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1.
Phys Rev Lett ; 132(24): 246501, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949356

RESUMO

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

2.
Nat Commun ; 15(1): 4130, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755189

RESUMO

Compared to transition metal dichalcogenide (TMD) monolayers, rhombohedral-stacked (R-stacked) TMD bilayers exhibit remarkable electrical performance, enhanced nonlinear optical response, giant piezo-photovoltaic effect and intrinsic interfacial ferroelectricity. However, from a thermodynamics perspective, the formation energies of R-stacked and hexagonal-stacked (H-stacked) TMD bilayers are nearly identical, leading to mixed stacking of both H- and R-stacked bilayers in epitaxial films. Here, we report the remote epitaxy of centimetre-scale single-crystal R-stacked WS2 bilayer films on sapphire substrates. The bilayer growth is realized by a high flux feeding of the tungsten source at high temperature on substrates. The R-stacked configuration is achieved by the symmetry breaking in a-plane sapphire, where the influence of atomic steps passes through the lower TMD layer and controls the R-stacking of the upper layer. The as-grown R-stacked bilayers show up-to-30-fold enhancements in carrier mobility (34 cm2V-1s-1), nearly doubled circular helicity (61%) and interfacial ferroelectricity, in contrast to monolayer films. Our work reveals a growth mechanism to obtain stacking-controlled bilayer TMD single crystals, and promotes large-scale applications of R-stacked TMD.

3.
Nat Commun ; 14(1): 6421, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828069

RESUMO

Controllable growth of two-dimensional (2D) single crystals on insulating substrates is the ultimate pursuit for realizing high-end applications in electronics and optoelectronics. However, for the most typical 2D insulator, hexagonal boron nitride (hBN), the production of a single-crystal monolayer on insulating substrates remains challenging. Here, we propose a methodology to realize the facile production of inch-sized single-crystal hBN monolayers on various insulating substrates by an atomic-scale stamp-like technique. The single-crystal Cu foils grown with hBN films can stick tightly (within 0.35 nm) to the insulating substrate at sub-melting temperature of Cu and extrude the hBN grown on the metallic surface onto the insulating substrate. Single-crystal hBN films can then be obtained by removing the Cu foil similar to the stamp process, regardless of the type or crystallinity of the insulating substrates. Our work will likely promote the manufacturing process of fully single-crystal 2D material-based devices and their applications.

4.
Biosensors (Basel) ; 12(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36551053

RESUMO

Sodium alginate (SA) was used to functionalize the surfaces of silver nanoparticles (AgNPs) to form SA-AgNPs for sensing dimethoate with a rapid and sensitive visual readout. UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and zeta potential measurements were used to characterize SA-AgNPs that were synthesized under the ideal conditions. SA-AgNPs were spherical with an average size of 14.6 nm. The stability of SA-AgNPs was investigated with changes in pH, salinity, and storage time. This colorimetric assay of dimethoate relied on the change in the absorption ratio (A475/A400) of SA-AgNPs, resulting in their aggregation caused by dimethoate, leading to a visual change for SA-AgNPs from yellow to pale yellow. As a result, the absorption ratio (A475/A400) of SA-AgNPs showed good linearity in the range of 0.05 to 2.0 ppm (R2 = 0.9986) with a limit of detection (LOD) of 30 ppb. Adding other pesticides did not significantly change the absorption ratio of SA-AgNPs, indicating its high selectivity as a colorimetric assay. The sensor was successfully used to detect dimethoate in actual water samples.


Assuntos
Dimetoato , Nanopartículas Metálicas , Colorimetria/métodos , Alginatos , Prata/química , Nanopartículas Metálicas/química , Sódio , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Nat Mater ; 21(11): 1263-1268, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36109673

RESUMO

The production of large-area twisted bilayer graphene (TBG) with controllable angles is a prerequisite for proceeding with its massive applications. However, most of the prevailing strategies to fabricate twisted bilayers face great challenges, where the transfer methods are easily stuck by interfacial contamination, and direct growth methods lack the flexibility in twist-angle design. Here we develop an effective strategy to grow centimetre-scale TBG with arbitrary twist angles (accuracy, <1.0°). The success in accurate angle control is realized by an angle replication from two prerotated single-crystal Cu(111) foils to form a Cu/TBG/Cu sandwich structure, from which the TBG can be isolated by a custom-developed equipotential surface etching process. The accuracy and consistency of the twist angles are unambiguously illustrated by comprehensive characterization techniques, namely, optical spectroscopy, electron microscopy, photoemission spectroscopy and photocurrent spectroscopy. Our work opens an accessible avenue for the designed growth of large-scale two-dimensional twisted bilayers and thus lays the material foundation for the future applications of twistronics at the integration level.

6.
Appl Opt ; 60(3): 662-669, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33690435

RESUMO

In this study, we demonstrate a novel, to the best of our knowledge, integrated indium phosphide (InP) and silicon nitride (Si3N4) waveguide platform, which is based on interlayer coupling, to achieve heterogeneous integration of a photodetector and waveguide ring resonator firstly. In order to improve the gyro bias stability, the Si3N4 and InP waveguides were designed with a high polarization extinction ratio and ultra-low loss. Three-dimensional finite difference time domain methods are used to optimize the InP taper dimensions to provide efficient optical coupling between the Si3N4 and InP waveguides. The optical coupler with a length of 100 µm is designed to achieve optical coupling between the Si3N4 and InP waveguides while maintaining its state of polarization all the way from the taper waveguides. The coupling efficiency of the optimized interlayer coupler has been improved to about 99.5%.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-904753

RESUMO

Objective To optimize the synthesis method of 18F-T807 and study preliminary biodistribution. Methods 18F-T807 was synthesized using an optimized method in TRACERlab FXFN synthesizer with a t-BOC(t-Butyloxy carbonyl)-protected 18F-T807 precursor NPPI-9 as starting material, improving experimental conditions for synthesis, then QC and biodistribution study in Wistar rats conducted. Results The improved synthesis conditions increased the synthesis yield from 20.5%±6.1% to 25.7%±5.8%. QC met the standard. Wistar rats had higher intake in kidney, liver, blood and lowest intake in brain, heart, lung. Conclusion The optimized synthesis method to synthesize 18F-T807 is simple and easy, and high yield, which can meet the needs of scientific research and clinical practice.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-906156

RESUMO

Objective:To identify 24 <italic>Rana</italic> species such as <italic>Rana dybowskii</italic> by mitochondrial cytochrome C oxidase subunit I (<italic>CO</italic>Ⅰ) gene-based DNA barcoding and build the neighbour-joining (NJ) tree for hierarchical cluster analysis, so as to provide a basis for the identification and classification of <italic>Rana</italic> species as well as the discovery of new species. Method:<italic>R. dybowskii</italic>, <italic>R. chensinensis</italic>, <italic>R. amurensis</italic>, <italic>R. culaiensi</italic>s, and <italic>R. huanrenesis</italic>, ten for each species, were collected for DNA extraction and polymerase chain reaction (PCR) amplification<italic> </italic>and sequencing. A total of 50 <italic>CO</italic>Ⅰ gene sequences were obtained. Then 163 <italic>CO</italic>Ⅰ gene sequences for 24 species of <italic>Rana</italic> and one <italic>CO</italic>Ⅰ gene sequence for <italic>Pelophylax</italic>,<italic> Odorrana</italic>, <italic>Nidirana</italic>, <italic>Hylarana</italic>, and <italic>Amolops</italic> were harvested from GenBank. After sequence alignment by MEGA X, the parsimony-informative sites of <italic>CO</italic>Ⅰ gene sequences were analyzed and the intraspecific and interspecific genetic distances were calculated, followed by the built of NJ tree and hierarchical cluster analysis. Result:The <italic>CO</italic>Ⅰ gene sequences of 24<italic> Rana</italic> species including <italic>R. dybowskii</italic> were 554 bp in length and there were 210 parsimony-informative sites in total. The intraspecific genetic distance of each species was smaller than 2%. Except that the interspecific genetic distance between <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> was 0.004, the genetic distances between the other species ranged from 0.024 to 0.228. <italic>R. sangzhiensis</italic> and <italic>R. zhengi</italic> were clustered into one branch and some <italic>R. dybowskii</italic> and <italic>R. uenoi</italic> into one branch. There were two separate branches for <italic>R. chensinensis</italic> and the other species were all clustered independently. Conclusion:<italic>CO</italic>Ⅰ-based DNA barcoding enabled the identification of 24 species of <italic>Rana</italic> including <italic>R.dybowskii</italic>. The findings supported that <italic>R. sangzhiensis</italic>, <italic>R. zhengi</italic>, <italic>R. coreana</italic>, and <italic>R. kunyuensis</italic> were the same species. One branch of <italic>R. chensinensis </italic>might be one of the four undownloaded species in Ranidae or a new species. The results have demonstrated that <italic>CO</italic>Ⅰ-based DNA barcoding allows not only the identification of 24 species of Rana including <italic>R. dybowskii </italic>but also the classification of ranidae species and the discovery of new species or subspecies.

9.
Mol Immunol ; 123: 106-115, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32485469

RESUMO

Hepatocytes are the targets in autoimmune hepatitis (AIH) that results in T cell-dependent liver injury. However, hepatocytes may also affect the hepatic T cells in AIH, but the underlying mechanisms are not fully understood. Here we report that hepatocytes could secrete galectin-9 (Gal-9) to suppress the intrahepatic production of Th1 cytokine IFN-γ and restrict AIH development, but hepatocyte damage resulted in opposite effects due to release of TLR2/4 ligands that promoted the intrahepatic production of IL-1ß, IL-6, and IL-12. Through Tim-3, Gal-9 could efficiently suppress the intrahepatic T cell activation despite presence of TLR2/4 ligands, thus attenuating Th1 response in AIH. Intriguingly, intrahepatic IL-6/IL-12 suppressed the effect of TGF-ß on Treg cells. Therefore, in AIH, Gal-9 promoted Foxp3 expression and function of hepatic Treg cells through TL1A signaling, although Treg function was still impaired, compared with that in naive state. Due to its promoting effect on Treg function, together with its effect on T effector cells in a Tim-3-independent way, Gal-9 could attenuate intrahepatic IFN-γ production by hindering the increase of hepatic CD4+CD43+ T cells resulting from extrahepatic T cell activation. TLR2/4 ligands attenuated the effects of Gal-9 on Treg cells and CD4+CD43+ T cells by increasing intrahepatic IL-6 and IL-12. Blocking TLR2/4 ligands could efficiently suppress intrahepatic IFN-γ production, liver injury, and hepatic fibrosis. These findings suggest that hepatocytes paradoxically affect Th1 response in AIH due to Gal-9 expression and TLR2/4 ligands release, and that targeting TLR2/4 signaling may provide an important approach in the therapeutic strategy for AIH.


Assuntos
Galectinas/metabolismo , Hepatite Autoimune/metabolismo , Hepatócitos/fisiologia , Interferon gama/metabolismo , Fígado/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Células Cultivadas , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Ligantes , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/metabolismo
10.
Immunol Lett ; 218: 44-50, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31794800

RESUMO

Autoimmune hepatitis (AIH) is a chronic liver disease mediated by immunity, and could lead to liver fibrosis and hepatocellular carcinoma. However, the mechanisms for breaking hepatic tolerance and driving AIH still remain elusive. We herein reported that the non-specific liver inflammation triggered by carbon tetrachloride (CCl4) recruited high numbers of CD4+T, CD8+T and B cells, and elevated the expression of proinflammaitory cytokines in Balb/c mice, further breaking liver tolerance and inducing autoimmune response, AIH inflammation and liver fibrosis in the presence of CYP2D6 antigen mimicry. In contrast, adenovirus infection could not break liver tolerance and induce AIH in Balb/c mice even in the presence of CYP2D6 antigen mimicry. These results suggested that genetic predisposition could determine liver tolerance in Balb/c mice. The chemical induced inflammation in the liver breaks tolerance and might be considered important for the initiation and development of AIH in Balb/c mice.


Assuntos
Autoimunidade , Suscetibilidade a Doenças , Hepatite Autoimune/etiologia , Tolerância Imunológica , Adenoviridae/imunologia , Animais , Autoantígenos/imunologia , Biomarcadores , Biópsia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Tetracloreto de Carbono/efeitos adversos , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Feminino , Hepatite Autoimune/metabolismo , Hepatite Autoimune/patologia , Imuno-Histoquímica , Camundongos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
13.
J Cell Commun Signal ; 13(3): 369-380, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30739244

RESUMO

TGF-ß1 is a main inducer of epithelial to mesenchymal transition (EMT). However, many breast cancer cells are not sensitive to the EMT induction by TGF-ß1 alone. So far, the mechanisms underlying the induction of TGF-ß1-insensitive breast cancer cells remains unclear. Here we report that TNF-α can induce EMT and invasiveness of breast cancer cells which are insensitive to TGF-ß1. Intriguingly, TGF-ß1 could cooperate with TNF-α to promote the EMT and invasiveness of breast cancer cells. The prolonged co-stimulation with TGF-ß1 and TNF-α could enhance the sustained activation of Smad2/3, p38 MAPK, ERK, JNK and NF-κB pathways by enhancing the activation of TAK1, which was mediated by the gradually up-regulated TßRs. Except for JNK, all of these pathways were required for the effects of TGF-ß1 and TNF-α. Importantly, the activation of p38 MAPK and ERK pathways resulted in a positive feed-back effect on TAK1 activation by up-regulating the expression of TßRs, favoring the activation of multiple signaling pathways. Moreover, SLUG was up-regulated and required for the TGF-ß1/TNF-α-induced EMT and invasiveness. In addition, SLUG could also enhance the activation of signaling pathways by promoting TßRII expression. These findings suggest that the up-regulation of TßRs contributes to the sustained activation of TAK1 induced by TGF-ß1/TNF-α and the following activation of multiple signaling pathways, resulting in EMT and invasiveness of breast cancer cells.

14.
Int Immunopharmacol ; 69: 184-193, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30735937

RESUMO

T cell-dependent liver injury is an important reason for the massive hepatic damage and cirrhosis. So far it is unclear whether the development of the disease could be efficiently suppressed by anti-inflammatory cytokine that modulates innate immune cells. Here we report that anti-inflammatory cytokine IL-37 could efficiently suppress the sustained hepatic expression of IFN-γ and TNF-α, two critical cytokines for inducing hepatocyte apoptosis and liver fibrosis in T cell-dependent liver injury. IL-37 could directly suppress IFN-γ/TLR4 ligand-induced M1 activation of macrophages, thus reducing the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-12. Moreover, IL-37 attenuated Th1 response in vivo and increased the expression of Th2 cytokines IL-4 and IL-13, which in turn promoted M2 activation of macrophages in the liver. The increase of M2 activation not only further reduced TNF-α, IL-1ß and IL-12 expression, but also increased IL-10 and IL-1Ra expression in macrophages, thus more efficiently suppressing the hepatic IFN-γ expression. By suppressing IFN-γ/TNF-α expression, IL-37 suppressed the up-regulation and activation of MLKL that drives hepatocellular necrosis in T cell-dependent liver damage. Accordingly, IL-37 efficiently reduced liver injury and hepatic inflammation after the repeated ConA challenge and the induction of autoimmune hepatitis, and also suppressed hepatic fibrosis resulting from the sustained liver damage. This study showed that the direct and indirect effect of IL-37 on macrophages could reduce the hepatic TNF-α expression, and also modulate IL-1ß/IL-12 and IL-10/IL-1Ra expression to suppress the hepatic IFN-γ expression, thus suppressing the development of T cell-dependent liver injury such as autoimmune hepatitis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Hepatócitos/fisiologia , Interleucina-1/uso terapêutico , Macrófagos/fisiologia , Linfócitos T/imunologia , Animais , Células Cultivadas , Concanavalina A , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Terapia de Imunossupressão , Interferon gama/metabolismo , Camundongos , Receptores de Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Nat Commun ; 9(1): 1739, 2018 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-29712898

RESUMO

Chemoresistance is a major unmet clinical obstacle in ovarian cancer treatment. Epigenetics plays a pivotal role in regulating the malignant phenotype, and has the potential in developing therapeutically valuable targets that improve the dismal outcome of this disease. Here we show that a series of transcription factors, including C/EBPß, GCM1, and GATA1, could act as potential modulators of histone methylation in tumor cells. Of note, C/EBPß, an independent prognostic factor for patients with ovarian cancer, mediates an important mechanism through which epigenetic enzyme modifies groups of functionally related genes in a context-dependent manner. By recruiting the methyltransferase DOT1L, C/EBPß can maintain an open chromatin state by H3K79 methylation of multiple drug-resistance genes, thereby augmenting the chemoresistance of tumor cells. Therefore, we propose a new path against cancer epigenetics in which identifying and targeting the key regulators of epigenetics such as C/EBPß may provide more precise therapeutic options in ovarian cancer.


Assuntos
Biomarcadores Tumorais/genética , Proteína beta Intensificadora de Ligação a CCAAT/genética , Cromatina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética , Histonas/genética , Neoplasias Ovarianas/genética , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Linhagem Celular Tumoral , Cromatina/química , Cisplatino/farmacologia , Proteínas de Ligação a DNA , Bases de Dados Factuais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo , Histona-Lisina N-Metiltransferase , Histonas/metabolismo , Humanos , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Cultura Primária de Células , Prognóstico , Análise de Sobrevida , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
Mol Immunol ; 99: 171-181, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29793131

RESUMO

Autoimmune hepatitis (AIH), a serious autoimmune liver disease, can be a lifelong illness, leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). So far the mechanisms for disease initiation are largely unknown. Here we report that the amplified non-AIH liver inflammation could promote the initiation of AIH due to the sustained increase of IL-6, IL-12, IL-4, and IL-25 in the liver. The liver injury resulting from virus (adenovirus) or chemicals (CCl4) could induce an amplified (stronger/long-lasting) hepatic inflammation by releasing the ligands for TLR2/TLR4. The amplified inflammation resulted in the increase of multiple cytokines and chemokines in the liver. Among them, the sustained increase of IL-6/IL-12 resulted in the activation of STAT3 and STAT4 in hepatic CD4+CD25+ Treg cells, thus suppressing Foxp3 gene expression to reduce the suppressive function of Treg cells in the liver, but not those in the spleen. The increase of IL-12 and the impairment of Treg function promoted Th1 response in presence of self-mimicking antigen (human CYP2D6). Intriguingly, the amplified inflammation resulted in the increase of IL-4 and IL-25 in the liver. The moderate increase of IL-4 was sufficient for cooperating with IL-25 to initiate Th2 response, but inefficient in suppressing Th1 response, favoring the initiation of autoimmune response. Consequently, either adenovirus/CYP2D6 or CCl4/CYP2D6 could induce the autoimmune response and AIH in the mice, leading to hepatic fibrosis. The findings in this study suggest that the amplified non-AIH inflammation in the liver could be a driving force for the initiation of autoimmune response and AIH.


Assuntos
Autoimunidade/imunologia , Hepatite Autoimune/imunologia , Inflamação/imunologia , Fígado/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Feminino , Interleucinas/imunologia , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/imunologia
17.
Oncotarget ; 8(20): 33501-33514, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28432279

RESUMO

IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1ß and IL-6. IL-1ß stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.


Assuntos
Interleucinas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Fenótipo , Animais , Biomarcadores , Citocinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Imunomodulação , Interleucinas/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Neoplasias/imunologia , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Infiltração de Neutrófilos/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Transcrição STAT3/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
18.
Oncotarget ; 8(17): 28418-28430, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28415700

RESUMO

Circulating tumor cells (CTCs) have been studied well in the prognosis for malignant diseases as liquid biopsy, but their contribution to tumor metastasis is not clearly defined. Here we report that CTCs could promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation and neutrophil recruitment to pre-metastatic organs. Depletion of neutrophils in vivo could effectively abrogate the promoting effect of CTCs on tumor cell metastasis. In the presence of CTCs, the pro-tumor function of neutrophils was augmented, whereas the antitumor function of neutrophils was suppressed. Mechanically, CTC-derived ligands for TLR2 and TLR4 (TLR2/4) induced the systemic inflammation, thus increasing the production of proinflammatory cytokines such as G-CSF and IL-6 that could induce the conversion of neutrophil function from tumor-suppressing to tumor-promoting. Moreover, CTCs induced the production of endogenous TLR2/4 ligands such as S100A8, S100A9, and SAA3, which may amplify the stimulating effect that induces the expression of proinflammatory cytokines. The promoting effect of CTCs on tumor cell metastasis could be abrogated by suppressing inflammatory response with IL-37, an anti-inflammatory cytokine, or blocking CTC-derived ligands for TLR2/4. Identification of the metastatic axis of CTCs/systemic inflammation/neutrophils may provide potential targets for preventing tumor cell metastasis.


Assuntos
Inflamação/patologia , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores , Degranulação Celular/genética , Degranulação Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Inflamação/etiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Ligantes , Melanoma Experimental , Camundongos , Metástase Neoplásica , Neoplasias/complicações , Neoplasias/genética , Neoplasias/metabolismo , Células Neoplásicas Circulantes/metabolismo , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo
19.
Clin Cancer Res ; 23(1): 214-224, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27401250

RESUMO

PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR.


Assuntos
Células Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Neoplasias/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Linfangiogênese , Metástase Linfática , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Camundongos Nus , Neoplasias/patologia , Receptor ErbB-2/metabolismo , Transdução de Sinais , Proteína rhoA de Ligação ao GTP/metabolismo
20.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 33(1): 34-6, 2017 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30070794

RESUMO

Objective To investigate the therapeuctic effect of one-stage reconstruction of distal urethra with free graft of tublar oral mucosa. . Methods: Two strips of oral mucosa graft(0.4-0.6 cm in width),were harvested and sutured around an oiled silk roll to form mucosa tube. The mucosa tube was used to reconstruct distal urethra. Postoperative pressure dressing and earlier urination were recommended Results: From May 2007 to October 2015,16 cases with distal urethra defect or stenosis were treated with this method. The urethra defect was 2-4 cm in length. Urethral fistula happened in 3 patients. All the other 13 cases healed primarily.10 cases were followed up for 1-5 years by telephone with normal function. Conclusions: One-stage reconstruction with free graft of bulbar oral mucosa is suitable and reliable for distal urethra defect less than 4 cm in length.


Assuntos
Mucosa Bucal/transplante , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/transplante , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Feminino , Humanos , Masculino
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