STEROIDS
·
2024
·
IF 2.1
Jinwen Chen,Wei Chen,Xiaoyu Li,Yiping Ye,Wenkang Huang,Lijuan Gao,Meng Zhang
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers that results in death in worldwide. The Hedgehog (HH) signalling pathway regulates the initiation and progression of CRC. Inhibiting the HH pathway has been presented as a potential treatment strategy in recent years. Cynanbungeigenin C (CBC) is a new type of C 21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility. In this study, six new CBC derivatives were synthesized through the structural modification of CBC, and four of them showed better water solubility than CBC. Moreover, their antiproliferative activities on CRC were evaluated. It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC. Mechanistically, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway according to qRT–PCR and Western blotting analysis. Furthermore, Cellular Thermal Shift Assay results indicated that CBC-1 regulated this signalling pathway by targeting glioma‑associated oncogene (GLI 1).In addition, cell apoptosis was induced increasingly by transfection with GLI 1 siRNA or treatment with CBC-1 to downregulate GLI 1. Last, the in vivo results demonstrated that CBC-1 significantly reduced tumour size and downregulated GLI 1 in CRC. Therefore, this study suggests that CBC-1, a new GLI 1 inhibitor derived from natural products, may be developed as a potential antitumour candidate for CRC treatment.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Ya-Ling Chen,Yi Wang,Qiu-Yu Fang,Tong Wang,Cong Chen,Tong-Yao Gao,Ming Wu,Wei-Ping Zhang,Yun-Bi Lu
Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD + -consumption enzyme. PARP-1 hyperactivity causes intracellular NAD + deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.
研究领域:
神经科学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
APPLIED CATALYSIS B-ENVIRONMENTAL
·
2018
·
IF 11.698
Tong-Yang Song,Zhao-Xia Dong,Jian-Dong Song,Xiao-Xia Wang,Guan-Qun Xie,Meng-Fei Luo,Ji-Qing Lu
Dehydrochlorination of 1, 1, 2-trichloroethane was performed on SiO 2 supported alkali metal (Na. K, Cs) and transition metal (Mn, Ni, Zn) catalysts. The surface basicity or acidity of the catalyst exerted great influence on catalytic behaviors. The catalysts with higher amount of base or acid sites resulted in higher activity due to more adsorption sites for reactant. The basic catalysts (Cs/SiO 2 and K/SiO 2 ) tended to form vinylidene chloride with a selectivity up to 80 %; the neutral catalysts (Na/SiO 2 and SiO 2 ) tended to form 1, 2-dichloroethene with a selectivity up to about 80 %; the acidic catalysts (Zn/SiO 2 , Mn/SiO 2 and Ni/SiO 2 ) tended to form 1, 2-dichloroethene with a selectivity up to 96 %. Proposed reaction mechanisms included an E1cb mechanism with a carbanion intermediate on the basic catalysts, an E2 concerted mechanism on the neutral catalysts, and an E1 mechanism with a carbonium intermediate on the acidic catalysts.
研究领域:
化学工程
·
催化科学
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DOI
高影响因子
ANALYTICAL LETTERS
·
2012
·
IF 1.016
Meirong Liu,Shuhua Zhu,Jie Zhou
A new, sensitive, and simple HPLC method was described for the determination of 1-aminocyclopropane-1-carboxylic acid (ACC) in apple and peach extracts. The method was based on the derivatization of ACC with fluorescamine in borate buffer systems of pH 8.0 to yield a highly fluorescent product. The experimental parameters affecting the derivatization reaction efficiency were optimized by fluorimetric analysis. Under optimum derivatization conditions, the derivative product of ACC in apple and peach extracts without extra purification was successfully chromatographed on a C-18 column by HPLC coupled to fluorescence detection. The derivative product of ACC with fluorescamine could be well separated from other concomitant substances or their derivatives that might interfere with the determination of ACC. The linearity of ACC was measured in the range of 23.82–238.82 µg · L−1 with a good correlation coefficient of 0.9997. Based on signal-to-noise ratio of 3, a low detection limit of 5.0 µg · L−1 could be reached. The proposed method was applied successfully to the determination of ACC in the crude apple and peach extracts without extra purification with low RSDs of 0.19–1.9% and good recoveries of 90.89–104.4%. The sensitive HPLC quantitative method is of great significance for the investigations of ACC metabolism in plants.
研究领域:
植物学
·
分析化学
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产品关联
DOI
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2018
·
IF 2.196
Bing Jia,Liping Wang,Mengmeng Yan,Hai Liu,Yingmin Yu,Qingsong Li
Liquid–liquid equilibrium (LLE) data for ternary systems of water + 2,2,3,3-tetrafluoro-1-propanol + anisole/1-octanol were determined at temperatures of 298.2, 308.2, and 318.2 K under 101.3 kPa. The distribution coefficients and separation factors were calculated from experimental LLE data, which indicated that anisole/1-octanol extracted 2,2,3,3-tetrafluoro-1-propanol from aqueous solution with high efficiency. The consistency of the experimental LLE data was assessed by the Othmer–Tobias and Hand equations. Meanwhile, the NRTL and UNIQUAC models were successfully applied to regress and correlate the experimental data, presenting the root-mean-square deviations (RMSD) less than 1.0%. The relevant binary interaction parameters of these two models were also regressed.
研究领域:
化学工程
·
物理化学
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DOI
高影响因子
ENVIRONMENTAL AND EXPERIMENTAL BOTANY
·
2023
·
IF 5.7
Yueyao Tang,Xiaojiao Chen,Hao Zhang,Xue Sun,Nianjun Xu
Severe marine pollution caused by excessive copper (Cu) has resulted in a great threat to marine biosystems. Gracilariopsis lemaneiformis , the main economically important cultivated macroalgal species of coastal China, is affected by Cu. 1-Aminocyclopropane-1-carboxylic acid (ACC), the direct precursor of ethylene, acts as a potential signaling molecule for plants to defend against heavy metal stress. In the present study, the role of ACC in alleviating Cu stress in G. lemaneiformis was explored by measuring physiological indicators and by performing a comparative transcriptome analysis. Excess Cu reduced photosynthetic rates and relative growth rates, increased Cu accumulation and malondialdehyde levels and induced the antioxidant system in G. lemaneiformis . ACC was found to inhibit the expression of genes encoding Cu transport proteins , greatly decrease Cu accumulation and MDA contents and relieve the inhibition of G. lemaneiformis growth caused by Cu stress. In addition, the expression of most antioxidant synthesis-related genes encoding SOD and APX was downregulated by ACC, and the activity of antioxidant enzymes was reduced. Moreover, ACC stimulated jasmonate acid (JA) synthesis to increase endogenous JA contents and activated pathways related to translation, photosynthesis, and nitrogen metabolism , while ACC did not stimulate the expression of genes involved in ethylene signaling pathways. These findings provide insight into the molecular mechanisms of Cu stress resistance in G. lemaneiformis and benefit the breeding and cultivation of G. lemaneiformis .
研究领域:
海洋生物学
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植物生理学
·
分子生物学
·
环境科学
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DOI
高影响因子
Tissue Barriers
·
2024
·
IF 3.6
Qi Cao,Wei Zeng,Jingmin Nie,Yongjun Ye,Yanchao Chen
Impairment of the blood – brain barrier (BBB) and subsequent inflammatory responses contribute to the development of human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND). Apelin-13, the most abundant member of the apelin family, acts as the ligand of the angiotensin receptor-like 1 (APJ). However, its pharmacological function in HAND and its underlying mechanism are unknown. In the current study, we report that the presence of HIV-1 Tat reduced the levels of Apelin-13 and APJ in the cortex tissue of mice. Importantly, Apelin-13 preserved BBB integrity against HIV-1 Tat in mice by increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludin. Interestingly, increased macrophage infiltration, indicated by elevated CD68-positive staining was observed in the cortex after stimulation with HIV-1, which was mitigated by the administration of Apelin-13. Correspondingly, Apelin-13 reduced the expression of monocyte chemoattractant protein-1; (MCP-1). An in vitro two-chamber and two-cell trans-well assay demonstrated that HIV-1 Tat challenge significantly promoted macrophage migration, which was notably attenuated by the introduction of Apelin-13. Accordingly, treatment with Apelin-13 restored the HIV-1 Tat-induced reduction of occludin and ZO-1, while preventing the upregulation of MCP-1 in human brain microvascular endothelial cells (HBMVECs). Our results suggest that Apelin-13 may reduce macrophage infiltration into brain tissues and mitigate BBB dysfunction in patients with HAND.
研究领域:
神经科学
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免疫学
·
药理学
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2023
·Vol. 6
·期 1
·1-12
·
IF 5.9
Wang You-Yuan,Zhen Cheng,Hu Wei,Huang Hui-Huang,Li Yan-Jun,Zhou Ming-Ju,Li Jing,Fu Yu-Long,Zhang Peng,Li Xiao-Yu,Yang Tao,Song Jin-Wen,Fan Xing,Zou Jun,Meng Si-Run,Qin Ya-Qin,Jiao Yan-Mei,Xu Ruonan,Zhang Ji-Yuan,Zhou Chun-Bao,Yuan Jin-Hong,Huang Lei,Shi Ming,Cheng Liang,Wang Fu-Sheng,Zhang Chao
CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.
研究领域:
免疫学
·
病毒学
·
代谢学
·
HIV/AIDS研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANTIBIOTICS
·
2021
·Vol. 74
·期 9
·574-579
·
IF 2.649
Ge Ying,Kang Peng-Wei,Li Jia-Qi,Gao Han,Zhai Le,Sun Le-Yun,Chen Cheng,Yang Ke-Wu
The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones ( 1a - 1m ) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC 50 in the range of 0.88–20.2 µM, and 1a and 1f were found to be the potent inhibitors (IC 50 = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml −1 ) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.
研究领域:
微生物学
·
药理学
·
感染病学
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DOI
PubMed
高影响因子
Materials Today Sustainability
·
2024
·
IF 7.1
Weijiong Dai,Jing Zhao,Zongqiang Liu,Yan Wang,Jiajun Zheng,Ruifeng Li
Plate-like TS-1 zeolites offering a short diffusion pathway along the b- axis are highly desirable catalysts in the reaction of alkene epoxidation. Herein, we successfully developed a simple synthetic strategy toward reducing the thickness along the b -axis of TS-1 zeolite crystals, l -lysine adopted as a zeolite growth modifier was firstly proposed to prepare plate-like TS-1 zeolite. Meanwhile, through tuning the preliminary aging time, plate-like TS-1 zeolites with thickness in the range of 80–1000 nm can be controllable obtained. In this work, the synthesis parameters controlling the formation of plate-like TS-1 zeolites are studied, and the factors controlling the zeolite growth were well elucidated. Compared with the conventional TS-1 zeolite as well as the plate-like TS-1 synthesized in the fluoride-containing medium, the obtained plate-like TS-1 shows improved catalytic performances in catalyzing epoxidation of 1-hexene.
研究领域:
材料科学
·
催化化学
·
合成化学
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产品关联
DOI
高影响因子
CHEMISTRY & BIODIVERSITY
·
2021
·Vol. 18
·期 4
·e2001007
·
IF 2.408
Yan Zhao,Yu Wang,Min Zhang,Yugang Gao,Zhaowei Yan
Ginsenosides (20 S )-Rg3 and (20 R )-Rg3 are famous rare ginsenosides from red ginseng, and their configurations in C-20 are different. This study aimed to investigate the protective mechanism of ginsenosides (20 S )-Rg3 and (20 R )-Rg3 on H 2 O 2 -induced H9C2 cells and compare their activity. The results showed that the ginsenosides (20 S )-Rg3 and (20 R )-Rg3 could increase the cell activity and the levels of GSH-Px, SOD and CAT, and decrease activities of LDH, MDA and ROS. Further studies showed that ginsenosides (20 S )-Rg3 and (20 R )-Rg3 could prevent oxidative stress injury of H9C2 cells by H 2 O 2 through the Keap-1/Nrf2/HO-1 pathway. But the ML385 counteracts these effects. Interestingly, among these results, ginsenoside (20 R )-Rg3 was superior to (20 S )-Rg3, indicating that ginsenoside (20 R )-Rg3 have a stronger effect of antioxidative stress. This study reflected that ginsenoside (20 R )-Rg3 could be used as a potential Nrf2 activator and a safe effective Chinese herbal monomer in the treatment of cardiovascular disease.
研究领域:
药理学
·
心脏病学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2020
·
IF 2.888
Lemeng Wang,Chi Fang,Xiaoqian Du,Kun Fu,Xiangfeng Tian,Pan Zhang,Dong Fu
The surface tensions ( γ ) and viscosities ( η ) of 1-dimethylamino-2-propanol (DMA2P) − 1-(2-aminoethyl)piperazine (AEP) and DMA2P − 1,5-diamino-2-methylpentane (DAMP) were measured and correlated. According to the CO 2 capture temperature from the thermal power plant flue gas (around 313 K), the experimental temperatures were selected to be 303.2 K, 313.2 K and 323.2 K. The mass fractions of DMA2P ranged from 0.300 to 0.500, and those for activators (AEP and DAMP) ranged from 0.050 to 0.150. Temperature and composition dependences of γ and η were demonstrated on the basis of experiments and calculations. The activation energy ( E a) was estimated from the temperature dependence of viscosity. Analytical formulations of surface entropy ( S S ) and surface enthalpy ( H S ) were deduced from the analytical equation of γ . S S and H S were calculated and their variations with respect to mass fraction were analyzed.
研究领域:
物理化学
·
环境科学
✓ 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）