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1.
Nature ; 613(7943): 268-273, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36631645

RESUMEN

In the presence of a large perpendicular electric field, Bernal-stacked bilayer graphene (BLG) features several broken-symmetry metallic phases1-3 as well as magnetic-field-induced superconductivity1. The superconducting state is quite fragile, however, appearing only in a narrow window of density and with a maximum critical temperature Tc ≈ 30 mK. Here we show that placing monolayer tungsten diselenide (WSe2) on BLG promotes Cooper pairing to an extraordinary degree: superconductivity appears at zero magnetic field, exhibits an order of magnitude enhancement in Tc and occurs over a density range that is wider by a factor of eight. By mapping quantum oscillations in BLG-WSe2 as a function of electric field and doping, we establish that superconductivity emerges throughout a region for which the normal state is polarized, with two out of four spin-valley flavours predominantly populated. In-plane magnetic field measurements further reveal that superconductivity in BLG-WSe2 can exhibit striking dependence of the critical field on doping, with the Chandrasekhar-Clogston (Pauli) limit roughly obeyed on one end of the superconducting dome, yet sharply violated on the other. Moreover, the superconductivity arises only for perpendicular electric fields that push BLG hole wavefunctions towards WSe2, indicating that proximity-induced (Ising) spin-orbit coupling plays a key role in stabilizing the pairing. Our results pave the way for engineering robust, highly tunable and ultra-clean graphene-based superconductors.

2.
Nature ; 623(7989): 942-948, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37968401

RESUMEN

Magic-angle twisted trilayer graphene (MATTG) exhibits a range of strongly correlated electronic phases that spontaneously break its underlying symmetries1,2. Here we investigate the correlated phases of MATTG using scanning tunnelling microscopy and identify marked signatures of interaction-driven spatial symmetry breaking. In low-strain samples, over a filling range of about two to three electrons or holes per moiré unit cell, we observe atomic-scale reconstruction of the graphene lattice that accompanies a correlated gap in the tunnelling spectrum. This short-scale restructuring appears as a Kekulé supercell-implying spontaneous inter-valley coherence between electrons-and persists in a wide range of magnetic fields and temperatures that coincide with the development of the gap. Large-scale maps covering several moiré unit cells further reveal a slow evolution of the Kekulé pattern, indicating that atomic-scale reconstruction coexists with translation symmetry breaking at a much longer moiré scale. We use auto-correlation and Fourier analyses to extract the intrinsic periodicity of these phases and find that they are consistent with the theoretically proposed incommensurate Kekulé spiral order3,4. Moreover, we find that the wavelength characterizing moiré-scale modulations monotonically decreases with hole doping away from half-filling of the bands and depends weakly on the magnetic field. Our results provide essential insights into the nature of the correlated phases of MATTG in the presence of strain and indicate that superconductivity can emerge from an inter-valley coherent parent state.

3.
Nature ; 598(7881): 434-438, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34469942

RESUMEN

To access superconductivity via the electric field effect in a clean, two-dimensional device is a central goal of nanoelectronics. Recently, superconductivity has been realized in graphene moiré heterostructures1-4; however, many of these structures are not mechanically stable, and experiments show signatures of strong disorder. Here we report the observation of superconductivity-manifesting as low or vanishing resistivity at sub-kelvin temperatures-in crystalline rhombohedral trilayer graphene5,6, a structurally metastable carbon allotrope. Superconductivity occurs in two distinct gate-tuned regions (SC1 and SC2), and is deep in the clean limit defined by the ratio of mean free path and superconducting coherence length. Mapping of the normal state Fermi surfaces by quantum oscillations reveals that both superconductors emerge from an annular Fermi sea, and are proximal to an isospin-symmetry-breaking transition where the Fermi surface degeneracy changes7. SC1 emerges from a paramagnetic normal state, whereas SC2 emerges from a spin-polarized, valley-unpolarized half-metal17 and violates the Pauli limit for in-plane magnetic fields by at least one order of magnitude8,9. We discuss our results in view of several mechanisms, including conventional phonon-mediated pairing10,11, pairing due to fluctuations of the proximal isospin order12, and intrinsic instabilities of the annular Fermi liquid13,14. Our observation of superconductivity in a clean and structurally simple two-dimensional metal provides a model system to test competing theoretical models of superconductivity without the complication of modelling disorder, while enabling new classes of field-effect controlled electronic devices based on correlated electron phenomena and ballistic electron transport.

4.
Nature ; 598(7881): 429-433, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34469943

RESUMEN

Ferromagnetism is most common in transition metal compounds where electrons occupy highly localized d orbitals. However, ferromagnetic order may also arise in low-density two-dimensional electron systems1-5. Here we show that gate-tuned van Hove singularities in rhombohedral trilayer graphene6 drive spontaneous ferromagnetic polarization of the electron system into one or more spin and valley flavours. Using capacitance and transport measurements, we observe a cascade of transitions tuned to the density and electronic displacement field between phases in which quantum oscillations have fourfold, twofold or onefold degeneracy, associated with a spin- and valley-degenerate normal metal, spin-polarized 'half-metal', and spin- and valley-polarized 'quarter-metal', respectively. For electron doping, the salient features of the data are well captured by a phenomenological Stoner model7 that includes valley-anisotropic interactions. For hole filling, we observe a richer phase diagram featuring a delicate interplay of broken symmetries and transitions in the Fermi surface topology. Finally, we introduce a moiré superlattice using a rotationally aligned hexagonal boron nitride substrate5,8. Remarkably, we find that the isospin order is only weakly perturbed, with the moiré potential catalysing the formation of topologically nontrivial gapped states whenever itinerant half- or quarter-metal states occur at half- or quarter-superlattice band filling. Our results show that rhombohedral graphene is an ideal platform for well-controlled tests of many-body theory, and reveal magnetism in moiré materials4,5,9,10 to be fundamentally itinerant in nature.

5.
Phys Rev Lett ; 132(4): 046603, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38335366

RESUMEN

Bernal bilayer graphene hosts even-denominator fractional quantum Hall states thought to be described by a Pfaffian wave function with non-Abelian quasiparticle excitations. Here, we report the quantitative determination of fractional quantum Hall energy gaps in bilayer graphene using both thermally activated transport and by direct measurement of the chemical potential. We find a transport activation gap of 5.1 K at B=12 T for a half filled N=1 Landau level, consistent with density matrix renormalization group calculations for the Pfaffian state. However, the measured thermodynamic gap of 11.6 K is smaller than theoretical expectations for the clean limit by approximately a factor of 2. We analyze the chemical potential data near fractional filling within a simplified model of a Wigner crystal of fractional quasiparticles with long-wavelength disorder, explaining this discrepancy. Our results quantitatively establish bilayer graphene as a robust platform for probing the non-Abelian anyons expected to arise as the elementary excitations of the even-denominator state.

7.
Phys Rev Lett ; 129(8): 087701, 2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36053708

RESUMEN

Ohm's law describes the proportionality of the current density and electric field. In solid-state conductors, Ohm's law emerges due to electron scattering processes that relax the electrical current. Here, we use nitrogen-vacancy center magnetometry to directly image the local breakdown of Ohm's law in a narrow constriction fabricated in a high mobility graphene monolayer. Ohmic flow is visible at room temperature as current concentration on the constriction edges, with flow profiles entirely determined by sample geometry. However, as the temperature is lowered below 200 K, the current concentrates near the constriction center. The change in the flow pattern is consistent with a crossover from diffusive to viscous electron transport dominated by electron-electron scattering processes that do not relax current.

8.
Biochem Biophys Res Commun ; 508(1): 159-168, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30473218

RESUMEN

The transcription factor Krüppel-like factor 5 (KLF5) is highly expressed in many cancers and serves as a prognostic factor. However, the function of KLF5 in hepatocellular carcinoma (HCC) is unclear. In this study, we found that KLF5 was significantly overexpressed in HCC cell lines and specimens, and high KLF5 expression predicted a poor prognosis for HCC patients. Then, we studied the effects of KLF5 on the proliferation, apoptosis, migration and invasion of HCC cells in vitro and vivo. The inhibition of KLF5 markedly inhibited HCC growth and metastasis, while KLF5 overexpression promoted these processes. In addition, we observed that KLF5 could promote the epithelial-mesenchymal transition (EMT) in HCC via the PI3K/AKT/Snail signaling pathway. The silencing of KLF5 in HCC cell lines downregulated the expression of N-cadherin, Vimentin and Snail and increased the expression of the epithelial marker E-cadherin. The expression of MMP2 and MMP9 was also decreased in KLF5-silenced HCC cells. However, opposite results were observed in the KLF5-overexpressing group. These results indicate that KLF5 plays a significant role in HCC progression and metastasis and induces EMT via activating PI3K/AKT/Snail signaling, and the inhibition of KLF5 may be a potential treatment modality for patients with HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/secundario , Proliferación Celular , Células Cultivadas , Femenino , Humanos , Factores de Transcripción de Tipo Kruppel/deficiencia , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad
9.
Artículo en Inglés | MEDLINE | ID: mdl-38607616

RESUMEN

The unique metal-insulator transition of VO2 is very suitable for dynamic electromagnetic (EM) regulation materials due to its sharp change in electrical conductivity. Here, we have developed an off/on switchable electromagnetic interference (EMI) shielding composite by interconnecting VO2 nanowires (NWs) in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to form conductive networks, resulting in outstanding performance at the X and Ku bands with maximum change values of 44.8 and 59.4 dB, respectively. The unique insulator-to-metal transition (IMT) of VO2 NWs has dominated the variation of polarization loss (εp″) and conductivity loss (εσ″) for the composites, which is the mechanism of EMI shielding switching between off and on states. Furthermore, the composite exhibits good cycling stability of the off/on switchable EMI shielding performance and has excellent mechanical properties, especially with 200 times abrasion resistance without obvious weight loss. This study provides a unique approach for dynamic switching of EM response with the potential to construct practical intelligent EM response systems for next-generation smart electromagnetic devices in various scenarios.

10.
Apoptosis ; 18(1): 28-42, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23054084

RESUMEN

We aimed to investigate the relationship between the synthesis of hydrogen sulfide (H(2)S) and the pancreatic acinar cell apoptosis in severe acute pancreatitis (SAP) rats, as well as analyse the potential apoptotic pathway involved in this process. Sixty rats had been equally divided into four groups: sham, SAP, SAP + sodium hydrosulfide (NaHS) and SAP + DL-propargylglycine (PAG). 24 h after SAP induction, all surviving animals of each group were sacrificed to collect blood and tissue samples for the following measurements: the level of serum H(2)S as well as the levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), H(2)S synthesizing activity, CSE mRNA and protein expression, maleic dialdehyde (MDA) and myeloperoxidase (MPO) activity, the expression of Bax, Bcl-2, caspase-3, -8 and -9, the release of cytochrome c and the activation of nuclear factor-kappa B (NF-κB), ERK1/2, JNK1/2 and p38 in pancreas. Furthermore, in situ detection of cell apoptosis was examined and the severity of pancreatic damage was analyzed by pathological grading and scoring. Results Significant differences in every index except IL-10 had been found between the SAP, NaHS and PAG groups (P < 0.05). Treatment with PAG obviously induced the pancreatic acinar cell apoptosis as well as improved all the pathological changes and inflammatory parameters. In contrast, administration of NaHS significantly attenuated apoptosis in the pancreas and aggravated the severity of pancreatic damage. Moreover, the expressions of caspase-3, -8, -9 and the release of cytochrome c were all increased in the apoptotic cells, and the activity of NF-κB as well as the phosphorylation of ERK1/2, JNK1/2 and p38 decreased accompanying with the reduction of the serum H(2)S level. H(2)S plays a pivotal role in the regulation of pancreatic acinar cell apoptosis in SAP rats. The present results showed that inhibition of H(2)S synthesis provided protection for SAP rats via inducing acinar cell apoptosis. This process acted through both extrinsic and intrinsic apoptotic pathways, and may be regulated by reducing the activity of NF-κB.


Asunto(s)
Apoptosis/efectos de los fármacos , Sulfuro de Hidrógeno/sangre , Pancreatitis Aguda Necrotizante/prevención & control , Aldehídos/sangre , Alquinos/farmacología , Animales , Caspasas/metabolismo , Cistationina gamma-Liasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Sulfuro de Hidrógeno/metabolismo , Interleucina-10/sangre , Masculino , Páncreas/citología , Páncreas/patología , Pancreatitis Aguda Necrotizante/patología , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Sulfuros/farmacología , Factor de Necrosis Tumoral alfa/sangre
11.
Zhonghua Wai Ke Za Zhi ; 50(5): 446-51, 2012 May.
Artículo en Zh | MEDLINE | ID: mdl-22883954

RESUMEN

OBJECTIVE: To investigate the function of nuclear factor (NF)-κB in the epithelial to mesenchymal transition induced by hypoxia in pancreatic cancer cells. METHODS: For cultured pancreatic cancer cells (BxPC-3 and Panc-1) under hypoxic and normoxic conditions, the differences in the morphology were observed by optical microscope. The expression of markers of epithelial and mesenchymal phenotypes, E-cadherin, vimentin and N-cadherin, were determined by Western blot. NF-κB P65 activity was measured by electrophoretic mobility shift assay. Invasion and gemcitabine resistance of pancreatic cancer cells were evaluated in matrigel invasion assay and cell counting kit-8 assay. Both molecular and pharmacologic means of inhibiting NF-κB P65 were used in these hypoxic cells and then the above resulting phenotypes were compared with those of the control-treated cells. RESULTS: After cultured pancreatic cancer cells under hypoxic conditions for 48 h, normoxic cells exhibited a polygonal shape and formed tight clusters of cells, whereas hypoxic cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character and resistance to gemcitabine; hypoxic cells exhibited an suppression of E-cadherin and increase in vimentin and N-cadherin expression. NF-κB P65 activity was elevated in hypoxic cells. On the contrary, on molecular or pharmacologic inhibition of NF-κB P65, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype. CONCLUSIONS: Pancreatic cancer cells underwent epithelial to mesenchymal transition exposed to hypoxia, exhibited highly invasive and drug resistant phenotype. Inhibition of NF-κB P65 under hypoxic conditions, pancreatic cancer cells regained expression of E-cadherin, lost expression of N-cadherin, and reversed their highly invasive and drug resistant phenotype.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias Pancreáticas/patología , Factor de Transcripción ReIA/metabolismo , Antígenos CD/metabolismo , Cadherinas/metabolismo , Hipoxia de la Célula , Línea Celular Tumoral , Resistencia a Antineoplásicos , Humanos , Neoplasias Pancreáticas/metabolismo , Vimentina/metabolismo
12.
Environ Sci Pollut Res Int ; 29(1): 1532-1545, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34355321

RESUMEN

As an inevitable industrial by-product, polyaluminum chloride residue (PACR) will cause serious harm to the environment if directly buried and dumped. The aim of this paper was searched a new economical, environmental, and practical way of utilization for PACR. In this paper, a novel non-burning PACR compound filler was made from mainly PACR. The prepared compound filler has excellent physical properties and phosphate adsorption efficiency of up to 99.9%. Static adsorption experiments showed that the adsorption process of phosphorus by the compound filler conformed to the pseudo-second-order kinetic model and intra-particle diffusion model. Langmuir and Freundlich isotherm models described the phosphorus adsorption process well, and the maximum phosphate adsorption capacity arrived at 42.55 mg/g. The phosphate adsorption by the compound filler is a spontaneous endothermic process. The main mechanisms are ligand exchange and Lewis acid-base interactions; calcium and aluminum play important roles in the adsorption of phosphorus by the compound filler. Dynamic column experiments showed that as much as 90% of the phosphorus removal by compound filler, and the phosphorus concentration decreased from 1 to ~0.1mg/L. The results provide a new waste resource utilization method for PACR and show the good application potential of prepared compound filler in constructed wetlands.


Asunto(s)
Fosfatos , Contaminantes Químicos del Agua , Adsorción , Hidróxido de Aluminio , Concentración de Iones de Hidrógeno , Cinética , Fósforo , Contaminantes Químicos del Agua/análisis
13.
Science ; 375(6582): 774-778, 2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35025604

RESUMEN

In conventional superconductors, Cooper pairing occurs between electrons of opposite spin. We observe spin-polarized superconductivity in Bernal bilayer graphene when doped to a saddle-point van Hove singularity generated by large applied perpendicular electric field. We observe a cascade of electrostatic gate-tuned transitions between electronic phases distinguished by their polarization within the isospin space defined by the combination of the spin and momentum-space valley degrees of freedom. Although all of these phases are metallic at zero magnetic field, we observe a transition to a superconducting state at finite B‖ ≈ 150mT applied parallel to the two-dimensional sheet. Superconductivity occurs near a symmetry breaking transition, and exists exclusively above the B‖-limit expected of a paramagnetic superconductor with the observed transition temperature TC ≈ 30mK, consistent with a spin-triplet order parameter.

14.
Sci Rep ; 11(1): 1723, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462376

RESUMEN

There was a fast growth in the number and the formation of emergency department (ED) visits in China during the twenty-first century. As a result, engaging special medical model will be essential to decompressing the ED visits. To do this, it will be important to understand which specific aspects to focus interventions on for the greatest impact. To characterize the emergency surgery patients who were seen and discharged from ED. Retrospective cohort study of hospitalized emergency surgery patients currently under the care from specialists presenting to an urban, university affiliated hospital between 01 January 2018 and 1 January 2019. This study will highlight some of the controversies and challenges and key lessons learned. During the study period there were 231,229 ED visits; 4100 of these patients were admitted for Acute care surgery (ACS) service. Multivariate analysis identified age ≧ 65 (p = 0.023; odds ratio, OR = 2.66), ACS model (p = 0.000, OR = 0.18), ICU stay (p = 0.000, OR = 118.73) as factors associated with in-hospital mortality. There was a increase in length of stay between young and elderly postoperative patients when stratifying patients by age (11.67 ± 9.48 vs 13.95 ± 9.11 p < 0.05). ED overcrowding is not just an ED problem. ED overcrowding is a systems problem requiring a systematic facility-wide multidisciplinary response. Continuous and high-quality surveillance data across China are needed to estimate the acute care surgery model which used to deal with ED overcrowding.


Asunto(s)
Cuidados Críticos/estadística & datos numéricos , Servicio de Urgencia en Hospital/organización & administración , Mortalidad Hospitalaria/tendencias , Tiempo de Internación/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Procedimientos Quirúrgicos Operativos/normas , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Estudios Retrospectivos , Procedimientos Quirúrgicos Operativos/métodos , Factores de Tiempo , Adulto Joven
15.
Zhonghua Wai Ke Za Zhi ; 48(18): 1383-6, 2010 Sep 15.
Artículo en Zh | MEDLINE | ID: mdl-21092572

RESUMEN

OBJECTIVE: To summary the experience of the surgical comprehensive treatment of severe acute pancreatitis (SAP). METHODS: From July 1999 to December 2009, a total of 506 patients suffered SAP were admitted with a mean APACHE II score 12.8 ± 4.6. There were 270 male and 236 female, aged from 16 to 89 years, mean age 43 years. SAP patients were treated by the SAP treatment team which consisted of pancreatic specialized and multidisciplinary doctors. Two hundreds and thirty-four cases (46.2%) received non-operative treatment and 272 cases (53.8%) received surgical intervention. RESULTS: In 506 cases, 445 patients were cured and 52 patients died (31 died in early stage, 21 died in later stage), 9 cases discharged automatically. The overall incidence of complication, overall mortality and overall curative rate were 29.4% (149/506), 10.3% (52/506) and 87.9% (445/506), respectively. The incidences of complication in non-operative group and in surgical intervention group were 27.8% (65/234) and 30.9% (84/272), respectively (P > 0.05). The mortality in non-operative group and in surgical intervention group were 9.4% (22/234) and 11.0% (30/272), respectively (P > 0.05). The curative rates in non-operative group and in surgical intervention group were 90.6% (212/234) and 85.7% (233/272), respectively (P > 0.05). CONCLUSIONS: Patients should be treated in ICU in the early phase of the disease when APACHE II score > 10. Pancreatic specialized and multidisciplinary team treatment, appropriate choice of timing, indication and procedure of surgical intervention and details of drainage are vital to the prognosis of SAP.


Asunto(s)
Pancreatitis/cirugía , APACHE , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
16.
World J Emerg Surg ; 14: 16, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30976293

RESUMEN

The aim of this article is to describe briefly about Chinese ACS surgeons' work status. It is an undeniable fact that the analysis of ED and ACS resources shows negative tendencies and high work overload, resulting in low patient safety and quality of care. And, there was a substantial shortage of surgeons in the subspecialty. So, a set of strategic measures and state policies should be prioritized.


Asunto(s)
Cuidados Críticos/métodos , Cirujanos/tendencias , China , Cuidados Críticos/tendencias , Humanos , Satisfacción en el Trabajo
17.
Science ; 360(6384): 62-66, 2018 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-29496958

RESUMEN

Topologically ordered phases are characterized by long-range quantum entanglement and fractional statistics rather than by symmetry breaking. First observed in a fractionally filled continuum Landau level, topological order has since been proposed to arise more generally at fractional fillings of topologically nontrivial Chern bands. Here we report the observation of gapped states at fractional fillings of Harper-Hofstadter bands arising from the interplay of a magnetic field and a superlattice potential in a bilayer graphene-hexagonal boron nitride heterostructure. We observed phases at fractional filling of bands with Chern indices [Formula: see text] Some of these phases, in [Formula: see text] and [Formula: see text] bands, are characterized by fractional Hall conductance-that is, they are known as fractional Chern insulators and constitute an example of topological order beyond Landau levels.

18.
FEBS J ; 283(4): 738-56, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26683671

RESUMEN

Molecular hydrogen (H2 ) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis (AP) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein-protein interaction networks of these proteins. The results triggered our interest in mitogen-activated protein kinase (MAPK) and heat shock cognate 71 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK, and activated NF-κB and the expression of tumor necrosis factor α and interleukin-1ß, while simultaneously preventing the translocation of phospho-ERK, phospho-JNK, and phospho-p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression.


Asunto(s)
Proteínas del Choque Térmico HSC70/metabolismo , Hidrógeno/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Pancreatitis/metabolismo , Enfermedad Aguda , Animales , Línea Celular , Modelos Animales de Enfermedad , Proteínas del Choque Térmico HSC70/genética , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Pancreatitis/enzimología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley
19.
PLoS One ; 11(4): e0154483, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27115738

RESUMEN

Acute pancreatitis (AP) is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2) is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight). Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP.


Asunto(s)
Ceruletida/efectos adversos , Hidrógeno/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Ácido Taurocólico/efectos adversos , Amilasas/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citocinas/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Hidrógeno/farmacología , Lipasa/metabolismo , Masculino , Ratones , Pancreatitis/inducido químicamente , Pancreatitis/enzimología , Ratas
20.
PLoS One ; 7(8): e43826, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22952775

RESUMEN

Despite rapid advances in chemotherapy and surgical resection strategies, pancreatic cancer remains the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 5%. Therefore, novel therapeutic agents for the prevention and treatment of pancreatic cancer are urgently needed. The aim of this study was to investigate the effect of pristimerin, a quinonemethide triterpenoid compound isolated from Celastraceae and Hippocrateaceae, on inhibition of cell proliferation and induction of apoptosis in three pancreatic cancer cells, BxPC-3, PANC-1 and AsPC-1, in both monotherapy and in combination with gemcitabine. Treatment with pristimerin decreased the cell proliferation of all three pancreatic cancer cells in a dose- and time-dependent manner. Treatment of pancreatic cancer cells with pristimerin also resulted in G1-phase arrest which was strongly associated with a marked decrease in the level of cyclins (D1 and E) and cyclin-dependent kinases (cdk2, cdk4 and cdk6 ) with concomitant induction of WAF1/p21 and KIP1/p27. Pristimerin treatment also resulted in apoptotic cell death, cleavage of caspase-3, modulation in the expressions of Bcl-2 family proteins, inhibition of the translocation and DNA-binding activity of NF-κB. In addition, pristimerin potentiated the growth inhibition and apoptosis inducing effects of gemcitabine in all three pancreatic cancer cells, at least in part, by inhibiting constitutive as well as gemcitabine-induced activation of NF-κB in both its DNA-binding activity and transcriptional activity. Taken together, these data provide the first evidence that pristimerin has strong potential for development as a novel agent against pancreatic cancer.


Asunto(s)
Anticarcinógenos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Desoxicitidina/análogos & derivados , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Neoplasias Pancreáticas/patología , Triterpenos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , ADN/metabolismo , Desoxicitidina/farmacología , Sinergismo Farmacológico , Humanos , FN-kappa B/metabolismo , Triterpenos Pentacíclicos , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Gemcitabina
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