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1.
Seizure ; 88: 138-142, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33895389

RESUMO

BACKGROUND: To determine treatment effects on the incidence of post-stroke epilepsy (PSE) using different doses of statin, a prospective hospital-based cohort study was designed to explore whether a double-dose statin treatment can better prevent the occurrence of PSE. METHODS: A total of 1152 patients with newly diagnosed ischemic stroke admitted to our hospital from March to August 2017 were selected, 1033 of whom were followed-up. Patients were divided into two treatment groups:(1) standard-dose (20 mg atorvastatin or 10 mg rosuvastatin,daily oral; 788 patients); and (2) double-dose (40 mg atorvastatin or 20 mg rosuvastatin, daily oral; 245 patients).At 18 months follow-up was conducted to compare the incidence of PSE between groups. RESULTS: In general, in the standard-dose group we observed two cases of early seizure (ES) (0.25%), 22 cases oflate seizure (LS) (2.79%) and 20 cases of PSE (2.54%). In the double-dose group, onepatient had ES (0.41%), two patients had LS (0.82%), and onepatient had PSE (0.41%). The incidence of PSE was significantly lower in the double-dose group as compared to the standard-dose group. There was a higher proportion of PSE in patients younger than 65 years and in males. Three patients had ES; one presented with focal aware seizure (FAS), and two had focal to bilateral tonic-clonic seizure (FBTCS). Among the 21 patients with PSE, there were two cases of FAS, five cases of focal impaired awareness seizure (FIAS), five cases of FBTCS, and nine cases of GTCS, suggesting that partial seizure is the most common type of PSE. Cerebral cortex was involved in 85.75% of cases with PSE, and multiple lobes were involved in 61.9% of cases with PSE. CONCLUSION: Increasing the dose of statin treatment during the acute phase of ischemic stroke reduces the incidence of PSE. Further research is needed to understand the mechanisms underlying the potential preventative effects of statins against PSE.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33693962

RESUMO

INTRODUCTION: Glioblastoma (GBM) is a complex disease with high intratumoral heterogeneity, understanding the molecular characteristics of intratumoral heterogeneity accurately is the basis for precision treatment. Although the existing typing strategy based on tumor molecular characteristics has a positive effect, there is still room for improvement, which is mainly because the traditional typing is completed based on the sequencing data of tissue samples, that is, the obtained data are the average level of patient tumor tissues, masking the intratumoral heterogeneity of a single patient and cannot reflect the real level of patient tumor cells. At present, cancer molecular typing is mostly performed based on transcriptome (RNA-seq) without considering lncRNA molecules that are also tissue-specific and developmental stage-specific. Therefore, in this study, we used lncRNAs as typing markers and combined single-cell expression profiles to retype glioblastoma, providing new ideas for GBM molecular typing, and further analyzed the shortcomings of traditional therapies at the singlecell level based on typing results and proposed new precise therapeutic insights. METHODS: We downloaded GBM single-cell sequencing data from GSE84465 and performed a series of preprocessing. The intratumoral heterogeneity of patients at the single-cell level was revealed using t-SNE, and the room for improvement of the existing traditional histotyping method was revealed using heat map and density curve. Subsequently, to validate the feasibility of lncRNA typing, we compared the similarities and differences of expression patterns between lncRNAs and mRNAs in GBM cells. Then, we used the R package "Seurat" to perform unsupervised clustering of GBM cells for re-typing and performed a detailed analysis of the biological characteristics of each subtype, including differentially expressed lncRNAs and marker lncRNAs. For validation, we performed survival analysis on GBM tissue data from the TCGA database to reveal the impact of different subtypes on patient survival prognosis. Eventually, based on the results, we screened the therapeutic drugs of each subtype by targeting the downstream regulatory genes of lncRNAs and proposed a new precision therapeutic strategy. RESULTS: GBM has significant intratumoral heterogeneity at the single-cell level, with more than one traditional subtype highly expressed in each patient, which reflects the shortcomings of traditional histotyping. LncRNAs and mRNAs have similar expression patterns in GBM cells, and the expression coefficient of variation of lncRNAs is higher than that of mRNAs, meaning that lncRNAs will better reflect the intratumoral heterogeneity. GBM was reclassified into four subtypes by unsupervised clustering, with different subtypes having different biological characteristics. Survival analysis showed that patients with different subtype compositions had different prognostic outcomes, so different subtypes had different effects on patient prognosis. Based on this, 47 drugs were screened for treatment. There are both shared and unique drugs between different subtypes. A new precision treatment strategy was proposed: for patients with different subtypes, in addition to the combination of drugs targeting single subtype, drugs targeting multiple subtypes can also be selected. CONCLUSION: Intratumoral heterogeneity may lead to poor prognosis or recurrence after treatment, and more precise typing of GBM can be performed based on single-cell lncRNA expression profiles. The biological characteristics possessed by different subtypes will have different effects on patients, such as survival time. For different subtypes, there are both drugs targeting single subtype and drugs targeting multiple subtypes, and we prefer drugs targeting multiple subtypes because this strategy can maximize medication efficiency and reduce the types of medication to reduce risks and side effects.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33557516

RESUMO

Bimetallic organic frameworks (Bi-MOFs) have been recognized as one of the most ideal precursors to construct metal oxide semiconductor (MOS) composites, owing to their high surface area, various chemical structures, and easy removal of the sacrificial MOF scaffolds through calcination. Herein, we synthesized Zn/Ni Bi-MOF for the first time via a facile ion exchange postsynthetic strategy, formed a three-dimensional framework consisting of infinite one-dimensional chains that is unattainable through the direct solvothermal approach, and then transformed the Zn/Ni Bi-MOF into a unique ZnO/NiO heterostructure through calcination. Notably, the obtained sensor based on a ZnO/NiO heterostructure exhibits an ultrahigh response of 280.2 toward 500 ppm n-propanol at 275 °C (17.2-fold enhancement compared with that of ZnO), remarkable selectivity, and a limit of detection of 200 ppb with a notable response (2.51), which outperforms state-of-the-art n-propanol sensors. The enhanced n-propanol sensing properties may be attributed to the synergistic effects of several points including the heterojunction at the interface between the NiO and ZnO nanoparticles, especially a one-dimensional chain MOF template structure as well as the chemical sensitization effect of NiO. This work provides a promising strategy for the development of a novel Bi-MOF-derived MOS heterostructure or homostructure with well-defined morphology and composition that can be applied to the fields of gas sensing, energy storage, and catalysis.

4.
Chemosphere ; 269: 129394, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388568

RESUMO

In this study, magnetic Cu and Ni bimetallic particles embedded carbon sheets, namely as C@Cu-Ni, was derived via calcining a mixture of Cu-MOFs and Ni-MOFs (mass ratio = 4:6) under N2 protection and served as a catalyst for the degradation of 2,4,6-trichlorophenol (2,4,6-TCP) by peroxymonosulfate (PMS). The results showed that more than 98.5% of 2,4,6-TCP (10 mg L-1) was rapidly decomposed at initial pH = 5, PMS = 1 mM and catalyst dosage = 0.1 g L-1 within 30 min, accompanied by 42.47% removal of total organic carbon (TOC). This fully confirmed that C@Cu-Ni possessed excellent catalytic performance for PMS activation. The radical quenching experiments and electron paramagnetic resonance (EPR) investigation testified that the reactive oxygen species (ROS) included SO4•-, •OH, O2•- radicals and singlet oxygen (1O2), which were responsible for the rapid degradation of 2,4,6-TCP. Among them, O2•-and 1O2 played a decisive role. Cyclic voltammograms (CV) and electrochemical impedance spectroscopy (EIS) revealed that C@Cu-Ni material possessed superior electrical conductivity and electron transfer, improving its catalytic activity. What is more, C@Cu-Ni displayed excellent stability and could be consecutively used for five times without any decline of catalytic performance. The main intermediates of the 2,4,6-TCP degradation were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and possible pathways of 2,4,6-TCP degradation were further proposed. The extraordinary stability and superior catalytic activity of C@Cu-Ni coupled with its easy separation from wastewater due to magnetism suggest that the newly synthesized material may offer a promising alternative approach to efficiently degrade organic pollutants by PMS.


Assuntos
Peróxidos , Espectrometria de Massas em Tandem , Clorofenóis , Fenômenos Magnéticos
5.
Chemistry ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146415

RESUMO

A novel armour-type composite of metal organic framework-capsulated CoCu nanoparticles with Fe3O4 core (Fe3O4@SiO2-NH2-CoCu@UiO-66) has been designed and synthesized by the half-way injection method, which successfully serves as an efficient and recyclable catalyst for the selective transfer hydrogenation. In this half-way injection approach, the pre-synthetic Fe3O4@SiO2-NH2-CoCu was injected into the UiO-66 precursors solution halfway through the MOF budding period. The formed MOF armour could play a role of providing momentous additional catalytic sites besides CoCu nanoparticles, protecting CoCu nanoparticles and improving the catalyst stability, thus facilitating the selective transfer hydrogenation of nitrobenzaldehydes into corresponding nitrobenzyl alcohols in high selectivity (99%) and conversion (99%) rather than nitro group reduction products. Notably, this method achieves the precise assembly of MOF-capsulated composite, and the ingenious combination of MOF and nanoparticles exhibits excellent catalytic performance in the selective hydrogen transfer reaction, implementing a "1+1>2" strategy in catalysis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32975866

RESUMO

Substrate-supported metal-organic frameworks (MOFs) films are desired to realize their potential in practical applications. Herein, a novel substrate-seeding secondary-growth strategy is developed to prepare composites of uniform MOFs films on aerogel walls. Briefly, the organic ligand is "pre-seeded" onto the aerogel walls, and then a small amount of metal-ion solution is sprayed onto the prepared aerogel. The sprayed solution diffuses along the aerogel walls to form a continuous thin layer, which confines the nucleation reaction, promoting the formation of uniform MOFs films on the aerogel walls. The whole process is simple in operation, highly efficient, and eco-friendly. The resulting hierarchical MOFs/aerogel composites have abundant accessible active sites and enable excellent mass transfer, which endows the composite with outstanding catalytic activity and stability in both liquid-phase CO2 cycloaddition and electrochemical oxygen evolution reaction (OER) process.

7.
ACS Appl Mater Interfaces ; 12(38): 42971-42981, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32865972

RESUMO

Developing a simple strategy to fabricate high-performance hydrogen sensors with long-term stability remains quite challenging. Here, we report the H2-sensing performance of Pd-decorated PdO hollow shells (Pd/PdO HSs). In this novel system, the catalyst nanoparticles (Pd NPs) and semiconductor support (PdO) are interconvertible, which is different from traditional hydrogen-sensing systems such as Pd/TiO2 and Pd/ZnO. This Pd/PdO system exhibits multiple unique properties. First, well-distributed Pd NPs with controllable density can be decorated on PdO support through a one-step NaBH4 treatment during which PdO is partially reduced into Pd. Second, the decorated Pd NPs are physically inlaid in the PdO support, which not only prevents the agglomeration or detachment of Pd NPs but also enhances the electron transfer between Pd NPs and PdO. Third, Pd/PdO HSs can be reoxidized into PdO HSs once their sensing performance degrades, which repeatedly manipulates Pd/PdO HSs under the initial reduction process, leading to the reactivation of the sensing performance. With all these advantages, Pd/PdO HSs demonstrate a detection limit lower than 1 ppm, a response/recovery time to 1% H2 of 5 s/32 s at room temperature, and a repeatable reactivation ability. The strategy presented here is convenient and time saving and has no need to prefunctionalize the PdO surface for the decoration of catalyst NPs. Moreover, the unique reactivation ability of Pd/PdO system opens a new strategy toward extending the lifetime of H2 sensors.

8.
Langmuir ; 36(26): 7392-7399, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32493015

RESUMO

An interesting reversible shape and structure transformation between two types of two-dimensional (2D) metal-organic frameworks (MOFs) has been successfully achieved by the spray method. The ability to precisely control the morphology and structure of 2D MOFs is also developed by altering the amount of MOF precursors and reversing the spray order. Meanwhile, the mechanism of the transformation between two MOFs is studied and conversion is induced by the change of the acidity in the reaction system. In addition, the prepared non-interpenetrate CuBDC twists exhibit more remarkable catalytic performance in C-S coupling reaction than Cu(BDC)(DMF) nanosheets owing to the more unsaturated coordination copper active sites from the non-interpenetrate structure. The catalytic result reveals the relationship between structure and function.

9.
Environ Res ; 187: 109665, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32464448

RESUMO

Co3O4-SnO2/rice straw biochar (RSBC) was prepared for the first time via calcining oxalate precipitation precursor dispersed on the surface of RSBC and used as a catalyst for activating PMS to degrade sulfisoxazole (SIZ). The results demonstrated that Co3O4-SnO2/RSBC possessed much better catalytic performance than Co3O4, Co3O4-SnO2, Co3O4/RSBC, and SnO2/RSBC, which is ascribed to the synergy of Co3O4, SnO2 and RSBC. Approximately 98% of SIZ (50 mg/L) was decomposed by PMS (1 mmol/L) activated with Co3O4-SnO2/RSBC (0.1 g/L) within 5 min. The optimal degradation efficiency of SIZ was realized at the initial pH 9. Co3O4-SnO2/RSBC also displayed remarkable stability and reusability, and the degradation rate of SIZ maintained over 90% even after the fifth recycle run. The electron paramagnetic resonance (EPR) technique and quenching experiments proved singlet oxygen (1O2) to be the main reactive oxygen species (ROS) responsible for the SIZ decomposition in the Co3O4-SnO2/RSBC/PMS system. On the basis of the characterization analysis, the identification of the ROS and the SIZ degradation products, the possible mechanism and pathways of the SIZ degradation by a combination of PMS and Co3O4-SnO2/RSBC were further proposed. This study provides not only a new insight into non-radical mechanism for the heterogeneous activating PMS over Co3O4-SnO2/RSBC to degrade organic pollutants but also an eco-friendly synthetic route for exploring novel and efficient catalysts.


Assuntos
Oryza , Oxigênio Singlete , Carvão Vegetal , Peróxidos , Sulfisoxazol
10.
Nanotechnology ; 31(25): 255604, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32270766

RESUMO

Encapsulation of metal oxide nanoparticles (MO NPs) inside metal-organic frameworks (MOFs) has been realized successfully via surfactant-assisted nano-confined space strategy, which is a universal method for various MO NPs@MOFs. The size of MO NPs was limited by the confined nano-space and could be adjusted to a certain extent. The synthesis mechanism of MO NPs@MOFs was revealed via detailed structural characterizations and a series of control experiments. Surfactants introduced during MOFs (CuBDC, BDC = 1,4-benzenedicarboxylic acid) formation process plays a very important role in producing uniform voids of nano-confined space. Cu ions in MOF frameworks were directly used as precursors to fabricate CuO NPs in these confined void spaces. The synthesized CuO@CuBDC composites showed excellent catalytic activity in C-S cross-coupling reactions and dye pollutant photo-degradation reactions.

11.
ACS Sens ; 5(2): 303-307, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32039587

RESUMO

The detection of thiocyanate (SCN-) is particularly important in industrial effluents and biological fluids because of the toxic nature of SCN-. Herein, a metal-insulator-metal (MIM) resonator for visual detection of SCN- is presented based on a poly[(2-(methacryloyloxy)ethyl) trimethylammonium chloride] (PMETAC) brush. The MIM resonator exhibits obvious color change as the concentration of SCN- changes, which can be easily distinguished by the naked eyes. In addition, the as-prepared MIM resonator also shows the advantages of good anti-interference, excellent reusability, and fast response rate. Combining the above advantages, the proposed MIM resonator may provide a broad perspective for a wide variety of visible-light applications.

12.
Nanotechnology ; 31(16): 165504, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31899903

RESUMO

Cu3(PO4)2 flowers are reported for the first time as a solid precursor for the preparation of hierarchical CuO particles with sea urchin-like morphology in the absence of self-assembled templates or matrixes. In the alkaline condition, Cu3(PO4)2 transforms into Cu(OH)2 firstly, and then into CuO through dehydration at room temperature. Different from soluble Cu salt as precursor, the basic building blocks for CuO are continuously supplied in a controlled manner form Cu3(PO4)2 precursor, which ensures a nearly sustained supersaturated concentration that favors heterogeneous nucleation and progressive growth of sea urchin-like CuO particles. The gas sensing property of as-prepared sea urchin-like CuO particles to ethanol is investigated. The sea urchin-like CuO particles exhibit a good sensing performance in terms of high response, short response/recovery time, good selectivity, good reproducibility, and long-term stability. The facile strategy demonstrated here opens up a new strategy to fabricate hierarchical CuO particles with enormous potential from the perspective of practical application.

13.
Rapid Commun Mass Spectrom ; 34 Suppl 1: e8643, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31705568

RESUMO

RATIONALE: In chemical isotope labeling (CIL) liquid chromatography/mass spectrometry (LC/MS) metabolome analysis, the peak pairs of the same metabolite detected from different samples are aligned according to their mass and retention time (RT). Any RT shift of a peak pair in one of the sample files that falls outside the tolerance window will result in misalignment of the pair as a different metabolite. Thus, determination and correction of any significant RT shift are important to ensure the generation of high-quality metabolome results. METHODS: In CIL LC/MS, the heavy-isotope-labeled pooled sample is spiked into all light-isotope-labeled individual samples. As a result, in the analysis of labeled samples of the same type, many common metabolites are detectable with high intensity in all LC/MS runs. We have developed a method to select a few of these metabolites as internal RT reference markers to check the occurrence of any RT shift in an LC/MS run. If a significant shift is found, an expanded list of these markers with their RT values covering the entire LC RT window is selected to serve as internal RT calibrants to recalibrate the chromatogram to correct any RT shift. RESULTS: We developed a software program in R to perform RT check (RTC) and recalibration (RT-calib). This program can quickly determine the occurrence of any RT shift falling outside a user-defined threshold in an LC/MS run, thereby triggering a timely intervention to correct the problem (e.g., fixing a small leak or changing a column). In the analysis of 278 dansylation LC/MS runs of human urine samples, we show that the RT values can be corrected to be within a 30-second window. CONCLUSIONS: An RT-check method and program tailored to CIL LC/MS metabolome analysis have been developed for quick detection and correction of RT shifts during the course of running many metabolome samples.

14.
J Exp Clin Cancer Res ; 38(1): 457, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699152

RESUMO

BACKGROUND: MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. METHODS: Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. RESULTS: We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. CONCLUSION: These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer.


Assuntos
Actinas/metabolismo , Autofagossomos/metabolismo , Regulação da Expressão Gênica , Lisossomos/metabolismo , Miosina Tipo I/genética , Autofagossomos/ultraestrutura , Autofagia , Benzilisoquinolinas/química , Benzilisoquinolinas/farmacologia , Linhagem Celular Tumoral , Cromatografia Líquida , Humanos , Lisossomos/ultraestrutura , Espectrometria de Massas , Mitofagia , Ligação Proteica , Transdução de Sinais
15.
Chem Commun (Camb) ; 55(83): 12567-12570, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31577281

RESUMO

Amorphous bimetallic coordination polymers have been prepared by a mild room temperature solution phase method and utilized as an OER electrocatalyst. Their excellent performance with an overpotential of 228 mV at 10 mA cm-2 and a Tafel slope of 30.3 mV dec-1 exhibits their great potential in the field of the OER.

16.
ACS Appl Mater Interfaces ; 11(44): 41668-41675, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31623430

RESUMO

Dynamic color-changing nanomaterials have been widely investigated for applications in fields like optical sensors, wearable activity monitors, smart electronic devices, and anticounterfeiting materials due to the excellent ability to change their optical properties with external variation. Here, a simple metal-insulator-metal (MIM) trilayer Fabry-Perot resonance cavity with a poly(N-isopropylacrylamide) (PNIPAm) brush layer as a responsive element is reported as a thermal-induced colorimetric response platform. The dynamic changes of conformation and physical properties of PNIPAm brush layer in response to external signals give rise to a significant color change of the MIM Fabry-Perot resonance cavity. This MIM Fabry-Perot resonance cavity shows the advantages of dynamic color change, rapid response, good repeatability, and simple construction. Additionally, the as-prepared MIM cavity shows great potential in various applications such as color printing, multicolor indicator, and information anticounterfeiting.

17.
Chem Commun (Camb) ; 55(63): 9343-9346, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31313763

RESUMO

A hierarchical trimetallic coordination polymer film was prepared using a spray-assisted interface synthetic strategy and in situ deposited onto Ni foam (denoted as Co0.5Ni0.3Fe0.2BDC-HCPF/Ni foam). The as-prepared material exhibits a 3D network hierarchical structure with 1D interconnected nanofibers and can be directly used as an efficient OER electrocatalyst.

18.
Chem Commun (Camb) ; 55(57): 8293-8296, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31249996

RESUMO

A feasible and rapid one-step strategy has been developed to fabricate 2D metal-organic framework nanosheet (MOF-NS)@fiber composites at room temperature by spray technique, through which five kinds of MOF-NS@fiber were successfully prepared. The representative nanoscale CuBDC were synthesized on the surface of carbon fibers with homogeneous dispersion and high coverage.

19.
J Exp Clin Cancer Res ; 38(1): 225, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138329

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is often aggressive and associated with a poor prognosis. Due to the lack of available targeted therapies and to problems of resistance with conventional chemotherapeutic agents, finding new treatments for TNBC remains a challenge and a better therapeutic strategy is urgently required. METHODS: TNBC cells and xenograft mice were treated with a combination of chloroquine (CQ) and isorhamnetin (IH). Mitochondrial fission, apoptosis, and related signaling pathways were determined by flow cytometry, immunofluorescence, and related molecular biological techniques. RESULTS: The inhibition of autophagy/mitophagy by CQ selectively enhances IH-induced mitochondrial fission and apoptosis in TNBC cells but not in estrogen-dependent breast cancer cells. These events were accompanied by mitochondrial translocation of Bax and the release of cytochrome c. Mechanistically, these effects were associated with oxidative stress-mediated phosphorylation of CaMKII (Thr286) and Drp1 (S616), and subsequent mitochondrial translocation of CaMKII and Drp1. The interruption of the CaMKII pathway by genetic approaches (e.g. CaMKII mutant or siRNA) attenuated combination-mediated mitochondrial fission and apoptosis. The combination of CQ/IH was a marked inhibitor tumor growth, inducing apoptosis in the TNBC xenograft mouse model in association with the activation of CaMKII and Drp1 (S616). CONCLUSIONS: Our study highlights the critical role of ROS-mediating CaMKII/Drp1 signaling in the regulation of mitochondrial fission and apoptosis induced by combination of CQ/IH. These findings also suggest that IH could potentially be further developed as a novel chemotherapeutic agent. Furthermore, a combination of IH with classic autophagy/mitophagy inhibitor could represent a novel therapeutic strategy for the treatment of TNBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cloroquina/administração & dosagem , GTP Fosfo-Hidrolases/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/metabolismo , Quercetina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Cloroquina/farmacologia , Dinaminas , Feminino , Humanos , Camundongos , Dinâmica Mitocondrial/efeitos dos fármacos , Quercetina/administração & dosagem , Quercetina/farmacologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
J Am Soc Mass Spectrom ; 30(9): 1733-1741, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31140076

RESUMO

Chemical isotope labeling (CIL) LC-MS is a highly sensitive and quantitative method for metabolome analysis. Because of a large number of peaks detectable in a sample and the need of running many samples in a metabolomics project, any significant change in mass measurement accuracy during the whole period of running samples can adversely affect the downstream peak alignment and quantitative analysis. Herein, we report a rapid method to check the mass accuracy of individual spectra in each CIL LC-MS run in order to flag up any run containing spectra with accuracy drift that falls outside the expected error. The flagged run may be re-run or discarded before merging with other runs for peak alignment and analysis. This method is based on the observation that some background signals are commonly detected in almost all spectra collected in CIL LC-MS runs. A mass accuracy check (MAC) software program has been developed to first find the common background mass peaks and then use them as mass references to calculate any mass shifts over the course of multiple sample runs. Using a metabolome dataset of 324 human cerebrospinal fluid (CSF) samples and 35 quality control (QC) samples produced by CIL LC-MS, we show that this accuracy check method can streamline the initial raw data processing for downstream analysis in metabolomics.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Metaboloma , Metabolômica/métodos , Software , Calibragem , Isótopos de Carbono/química , Líquido Cefalorraquidiano/metabolismo , Compostos de Dansil/química , Confiabilidade dos Dados , Humanos , Marcação por Isótopo/métodos , Espectrometria de Massas/normas , Metabolômica/normas , Processamento de Sinais Assistido por Computador , Traumatismos da Medula Espinal/líquido cefalorraquidiano
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