TISSUE & CELL
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2022
·
IF 2.586
Jie Pan,Xiaoping Cai,Xiao Zheng,Xiaoyu Zhu,Jihong Feng,Xiaoqiu Wang
Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.
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ACS Applied Materials & Interfaces
·
2016
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IF 7.145
Xubo Zhao,Mingzhu Qi,Shuo Liang,Kun Tian,Tingting Zhou,Xu Jia,Jiagen Li,Peng Liu
Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation, and simple esterification reaction and self-assembled into stimuli-regulated amphiphilic micelles in aqueous solution. On the basis of the optimization of the morphology and particle size of the micelles via modulating the number of the photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from PEG43-b-P(AA76-co-NBA35-co-tBA9) with an average hydrodynamic diameter (Dh) of 163 nm was selected as a potential drug delivery system (DDS) for UV-triggered delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX-loading. Most importantly, the DOX-loaded PEG43-b-P(AA76-co-NBA35-co-tBA9) micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated physiological medium within 6 days without UV-irradiation, indicating their potential as leakage-free DDS. As in the acidic media mimicking the tumor microenvironment, a high cumulative DOX release ratio of 74.70% was achieved within 6 days after UV-irradiation for 20 min, showing a sustained release behavior. Under UV-irradiation, the photolabile o-nitrobenzyl moieties were cleaved off, the amphiphilic copolymer transformed into a water-soluble polymer, favoring the metabolism of drug carriers, and the micelles were demicellized to accelerate the drug release in a triggered or on-demand manner.
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2014
·Vol. 131
·期 17
·
IF 1.64
Chun-Hui Du,Xu-Min Ma,Chun-Jin Wu,Mei-Qiang Cai,Li-Guang Wu
A poly(methyl methacrylate) (PMMA)- b -poly[2-( N,N -dimethylamino) ethyl methacrylate] (PDMAEMA) block copolymer was successfully synthesized by a reversible addition–fragmentation chain-transfer method. The resulting copolymer was used to prepare poly(vinylidene fluoride) blend membranes via a phase-inversion technique. The polymorphism, structure, and properties of the blend membranes were investigated by Fourier transform infrared spectrometry, scanning electron microscopy (SEM), ζ potential analysis, and filtration. The results indicate that PMMA- b -PDMAEMA could migrate onto the surface of the membrane during the coagulation process, and more of the β-crystal phase appeared with the increase of the block copolymer in the membranes. The surface morphology and cross section of the membranes were also affected by the copolymer, as shown by SEM. The ζ-potential results show that the surface charges of the membrane could be changed from positive to negative at an isoelectric point as the pH increased. The blend membrane also exhibited good pH sensitivity, and its water flux showed a great dependence on pH. The filtration experiment also indicated that the blend membrane had good hydrophilicity and antifouling properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40685.
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Bioengineered
·
2022
·
IF 6.832
Fan-Cheng Kong,Li-Qin Lang,Jie Hu,Xia-Ling Zhang,Ming-Kang Zhong,Chun-Lai Ma
Drug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Here, we quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain hemorrhage controls (n = 10) by immunochemical staining. TET2 and ATP binding cassette subfamily B member 1 (ABCB1) expression patterns were determined in the isolated brain capillaries of DRE patients. TET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed no differences in expression. We also found that a particularly strong expression of TET2 in the vascular tissue of DRE patients. ABCB1 and TET2 have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In blood–brain barrier (BBB) model, TET2 depletion can cause attenuated expression and function of ABCB1. Data from a cohort study and experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE.
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Food Chemistry-X
·
2022
·
IF 6.443
Meilin Jing,Qingqing Jiang,Yamin Zhu,Daming Fan,Mingfu Wang,Yueliang Zhao
The effect of acrolein on the formation of the 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine (PhIP) was investigated in a chemical model. Acrolein was found to increase PhIP formation at each tested addition level. 0–0.2 mmol of acrolein increased PhIP formation dose-dependently, while high levels of acrolein (>0.2 mmol) did not further increase PhIP formation. Mechanistic study showed that acrolein addition decreased the residue of phenylalanine and creatinine, but increased the content of some key intermediates. Further analysis indicated that acrolein can react with phenylalanine, creatinine, and PhIP to form adducts. These results suggested that acrolein was able to contribute to PhIP formation as a consequence of its comprehensive ability to facilitate Strecker degradation of phenylalanine and react with phenylalanine, creatinine, and PhIP. In addition, oxidation of the tilapia fish increased the PhIP formation in the roasted fish patties, further supporting the potential contribution role of lipid oxidation products to the formation of PhIP.
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MEDICAL SCIENCE MONITOR
·
2020
·
IF 1.918
Yan Dong,Jun Yang,Liyuan Yang,Ping Li
Background Quercetin (Que) is reported to induce apoptosis of lung cancer cells. Src is closely related to the progression of non-small cell lung cancer (NSCLC) and can be modulated by Que in macrophages. In the current study, the interaction between Que and Src signaling in NSCLC cells was explored to explain the anti-NSCLC function of Que. Material/Methods NSCLC cell line HCC827 was subjected to the administrations of Que at different concentrations. The effect of Que on tumor cell proliferation was detected using MTT and colony formation assays. Then the effect on the migration and invasion abilities was assessed using scratch and Transwell assays. At molecular level, the changes in Src/Fn14/NF-κB signaling were determined using western blotting assays. The role of Src in the function of Que was further explored by inducing the expression of Src gene in NSCLC cells before Que administration. The results of the in vitro assays were verified using a NSCLC mice model. Results Que inhibited the proliferation and anchorage-independent growth of NSCLC cells. Additionally, Que delayed in the gap closure rate in scratch assays and decreased the membrane-penetrating cell number in Transwell assays. At a molecular level, Que suppressed the expression of Src, which subsequently inhibited Fn14/NF-κB signaling. In in vivo assays, Que inhibited the growth of solid tumors. After the overexpression of Src in NSCLC cells, the anti-NSCLC effect of Que was blocked by inducing NSCLC proliferation and metastasis, and by activating Fn14/NF-κB signaling. Moreover, the induced level of Src promoted the growth and metastasis potential of solid tumors in mice. Conclusions Que exerted the anti-NSCLC effect by inhibiting Src-mediated Fn14/NF-κB pathway both in vitro and in vivo .
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PHARMACEUTICAL BIOLOGY
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2022
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IF 3.889
Shuhua Shen,Kungen Wang,Yihui Zhi,Yue Dong
Context Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can develop into metabolic associated fatty liver disease (MAFLD). Gypenosides (GP), the main phytochemical component of Gynostemma pentaphylla (Thunb.) Makino (Cucurbitaceae), have been applied for treatment of metabolic diseases.Objective We investigate how GP modulate MAFLD-related hepatic steatosis and intestinal barrier injury.Materials and methods In cell experiments, Caco-2 cells were treated with GP (150 or 200 μmol/L, 24 h), following lipopolysaccharide (LPS) exposure (10 μg/mL, 24 h) to mimic MAFLD in vitro. In in vivo experiments, control, model and model + GP groups were set. High fructose diet/high fat (HFD/HF)-fed (12 weeks) MAFLD rats received GP treatment (300 mg/kg, 6 weeks), followed by intra-peritoneal glucose tolerance test and histopathological examination of rat liver and intestinal mucosa using haematoxylin–eosin staining.Results GP at 200 μM significantly reversed LPS-induced decreases in transepithelial electrical resistance (TER) value (25%), protein expression of occludin (two fold) and ZO-1 (four fold), and the ratio of p-AMPK to AMPK (five fold), while partially repressing LPS-induced leakage of FD4 (50%) and LPS-induced increases in the Toll-like receptor 4 (TLR4) level (50%) and the ratio of p-p65 to p65 (55%). Compared with the model rats, rats with GP treatment presented a reduction in gain of weight and glucose tolerance. In addition, GP alleviated HFD/HF-induced histopathological abnormalities in rat liver and intestinal mucosa.Conclusions GP attenuates hepatic steatosis and intestinal barrier injury in MAFLD rats via the AMPK and TLR4/nuclear factor kappa B (NF-κB) pathways, providing a potential treatment for MAFLD patients.
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CURRENT CANCER DRUG TARGETS
·
2022
·Vol. 22
·期 9
·771-783
·
IF 2.907
Cui Zhi,Sun Shiqun,Li Jia,Li Jianing,Sha Tong,He Jie,Zuo Linjing
Background: Inhibitor of growth 4 (ING4) level was reported to be decreased in head and neck squamous cell carcinoma (HNSC) tissue, however, it is unknown whether and how ING4 participates in regulating the development of oral squamous cell carcinoma (OSCC). Objective: This study
aimed to investigate the role and mechanism of ING4 in OSCC. Methods: ING4 was forced to up- or down-regulated in two OSCC cell lines, and its effects on the malignant behavior of OSCC cells were investigated in vitro. The ubiquitination level of NF-kB p65 in ING4 upregulated cells was
measured by co-immunoprecipitation. Moreover, the effects of ING4 on the methylation level of ALDH1A2 were evaluated by methylation-specific polymerase chain reaction (MSP) assay. The role of ING4 in OSCC growth in vivo was observed in nude mice. Results: Our results showed that the expression
of ING4 in OSCC cell lines was lower than that in normal oral keratinocyte cells. In vitro, ING4 overexpression inhibited the proliferation, migration, and invasion of OSCC cell lines and ING4 silencing exhibited opposite results. We also demonstrated that ING4 overexpression promoted the
ubiquitination and degradation of P65 and reduced DNA methyltransferase 1 (DNMT1) expression and Aldehyde dehydrogenase 1A2 (ALDH1A2) methylation. Moreover, overexpression of p65 rescued the suppression of malignant behavior, induced by ING4 overexpression. In addition, ING4 negatively regulated
the growth of OSCC xenograft tumors in vivo. Conclusion: Our data evidenced that ING4 played a tumor-repressing role in OSCC in vivo and in vitro via NF-ΚB/DNMT1/ALDH1A2 axis.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2018
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IF 3.04
Jie-Fei Miao,Yan-Fu Peng,Shi Chen,Wei-Jie Gao,Qiu-Xing Yang,Peng Zhu,Jing Guo,Jinhua Tao,Lin Luo,Yanan Zhang,Yong Ling
This study aims to design and synthesize a novel harmine derivative N -(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC 50 value of 2.21 μM, which is nearly three-fold lower than SAHA (IC 50 = 6.26 µM), but also showed selective HDAC1/6 inhibitory effects in vitro. However, HBC had little effect on normal hepatic cells LO2. Furthermore, HBC simultaneously increased the acetylation of histone H3 , H4, and α-tubulin, induced hypochromism by electrostatical interaction with CT-DNA, triggered more significant cancer cell apoptosis and cell cycle arrest at G2/M than SAHA by inhibition of both CDK1 and cyclin B in a concentration dependent manner. In addition, scratch and invasion assay showed that HBC also dose-dependently suppressed migration and invasion capacities of highly metastatic HCC HepG2 cells through down-regulated the expression of tumor metastasis related proteins MMP-2 and MMP-9, significantly better than SAHA. Finally, HBC showed low acute toxicity to mice and significant growth inhibition of the hepatoma tumor in vivo. These results demonstrate that novel harmine-based HDAC inhibitor HBC not only exhibited selective HDAC1/6 inhibitory activity and significant in vitro and in vivo antitumor activity, but also possessed DNA binding effect, apoptosis induction, cell cycle arrest effects, and potent anti-metastasis mechanisms, which may hold great promise as therapeutic agent targeting HDAC1/6 for the intervention of human cancers.
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REACTIVE & FUNCTIONAL POLYMERS
·
2018
·
IF 2.975
Zhenglong Yang,Kangyu Fu,Jing Yu,Peiting Zhou,Zhihao Cheng
Temperature and pH double-response poly(t-butyl acrylate)- b -poly{[2-(dimethylamino) ethyl methacrylate]- co -[poly(ethylene glycol) methyl ether methacrylate]} (PtBA -b- P(DMAEMA- co -PEGMEMA)) were successfully prepared by RAFT polymerization and could be self-assembled into micelles . 1 H NMR, UV-vis absorbance and DLS measurements were used to characterize their structures and self-assembly behaviors. At the same time, the adsorption of organic dyes and the control of drug release were also introduced. The results showed that the critical micelle concentration of PtBA- b -P(DMAEMA- co -PEGMEMA) was 2.55 mg/L. As the value of pH increased from 2 to 11, their particle size decreased from 178 nm to 130 nm. PtBA- b -P(DMAEMA- co -PEGMEMA) was also temperature responsive, with the hydrophobic block grows, the temperature of the particle mutation would increase. Therefore, PtBA- b -P (DMAEMA- co -PEGMEMA) could control the transfer and release of organic dyes such as methyl red and dithizone through their pH-sensitive properties, and the process had good reversibility. Meanwhile, PtBA- b -P(DMAEMA- co -PEGMEMA) micelles could also deliver some specific hydrophobic anticancer drug , such as camptothecin (CPT). In conclusion, the copolymers synthesized in this work have potential applications in the fields of environmental protection and drug delivery.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Xiao-Liang Yuan,Shu-Chen Yu,Lu Xiao,Ting-Ting Qiu,Xiu-Juan Chen,Xi-Ru Wang,Fang-Qi Cao,Wen-Bin Liu
1-(5-Fluoropentyl)-N-(2-phenylpropan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-3-carboxamide (5F-CUMYL-P7AICA) represents a novel class of synthetic cannabinoids (SCs), constituting one of the most rapidly evolving groups of new psychoactive substances (NPS) that have been widely abused in recent years. However, precise qualitative analysis and accurate quantification pose significant challenges due to the lack of reference materials (RM) available for forensic drug prohibition and sentencing judges. Consequently, RM or certified reference materials (CRM) are essential for ensuring exact measurements and traceability of results in chemical analyses. The pure 5F-CUMYL-P7AICA candidate was autonomously synthesized through a two-step reaction process and subsequently purified via two-column chromatography. Two quantitative analytical methods were employed during the assessment of the pure 5F-CUMYL-P7AICA: quantitative nuclear magnetic resonance spectroscopy of hydrogen ( 1 H qNMR) method and mass balance (MB) method. For the 1 H qNMR, the mass fraction value reached 99.86% which could be traced back to the internal standard (benzoic acid). For the MB methods, the mass fraction value was 99.90% while the structurally related impurities of the candidate (0.05%), inorganic impurities (0.000006%), water (0.05%), and volatile organic solvent (0, or not detected) have been subtracted. Finally, the certified value was assigned to 99.9%, with an expanded uncertainty of 0.3% ( k = 2). Furthermore, the application of CRM would be finished in our subsequent work, and we anticipate that this high-purity CRM could play an essential role in the field of forensic science and sentencing judgement.
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ANALYTICA CHIMICA ACTA
·
2019
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IF 5.256
Jun Yao,Min Chen,Nannan Li,Chaohui Liu,Mei Yang
As an ideal alternative to bisphenol A (BPA), bisphenol S (BPS) has similar biotoxicity, teratogenicity , carcinogenicity and mutagenicity as BPA. Nevertheless, to date, a fast, sensitive and portable method for meeting on-site measurement of BPS had not been established. Hence, it was particularly urged to develop a fast and highly sensitive method for tracing BPS. Currently, a novel molecularly imprinted polymer (MIP) electrochemical sensor had been successfully fabricated for the detection of BPS, wherein the composite of three-doped carbon quantum dots (B, N, F-CQDs) and silver nanoparticles (AgNPs) were utilized as an electron conducting layer, and MIP was applied as recognition element of target molecules. The step-by-step fabrication process and the adsorption capacity of the modified electrode were evaluated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronocoulometry (CC). The results indicated that the synergy between B, N, F-CQDs and AgNPs dramatically improved the sensitivity of the electrode and achieved the amplification of the electrical signal. Meanwhile, the electrochemical activities of BPS were explored by CV and differential pulse voltammetry (DPV). And, the various parameters relating to the electrochemical kinetic properties of BPS were calculated. To the best of our knowledge, this was rarely reported in peer journals. The MIP remarkably improved the selectivity of the sensor owing to the specific recognition of the imprinted cavities. The linear response range of the new sensor was 1 × 10 −8 M to 5 × 10 −5 M with a detection limit of 1.12 × 10 −8 M and the electrode designed in this paper could meet the requirement of trace-level measurement of BPS in biological and environmental samples. Additionally, the sensor was used to determine BPS in plastic products with good anti-interference and acceptable recovery.
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