JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2022
·
IF 3.318
Zong-Qin Ma,Ying-Hui Wang,Yuan Peng,Xin Guo,Zhe Meng
In this paper, we developed a facile route for the preparation of a novel bimetal oxide affinity chromatography (MOAC) material. The TiO 2 /ZrO 2 @MoS 2 was constructed by the electrostatic interaction between titanium oxide/zirconia ( w : w , 10:1) and molybdenum disulfide nanosheet. The nanocomposite has the large specific surface area (186.30 m 2 ⋅g −1 ) and pore volume (0.37 cm 3 ⋅g −1 ). Compared with single-metal probes, the combination of bimetallic oxides probe (TiO 2 /ZrO 2 ) and hydrophilicity MoS 2 support offered multitudinous affinity sites for phosphopeptides capturing from tryptic digests of protein samples under 50% acetonitrile-1% trifluoroacetate conditions. Singnificant feasibility of the TiO 2 /ZrO 2 @MoS 2 nanomaterial for the enrichment of phosphopeptides under optimal conditions was proved via the bovine serum albumin (BSA) and the mixtures of β-casein. The phosphopeptide expression was identified using ultra-performance liquid chromatography (uHPLC) separation and-linear ion trap mass spectrometry (MS n ). With these affinity characters of TiO 2 /ZrO 2 @MoS 2 , it exhibited higher binding capacity (25 mg⋅g −1 ), better selectivity for phosphopeptides from β-casein/BSA (1:2000) tryptic digests, high sensitivity (1 fmol⋅µL −1 ) towards phosphopeptides from β-casein tryptic digests, and great reusability of 8 cycles test for capturing phosphopeptides. In addition, the TiO 2 /ZrO 2 @MoS 2 with high sensitivity and selectivity was successfully applied to enriching phosphopeptides from nonfat milk and human serum samples. More importantly, the TiO 2 /ZrO 2 @MoS 2 was further successfully applied to multi-phosphopeptides enrichment, 1779 serine, threonine and tyrosine phosphosites can be identified in A549 cell protein tryptic digest. Compared with commercial TiO 2 from enrichening 416 phosphopeptide from A549 cell lysates, the successful locating of 44 phosphosites were overlapped.
研究领域:
生物化学
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分析化学
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蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2023
·
IF 3.9
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
The resistance of cancer cells to anticancer drugs has been recognized as one of the main reasons for chemotherapy failure. Multidrug combination therapy is one of the most effective ways to solve this problem. Therefore, in this article, we designed and synthesized a pH/GSH dual-responsive camptothecin/doxorubicin (CPT/DOX) dual pro-drug synergistic treatment system with the aim of overcoming the resistance of non-small cell lung cancer A549/ADR cells to DOX. The pro-drug cRGD-PEOz-S-S-CPT (cPzT) was obtained by linking CPT to poly(2-ethyl-2-oxazoline) (PEOz) with endosomal escape properties through a GSH-responsive disulfide bond and modifying it with the targeted peptide cRGD. The pro-drug mPEG–NH–N=C-DOX (mPX) was synthesized by attaching DOX to polyethylene glycol (PEG) through acid-sensitive hydrazone bonds. The dual pro-drug micelles cPzT/mPX configured according to the CPT/DOX mass ratio of 3:1 showed a strong synergistic therapeutic effect at IC50 with a combined therapy index CI = 0.49, far less than 1. Moreover, with the further improvement of the inhibition rate, the 3:1 ratio showed a stronger synergistic therapeutic effect than other ratios. The cPzT/mPX micelles not only had better targeted uptake ability but also showed a better therapeutic effect in both 2D and 3D tumor suppression assays relative to free CPT/DOX and significantly enhanced the penetration ability into solid tumors. In addition, the results of confocal laser scanning microscopy (CLSM) showed that cPzT/mPX could effectively overcome the resistance of A549/ADR cells to DOX by delivering DOX into the nucleus to exert its effect. Thus, this dual pro-drug synergistic therapy system combining targeting and endosomal escape ability provides a possible strategy to overcome tumor drug resistance.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
·
2016
·Vol. 21
·期 8
·945-956
·
IF 2.495
Sun Dongdong,Mou Zhipeng,Li Nuan,Zhang Weiwei,Wang Yazhe,Yang Endong,Wang Weiyun
Two new ruthenium (II) polypyridyl complexes [Ru(MeIm) 4 (pip)] 2+ ( 1 ) and [Ru(MeIm) 4 (4-npip)] 2+ ( 2 ) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV–Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells’ migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2 . The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.
研究领域:
化学
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肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Xiuchun Li,Shanshan Yan,Jing Dai,Yi Lu,Yiqun Wang,Man Sun,Jinkang Gong,Yuan Yao
Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell–cell contact to become mesenchymal stem cells, which is important on development and embryogenesis, wound healing, and cancer metastasis. This research aims to investigate the effect of topological cue as modulating factor on the EMT by tuning the diameter of electrospinning nanofiber. The cell-nanofiber interaction between human lung epithelial cell A549 and electrospinning nanofibers composed of polyvinyl alcohol (PVA) and type I collagen were investigated. The electrospinning of regenerated PVA/Collagen nanofibers were performed with water/acetic acid as a spinning solvent and glutaraldehyde as a chemical cross-linker. Parameterization on concentration, applied voltage and feeding rate was finalized to generate smooth nanofibers with good homogeneity. The scanning electron microscopy result demonstrated that A549 cell appropriately achieved extended morphology by the filopodia attaching to the surface of the nanofibrous mats. When the diameter changed from 90 nm to 240 nm, the A549 cell was correspondingly express varied EMT related genes. Gene expression analysis was conducted by qPCR using three typical markers for detecting EMT: N-cadherin (NCad), Vimentin (Vim), and Fibronectin (Fib) . An increasing expression pattern was observed on cell culturing on 170 nm sample with respect to cell cultured on 90 nm and 240 nm. This result indicated the 170 nm PVA/Collagen nanofibers induce A549 cells to process epithelial–mesenchymal transition more seriously than those on 90 nm or 240 nm.
研究领域:
生物材料
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细胞生物学
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组织工程
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 190
·期 10
·1-14
·
IF 5.7
Liu Jian,Wen Changchun,Hu Miaomiao,Leng Nan,Lin Xiang-Cheng
MnO 2 nanosheets (MnO 2 NSs) were synthesized by one-step method, and MnO 2 NSs were applied to A549 cell chemodynamic Therapy (CDT). The cytotoxicity, redox ability, and reactive oxygen species production of MnO 2 NSs have been investigated, and differences in cell metabolism during CDT were determined using liquid chromatography-mass spectrometry (LC–MS/MS). In addition, the metabolites of A549 lung cancer cells affected by MnO 2 NSs treatment are identified; metabolite differences were identified by PCA, PLS-DA, orthogonal PLS-DA, and other methods; and these differences were analyzed using non-targeted metabolomics. We found that A549 cells which were treated by MnO 2 NSs have 17 different metabolites and 9 metabolic pathways that varied markedly. Owing to their unique composition, structure, and physicochemical properties, MnO 2 NSs and their composites have become a favored type of nanomaterial used for CDT in cancer therapy. This work provides insights into the mechanism underlying the effects of MnO 2 NSs on the tumor microenvironment of A549 lung cancer cells, effectively making up for the deficiency of the study on cellular mechanism of CDT-induced apoptosis of cancer cells. It could aid the development of cancer CDT treatment strategies and help improve the use of nanomaterials in the clinical field. Graphical Abstract
研究领域:
纳米技术
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癌症生物学
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代谢组学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND INDUSTRIAL HEALTH
·
2023
·
IF 1.9
Xueqi Liu,Wenwu Sun,Jianping Cao,Zhuang Ma
Smoking or occupational exposure leads to low concentrations of acrolein on the surface of the airways. Acrolein is involved in the pathophysiological processes of various respiratory diseases. Reports showed that acrolein induced an increase in mitochondrial reactive oxygen species (mROS). Furthermore, exogenous H₂O₂ was found to increase intracellular Zn2⁺ concentration ([Zn2⁺]ᵢ). However, the specific impact of acrolein on changes in intracellular Zn2⁺ levels has not been fully investigated. Therefore, this study aimed to investigate the effects of acrolein on mROS and [Zn2⁺]ᵢ in A549 cells. We used Mito Tracker Red CM-H2Xros (MitoROS) and Fluozin-3 fluorescent probes to observe changes in mROS and intracellular Zn2⁺. The results revealed that acrolein increased [Zn2⁺]ᵢ in a time- and dose-dependent manner. Additionally, the production of mROS was observed in response to acrolein treatment. Subsequent experiments showed that the intracellular Zn2⁺ chelator TPEN could inhibit the acrolein-induced elevation of [Zn2⁺]ᵢ but did not affect the acrolein-induced mROS production. Conversely, the acrolein-induced elevation of mROS and [Zn2⁺]ᵢ were significantly decreased by the inhibitors of ROS formation (NaHSO₃, NAC). Furthermore, external oxygen free radicals increased both [Zn2⁺]ᵢ levels and mROS production. These results demonstrated that acrolein-induced elevation of [Zn2⁺]ᵢ in A549 cells was mediated by mROS generation, rather than through a pathway where [Zn2⁺]ᵢ elevation leads to mROS production.
研究领域:
呼吸系统疾病
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细胞生物学
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氧化应激
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Qingying Shi,Jingchun Tang,Lan Wang,Rutao Liu,John P. Giesy
Awareness of risks posed by widespread presence of nanoplastics (NPs) and bioavailability and potential to interact with organic pollutants has been increasing. Inhalation is one of the more important pathways of exposure of humans to NPs. In this study, combined toxicity of concentrations of polystyrene NPs and various phthalate esters (PAEs), some of the most common plasticizers, including dibutyl phthalate (DBP) and di-(2-ethyl hexyl) phthalate (DEHP) on human lung epithelial A549 cells were investigated. When co-exposed, 20 μg NPs/mL increased viabilities of cells exposed to either DBP or DEHP and the modulation of toxic potency of DEHP was greater than that of DBP, while the 200 μg NPs/mL resulted in lesser viability of cells. PAEs sorbed to NPs decreased free phase concentrations ( C free ) of PAEs, which resulted in a corresponding lesser bioavailability and joint toxicity at the lesser concentration of NPs. The opposite effect was observed at the greater concentration of NPs, which may result from the dominated role of NPs in the combined toxicity. Furthermore, our data showed that oxidative stress and inflammatory reactions were mechanisms for combined cytotoxicities of PAEs and NPs on A549 cells. Results of this study emphasized the combined toxic effects and mechanisms on human lung cells, which are helpful for assessing the risk of the co-exposure of NPs and organic contaminants in humans.
研究领域:
环境科学
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毒理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2022
·Vol. 7
·期 29
·e202200922
·
IF 2.307
Xiangrui Meng,Qiao Zheng,Yuanyuan Sun,Qian Wang,Lan Wang,Ping Yuan,Xiao Song,Yuqing Miao
Graphical The present study aimed to explore new higher-H 2 O 2 -content and faster-H 2 O 2 -release rate peroxide compounds for treatment of lung cancer. The results showed that CP−B has extremely low side effects and potentially tumor treatment capabilities. Finally, it was found that CP−B up-regulate the INS-IGF2 gene and it was closely related to the PI3 K/AKT signaling pathway. Lung cancer is one of the malignant tumors with the leading morbidity and mortality worldwide. H 2 O 2 is an important oxidant, and lethal to tumor cells. The present study aimed to explore new higher-H 2 O 2 -content and faster-H 2 O 2 -release rate carbamide peroxide (CP) compounds for treatment of lung cancer. The CP added with benzoic acid termed CP−B was applied in the research. Fenton reaction was used to determine the content and rate of H 2 O 2 release by degrading organic small molecule dyes. The results showed that CP−B could be decolorized 200 mg/L RhB solution within 60 s. The phenotype was analyzed by vitro experiment the effects of the CP compound on A549 lung cancer cell line. The results showed that CP−B had a significant effect on pro-apoptosis, anti-proliferation and anti-migration of A549 cells. Using RNA seq, it was found that CP−B might up-regulate the INS-IGF2 gene and it was closely related to the PI3 K/AKT signaling pathway. Finally, in vivo experiments indicated that CP−B has extremely low side effects and potentially tumor treatment capabilities.
研究领域:
肿瘤学
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药理学
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分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2023
·Vol. 47
·期 26
·12431-12444
·
IF 3.3
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
Polyethylene glycol (PEG), which can impart long cycling performance to drug carriers, has been commonly used for drug carrier modification. However, PEG modification impedes cellular uptake of drug carriers and intracellular release of drugs, a problem known as the “PEG dilemma” that limits its application. In this study, we designed and synthesized mPEG-NCH-DOB molecules with acid-sensitive hydrazone bonding for the responsive removal of PEG. Drug-loaded lipid PHDGX for doxorubicin (DOX) delivery was obtained by compounding mPEG-NCH-DOB with lipid DOPG, which possess the capability for long cycling, and acid-sensitive PEG-removal to accelerate drug release and enhance cellular uptake. mPEG-NCH-DOB could reach 50% fracture rate after 24 h at pH 5.0. The cytotoxicity assay and flow cytometry (FCM) results showed that PHDGX could enter A549/ADR cells more easily than free DOX at low DOX concentrations and has stronger anti-cancer ability. Through a confocal laser-scanning microscopy (CLSM) study, PHDGX was found to enter the nucleus of A549/ADR cells more easily than free DOX at the same time point, which indicated that PHDGX could overcome the DOX resistance of A549/ADR at low DOX concentrations. The 3D tumor microsphere (MC) growth inhibition assay showed that PHDGX not only has the best MC inhibition ability but also has better MC penetration ability than free DOX. Therefore, this drug-loaded liposome has good stability under conventional conditions and responsive PEG removal in the tumor acid environment, offering a potential strategy for utilizing PEG in drug carrier modification and overcoming tumor resistance to free drugs.
研究领域:
药学
·
纳米技术
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癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
APOPTOSIS
·
2019
·Vol. 24
·期 3
·312-325
·
IF 4.021
Zhang Cheng-cheng,Li Chen-guang,Wang Yao-feng,Xu Li-hui,He Xian-hui,Zeng Qiong-zhen,Zeng Chen-ying,Mai Feng-yi,Hu Bo,Ouyang Dong-yun
Gasdermin E (GSDME) has an important role in inducing secondary necrosis/pyroptosis. Upon apoptotic stimulation, it can be cleaved by activated caspase-3 to generate its N-terminal fragment (GSDME-NT), which executes pyroptosis by perforating the plasma membrane. GSDME is expressed in many human lung cancers including A549 cells. Paclitaxel and cisplatin are two representative chemotherapeutic agents for lung cancers, which induce apoptosis via different action mechanisms. However, it remains unclear whether they can induce GSDME-mediated secondary necrosis/pyroptosis in lung A549 cancer cells. Here we showed that both paclitaxel and cisplatin evidently induced apoptosis in A549 cells as revealed by the activation of multiple apoptotic markers. Notably, some of the dying cells displayed characteristic morphology of secondary necrosis/pyroptosis, by blowing large bubbles from the cellular membrane accompanied by caspase-3 activation and GSDME-NT generation. But the ability of cisplatin to induce this phenomenon was much stronger than that of paclitaxel. Consistent with this, cisplatin triggered much higher activation of caspase-3 and generation of GSDME-NT than paclitaxel, suggesting that the levels of secondary necrosis/pyroptosis correlated with the levels of active caspase-3 and GSDME-NT. Supporting this, caspase-3 specific inhibitor (Ac-DEVD-CHO) suppressed cisplatin-induced GSDME-NT generation and concurrently reduced the secondary necrosis/pyroptosis. Besides, GSDME knockdown significantly inhibited cisplatin- but not paclitaxel-induced secondary necrosis/pyroptosis. These results indicated that cisplatin induced higher levels of secondary necrosis/pyroptosis in A549 cells than paclitaxel, suggesting that cisplatin may provide additional advantages in the treatment of lung cancers with high levels of GSDME expression.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Management and Research
·
2023
·
IF 3.3
Ping Huang,Shi-Xia Du
Objective The effect of PUE on enhancing the anti-cancerous efficacy of DDP on drug-resistant A549/DDP cancer and the underlying mechanisms were thoroughly investigated.Materials and Methods The cytotoxicity of PUE, DDP, and PUE + DDP to A549 cells and A549/DDP cells, respectively, is determined by cell apoptosis experiments. Anti-proliferation effect of PUE, DDP, and PUE + DDP on A549 cells and A549/DDP cells is evaluated by the cell cloning assay. Qualitative and quantitative analysis of the levels of PUE, DDP, and PUE + DDP of cell proliferation-related genes and proteins expressions in A549/DDP cells are determined by Western blot assay. The levels of VEGF in A549/DDP cells after different treatment strategies are determined by ELISA assay. Qualitative and quantitative determination of VEGF expression in tumor tissues are done by immunohistochemical staining.Results In vitro cellular experiments revealed that co-incubation of A549/DDP cells with PUE and DDP led to a dramatically decreased cell viability and cell survival rate compared with the cells only treated by DDP. Such a stimulating effect of PUE on DDP was further confirmed in vivo with results shown that the A549/DDP cancer-bearing mice treaded by combination therapy achieved the lowest tumor growth rate and longest survival time.Conclusion Taking these results together, we can draw the conclusion that the PUE enhances the anti-tumor effect of DDP on the drug-resistant A549 cancer in vivo and in vitro through activation of the Wnt signaling pathway.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2021
·Vol. 8
·期 9
·2660-2675
·
IF 8.131
Qingying Shi,Jingchun Tang,Xiaomei Liu,Rutao Liu
The widespread presence of nanoplastics (NPs), with small particle sizes and high specific surface area, leads to the exposure and potential health risk for humans. The plastic particles widely detected in the indoor and outdoor air imply potential threats to the human respiratory system. However, the impact of aging NPs on their toxicity has been poorly considered, although it is an inevitable process suffered by them once they enter the environment. In this study, the aging of polystyrene (PS) NPs by photodegradation under ultraviolet irradiation for 2 months was investigated, and the toxicities of pristine and aged NPs to human lung epithelial A549 cells were compared. The results revealed alterations in the physicochemical properties with the size of NPs reduced and the abundant oxygen-containing groups formed on the surface. The toxic effects of the pristine and aged NPs at the cellular level on the cell viability, oxidative stress, membrane damage and mitochondrial dysfunction were illustrated in A549 cells, indicating that the aged NPs exhibited greater cytotoxicity than pristine NPs and this toxicity was in a positively aging time-related manner. Transcriptome analysis further revealed the impacts of aged NPs on A549 cells at the molecular level, wherein the aged NPs presented aggravated interference in gene expression, reconfirming the elevated toxicity of NPs after ultraviolet-induced photodegradation. This study highlights the importance of photodegradation on the toxicity of NPs in human health, which is of great significance for the risk assessment of NPs.
研究领域:
环境科学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 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）