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1.
Nat Microbiol ; 4(8): 1378-1388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31110366

RESUMO

Mycobacterium tuberculosis (Mtb)-derived components are usually recognized by pattern recognition receptors to initiate a cascade of innate immune responses. One striking characteristic of Mtb is their utilization of different type VII secretion systems to secrete numerous proteins across their hydrophobic and highly impermeable cell walls, but whether and how these Mtb-secreted proteins are sensed by host immune system remains largely unknown. Here, we report that MPT53 (Rv2878c), a secreted disulfide-bond-forming-like protein of Mtb, directly interacts with TGF-ß-activated kinase 1 (TAK1) and activates TAK1 in a TLR2- or MyD88-independent manner. MPT53 induces disulfide bond formation at C210 on TAK1 to facilitate its interaction with TRAFs and TAB1, thus activating TAK1 to induce the expression of pro-inflammatory cytokines. Furthermore, MPT53 and its disulfide oxidoreductase activity is required for Mtb to induce the host inflammatory responses via TAK1. Our findings provide an alternative pathway for host signalling proteins to sense Mtb infection and may favour the improvement of current vaccination strategies.

2.
Am J Otolaryngol ; 40(4): 573-576, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31109803

RESUMO

PURPOSE: Metabolic syndrome (MetS) was reported to a risk factor of developing idiopathic sudden sensorineural hearing loss (ISSNHL), but limited data exist on its effect on the recovery. The purpose of this study was to evaluate the impact of (MetS) and its components on recovery of patients with ISSNHL. MATERIAL AND METHODS: 228 ISSNHL patients were divided into MetS group and Non-MetS group according to the diagnostic criteria of MetS, and demographic and clinical characteristics and hearing recovery were reviewed between two groups. RESULTS: In total, 86 (37.7%) patients in MetS group, and 142 (62.3%) patients in Non-MetS group. The rate of hypertension, diabetes mellitus, low HDL-C, high TG and obesity were significantly higher in the MetS group than those in the Non-MetS group (P < 0.05). The complete recovery rate and partial recovery rate were significantly lower in the MetS group than those in the Non-MetS group. According to the multivariate analysis, MetS was significantly associated with a poor prognosis; high initial hearing threshold and presence of diabetes mellitus were correlated with a poor prognosis (P < 0.05). CONCLUSIONS: These results suggest that MetS has a negative impact on the hearing recovery of ISSNHL. High initial hearing threshold and diabetes mellitus were indictors of a poor prognosis of ISSNHL.

3.
ACS Nano ; 13(4): 4111-4123, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30883090

RESUMO

We propose a strategy for assembling spherical nanoparticles (NPs) into anisotropic architectures in a polymer matrix. The approach takes advantage of the interfacial tension between two mutually immiscible polymers forming a bilayer and differences in the compatibility of the two polymer layers with polymer grafts on particles to trap NPs within two-dimensional planes parallel to the interface. The ability to precisely tune the location of the entrapment planes via the NP grafting density, and to trap multiple interacting particles within distinct planes, can then be used to assemble NPs into unconventional arrangements near the interface. We carry out molecular dynamics simulations of polymer-grafted NPs in a polymer bilayer to demonstrate the viability of the proposed approach in both trapping NPs at tunable distances from the interface and assembling them into a variety of unusual nanostructures. We illustrate the assembly of NP clusters, such as dimers with tunable tilt relative to the interface and trimers with tunable bending angle, as well as anisotropic macroscopic phases, including serpentine and branched structures, ridged hexagonal monolayers, and square-ordered bilayers. We also develop a theoretical model to predict the preferred positions and free energies of NPs trapped at or near the interface that could help guide the design of polymer-grafted NPs for achieving target NP architectures. Overall, this work suggests that interfacial assembly of NPs could be a promising approach for fabricating next-generation polymer nanocomposites with potential applications in plasmonics, electronics, optics, and catalysis where precise arrangement of polymer-embedded NPs is required for function.

4.
Nat Commun ; 10(1): 746, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765691

RESUMO

Excessive or uncontrolled release of proinflammatory cytokines caused by severe viral infections often results in host tissue injury or even death. Phospholipase C (PLC)s degrade phosphatidylinositol-4, 5-bisphosphate (PI(4,5)P2) lipids and regulate multiple cellular events. Here, we report that PLCß2 inhibits the virus-induced expression of pro-inflammatory cytokines by interacting with and inhibiting transforming growth factor-ß-activated kinase 1 (TAK1) activation. Mechanistically, PI(4,5)P2 lipids directly interact with TAK1 at W241 and N245, and promote its activation. Impairing of PI(4,5)P2's binding affinity or mutation of PIP2-binding sites on TAK1 abolish its activation and the subsequent production of pro-inflammatory cytokines. Moreover, PLCß2-deficient mice exhibit increased expression of proinflammatory cytokines and a higher frequency of death in response to virus infection, while the PLCß2 activator, m-3M3FBS, protects mice from severe Coxsackie virus A 16 (CVA16) infection. Thus, our findings suggest that PLCß2 negatively regulates virus-induced pro-inflammatory responses by inhibiting phosphoinositide-mediated activation of TAK1.


Assuntos
Infecções por Coxsackievirus/metabolismo , Citocinas/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfolipase C beta/metabolismo , Animais , Células Cultivadas , Cercopithecus aethiops , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/virologia , Citocinas/genética , Enterovirus/fisiologia , Ativação Enzimática , Regulação da Expressão Gênica , Células HEK293 , Humanos , MAP Quinase Quinase Quinases/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipase C beta/genética , Ligação Proteica , Células Vero
5.
Nature ; 563(7729): 131-136, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30356214

RESUMO

Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING-IRF3-type I IFN signalling cascade1,2. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response3,4, but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy.

6.
Nat Commun ; 9(1): 4295, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30327467

RESUMO

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches.

7.
J Infect Dis ; 218(2): 312-323, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29228365

RESUMO

Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global threat to human health, but knowledge of the molecular mechanisms underlying the pathogenesis of tuberculosis is still limited. Although Notch4, a member of the Notch receptor family, is involved in the initiation of mammary tumors, its function in M. tuberculosis infection remains unclear. In this study, we found that Notch4-deficient mice were more resistant to M. tuberculosis infection, with a much lower bacterial burden and fewer pathological changes in the lungs. Notch4 inhibited M. tuberculosis-induced production of proinflammatory cytokines by interaction with TAK1 and inhibition of its activation. Furthermore, we found that Notch intracellular domain 4 prevented TRAF6 autoubiquitination and suppressed TRAF6-mediated TAK1 polyubiquitination. Finally, Notch inhibitors made mice more resistant to M. tuberculosis infection. These results suggest that Notch4 is a negative regulator of M. tuberculosis-induced inflammatory response, and treatment with a Notch inhibitor could serve as a new therapeutic strategy for tuberculosis.

8.
Nanoscale ; 9(37): 13915-13921, 2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28902192

RESUMO

Using liquid cell TEM, we imaged the formation of CoO nanoparticle rings. Nanoparticles nucleated and grew tracing the perimeter of droplets sitting on the SiNx solid substrate, and finally formed necklace-like rings. By tracking single nanoparticle trajectories during the ring formation and an estimation of the forces between droplets and nanoparticles using a simplified model, we found the junction of liquid nanodroplets with a solid substrate is the attractive site for CoO nanoparticles. Coalescing droplets were capable of pushing nanoparticles to the perimeter of the new droplet and nanoparticles on top of the droplets rolled off toward the perimeter. We propose that the curved surface morphology of the droplets created a force gradient that contributed to the assembly of nanoparticles at the droplet perimeter. Revealing the dynamics of nanoparticle movements and the interactions of nanoparticles with the liquid nanodroplet provides insights on developing novel self-assembly strategies for building precisely defined nanostructures on solid substrates.

9.
Nano Lett ; 17(8): 5119-5125, 2017 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-28737928

RESUMO

With the rapid development of nanoscale structuring technology, the precision in the etching reaches the sub-10 nm scale today. However, with the ongoing development of nanofabrication the etching mechanisms with atomic precision still have to be understood in detail and improved. Here we observe, atom by atom, how preferential facets form in CaO crystals that are etched by an electron beam in an in situ high-resolution transmission electron microscope (HRTEM). An etching mechanism under electron beam irradiation is observed that is surprisingly similar to chemical etching and results in the formation of nanofacets. The observations also explain the dynamics of surface roughening. Our findings show how electron beam etching technology can be developed to ultimately realize tailoring of the facets of various crystalline materials with atomic precision.

10.
Eur J Immunol ; 47(9): 1414-1426, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28744851

RESUMO

The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required. Post-translational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are crucial for this immune homeostasis in antiviral responses. Canonical PTMs including phosphorylation and ubiquitination have been extensively studied and other PTMs such as methylation, acetylation, SUMOylation, ADP-ribosylation and glutamylation are being increasingly implicated in antiviral innate immunity. Here we summarize our recent understanding of the most important PTMs regulating the antiviral innate immune response, and their role in virus-related immune pathogenesis.


Assuntos
DNA Viral/imunologia , Imunidade Inata , Processamento de Proteína Pós-Traducional , RNA Viral/imunologia , Viroses/imunologia , Animais , Humanos , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , NF-kappa B/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo
11.
Infect Immun ; 85(9)2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28652310

RESUMO

Exoenzyme Y (ExoY) is a type III secretion system effector found in 90% of the Pseudomonas aeruginosa isolates. Although it is known that ExoY is a soluble nucleotidyl cyclase that increases the cytoplasmic levels of nucleoside 3',5'-cyclic monophosphates (cNMPs) to mediate endothelial Tau phosphorylation and permeability, its functional role in the innate immune response is still poorly understood. Transforming growth factor ß-activated kinase 1 (TAK1) is critical for mediating Toll-like receptor (TLR) signaling and subsequent activation of NF-κB and AP-1, which are transcriptional activators of innate immunity. Here, we report that ExoY inhibits proinflammatory cytokine production through suppressing the activation of TAK1 as well as downstream NF-κB and mitogen-activated protein (MAP) kinases. Mice infected with ExoY-deficient P. aeruginosa had higher levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), more neutrophil recruitment, and a lower bacterial load in lung tissue than mice infected with wild-type P. aeruginosa Taken together, our findings identify a previously unknown mechanism by which P. aeruginosa ExoY inhibits the host innate immune response.


Assuntos
Proteínas de Bactérias/metabolismo , Glucosiltransferases/metabolismo , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Imunidade Inata , MAP Quinase Quinase Quinases/antagonistas & inibidores , Fósforo-Oxigênio Liases/metabolismo , Pseudomonas aeruginosa/patogenicidade , Animais , Proteínas de Bactérias/genética , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Deleção de Genes , Glucosiltransferases/genética , Humanos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fósforo-Oxigênio Liases/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/enzimologia , Fator de Transcrição AP-1/metabolismo
12.
Small ; 13(27)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28556596

RESUMO

The surface energy and surface stability of Ag nanocrystals (NCs) are under debate because the measurable values of the surface energy are very inconsistent, and the indices of the observed thermally stable surfaces are apparently in conflict. To clarify this issue, a transmission electron microscope is used to investigate these problems in situ with elaborately designed carbon-shell-capsulated Ag NCs. It is demonstrated that the {111} surfaces are still thermally stable at elevated temperatures, and the victory of the formation of {110} surfaces over {111} surfaces on the Ag NCs during sublimation is due to the special crystal geometry. It is found that the Ag NCs behave as quasiliquids during sublimation, and the cubic NCs represent a featured shape evolution, which is codetermined by both the wetting equilibrium at the Ag-C interface and the relaxation of the system surface energy. Small Ag NCs (≈10 nm) no longer maintain the wetting equilibrium observed in larger Ag NCs, and the crystal orientations of ultrafine Ag NCs (≈6 nm) can rotate to achieve further shape relaxation. Using sublimation kinetics, the mean surface energy of Ag NCs at 1073 K is calculated to be 1.1-1.3 J m-2 .

13.
Nat Commun ; 8: 14889, 2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28401911

RESUMO

Cation exchange (CE) has been recognized as a particularly powerful tool for the synthesis of heterogeneous nanocrystals. At present, CE can be divided into two categories, namely ion solvation-driven CE reaction and thermally activated CE reaction. Here we report an electrically driven CE reaction to prepare individual nanostructures inside a transmission electron microscope. During the process, Cd is eliminated due to Ohmic heating, whereas Cu+ migrates into the crystal driven by the electrical field force. Contrast experiments reveal that the feasibility of electrically driven CE is determined by the structural similarity of the sulfur sublattices between the initial and final phases, and the standard electrode potentials of the active electrodes. Our experimental results demonstrate a strategy for the selective growth of individual nanocrystals and provide crucial insights into understanding of the microscopic pathways leading to the formation of heterogeneous structures.

14.
Sci Rep ; 7: 46510, 2017 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-28406228

RESUMO

Electrokinetic instability refers to unstable electric field-driven disturbance to fluid flows, which can be harnessed to promote mixing for various electrokinetic microfluidic applications. This work presents a combined numerical and experimental study of electrokinetic ferrofluid/water co-flows in microchannels of various depths. Instability waves are observed at the ferrofluid and water interface when the applied DC electric field is beyond a threshold value. They are generated by the electric body force that acts on the free charge induced by the mismatch of ferrofluid and water electric conductivities. A nonlinear depth-averaged numerical model is developed to understand and simulate the interfacial electrokinetic behaviors. It considers the top and bottom channel walls' stabilizing effects on electrokinetic flow through the depth averaging of three-dimensional transport equations in a second-order asymptotic analysis. This model is found accurate to predict both the observed electrokinetic instability patterns and the measured threshold electric fields for ferrofluids of different concentrations in shallow microchannels.

15.
Adv Mater ; 29(10)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28084654

RESUMO

A scalable, low-temperature solution process is used to synthesize precursor material for Pb-doped Bi0.7 Sb1.3 Te3 thermoelectric nanocomposites. The controllable Pb-doping leads to the increase in the optical bandgap, thus delaying the onset of bipolar conduction. Furthermore, the solution synthesis enables nanostructuring, which greatly reduces thermal conductivity. As a result, this material exhibits a zT = 1 over the 513-613 K range.

16.
Electrophoresis ; 38(5): 572-579, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27557612

RESUMO

Electroosmotic flow is the transport method of choice in microfluidic devices over traditional pressure-driven flow. To date, however, studies on electroosmotic flow have been almost entirely limited to inside microchannels. This work presents the first experimental study of Joule heating effects on electroosmotic fluid entry from the inlet reservoir (i.e., the well that supplies fluids and samples) to the microchannel in a polymer-based microfluidic chip. Electrothermal fluid circulations are observed at the reservoir-microchannel junction, which grow in size and strength with the increasing alternating current to direct current voltage ratio. Moreover, a 2D depth-averaged numerical model is developed to understand the effects of Joule heating on fluid temperature and flow fields in electrokinetic microfluidic chips. This model overcomes the problems encountered in previous unrealistic 2D and costly 3D models, and is able to predict the observed electroosmotic entry flow patterns with a good agreement.


Assuntos
Eletro-Osmose , Temperatura Alta , Simulação por Computador , Modelos Teóricos
17.
Cell Signal ; 28(9): 1292-303, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27234131

RESUMO

CD36, a scavenger receptor, plays an important role in the progression of atherosclerosis through its interaction with oxidized low-density lipoprotein (ox-LDL). Porphyromonas gingivalis (P. gingivalis, Pg) has been shown to promote macrophage-derived foam cell formation by affecting the expression of CD36. However, the regulatory role of CD36 in macrophages infected with Pg remains largely unknown. Therefore, the aim of the present study was to explore the molecular mechanism of Pg induced CD36 expression in macrophages. Our results showed that Pg promoted ox-LDL uptake by macrophages and the formation of foam cells. Pg infection increased CD36 mRNA and protein levels in ox-LDL-untreated macrophages. Moreover, small interferon RNA (siRNA) targeting CD36 significantly reduced foam cell formation induced by Pg. Additionally, Pg stimulated nuclear translocation of p65, which directly bound to the promoters of CD36 to facilitate its transcription. Inhibition of p65, NF-κB or ERK1/2 blocked Pg-induced CD36 production; whereas, overexpression of NF-κB subunits p65 and p50 upregulated CD36. Furthermore, Ras inhibitors significantly attenuated ERK1/2 activation and CD36 expression. Taken together, the data indicated that stimulation of the ERK/NF-κB pathway by Pg led to transactivation of the CD36 promoters, thereby upregulating CD36 expression in the infected macrophages. These findings may help design new treatment strategies in atherosclerosis.


Assuntos
Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/microbiologia , Antígenos CD36/genética , Sistema de Sinalização das MAP Quinases , Macrófagos Peritoneais/microbiologia , NF-kappa B/metabolismo , Porphyromonas gingivalis/fisiologia , Regulação para Cima/genética , Animais , Infecções por Bacteroidaceae/patologia , Antígenos CD36/metabolismo , Feminino , Células Espumosas/metabolismo , Células Espumosas/microbiologia , Células Espumosas/patologia , Células HEK293 , Humanos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas/genética , Ligação Proteica , Subunidades Proteicas/metabolismo , Células RAW 264.7
18.
Nat Immunol ; 17(4): 397-405, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26928339

RESUMO

The signaling adaptor TRAF3 is a highly versatile regulator of both innate immunity and adaptive immunity, but how its phosphorylation is regulated is still unknown. Here we report that deficiency in or inhibition of the conserved serine-threonine kinase CK1ɛ suppressed the production of type I interferon in response to viral infection. CK1ɛ interacted with and phosphorylated TRAF3 at Ser349, which thereby promoted the Lys63 (K63)-linked ubiquitination of TRAF3 and subsequent recruitment of the kinase TBK1 to TRAF3. Consequently, CK1ɛ-deficient mice were more susceptible to viral infection. Our findings establish CK1ɛ as a regulator of antiviral innate immune responses and indicate a novel mechanism of immunoregulation that involves CK1ɛ-mediated phosphorylation of TRAF3.


Assuntos
Caseína Quinase Iépsilon/imunologia , Imunidade Inata/imunologia , Interferon beta/imunologia , Fator 3 Associado a Receptor de TNF/imunologia , Animais , Caseína Quinase Iépsilon/antagonistas & inibidores , Caseína Quinase Iépsilon/genética , Ensaio de Imunoadsorção Enzimática , Células HEK293 , Células HeLa , Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Humanos , Interferon Tipo I/biossíntese , Interferon Tipo I/imunologia , Interferon beta/biossíntese , Espectrometria de Massas , Camundongos , Camundongos Knockout , Fosforilação , Proteínas Serina-Treonina Quinases , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Rhabdoviridae/imunologia , Fator 3 Associado a Receptor de TNF/genética , Ubiquitinação , Vesiculovirus/imunologia , Febre do Nilo Ocidental/imunologia , Vírus do Nilo Ocidental/imunologia
19.
Biomicrofluidics ; 9(4): 044102, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26221197

RESUMO

Trapping and preconcentrating particles and cells for enhanced detection and analysis are often essential in many chemical and biological applications. Existing methods for diamagnetic particle trapping require the placement of one or multiple pairs of magnets nearby the particle flowing channel. The strong attractive or repulsive force between the magnets makes it difficult to align and place them close enough to the channel, which not only complicates the device fabrication but also restricts the particle trapping performance. This work demonstrates for the first time the use of a single permanent magnet to simultaneously trap diamagnetic and magnetic particles in ferrofluid flows through a T-shaped microchannel. The two types of particles are preconcentrated to distinct locations of the T-junction due to the induced negative and positive magnetophoretic motions, respectively. Moreover, they can be sequentially released from their respective trapping spots by simply increasing the ferrofluid flow rate. In addition, a three-dimensional numerical model is developed, which predicts with a reasonable agreement the trajectories of diamagnetic and magnetic particles as well as the buildup of ferrofluid nanoparticles.

20.
Int J Clin Exp Pathol ; 7(7): 3752-62, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25120751

RESUMO

Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation, invasion and/or angiogenesis. LAP3 is one important member of this family. However, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3 expression was significantly up-regulated in HCC tissues as well as cells and was closely correlated with lower differentiation, positive lymph node metastasis and high Ki-67 expression, indicating a poor prognosis. Then cell viability assays, flow cytometry assays, wound-healing assays and matrigel invasion assays were performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to cisplatin, thus promoting the cell death of HCC cells. Collectively, our results indicated that up-regulated expression of LAP3 might contribute to the proliferation and metastasis of HCC. Our data gains greater insight into the cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing potential therapeutic strategies for clinical trials.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Leucil Aminopeptidase/biossíntese , Neoplasias Hepáticas/patologia , Adulto , Idoso , Western Blotting , Carcinoma Hepatocelular/enzimologia , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/enzimologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Transfecção , Regulação para Cima
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