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1.
Chem Asian J ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012454

RESUMO

Until now, the synthesis of Rh particles with unusual three-dimensional (3D) nanostructures is still challenging. 3D nanostructure enables fast ion/molecule transport and possesses plenty of exposed active surface, and therefore it is of great interest to construct 3D Rh particle catalyst for N 2 reduction reaction (NRR). Herein, for the first time, we proposed a reactive ionic liquid strategy for fabricating unusual 3D Rh particles with nanowires as the subunits. The ionic liquid n -octylammonium formate simultaneously worked as reaction medium, reductant and template for the successful construction of 3D Rh particles. The as-prepared 3D Rh particles demonstrated excellent activity for electrocatalytic N 2 fixation in 0.1 M KOH electrolyte under ambient conditions with a high NH 3 yield of 35.58 µg h -1 mg cat. -1 at -0.2 V (vs. RHE), surpassing most of the state-of-the-art noble metal catalysts. Our reactive ionic liquid strategy thus holds great promise for rational construction of high-performance electrocatalysts toward NRR.

2.
Int J Biol Macromol ; 145: 145-153, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31846660

RESUMO

Heat-moisture treatment (HMT) of starch is defined as a physical method to change its properties. Compared with maize and potato, starches from common buckwheat (Xinong9976 and Pingqiao2) were isolated and its morphology and physicochemical properties investigated by scanning electron microscope (SEM), X-ray diffraction (XRD), ATR-FTIR analysis, rapid viscosity analyzer (RVA) and differential scanning calorimeter (DSC) were studied before and after HMT. The experimental results showed that there were obvious differences between native starch (NS) and resistant starch (RS) of common buckwheat. HMT altered the A-type crystalline pattern and the degree of short-range order of common buckwheat starches and significantly decreased water solubility, swelling power (70-90 °C), freeze-thaw stability and pasting properties and increased oil and water absorption capacities, light transmittance as well as thermal stability. This study shows that the NS and RS of common buckwheat can be used as the suitable raw materials in food processing.

3.
Int J Mol Sci ; 20(24)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31817460

RESUMO

Pea (Pisum sativum L.), as a major source of plant protein, is becoming one of the major cultivated crop species worldwide. In pea, the pericarp is an important determinant of the morphological characteristics and seed yield. To investigate the molecular mechanism of pericarp elongation as well as sucrose and starch accumulation in the pods of different pea cultivars, we performed transcriptomic analysis of the pericarp of two types of pea cultivar (vegetable pea and grain pea) using RNA-seq. A total of 239.44 Gb of clean sequence data were generated, and were aligned to the reference genome of Pisum sativum L. In the two samples, 1935 differentially expressed genes (DEGs) were identified. Among these DEGs, three antioxidant enzyme superoxide dismutase (SOD) were detected to have higher expression levels in the grain pea pericarps at the pod-elongating stages. Otherwise, five peroxidase (POD)-encoding genes were detected to have lower expression levels in the vegetative pericarps at the development stage of pea pod growth. Furthermore, genes related to starch and sucrose metabolism in the pea pod, such as SUS, INV, FBA, TPI, ADPase, SBE, SSS, and GBSS, were found to be differentially expressed. The RNA-seq data were validated through real-time quantitative RT-PCR of 13 randomly selected genes. Our findings provide the gene expression profile of, as well as differential expression information on, the two pea cultivars, which will lay the foundation for further studies on pod development and nutrition accumulation in the pea and provide valuable information for pea cultivar improvement.

4.
Medicine (Baltimore) ; 98(49): e18134, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804323

RESUMO

BACKGROUND: Essential hypertension is one of the most common chronic diseases in the world and a major risk factor for cardiovascular and cerebrovascular diseases. Hypertension often leads to a variety of complications, of which vascular endothelial dysfunction is an important part. Traditional Chinese medicine (TCM) combined with western medicine can significantly improve vascular endothelial function in patients with hypertension, but it has not been systematically evaluated for efficacy and safety of essential hypertension. Therefore, we aim to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCM combined with western medicine in improving vascular endothelial function in patients with essential hypertension. METHODS: We will search PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, China Science Journal Database (VIP Database) and China Biomedical Literature Database (CBM). Clinical trial registrations, potential grey literature, related conference abstracts, and reference lists of identified studies will also be retrieved. The electronic database will be searched for literatures published from the beginning to October 2018. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. Changes in blood pressure and endothelial function will be assessed as primary outcomes. Drug use, disease progression and adverse events will be assessed as secondary outcomes. RevMan V.5.3.5 will be used for meta-analysis. RESULTS: This systematic review and meta-analysis will provide high-quality evidence from a variety of aspects, including efficacy, blood pressure, vascular endothelial function and adverse reactions, to assess the efficacy and safety of TCM combined with western medicine in patients with hypertension. CONCLUSION: This systematic review will determine whether TCM combined with western medicine provides evidence for effective intervention of vascular endothelial function in patients with essential hypertension. ETHICS AND DISSEMINATION: This systematic review and meta-analysis of randomized controlled trials does not require ethical recognition, and the results of this paper will be published in an open access, internationally influential academic journal. PROSPERO REGISTRATION NUMBER: CRD42019140743.


Assuntos
Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Hipertensão Essencial/tratamento farmacológico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1357-1363, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852643

RESUMO

ObjectiveInvestigate the effect and mechanism of metformin on the development of metabolic syndrome related atherosclerosis.MethodTransfecting EGFP-CLIP170 or EGFP-Pdlim5 plasmid to the mouse aortic smooth muscle cell line, to test the expression of p-AMPK, pCLIP-170 and pPdlim5, and observe the microtubule or the actin skeleton system by immunofluorescence staining. Scratch the cells to perform wound healing experiment, stimulating the cells with gradient metformin (0, 0.5, 1 mmol/L) for 8 h, and observe the change of the scratch size and the dynamic change of cell skeleton and migration in vitro. ApoE-/- mice were injected with streptozotocin and followed by 8 weeks of high fat diet to induce metabolic syndrome model. In the therapeutic group, mice were treated metformin (Met) instead of saline in control group (Control, CTL group). In the end, the whole aorta and its root were isolated and performed oil red O staining and immol/Lunostaining of α-SMA to evaluate the migration of smooth muscle cells and the accumulation of lipids in the aorta.ResultsMouse aortic smooth muscle cells showed an enhanced stress fiber and focal adhesion which representing the dynamic change of actin skeleton after Met stimulation, while the tubulin system rarely showed any change to Met. In animal model, The staining of α-SMA showed smooth muscle cells migrated to the intima or even to the lipid area from the media of aorta in CTL group compared to the Met group. Oil red O staining showed a reduced accumulation of lipids in the Met group than the controls (P < 0.05).ConclusionMetformin reduces the formation of atherosclerosis by inhibiting the migration of smooth muscle cells through modulating cellular actin skeleton system in mice.


Assuntos
Aterosclerose , Actinas , Animais , Apolipoproteínas E , Metformina , Camundongos , Músculo Liso Vascular , Miócitos de Músculo Liso
6.
Appl Opt ; 58(32): 8757-8764, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31873653

RESUMO

Based on interference technology, a cloud particle measurement system is designed. The scattering angle of the system is selected as 90°. The iterative mean filter algorithm is modified, and the system testing using laboratory measurement is completed. The measurement of the spectral distribution of warm cloud particles in a cloud chamber is realized. Similar particle-sized distributions are observed under different pressures, and the particle size is mainly distributed in the range of 5 to 50 µm. The peak appears at particle sizes of 20 to 30 µm. This system features potential applications in cloud microphysics research.

7.
ACS Appl Mater Interfaces ; 11(46): 42904-42916, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657540

RESUMO

Potentiating systemic immunity against breast cancer is in the most urgent demand as breast cancer is less sensitive to immune checkpoint blockade. Although phototherapy and some chemotherapy can trigger immunogenic cell death (ICD) for T cell-mediated antitumor immune response, their immunotherapy efficacy is severely restricted by insufficient phototherapeutic capability and severe multidrug resistance (MDR). Inspired by both the hypersensitivity to phototherapy and the key role of MDR for mitochondria, a rationally engineered immunity amplifier via mitochondria-targeted photochemotherapeutic nanoparticles was, for the first time, achieved to fight against low-immunogenic breast cancer without additional immune agents. The newly synthesized task-specific mitochondria-targeted IR780 derivative (T780) was integrated with chemotherapeutic doxorubicin (DOX) to form multifunctional nanoparticles via an assembling strategy along with bovine serum albumin (BSA) as a biomimetic corona (BSA@T780/DOX NPs). The in situ enhancement in both phototherapy and MDR reversal by targeting mitochondria with BSA@T780/DOX NPs boosted highly efficient ICD toward excellent antitumor immune response. The newly developed strategy not only eradicated the primary tumor but also eliminated the bilateral tumors efficiently, as well as preventing metastasis and postsurgical recurrence, demonstrating great interest for fighting against low-immunogenic breast cancer.

8.
Nano Lett ; 19(9): 6647-6657, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31409072

RESUMO

The antitumor immune response involves a cascade of three phases, namely, antigen presentation (Phase I), lymphocyte activation and proliferation/differentiation (Phase II), and tumor elimination (Phase III). Therefore, an ideal immunotherapy nanoplatform is one that can simultaneously execute these three phases. However, it is of great challenge to develop a single immunotherapy nanoplatform which can deliver individual immunoagent to their on-demand target sites for simultaneously tailoring three phases because of the different target sites restricted by three phases. Herein, for the first time we reported a three-in-one immunotherapy nanoplatform that can simultaneously execute these three phases. Chlorin e6 (Ce6)-conjugated hyaluronic acid (HC), dextro-1-methyl tryptophan (1-mt)-conjugated polylysine (PM) and anti-PD-L1 monoclonal antibodies (aPD-L1) were rationally designed as aPD-L1@HC/PM NPs via an assembling strategy. The step-by-step detachment of the antigen from near-infrared light irradiated HC component, the indoleamine-pyrrole 2,3-dioxygenase (IDO) pathway inhibitor 1-mt, and the anti-PD-L1 toward their on-demand target sites demonstrated the simultaneous tailoring of Phase I, Phase II, and Phase III, respectively, of the immunotherapy. The aPD-L1@HC/PM NPs were verified to be an excellent immunotherapy nanoplatform against tumor metastasis, relapse, and postsurgical regrowth because of the cascade-amplifying cancer-immunity cycle. The present all-immunity-phase-boosted immunotherapy strategy is of great interest for designing excellent immunotherapy treatments.

9.
ACS Appl Mater Interfaces ; 11(36): 32633-32646, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31429272

RESUMO

The concept of integrating immunogenic cell death (ICD) with tailoring the immunosuppressive tumor microenvironment (TME) is promising for immunotherapy. Photothermal therapy (PTT) could efficiently induce ICD, while an indoleamine 2,3-dioxygenase (IDO) inhibitor could convert the "cold" TME. Therefore, combination of PTT and the IDO inhibitor is an attractive approach for immunotherapy. Unfortunately, combination of PTT and the IDO inhibitor for tumor therapy is rarely reported. Herein, organic photothermal agent IR820 and IDO inhibitor 1-methyl-tryptophan (1MT) were, for the first time, designed to be an all-rolled-into-one molecule nanoplatform via a molecular engineering strategy. The designed IR820-1MT molecule could self-assemble into nanoparticles with remarkably high dual-therapeutic agent loading (88.8 wt %). Importantly, poor water solubility of 1MT and inadequate targeting and short lifetime of IR820 were all well solved within as-prepared IR820-1MT nanoparticles. The laser-triggered IR820-1MT nanoparticles remarkably enhanced accumulation of cytotoxic T cells, helper T cells, and memory T cells and simultaneously suppressed a proportion of regulatory T cells, resulting in excellent immunotherapy against tumor metastasis and recurrence. Our molecular engineering strategy provides a promising alternative option for design of a robust immunotherapy weapon against tumor metastasis and recurrence.

10.
Mikrochim Acta ; 186(8): 535, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317278

RESUMO

A porous aromatic framework (PAF) derived from triphenylamine (type PAF-41) was prepared and is shown to be a viable coating for fibrous solid-phase microextraction (SPME). PAF-41 can be easily synthesized and has a high surface area, a rich π-electron structure, and electron-rich nitrogen atoms in its framework. The PAF-41-coated fibrous SPME extractor was combined with a gas chromatographic separation and flame ionization detection. The method was applied to the quantitation of some aromatic organic compounds (AOCs), including polar amphetamine and methamphetamine and nonpolar ethylbenzene, o-, m- and p-xylenes, and styrene. The method was optimized after which a linear response is found for the 10-500 ng·mL-1 amphetamine and methamphetamine concentration ranges. The limits of detection are 1.0 and 0.5 ng·mL-1; and relative standard deviations for six repeated extractions with a single fiber are 5.3 and 6.7%. The method was applied for the determination of amphetamine and methamphetamine in spiked urine samples without any pretreatment except for dilution with water. The PAF-41 modified fiber also was applied to the extraction of styrene, xylenes and ethylbenzene. The enrichment capacities of the extractor for these AOCs were superior to those of commercial SPME extractors. Graphical abstract (a) Schemetic of the PAF-41-coated solid-phase microextraction (SPME) fiber. (b) Scanning electron microscope images of the PAF-41 fiber.

11.
Chem Asian J ; 14(17): 2995-3002, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31310427

RESUMO

The liquid structures of deep eutectic solvents (DESs) based on hydrated metal halides and their application as electrolytes have been widely studied. However, little attention has been paid to the direct use of this type of DES in the preparation of micro-/nanomaterials. Herein, an FeCl3 ⋅6 H2 O/urea DES was used in the one-step synthesis of NiFe-LDH_D with a nanoflower morphology. In alkaline media, this catalyst promoted excellent electrocatalytic activity for the oxidation of urea at potential of 1.32 V (vs. RHE) and for the oxygen-evolution reaction at a potential of 1.39 V to achieve a current density of 10 mA cm-2 . These results were superior to the results with NiFe-LDH/NF that was obtained from an aqueous solution of FeCl3 , as well as most of the previously reported transition-metal catalysts. Furthermore, NiFe-LDH_D/NF could be readily implemented as both a cathode and an anode for the electrolysis of urea and water splitting. The use of hydrated-metal-halide-based DESs for the preparation of LDH catalysts through a dipping-redox strategy should both enrich the research of DESs and offer guidance for the rational surface engineering of catalysts for the electrolysis of urea and overall water splitting with high performance.

12.
ACS Appl Mater Interfaces ; 11(31): 28307-28316, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31356048

RESUMO

Cardiovascular and cerebrovascular ischemic diseases seriously affect human health. Endovascular stent placement is an effective treatment but always leads to in-stent restenosis (ISR). Gene-eluting stent, which combines gene therapy with stent implantation, is a potential method to prevent ISR. In this study, an efficient gene-eluting stent was designed on the basis of one new nucleic acid delivery system to decrease the possibility of ISR. The reduction-responsive branched nucleic acid vector (SKP) with low cytotoxicity was first synthesized via ring-opening reaction. The impressive in vitro transfection performances of SKP were proved using luciferase reporter, enhanced green fluorescent protein plasmid, and vascular endothelial growth factor plasmid (pVEGF). Subsequently, SKP/pVEGF complexes were coated on the surfaces of pretreated clinical stents to construct gene-eluting stents (S-SKP/pVEGF). Antirestenosis performance of S-SKP/pVEGF was evaluated via implanting stents into rabbit aortas. S-SKP/pVEGF could lead to the localized upregulation of VEGF proteins, improve the progress of re-endothelialization, and inhibit the development of ISR in vivo. Such efficient pVEGF-eluting stent with responsive nucleic acid delivery systems is very promising to prevent in-stent restenosis of cerebrovascular diseases.


Assuntos
Técnicas de Transferência de Genes , Oclusão de Enxerto Vascular/prevenção & controle , Stents , Fator A de Crescimento do Endotélio Vascular , Animais , Oclusão de Enxerto Vascular/genética , Oclusão de Enxerto Vascular/metabolismo , Oclusão de Enxerto Vascular/patologia , Coelhos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
13.
Chem Commun (Camb) ; 55(51): 7370-7373, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31173021

RESUMO

A task-specific ionic liquid strategy was, for the first time, proposed for designing oxygen vacancy-rich α-Fe2O3 nanocubes toward electrocatalytic N2 fixation to NH3 under ambient conditions, offering a NH3 formation rate of 32.13 µg h-1 mgcat-1 with a faradaic efficiency of 6.63% at -0.3 V vs. the reversible hydrogen electrode.

14.
J Sep Sci ; 42(14): 2390-2397, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31038270

RESUMO

Maleic hydrazide has been extensively used as an effective growth regulator in tobacco sucker control. After application, maleic hydrazide distributes itself throughout the tobacco plant where it can exist as free, or forms glucoside conjugates with glucose, or becomes bound with lignin. Among them, free maleic hydrazide and its glucoside conjugates are extractable under conventional solvent extraction, while lignin bound maleic hydrazide is claimed to be non-extractable. Herein, an autoclave extraction method has been developed to extract maleic hydrazide effectively, in which tobacco samples are extracted in an autoclave at 130°C for 1 h using 4 M hydrochloric acid. Under such pressurized hot acidic water conditions, lignin bound maleic hydrazide can be released. Meanwhile, glucoside conjugates are hydrolyzed. Total maleic hydrazide is detected by liquid chromatography coupled with tandem mass spectrometry, and the quantitative results coincide well with that obtained from the international standard method. The proposed autoclave extraction with liquid chromatography and tandem mass spectrometry method exhibits excellent linearity in the range of 5-200 mg/kg (R2  = 0.9998), the matrix matched limit of detection and limit of quantification is 0.68 and 2.27 mg/kg, respectively. This method is simple and improves sample capacity, providing an effective approach to monitoring maleic hydrazide residues in tobacco.


Assuntos
Hidrazida Maleica/análise , Resíduos de Praguicidas/análise , Tabaco/química , Cromatografia Líquida , Espectrometria de Massas em Tandem
15.
J Colloid Interface Sci ; 545: 172-183, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878783

RESUMO

Graphene oxide (GO), as a drug delivery carrier, has attracted considerable attention because of its interesting properties. However, GO tends to aggregate in aqueous solution. Amphiphilic molecules are usually necessary to stabilize GO. The introduction of these non-functional macromolecules on the one hand reduces drug loading, but on the other hand may cause unpredictable side effects. This study proposes a new strategy for stabilizing GO with a functional photothermal agent, IR820 (new indocyanine green) derivative. IR820 derivative results from the conjugation of active targeted lactobionic acid (LA) with IR820 for the formation of IR820-LA. IR820-LA features central aromatic groups that can associate with the GO basal plane through π-π interactions. The flanking moiety of hydrophilic LA and sulfonic groups thus provides steric stabilization of GO in aqueous solution. Moreover, IR820-LA endows GO/doxorubicin (GO/DOX) nanovehicles with fluorescence imaging ability and actively targeted chemo-photothermal therapy. Experimental results both in vitro and in vivo have indicated its good chemo-photothermal therapeutic effect according to its active tumor targeting ability and pH-sensitive drug release characteristics. Therefore, our GO/DOX/IR820-LA nanohybrids can be excellent nanoplatforms for active tumor-targeted chemo-photothermal therapy with imaging guidance.


Assuntos
Dissacarídeos/metabolismo , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Corantes Fluorescentes/química , Grafite/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Humanos , Camundongos , Terapia de Alvo Molecular/métodos , Imagem Óptica/métodos , Tamanho da Partícula , Fototerapia/métodos , Propriedades de Superfície
16.
Chirality ; 31(5): 353-361, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30849198

RESUMO

A quick, green, and sensitive method for chiral separation and determination of fluazifop-butyl enantiomers in tobacco and soil was established by ultra-performance convergence chromatography with tandem mass spectrometry (UPC2 -MS/MS). The baseline separation was obtained on an ACQUITY UPC2 Trefoil CEL2 column in 4 minutes with CO2 and methanol as mobile phase. Column temperature, auto back pressure regulator pressure (ABPR), and modifier solvent were optimized to obtain the best separation efficiency. Under the optimal conditions, the recoveries of both enantiomers were 82.8% to 99.5% with relative standard deviations (RSDs) less than 5.5% at three different concentration levels in two matrices. Good coefficients of determination (R2  ≥ 0.9976) were achieved over the concentration range of 10 to 500 ng/mL. The limits of detection (LODs) for all enantiomers in the two matrices varied from 1.6 to 2.1 µg/kg, and the limits of quantification (LOQs) did not exceed 7.0 µg/kg. The proposed method was then successfully applied to analyze authentic samples, confirming that it was a green, convenient, and reliable strategy for the analysis of fluazifop-butyl enantiomers in tobacco and soil.

17.
J Chromatogr A ; 1595: 207-214, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-30827697

RESUMO

4-(methylintrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are the most prevalent and toxic tobacco specific nitrosamines (TSNAs). Due to their carcinogenicity, knowledge of the composition of NNK and NNN in tobacco is necessary. Herein, a sensitive and rapid method, which employs autoclave extraction-supercritical fluid chromatography/tandem mass spectrometry (SFC-MS/MS), has been developed for the analysis of NNK and NNN in tobacco. Both water-soluble and matrix-bound NNK and NNN were extracted with 100 mM ammonium acetate in an autoclave (130 °C, 4 h), and the aqueous extract was subjected to solvent replacement prior to SFC-MS/MS analysis. NNK and NNN were effectively separated within 5 min by using supercritical CO2 as the main mobile phase coupled with a co-solvent of methanol. Excellent linearity was obtained with coefficients of determination (R2) greater than 0.9997 in the range of 1-160 ng/mL and 5-800 ng/mL for NNK and NNN, respectively. The recoveries were in the range of 92.5-110.0% at different spiked levels of real samples. 12 tobacco samples which include 3 typical tobacco varieties of burley, flue-cured, and oriental tobaccos had been analyzed, and the fraction of matrix-bound NNK was determined as well. In addition, a comparison between the proposed SFC-MS/MS method and a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) internal standard method was conducted. Both techniques exhibit comparable analysis results, but peak splitting of NNN was observed by LC-MSMS due to the existence of E/Z isomers, while SFC-MS/MS offers great improvement through elution condition optimization, demonstrating the applicability of SFC-MS/MS as an alternative tool for NNK and NNN analysis.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia com Fluido Supercrítico , Nitrosaminas/isolamento & purificação , Espectrometria de Massas em Tandem , Tabaco/química , Carcinógenos/análise , Carcinógenos/isolamento & purificação , Nitrosaminas/análise
18.
Connect Tissue Res ; 60(2): 107-116, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29609502

RESUMO

PURPOSE: Extracellular-regulated kinase 5 (ERK5) is thought to regulate osteoblast proliferation. To further understand how ERK5 signaling regulates osteoblast proliferation induced by fluid shear stress (FSS), we examined some potential signaling targets associated with ERK5 in MC3T3-E1 cells. METHODS: MC3T3-E1 cells were treated with XMD8-92 (an ERK5 inhibitor) or Cyclosporin A (CsA, a nuclear factor of activated T cells (NFAT) c1 inhibitor) and/or exposed to 12 dyn/cm2 FSS. Phosphorylated-ERK5 (p-ERK5) and expression levels of NFATc1, ERK5, E2F2, and cyclin E1 were analyzed by western blot. The mRNA levels of genes associated with cell proliferation were analyzed by Polymerase Chain Reaction (PCR) array. Subcellular localization of p-ERK5 and NFATc1 were determined by immunofluorescence. Cell proliferation was evaluated by MTT assay. RESULTS: NFATc1 expression was up-regulated by FSS. XMD8-92 only blocked ERK5 activation; however, CsA decreased NFATc1 and p-ERK5 levels, including after FSS stimulation. Exposure to NFATc1 inhibitor or ERK5 inhibitor resulted in decreased E2F2 and cyclin E1 expression and proliferation by proliferative MC3T3-E1 cells. Furthermore, immunofluorescence results illustrated that NFATc1 induced ERK5 phosphorylation, resulting in p-ERK5 translocation to the nucleus. CONCLUSIONS: Our results reveal that NFATc1 acts as an intermediate to promote the phosphorylation of ERK5 induced by FSS. Moreover, activated NFATc1-ERK5 signaling up-regulates the expression of E2F2 and cyclin E1, which promote osteoblast proliferation.

19.
Atherosclerosis ; 280: 99-108, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30500605

RESUMO

BACKGROUND AND AIMS: It has been well established that ezetimibe blocks cholesterol absorption to prevent the negative effects of a high-fat diet in atherosclerosis. However, the exact mechanism is unknown. Here we use a transgenic zebrafish, which expresses different fluorescent proteins on either endothelial cells or granulocytes and macrophages, to explore the specific mechanism of ezetimibe and its role in reducing atherosclerosis-related hypercholesteremia. METHODS: Zebrafish larvae were exposed to a control diet, high cholesterol diet (HCD) or a HCD with ezetimibe treatment. Both the control diet and high cholesterol diet were mixed with red or green fluorophore labeled cholesteryl ester to trace lipid distribution. Isobaric tags were used for relative and absolute quantification to examine protein expression profiles of zebrafish larvae in the different treatment groups. To knock down Apo A-II and investigate the role of Apo A-II in the anti-atherosclerotic function of ezetimibe, we used morpholinos to target zebrafish Apoa2 mRNA. To confirm ezetimibe regulatory role on Apo A-II expression, siRNA against HNF4, PPARα, and SREBP1 were transfected into HepG2 cells. RESULTS: The results show that ezetimibe increased the expression of Apo A-II but failed to reduce vascular lipid accumulation and macrophage recruitment induced by the HCD diet when Apo A-II was knocked down. Finally, we found that ezetimibe increased the expression of Apo A-II through HNF4 and PPARα transcriptional factors. CONCLUSIONS: Our data indicates that ezetimibe may not only prevents atherosclerosis by inhibiting cholesterol absorption in the intestine, but also by increasing the expression of Apo A-II in hepatocytes, thereby enhancing reverse cholesterol transport and removing excess cholesterol from the periphery.

20.
Acta Biomater ; 84: 356-366, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30502480

RESUMO

Self-assembled nanovehicles of chemotherapy drug with photothermal agent are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most of the drugs and photothermal agents have poor water solubility and poor interactions to drive the formation of self-assembled nanovehicles, which is a bottleneck of co-assembled drug/photothermal agent for cancer therapy. Here, we proposed a versatile strategy to create self-assembled chemo-photothermal therapy nanoplatform based on the chemical modification of photothermal agent and drug. The IR-780 and camptothecin (CPT) were chosen as the studied models since they are important photothermal agent and anticancer drug, both of which have such poor water solubility with strong itself molecular interactions that they cannot co-assemble together. IR-780 was modified with an active targeting ligand lactobionic acid (LA) to result in amphiphilic IR780-LA while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through a disulfide linkage to realize its assembly. Well-defined nanoparticles (NPs) could be created through the co-assembling of IR780-LA and CPT-ss-CPT. The IR780-LA/CPT-ss-CPT nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive and enhanced synergistic chemo-photothermal therapy nanoplatform against tumors. Specifically, our chemical modification strategy offers a universal way to create self-assembled chemo-photothermal therapy nanoplatform, which solves the bottleneck of co-assembled drug/photothermal agent for cancer therapy. STATEMENT OF SIGNIFICANCE: Self-assembled nanoparticles of chemotherapeutics with photothermic drugs are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most drugs have too poor solubility and interactions to form into self-assembled nanoparticles. We proposed a versatile strategy to create co-assembled chemo-photothermal therapy nanoparticles based on the chemical modification of common drugs. The IR-780 was modified with an active targeting ligand LA to result in amphiphilic IR780-LA molecules, while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through disulfide linkage. Well-defined IR780-LA/CPT-ss-CPT nanoparticles were created through the co-assembling of IR780-LA and CPT-ss-CPT. The nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive, active targeting chemo-photothermal therapy nanoplatform against tumors. Our strategy offers a versatile way to construct smart chemo-photothermal therapy nanoplatform from common drugs.

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