoptosis. In vivo , PHLDA1 silencing facilitated functional recovery and reduced cerebral infarct volume. Mechanistically, PHLDA1 knockdown promoted PPARγ nuclear translocation, which may mediate the effects on reversion of mitochondrial functions and alleviation of ER stress. In summary, PHLDA1 knockdown alleviates neuronal ischemic injuries in mice. PPARγ activation and mitochondrial dysfunction and endoplasmic reticulum stress attenuation are involved in the underlying mechanisms.
研究领域:
神经科学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2015
·
IF 2.605
Renping Cao,Qingqiang Xiong,Wenjie Luo,Donglan Wu,Xiao Fen,Xiaoguang Yu
A series of SrAl [4−(4 x )/3] O 7 : x Mn 4+ (0≤ x ≤1.4 mol%) and Sr (1−0.06/2) Al [4−(4×0.008)/3] O 7 :0.008Mn 4+ ,0.06R + (R + =Li + , Na + , and K + ) phosphors are synthesized by a conventional solid-state reaction method in air. The PLE bands peaking at~325, 395, and 470 nm and the strongest PL band peaking at~660 nm are assigned to the 4 A 2 → 4 T 1 transition of Mn 4+ ion and O 2− –Mn 4+ change transfer band, 4 A 2 → 2 T 1 , 4 A 2 → 4 T 2 , and 2 E → 4 A 2 transitions, respectively. The optimum Mn 4+ doping concentration is about 0.8 mol%. Li + , Na + , and K + ions used as charge compensator can improve observably the PL intensity of SrAl 4 O 7 :Mn 4+ phosphor with excitation 325 nm. The fluorescence lifetimes of SrAl [4−(4×0.008)/3] O 7 :0.008Mn 4+ and Sr [1−0.06/2] Al [4−(4×0.008)/3] O 7 :0.008Mn 4+ ,0.06 R + (R + =Li + , Na + , and K + ) are 0.958, 0.97, 1.113 and 0.965 ms, respectively. The luminous mechanism is explained by schematic energy level diagram of Mn 4+ ion. These experiment results indicate that SrAl 4 O 7 :Mn 4+ ,R + (R + =Li + , Na + , and K + ) phosphors can be used as red emitting phosphor candidate for white LEDs based on a UV (~325 nm) and near UV (~395 nm) bands of LEDs chip.
研究领域:
材料科学
·
光学工程
✓ 已验证
产品关联
DOI
高影响因子
NEUROSCIENCE
·
2024
·
IF 2.9
Xinyue Zhang,Xiao Wang,Le Yin,Dan Wang,Hong Jiao,Xiaodan Liu,Jiaolin Zheng
HECT domain and Ankyrin repeat-containing E3 ubiquitin protein ligase 1 (HACE1) is an E3 ubiquitin ligase involving oxidative stress, an important contributor in cerebral ischemia–reperfusion injury (CIRI). It was proposed to be associated with the PI3K/AKT pathway and Nrf2 nuclear translocation, which are important players of oxidative stress. Therefore, we supposed that HACE1 might affect CIRI by regulating the PI3K/AKT/Nrf2 pathway. Here, we used the transient middle cerebral artery occlusion-reperfusion (tMCAO/R) model to induce CIRI in rats and found lower HACE1 expression in ischemic rats compared with the control. To explore the exact role of HACE1, the lentivirus vector carrying the HACE1 sequence was administrated to rats by intracerebroventricular injection (1 × 10 9 TU/mL, 9 μL) one week before tMCAO/R operation. HACE1 overexpression alleviated tMCAO/R-induced brain damage in rats. Further studies revealed that it reduced oxidative stress via activating the PI3K/AKT/Nrf2 pathway, thereby inhibiting neuronal apoptosis in the ischemic penumbra of rats with CIRI. Then, differentiated PC12 cells were cultured in oxygen-glucose deprivation-reoxygenation (OGD/R) conditions (OGD: 1 % O 2 , 94 % N2, and 5 % CO 2 ; R: normal atmosphere) to simulate CIRI in vitro . Similarly, HACE1 overexpression inhibited neuronal apoptosis caused by OGD/R treatment. The PI3K inhibitor LY294002 reversed the inhibitory effects of HACE1 overexpression on oxidative stress in OGD/R-injured cells, accompanied by the inactivated AKT/Nrf2 pathway. Altogether, our results suggest that HACE1 protects against oxidative stress-induced neuronal apoptosis in CIRI by activating the PI3K/AKT/Nrf2 pathway, providing a new insight into the CIRI treatment.
研究领域:
神经科学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENZYME AND MICROBIAL TECHNOLOGY
·
2021
·
IF 3.493
Qinghua Shi,Yutian Jia,Huibin Wang,Shang Li,Hengyu Li,Jiyang Guo,Tong Dou,Bin Qin,Song You
The ene reductases (ERs) from the old yellow enzymes (OYEs) family have the ability to reduce activated alkenes to generate up to two stereocenters, therefore they have been received extensive attention as powerful biocatalysts. In this study, through gene mining, four ERs were identified from the genomes of Ensifer adhaerens , Pseudomonas fluorescens , and Pseudomonas veronil . The biocatalytic properties of these four ERs were identified, and their applications in the synthesis process of dihydrocarvone and profen derivatives were further evaluated. Among them, three ERs (EaER2, PvER1, and PvER2) belonging to the classic OYEs showed the best catalytic activity at 30 °C and pH 7.0 (100 mM potassium phosphate buffer) and the PfER2, which belongs to the thermophilic-like OYEs exhibited the best catalytic at 40 °C and pH 7.0 (100 mM potassium phosphate buffer). When exploring the influence of organic solvents on the catalytic efficiency, it was found that the four ERs were more sensitive to toluene and had tolerance to several other selected organic solvents. In addition, EaER2, PfER2, PvER1 and PvER2 showed excellent catalytic activity toward carvone, and the stereoselectivity of PvER2 toward carvone could reach up to 88.7 % de. EaER2 and PfER2 can catalyze the synthesis of a variety of profen derivatives with a stereoselectivity over 99 % ee. Moreover, through homology modeling and molecular docking, we preliminarily explained the mechanism of catalytic activity and stereoselectivity of the four ERs, which provided a solid base on the rational design of their stereo-preference in the future. The discovery of EaER2, PfER2, PvER1, and PvER2 provides four new enzyme sources for the study of the OYEs family and enriches the biocatalytic toolbox of ERs. Our exploration of the enzymatic properties of these four ERs will provide the sufficient data basis for future research and industrialization progress.
研究领域:
生物化学
·
酶工程
·
合成生物学
✓ 已验证
DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2019
·
IF 4.153
Fanfan Fan,Haikuan Yuan,Yonghao Feng,Fengjiao Liu,Lijuan Zhang,Xijian Liu,Xueyan Zhu,Wei An,Sohrab Rohani,Jie Lu
In this work, the solubilities of (R)- and (R,S)-crizotinib in six solvents including methanol, ethanol, 1-propanol, 1-butanol, ethyl acetate, and n-hexane were first measured by a static method in the temperature range from 273.15 to 323.15 K at atmospheric pressure. Then, molecular simulations were performed to predict the crystal structures of (R)-crizotinib and (R,S)-crizotinib from their powder X-ray diffractograms and the solubilities in the above organic solvents using the Gibbs free energy calculation approach via the sublimation cycle. The results showed that the solubilities of (R)- and (R,S)-crizotinib in the selected solvents generally increased with the increasing temperature, and at room temperature the molar fraction solubility order was methanol > 1-butanol > 1-propanol > ethanol > ethyl acetate > n-hexane. The (R)-crizotinib crystal had a monoclinic unit cell, while the (R,S)-crizotinib crystal had a triclinic one. In particular, though it was first applied to the solubility estimation for water-insoluble drug compounds in organic solvents, the Gibbs energy calculation approach developed gave a desirable solubility prediction performance with a root-mean-square error (RMSE) of 0.7638 log S units for (R)-crizotinib and 1.1577 log S units for (R,S)-crizotinib in the selected solvents, respectively. Furthermore, the difference in the solubilities of (R)-crizotinib in different solvents mainly resulted from the different Gibbs free energies for solvation between solute and solvent other than those for sublimation. However, as to the difference in the solubilities of (R)- and (R,S)-crizotinib in the same solvent, the Gibbs free energy for sublimation made more of a contribution than that for solvation. Finally, on the basis of the solid-state characterization, the nature of crystalline (R,S)-crizotinib was confirmed to be a racemic compound. All these results shall provide pharmaceutical industry with a better understanding of this chiral system for crystallization resolution.
✓ 已验证
DOI
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2022
·Vol. 46
·期 2
·171-181
·
IF 3.434
Zhang Yin-Jun,Wei Li-Tian,Zhou Ming-Peng,Wei Chun,Yu Xin-Jun
( R )-N-(2,6-dimethylphenyl) aminopropionic acid methyl ester (( R )-DMPM) is an important chiral intermediate of the fungicide N-(2,6-Dimethylphenyl)-N-(methoxyacetyl)-alanine methyl ester (( R )-Metalaxyl). In this study, (1) D3520 (macroporous acrylic anion resin), selected from the ten resins, was used to immobilize the esterase from Pseudochrobactrum asaccharolyticum WZZ003 (PAE07) for resoluting the ( R,S )-DMPM to obtain ( R )-DMPM. (2) Up to 20 g/L PAE07 could be immobilized onto D3520 with a high enzymatic activity of 32.4 U/g. Moreover, the Km and Vmax values of 19.1 mM and 2.8 mM/min for D3520-immobilized PAE07 indicated its high activity and stereoselectivity. (3) The optimal temperature and pH for the immobilized PAE07 were 40 ℃ and 8.0, and substrate concentration was up to 0.35 M. After 15 h reaction, the conversion rate from ( R,S )-DMPM to ( R )-DMPM was 48.0% and the e.e.p and E values were 99.5% and 1393.0, respectively. In scale-up resolution, 200 g/L substrate and 12.5 g immobilized esterase PAE07 condition, a conversion rate from substrate to product of 48.1% and a product e.e.p of 98% were obtained within 12 h, with the activity of immobilized PAE07 retained 80.2% after 5 cycles of reactions. These results indicated that the D3520-immobilized esterase PAE07 had great potential for enzymatic resolution of ( R,S )-DMPM to prepare ( R )-Metalaxyl.
研究领域:
生物化学
·
酶工程
·
有机合成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF LUMINESCENCE
·
2020
·
IF 3.28
Xing Cao,Shichang Sun,Bing Lu,Yan Liu,Rui Ma,Huiqun Cao,Hongzhi Ma,Hexun Huang
In order to overcome the shortcomings of insufficient red light component and poor thermal stability of commercial white light emitting diode (WLED), YAG:Ce, R (R: Gd 3+ , Pr 3+ , Gd 3+ and Pr 3+ ) fluorescent thin films were prepared by pulse laser deposition (PLD). The composition and microstructure, photoluminescence properties, and red-enhanced mechanism of co-doped YAG fluorescent thin films, as well as the electroluminescence behavior of the corresponding WLEDs were investigated. Results showed that the doping of Pr 3+ caused the emission spectrum energy of Ce 3+ to migrate, and an emission peak appeared at 606 nm in the red region. The doping of Gd 3+ caused the emission spectrum of Ce 3+ to shift to the red region, and the main peak position of the Ce 3+ emission spectrum is red-shifted from 523 nm to 548 nm. The YAG:Ce,Pr,Gd fluorescent film not only realized the improvement of red light components and red-shift, but also increased the energy transmission efficiency from 33.3% to 51.9%. Moreover, results of the color coordinate analysis also showed that the co-doping of Gd 3+ and Pr 3+ made the luminescence closer to the red region, reducing the color temperatures and hues changed to warm. Thus, tri-doped transparent fluorescent thin film were prospective for WLED application.
研究领域:
材料科学
·
光学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Xiaodan Tan,Wenjia Guo,Zhe Peng,Chao Gu,Pu Xiang,Yujun Tu,Huizhi Fei,Xia Liu,Yi Lu,Miaomiao Li,Hong Wang,Ying Luo,Junqing Yang
Based on the previous studies, this study was carried out to explore the interaction of LncRNA-Malat1/miR-211-5p in cerebral ischemia reperfusion injury (CIRI). Firstly, the expression changes of LncRNA-MALAT1 and miR-211-5p in ischemia patients’ blood were determined, and the binding sites of them were predicted by bioinformatics. Furthermore, middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established in adult male SD rats , and primary neuronal oxygen-glucose deprivation/reoxygen-glucose reoxygenation (OGD/R) was established in vitro. The results showed that LncRNA-MALAT1 was significantly up-regulated and miR-211-5p down-regulated in the peripheral blood of patients with ischemic stroke, and the expression changes were negatively correlated. Bioinformatics prediction results showed that LncRNA-MALAT1 had a binding site with miR-211-5p. We also found that LncRNA-Malat1 was significantly up-regulated while miR-211-5p down-regulated in rat cortex tissue and primary neurons treated with OGD/R. In addition, lentivirus interfered with LV-Malat1-RNAi decreased the expression of LncRNA-Malat1 and promoted the up-regulation of miR-211-5p. Combination of LV-Malat1-RNAi and miR-211-5p inhibitor significantly reversed the protective effect of down-regulation of LncRNA-Malat1. Inhibition of LncRNA-Malat1 expression alleviated the neurological deficit score after MCAO/R, improved histopathological damage, and reduced the size of cerebral infarction . Combined administration of LV-Malat1-RNAi + Antagomir-211-5p reversed these effects above. In short, our data suggest that LncRNA-Malat is involved in the occurrence and development of cerebral ischemia reperfusion injury by acting on miR-211-5p and is then regulating the expression of COX-2.
研究领域:
神经科学
·
分子生物学
·
医学遗传学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Integrative Neuroscience
·
2024
·Vol. 23
·期 11
·196
·
IF 2.5
Yan Shi,Yufeng Yang,Juntong Liu,Jinling Zheng
Background:
Avicularin (AL), an ingredient of Banxia, has anti-inflammatory properties in cerebral disease and regulates polarization of macrophages, but its effects on ischemic stroke (IS) damage have not been studied.
Methods:
In vivo, AL was administered by oral gavage to middle cerebral artery occlusion/reperfusion (MCAO/R) C57BL/6J mice in doses of 1.25, 2.5, and 5 mg/kg/day for seven days, and, in vitro, AL was added to treat oxygen-glucose deprivation (OGD)-BV2 cells. Modified neurological severity score, Triphenyltetrazolium chloride (TTC) staining, brain-water-content detection, TdT-mediated dUTP nick-end labeling (TUNEL) assay, flow cytometry, immunofluorescence assay, Enzyme linked immunosorbent assay (ELISA), and Western-blot analysis were used to investigate the functions and mechanism of the effect of AL treatment on IS. The exosomes of AL-treated microglia were studied by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and Western-blot analysis.
Results:
AL treatment reduced the neurological severity score, infarct volume, brain-water content, neuronal apoptosis, and the release of inflammatory factors, that were induced by MCAO/R. Notably, M2 microglia polarization was promoted but M1 microglia polarization was inhibited by AL in the ischemic penumbra of MCAO/R mice. Subsequently, anti-inflammatory and polarization-regulating effects of AL were verified in vitro. Suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation was found in the ischemic penumbra of animal and Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) cells treated with AL, as evidenced by decreasing NLRP3-inflammasome-related protein and downstream factors. After AL treatment, the anti-apoptosis effect of microglial exosomes on OGD/R primary cortical neurons was increased.
Conclusion:
AL reduce inflammatory responses and neuron death of IS-associated models by regulating microglia polarization by the NLRP3 pathway and by affecting microglial exosomes.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2022
·
IF 3.708
Hanshu Zhao,Yushuang Liu,Nan Chen,Hongyi Yu,Sihan Liu,Meihe Qian,Zhongling Zhang
Cerebral ischemia/reperfusion injury is the main cause of neurological deficit following stroke. Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is increasingly recognized as a critical determinant in immunological regulation and cell apoptosis, but its role in neuroinflammation during cerebral ischemia/reperfusion injury remains to be elucidated. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) in C57BL/6 mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in BV-2 cells were used as models in vivo and in vitro , respectively. MACO/R mice and OGD/R cells were treated with scramble or PHLDA1 small interfering RNAs (siRNAs) to achieve the goal of PHLDA1 knockdown. The results showed that the expression of PHLDA1 was significantly increased in MCAO/R mice and OGD/R cells compared to their normal controls, respectively. Mice treated with PHLDA1 siRNA exhibited a lower degree of infarct volume and brain water content compared to the NC siRNA-treated mice. Notably, PHLDA1 knockdown switched the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype by decreasing the expression of M1 markers (i.e., CD16, TNF-α, IL-6 and IFN-γ, and iNOS) and elevating the expression of M2 markers (i.e., CD206, IL-4, IL-10, and Arg-1). Moreover, PHLDA1 knockdown suppressed the NLRP3 inflammasome activation by reducing NLRP3, ASC, cleaved caspase 1 and cleaved IL-1β expression. In summary, these results suggest that PHLDA1 blockade effectively alleviates the ischemia/reperfusion-induced cerebral injury by switching microglial M1/M2 polarization and inhibiting NLRP3 inflammasome activation. Targeting PHLDA1 could be considered as a novel strategy in the treatment against post-ischemic brain injury.
研究领域:
神经科学
·
免疫学
·
分子生物学
·
细胞生物学
✓ 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）