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1.
Adv Mater ; 36(18): e2308799, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38270498

RESUMO

The heterogeneity, species diversity, and poor mechanical stability of solid electrolyte interphases (SEIs) in conventional carbonate electrolytes result in the irreversible exhaustion of lithium (Li) and electrolytes during cycling, hindering the practical applications of Li metal batteries (LMBs). Herein, this work proposes a solvent-phobic dynamic liquid electrolyte interphase (DLEI) on a Li metal (Li-PFbTHF (perfluoro-butyltetrahydrofuran)) surface that selectively transports salt and induces salt-derived SEI formation. The solvent-phobic DLEI with C-F-rich groups dramatically reduces the side reactions between Li, carbonate solvents, and humid air, forming a LiF/Li3PO4-rich SEI. In situ electrochemical impedance spectroscopy and Ab-initio molecular dynamics demonstrate that DLEI effectively stabilizes the interface between Li metal and the carbonate electrolyte. Specifically, the LiFePO4||Li-PFbTHF cells deliver 80.4% capacity retention after 1000 cycles at 1.0 C, excellent rate capacity (108.2 mAh g-1 at 5.0 C), and 90.2% capacity retention after 550 cycles at 1.0 C in full-cells (negative/positive (N/P) ratio of 8) with high LiFePO4 loadings (15.6 mg cm-2) in carbonate electrolyte. In addition, the 0.55 Ah pouch cell of 252.0 Wh kg-1 delivers stable cycling. Hence, this study provides an effective strategy for controlling salt-derived SEI to improve the cycling performances of carbonate-based LMBs.

2.
Adv Mater ; 35(39): e2302828, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37341309

RESUMO

The lithium-metal anode is a promising candidate for realizing high-energy-density batteries owing to its high capacity and low potential. However, several rate-limiting kinetic obstacles, such as the desolvation of Li+ solvation structure to liberate Li+ , Li0 nucleation, and atom diffusion, cause heterogeneous spatial Li-ion distribution and fractal plating morphology with dendrite formation, leading to low Coulombic efficiency and depressive electrochemical stability. Herein, differing from pore sieving effect or electrolyte engineering, atomic iron anchors to cation vacancy-rich Co1- x S embedded in 3D porous carbon (SAFe/CVRCS@3DPC) is proposed and demonstrated as catalytic kinetic promoters. Numerous free Li ions are electrocatalytically dissociated from the Li+ solvation complex structure for uniform lateral diffusion by reducing desolvation and diffusion barriers via SAFe/CVRCS@3DPC, realizing smooth dendrite-free Li morphologies, as comprehensively understood by combined in situ/ex situ characterizations. Encouraged by SAFe/CVRCS@3DPC catalytic promotor, the modified Li-metal anodes achieve smooth plating with a long lifespan (1600 h) and high Coulombic efficiency without any dendrite formation. Paired with the LiFePO4 cathode, the full cell (10.7 mg cm-2 ) stabilizes a capacity retention of 90.3% after 300 cycles at 0.5 C, signifying the feasibility of using interfacial catalysts for modulating Li behaviors toward practical applications.

3.
Soft Robot ; 10(5): 1001-1014, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37074447

RESUMO

Soft robots equipped with multifunctionalities have been increasingly needed for secure, adaptive, and autonomous functioning in unknown and unpredictable environments. Robotic stacking is a promising solution to increase the functional diversity of soft robots, which are required for safe human-machine interactions and adapting in unstructured environments. However, most existing multifunctional soft robots have a limited number of functions or have not fully shown the superiority of the robotic stacking method. In this study, we present a novel robotic stacking strategy, Netting-Rolling-Splicing (NRS) stacking, based on a dimensional raising method via 2D-to-3D rolling-and-splicing of netted stackable pneumatic artificial muscles to quickly and efficiently fabricate multifunctional soft robots based on the same, simple, and cost-effective elements. To demonstrate it, we developed a TriUnit robot that can crawl 0.46 ± 0.022 body length per second (BL/s) and climb 0.11 BL/s, and can carry a 3 kg payload while climbing. Also, the TriUnit can be used to achieve novel omnidirectional pipe climbing including rotating climbing, and conduct bionic swallowing-and-regurgitating, multi-degree-of-freedom manipulation based on their multimodal combinations. Apart from these, steady rolling, with a speed of 0.19 BL/s, can be achieved by using a pentagon unit. Furthermore, we applied the TriUnit pipe climbing robot in panoramic shooting and cargo transferring to demonstrate the robot's adaptability for different tasks. The NRS stacking-driven soft robot here has demonstrated the best overall performance among existing stackable soft robots, representing a new and effective way for building multifunctional and multimodal soft robots in a cost-effective and efficient way.

4.
ACS Nano ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607402

RESUMO

Lithium-sulfur (Li-S) batteries exhibit unparalleled theoretical capacity and energy density than conventional lithium ion batteries, but they are hindered by the dissatisfactory "shuttle effect" and the sluggish conversion kinetics owing to the low lithium ion transport kinetics, resulting in rapid capacity fading. Herein, a catalytic two-dimensional heterostructure composite is prepared by evenly grafting mesoporous carbon on the MXene nanosheet (denoted as OMC-g-MXene), serving as interfacial kinetic accelerators in Li-S batteries. In this design, the grafted mesoporous carbon in the heterostructure can not only prevent the stack of MXene nanosheets with the enhanced mechanical property but also offer a facilitated pump for accelerating ion diffusion. Meanwhile, the exposed defect-rich OMC-g-MXene heterostructure inhibits the polysulfide shuttling with chemical interactions between OMC-g-MXene and polysulfides and thus simultaneously enhances the electrochemical conversion kinetics and efficiency, as fully investigated by in situ/ex situ characterizations. Consequently, the cells with OMC-g-MXene ion pumps achieve a high cycling capacity (966 mAh g-1 at 0.2 C after 200 cycles), a superior rate performance (537 mAh g-1 at 5 C), and an ultralow decaying rate of 0.047% per cycle after 800 cycles at 1 C. Even employed with a high sulfur loading of 7.08 mg cm-2 under lean electrolyte, an ultrahigh areal capacity of 4.5 mAh cm-2 is acquired, demonstrating a future practical application.

5.
ACS Nano ; 16(11): 17729-17760, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36305602

RESUMO

Lithium metal anodes are ideal for realizing high-energy-density batteries owing to their advantages, namely high capacity and low reduction potentials. However, the utilization of lithium anodes is restricted by the detrimental lithium dendrite formation, repeated formation and fracturing of the solid electrolyte interphase (SEI), and large volume expansion, resulting in severe "dead lithium" and subsequent short circuiting. Currently, the researches are principally focused on inhibition of dendrite formation toward extending and maintaining battery lifespans. Herein, we summarize the strategies employed in interfacial engineering and current-collector host designs as well as the emerging electrochemical catalytic methods for evolving-accelerating-ameliorating lithium ion/atom diffusion processes. First, strategies based on the fabrication of robust SEIs are reviewed from the aspects of compositional constituents including inorganic, organic, and hybrid SEI layers derived from electrolyte additives or artificial pretreatments. Second, the summary and discussion are presented for metallic and carbon-based three-dimensional current collectors serving as lithium hosts, including their functionality in decreasing local deposition current density and the effect of introducing lithiophilic sites. Third, we assess the recent advances in exploring alloy compounds and atomic metal catalysts to accelerate the lateral lithium ion/atom diffusion kinetics to average the spatial lithium distribution for smooth plating. Finally, the opportunities and challenges of metallic lithium anodes are presented, providing insights into the modulation of diffusion kinetics toward achieving dendrite-free lithium metal batteries.

6.
Bioorg Med Chem ; 30: 115930, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33352390

RESUMO

The application of intensity-based H2O2-responsive fluorescence nanoprobe for circulating tumor cell detection was limited by the complex background and the nanoprobe uptake in each CTC. In this context, we developed a ratiometric fluorescence nanoprobe, on which a H2O2-responsive subunit and a stable subunit grafted working as a H2O2 detector and a reference, respectively. When responding to intracellular H2O2, the reference fluorescence (580 nm) maintained as a correction background while the detector fluorescence (450 nm) was turned on to conduct CTC enumeration and intracellular H2O2 evaluation. Two normal cells and three colon cancer cells were examined to evaluate their endogenous H2O2 with the ratiometric nanoprobe by flow cytometry and confocal laser scanning microscopy. CTC sample from colorectal cancer patients was used to validate the performance of the nanoprobe for CTC enumeration and H2O2 evaluation. The results indicated that not only CTC could be effectively identified based on the "turn on" fluorescence, but also the viability of the identified CTCs could be assessed with the intensity of the reference fluorescence to avoid the false-positive number. Moreover, the clinical results demonstrated that the viability CTC count combined with intracellular H2O2 content (described as I450/580)were related to the tumor TNM stage, which might provide significant guidance for clinical treatments.


Assuntos
Neoplasias Colorretais/diagnóstico , Corantes Fluorescentes/química , Peróxido de Hidrogênio/análise , Nanopartículas/química , Células Neoplásicas Circulantes/patologia , Animais , Células Cultivadas , Neoplasias Colorretais/metabolismo , Corantes Fluorescentes/síntese química , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos , Imagem Molecular , Estrutura Molecular , Células NIH 3T3 , Imagem Óptica
7.
Ophthalmic Physiol Opt ; 40(4): 491-501, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32495406

RESUMO

PURPOSE: The molecular mechanism of form-deprivation myopia is unclear. This study was aimed to investigate the roles of scleral DNA methylation and mRNA expression of IGF-1 and MMP-2 in a guinea pig model of form-deprivation myopia. METHODS: Seventy 2-week-old male guinea pigs were assigned to three groups: (1) zero week group that was used to collect baseline data; (2) monocular deprivation treatment (MDT) group, in which a thin slice of opaque latex glove was placed over the right eyes of the animals for four weeks, and the left eyes were untreated and served as the monocular contralateral control (MCC) group; (3) control group (CG), in which the animals grew four weeks, but received no manipulation. Animals in each group were evenly divided for DNA methylation assay and quantitative PCR (qPCR). After eye enucleation, the sclerae were harvested for DNA methylation assay and qPCR. The DNA methylation pattern in the promoter and exon regions of IGF-1 and MMP-2, along with the mRNA expression level of them, were determined by base-specific cleavage and mass spectrometry and qPCR, respectively. RESULTS: After four weeks of form-deprivation, DNA methylation at 4/8 cytosine-guanine sites in the IGF-1 promoter was significantly lower in the MDT eyes than in the MCC or CG eyes. In addition, the level of IGF-1 mRNA was moderately higher in MDT eyes compared to the MCC eyes and CG eyes. DNA methylation at 4/14 cytosine-guanine sites in the MMP-2 gene was very low, and no significant change was observed between the MDT eyes and the MCC or CG ones. However, the level of MMP-2 mRNA in MDT eyes was significant higher compared with MCC eyes and CG eyes, with an increase of 217% and 222%, respectively. CONCLUSIONS: In our guinea pig model of form-deprivation myopia, the methylation of four cytosine-guanine sites in the IGF-1 gene promoter was significantly lower in the sclera after four weeks of MDT, and the transcription level of scleral IGF-1 was moderately higher. Hence, the IGF-1 gene methylation might play a role in the pathogenesis of form-deprivation myopia in guinea pigs. The level of MMP-2 mRNA in the sclera of MDT eyes was significantly higher, but not regulated by the methylation pathway, as the methylation status of MMP-2 was unchanged.


Assuntos
DNA/genética , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Metaloproteinase 2 da Matriz/genética , Miopia/genética , RNA Mensageiro/genética , Animais , Modelos Animais de Doenças , Cobaias , Fator de Crescimento Insulin-Like I/biossíntese , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Miopia/metabolismo
8.
Soft Robot ; 7(5): 597-614, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32130078

RESUMO

Pneumatic artificial muscles (PAMs) are an extensively investigated type of soft actuator. However, the PAM motions have been limited somewhat to uniaxial contraction and extension, restraining the development of PAMs. Given the current strong interest in soft robotics, PAMs have been gaining renewed attention due to their excellent compliance and ease of fabrication. Herein, under the inspiration of the elephant trunk, a family of bending and helical extensile PAMs (HE-PAMs)/helical contractile PAMs (HC-PAMs) was proposed and analyzed. Through both experiment and analysis, a model of generalized bending behavior of PAMs was built and developed to investigate the properties of axial, bending, and helical PAMs in the same theoretical framework. The topological equivalence and bifurcation were found in the analysis and utilized to explain the behaviors of these different PAMs. Meanwhile, a coupled constant curvature and torsion kinematics model was proposed to depict the motion of PAMs more accurately and conveniently. Moreover, a soft tandem manipulator consisting of bending and helical PAMs was proposed to demonstrate their attractive potential.


Assuntos
Músculo Esquelético , Robótica , Desenho de Equipamento , Movimento (Física) , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia
9.
Bioorg Med Chem ; 28(4): 115284, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31959388

RESUMO

In situ detection of certain specific enzyme activities in cells is deeply attached to tumor diagnosis. Conventional enzyme-responsive fluorescent probes have difficulty detecting targeted enzymes in situ in cells due to the low detection accuracy caused by the spread of fluorescence probes. In order to solve this problem, we have designed and synthesized an enzyme-responsive, water-soluble fluorescent probe with AIE characteristics, which could aggregate and precipitate to produce in situ fluorescence when reacting with the targeted enzyme in cells. The AIE fluorophore (TPEQH) was utilized to design the enzyme-responsive, fluorescent probe (TPEQHA) by introducing a phosphate group on to it, which could be specifically decomposed by the targeted enzyme, namely alkaline phosphatase (ALP). In tumor cells, TPEQH was highly produced due to the interaction of phosphate on the TPEQHA and the overexpressed ALP. Water-insoluble TPEQH then precipitated and release fluorescence in situ, thereby successfully detecting the ALP. Furthermore, the expression level of ALP could be determined by the fluorescence intensity of TPEQH with higher accuracy due to the inhibition of TPEQH leak, which demonstrated a potential application of in suit ALP detection in both clinical diagnosis and scientific research of tumor.


Assuntos
Fosfatase Alcalina/análise , Corantes Fluorescentes/química , Fosfatase Alcalina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Imagem Óptica , Agregados Proteicos , Espectrometria de Fluorescência , Relação Estrutura-Atividade
10.
BMC Cancer ; 19(1): 825, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438998

RESUMO

BACKGROUND: To develop a new 18 high-risk human papillomavirus (HR HPV) detection and genotyping assay, which is important to evaluate the risk degree of HR HPV for causing cancers. METHODS: All 18 HR HPV and ß-globin relative DNA fragments were synthesized and cloned to a plasmid pUC57 to obtain their recombinant plasmids. Based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform, each of the 18 HR HPV genotypes were investigated using their constructed recombinant plasmids. The new 18 HR HPV genotyping assay was tested using 356 clinical specimens and the results were compared to ones detected by the Roche Cobas 4800 HPV assay (Cobas). The discrepant results between two assays were resolved by sequencing and genotyping methods. RESULTS: The new 18 HR HPV MALDI-TOF MS genotyping assay was developed using HPV recombination plasmids. The sensitivity was 103 to 102 copies/reaction for the all 18 HR HPV. This new developed HR HPV genotyping test was used to detect the clinical specimens. When the results on clinical samples detected by the new MALDI-TOF MS HPV test were compared with ones detected by the Roche Cobas 4800 HPV assay in terms of 14 HR HPV, the concordance was 80.1% (kappa coefficient, 0.60; 95% confidence interval [CI], 0.52-0.69). The discrepant results were resolved by sequencing and genotyping and suggests that the developed HR HPV assay is more sensitive and specific. CONCLUSIONS: The new developed 18 HR HPV detection method based on MALDI-TOF MS platform is a high-throughput assay for the all 18 HR HPV genotypes and a powerful complement to current detection methods.


Assuntos
Técnicas de Genotipagem , Ensaios de Triagem em Larga Escala , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Adulto , Idoso , DNA Viral , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Ensaios de Triagem em Larga Escala/métodos , Ensaios de Triagem em Larga Escala/normas , Humanos , Masculino , Pessoa de Meia-Idade , Plasmídeos/genética , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Adulto Jovem
11.
ACS Biomater Sci Eng ; 5(7): 3618-3630, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-33405743

RESUMO

Accurate and nondestructive detection of tumor-related mRNA in living cells is of great significance for tumor diagnosis. The universal technique for imaging mRNA in living cells is nucleic-acid-based fluorescent probes. However, the majority of developed nucleic-acid-based fluorescent probes were only designed to detect the targeted mRNA but could not avoid the interference arising from nuclease or other biological matrices, which results in inevitable false-positive signals. To overcome this dilemma, a new aggregation-induced emission (AIE) fluorophore and the fluorescence resonance energy transfer (FRET) principle were used to establish a novel AIE fluorophore-based molecular beacon (AIE-MB). The AIE fluorophore tetraphenylethylene-quinoxaline (TPEQ) was designed by incorporating quinoxalinone with one typical AIE active luminogen tetraphenylethene (TPE), which could acquire a wide range of excitation wavelength. On this basis, the AIE-MB was designed by labeling two fluorophores: the TPEQ acceptor and an aggregation-caused quenching (ACQ) fluorophore 7-amino-4-methylcoumarin acid (AMCA) donor. On the basis of these two fluorophores, the AIE-MB could exhibit three states: weak fluorescence at primary stage, blue fluorescence (specific signal) generated by pairing with target mRNA in tumor cells, and both blue and green fluorescence (false-positive signal) due to the endogenous degradation in normal cells. Obviously, the specific imaging for target mRNA in tumor cells and the false-positive signal resulting from endogenous degradation in normal cells could be accurately distinguished through the different fluorescence emission. As a result, in contrast to traditional nucleic-acid-based fluorescent probes, the AIE-MB could improve the accuracy of the tumor detection by efficiently differentiating both specific and false-positive signals, which showed potential application value in tumor diagnosis and biomedical research.

12.
ACS Biomater Sci Eng ; 5(2): 1023-1033, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33405793

RESUMO

Accurately distinguishing tumors from noncancerous inflammation and normal tissues is hugely significent for tumor diagnosis and therapy. However, tumor and inflammatory tissues have similar pathologic characteristics in their microenvironment, making differentiation very difficult. Here, a fluorescent cocktail nanoparticle capable of simultaneously detecting intracellular mRNA and H2O2 was designed to differentiate tumors from nontumor cells. To detect targeted mRNA in living cells, a DNA probe was generated using the fluorescence resonance energy transfer (FRET) principle. A pH-responsive amphiphilic polymer was synthesized to realize the transportation of the DNA probe. In addition, the polymer was conjugated with a coumarin-boronic acid ester (Cou-BE) H2O2 probe. According to the change in the fluorescence of Cou-BE, tumor and inflammatory cells could be distinguished from normal cells owing to their high concentration of H2O2. Because of the different concentrations of tumor-related mRNA in tumor and nontumor cells, the fluorescence intensity of the DNA probe-loaded nanoparticles inside tumor cells was different from that inside inflammatory cells. Therefore, our fluorescent cocktail strategy could discriminate simultaneously tumor, inflammation, and normal cells through the cooperative detection of intracellular mRNA and H2O2, which demonstrated potential application value in biomedical research and clinical diagnosis.

13.
Anal Chem ; 90(15): 9218-9225, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29940728

RESUMO

Ferroptosis is an iron-mediated, caspase-independent pathway of cell death that is accompanied with the accumulations of reactive oxygen species (ROS) and oxygenases, as well as being involved in many other pathophysiological procedures. However, specific and rapid monitoring of ferroptosis in living cells or tissues has not been achieved so far. Herein, a quinoxalinone-based fluorescent probe (termed as Quinos-4, or QS-4) with a reactive aromatic thioether moiety was designed for ferroptosis identification. Upon exposing it to high levels of ROS and hemeoxygenase-1 (HO-1), which are considered as the biochemical characteristics of ferroptosis, QS-4 could be oxidized into a sulfoxide derivative (QSO-4) and its original aggregation-induced enhanced red fluorescence emission could be converted to green fluorescence emission sharply. On the basis of this unique reaction-induced color conversion, this molecular probe can be employed for identifying the occurrence of ferroptosis both in vitro and in vivo.


Assuntos
Apoptose , Cor , Corantes Fluorescentes/química , Ferro/metabolismo , Western Blotting , Ensaio de Imunoadsorção Enzimática , Células HeLa , Heme Oxigenase-1/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo
14.
Bioconjug Chem ; 29(4): 1344-1351, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29513522

RESUMO

Owing to the high spatial and temporal resolution of light, light-related biotechnologies, for example, optogenetics, has wide ranging applications in neuroscience to control a subject's behavior. Applying light to control tumors' genetic behavior directly was still a challenge so far. Herein, we put forward a strategy of chemical optoepigenomics, in which an epigenetic regulator (vorinostat) and paclitaxel (PTX) were conjugated onto a light-sensitive chemical molecule. The activity of vorinostat could be precisely controlled by the light, which could minimize the off-target effect. After UV irradiation under 350 nm, the photocaged epigenetic regulator (vorinostat) was selectively released from the conjugate in a spatiotemporal manner, inhibiting the activity of histone deacetylase and then reversing the PTX resistance of tumor cells effectively.


Assuntos
Antineoplásicos/farmacologia , Preparações de Ação Retardada/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Vorinostat/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Células HeLa , Humanos , Células MCF-7 , Neoplasias/genética , Paclitaxel/administração & dosagem , Paclitaxel/química , Raios Ultravioleta , Vorinostat/administração & dosagem , Vorinostat/química
15.
Anal Chem ; 89(11): 5966-5975, 2017 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-28434219

RESUMO

In the clinic, numeration of circulating tumor cells (CTCs) plays a critical role in cancer diagnosis and treatment, but conventional CTC identification and counting that rely on specific antibodies to characterize a cell's surface antigens are costive and with limitations. Importantly, false positive or negative results may occur due to the high heterogeneity and epithelial-mesenchymal transition (EMT) of CTCs. Herein we demonstrate a novel and effective CTC detecting nanoprobe that could rapidly respond to the high level of endogenous H2O2 of CTCs and report the signal through fluorescence emission. Briefly, a hydrophobic coumarin-benzene boronic acid pinacol ester (Cou-Bpin) was grafted onto hydrophilic glycol chitosan (GC) to form an amphiphilic molecule, which further assembled into micellar nanoparticles in aqueous solution. This new nanoprobe was highly sensitive to H2O2 with a detection limit of 0.1 µM and could rapidly enter the cells within 30 min. Upon exposure to intracellular H2O2, the nanoprobe exhibited remarkable one-photon and two-photon luminescent characteristics, which were suitable for imaging of endogenous H2O2 of various human colorectal cancer cells and assist the identification of CTCs. Compared to a conventional CTC counting assay, the nanoprobe-based CTC numeration could overcome the false-negative findings due to the low expression of cytokeratin 19 (CK19). In a clinic test, CTC counting results based on the new nanoprobe match better to the postoperative pathological results of four clinic patients who had colorectal cancer at different stages.


Assuntos
Neoplasias Colorretais/diagnóstico , Peróxido de Hidrogênio/análise , Sondas Moleculares/química , Células Neoplásicas Circulantes , Permeabilidade da Membrana Celular , Quitosana/química , Feminino , Fluorescência , Humanos , Micelas , Imagem Molecular/métodos
16.
Free Radic Biol Med ; 78: 190-201, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25463279

RESUMO

Proinflammatory cytokine TNF-α-induced adhesion of leukocytes to endothelial cells plays a critical role in the early stage of atherosclerosis. Oxidative stress and redox-sensitive transcription factors are implicated in the process. Thus, compounds that mediate intracellular redox status and regulate transcription factors are of great therapeutic interest. Clematichinenoside (AR), a triterpene saponin isolated from the root of Clematis chinensis Osbeck, was previously demonstrated to have anti-inflammatory and antioxidative properties. However, little is known about the exact mechanism underlying these actions. Thus we performed a detailed study on its effect on leukocytes-endothelial cells adhesion with TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) and cell-free systems. First, we found that AR reduced TNF-α-induced VCAM-1 and ICAM-1 expression and their promoter activity, inhibited translocation of p65 and phosphorylation of IκBα, suppressed IκB kinase-ß (IKK-ß) activity, lowered O2(∙-) and H2O2 levels, tackled p47(phox) translocation, and decreased NOX4 NADPH oxidase expression. Second, we showed that AR exhibited no direct free radical scavenging ability in cell-free systems at concentrations that were used in intact cells. Besides, AR had no direct effect on the activity of IKK-ß that was extracted from TNF-α-stimulated HUVECs. We also found that p47 translocation, NOX4 expression, and reactive oxygen species (ROS) levels were up-regulated before IκB phosphorylation in TNF-α-induced HUVECs. Moreover, TNF-α-enhanced IKK-ß activity was also inhibited by (polyethylene glycol) PEG-catalase, N-acetylcysteine (NAC), and vitamin E. In conclusion, these results suggest that AR reduces VCAM-1 and ICAM-1 expression through NADPH oxidase-dependent IKK/NF-κB pathways in TNF-α-induced HUVECs, which finally suppress monocyte-HUVECs adhesion. This compound is potentially beneficial for early-stage atherosclerosis.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Quinase I-kappa B/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Western Blotting , Adesão Celular , Proliferação de Células , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Quinase I-kappa B/genética , Imunoprecipitação , Molécula 1 de Adesão Intercelular/genética , Leucócitos/citologia , Leucócitos/metabolismo , Monócitos/citologia , Monócitos/metabolismo , NADPH Oxidases/genética , NF-kappa B/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/genética
17.
Zhonghua Nei Ke Za Zhi ; 50(7): 580-4, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22041269

RESUMO

OBJECTIVE: To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. METHODS: Synchronized HMCs were divided into following groups: (1) Normal glucose control group (NG, 5.5 mmol/L glucose); (2) High glucose group (HG, 30 mmol/L glucose); (3) Mannitol group (Man, 5.5 mmol/L glucose + 24.5 mmol/L mannitol); (4) High glucose + fasudil group (HG + F, the concentrations of fasudil were 25, 50 and 100 µmol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK-I, connective tissue growth factor (CTGF)mRNA with real-time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin (FN), CTGF, TNFα in the supernatant. RESULTS: (1) RhoA, ROCK-I and CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time-dependence. Besides, there was no statistic significance by comparing Man and NG. (2)Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK-I, CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFα protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFα protein secretion was significantly reduced compared with HG. CONCLUSION: Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose-activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Transdução de Sinais/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Meios de Cultura/química , Fibronectinas/metabolismo , Glucose/metabolismo , Humanos , Inflamação , Fator de Necrose Tumoral alfa/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
18.
Diabetes Res Clin Pract ; 85(2): 166-70, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19523708

RESUMO

OBJECTIVE: To investigate urinary excretion of platelet-derived growth factor-BB (PDGF-BB) during the different stages of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) as well as its clinical significance. METHODS: Sixty-five cases with T2DM were divided into three groups: normoalbuminuric group [N-UAlb; urine albumin excretion (UAE) <30 mg/24 h, n=25], microalbuminuric group [M-UAlb; UAE 30-300 mg/24 h, n=20], and macroalbuminuric group [L-UAlb; UAE >300 mg/ 24 h, n=20]. The urinary excretion rates of PDGF-BB were determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) in all the cases and 27 subjects of control. RESULTS: The excretion rates of PDGF-BB in T2DM groups were markedly higher than that in control (P<0.001). Moreover, the excretion rates of PDGF-BB increased with the increase of UAE and there were significant differences among the three groups (P<0.05) except the groups of M-UAlb and L-UAlb. Urinary PDGF-BB was also positively correlated with UAE, triglyceride (TG), cholesterol (CHO), low-density lipoprotein (LDL) and negatively correlated with creatinine clearance (Ccr), high-density lipoprotein (HDL), while had no significance correlated with glycohemoglobin A1c (HbA1c). CONCLUSION: PDGF-BB might play a very important role in the initiation and progression of DN. Measurements of urine PDGF-BB in T2DM could be used for early diagnosis of diabetic renal dysfunction.


Assuntos
Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/epidemiologia , Fator de Crescimento Derivado de Plaquetas/urina , Adulto , Idoso , Albuminúria/epidemiologia , Análise de Variância , Becaplermina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-sis , Valores de Referência
19.
Chin Med J (Engl) ; 116(3): 469-71, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12781062

RESUMO

OBJECTIVE: To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF). METHODS: This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer. RESULTS: cTnT concentration was 0.181 +/- 0.536 ng/mL in CHF patients and 0.003 +/- 0.001 ng/mL in controls (P < 0.001). Patients were categorized according to the levels of heart function and left ventricular ejection fraction (LVEF). In the first group consisting of 105 patients with LVEF 35%, cTnT was 0.07 +/- 0.0 5 ng/mL (P < 0.01). In patients with NYHA class I, II, III and IV, cTnT values were 0.062 +/- 0.022 ng/mL, 0.113 +/- 0.121 mg/mL, 0.191 +/- 0.231 mg/ml and 0.384 +/- 0.211 mg/mL, respectively (class I vs class II P > 0.05, class II vs class III P < 0.01, class III vs class IV P < 0.01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF (r = -0.493, P < 0.001). CONCLUSIONS: This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.


Assuntos
Insuficiência Cardíaca/sangue , Troponina T/sangue , Adulto , Idoso , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda
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