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1.
J Am Chem Soc ; 146(14): 9688-9696, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38427795

RESUMEN

Nearly a decade has passed since the discovery of superconductivity in CrAs, but until now, the discovered structure types of chromium-based superconductors are still scanty. It is urgent to expand this family to decipher the interplay between magnetism and superconductivity penetratingly. Here, we report the observation of superconductivity in ferromagnet CrSbSe3 with a quasi-one-dimensional structure under high pressure. Under compression, CrSbSe3 undergoes an insulator-to-metal transition and sequential isostructural phase transitions accompanied by volume collapse. Superconductivity emerges at 32.8 GPa concomitant with metallization in CrSbSe3. A maximum superconducting transition temperature Tc of 7.7 K is achieved at 57.9 GPa benefiting from both the phonon softening and the enhanced p-d hybridization between Se and Cr in CrSbSe3. The discovery of superconductivity in CrSbSe3 expands the existing chromium-based superconductor family and sheds light on the search for concealed superconductivity in low-dimensional van der Waals materials.

2.
BMC Psychiatry ; 23(1): 867, 2023 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993797

RESUMEN

BACKGROUND: Increasing evidence shows that bone turnover markers (BTMs) and vitamin D can affect human cognitive function. However, there are few studies that have investigated the association between BTMs and cognitive function in chronic schizophrenia patients. The aim of this study was to investigate the relationship between BTMs and cognitive function in chronic schizophrenia patients with or without vitamin D insufficiency (VDI). METHODS: In all, 118 chronic schizophrenia patients were enrolled in this cross-sectional study. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was applied to evaluate the cognitive function of the subjects. Blood analysis included bone turnover markers, vitamin D levels, and glycolipid levels. RESULTS: Relative to 72 vitamin D-sufficient (VDS) patients, 46 VDI patients had higher bone resorption markers levels and lower bone formation markers levels. Regression analysis showed that, in the total sample, CTX and language function exhibited independent positive correlation (p = 0.027, R2 change = 0.042), and in the VDS group, procollagen type I N-terminal propeptide (PINP) was independently negatively correlated with language function (p = 0.031, R2 change = 0.065), while the positive correlation between osteopontin (OPN) and delayed memory remained in the VDI group (p = 0.036, R2 change = 0.083). CONCLUSION: Our study showed an association between the levels of BTMs and cognitive function among chronic schizophrenia patients. This correlation may have different mechanisms of action at different vitamin D levels.


Asunto(s)
Esquizofrenia , Deficiencia de Vitamina D , Humanos , Vitamina D , Estudios Transversales , Pueblos del Este de Asia , Esquizofrenia/complicaciones , Vitaminas , Deficiencia de Vitamina D/complicaciones , Remodelación Ósea , Cognición , Biomarcadores
3.
Phys Rev Lett ; 124(20): 206602, 2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32501105

RESUMEN

We report heat capacity measurements of SrCu_{2}(BO_{3})_{2} under high pressure along with simulations of relevant quantum spin models and map out the (P,T) phase diagram of the material. We find a first-order quantum phase transition between the low-pressure quantum dimer paramagnet and a phase with signatures of a plaquette-singlet state below T=2 K. At higher pressures, we observe a transition into a previously unknown antiferromagnetic state below 4 K. Our findings can be explained within the two-dimensional Shastry-Sutherland quantum spin model supplemented by weak interlayer couplings. The possibility to tune SrCu_{2}(BO_{3})_{2} between the plaquette-singlet and antiferromagnetic states opens opportunities for experimental tests of quantum field theories and lattice models involving fractionalized excitations, emergent symmetries, and gauge fluctuations.

4.
Proc Natl Acad Sci U S A ; 114(50): 13144-13147, 2017 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-29183981

RESUMEN

We report the observation of extraordinarily robust zero-resistance superconductivity in the pressurized (TaNb)0.67(HfZrTi)0.33 high-entropy alloy--a material with a body-centered-cubic crystal structure made from five randomly distributed transition-metal elements. The transition to superconductivity (TC ) increases from an initial temperature of 7.7 K at ambient pressure to 10 K at ∼60 GPa, and then slowly decreases to 9 K by 190.6 GPa, a pressure that falls within that of the outer core of the earth. We infer that the continuous existence of the zero-resistance superconductivity from 1 atm up to such a high pressure requires a special combination of electronic and mechanical characteristics. This high-entropy alloy superconductor thus may have a bright future for applications under extreme conditions, and also poses a challenge for understanding the underlying quantum physics.

5.
Nature ; 483(7387): 67-9, 2012 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-22367543

RESUMEN

Pressure has an essential role in the production and control of superconductivity in iron-based superconductors. Substitution of a large cation by a smaller rare-earth ion to simulate the pressure effect has raised the superconducting transition temperature T(c) to a record high of 55 K in these materials. In the same way as T(c) exhibits a bell-shaped curve of dependence on chemical doping, pressure-tuned T(c) typically drops monotonically after passing the optimal pressure. Here we report that in the superconducting iron chalcogenides, a second superconducting phase suddenly re-emerges above 11.5 GPa, after the T(c) drops from the first maximum of 32 K at 1 GPa. The T(c) of the re-emerging superconducting phase is considerably higher than the first maximum, reaching 48.0-48.7 K for Tl(0.6)Rb(0.4)Fe(1.67)Se(2), K(0.8)Fe(1.7)Se(2) and K(0.8)Fe(1.78)Se(2).

6.
Rep Prog Phys ; 80(11): 112501, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28937971

RESUMEN

In recent years, studying the Kondo insulator SmB6, a strongly correlated electron material that has been puzzling the community for decades, has again become an attractive topic due to the discovery of its unusual metallic surface state coexisting with the bulk insulating state. Many efforts have been made to understand the microphysics in SmB6, but some puzzles that have been hotly debated and argued have not been solved. In this article, based on the latest progress made in our high-pressure studies on SmB6 and the accumulating results reported by other groups, we propose a notion named the 'accompany-type valence fluctuation state', which possibly coexists with the bulk Kondo insulating ground state of SmB6. We expect that this notion could be taken as a common starting point for understanding in a unified way most of the low-temperature phenomena observed by different experimental investigations on SmB6, thus promoting the deciphering of the puzzles. We also expect that this notion could attract rigorous theoretical interpretation and further experimental investigation, or stimulate better thinking on the physics in SmB6.

7.
Nano Lett ; 16(11): 6870-6878, 2016 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-27786486

RESUMEN

The capabilities to tune the conduction properties of materials by doping or electric fields are essential for the design of electronic devices. However, in two-dimensional materials substitutional doping has been achieved in only a few systems, such as Nb substitutional doping in MoS2. Surface charge transfer is still one of the popular ways to control whether the conduction is dominated by holes or electrons. Here, we demonstrate that a capping layer of cross-linked poly(methyl methacrylate) modifies the potential in a black phosphorus (BP) layer so that conduction in the absence of an external electric field is dominated by electrons, rather than holes. Using this technique to form adjoining regions dominated by hole and electron conduction, a family of novel planar devices, such as BP-gated diodes, BP bidirectional rectifier, and BP logic inverters, can be fabricated. The devices are potentially useful for electronic applications, including rectification and switching.

8.
Rep Prog Phys ; 79(8): 084503, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27376406

RESUMEN

Finding the exotic phenomena in strongly correlated electron systems (SCESs) and understanding the corresponding microphysics have long been the research frontiers of condensed matter physics. The remarkable examples for the intriguing phenomena discovered in past years include unconventional superconductivity, heavy Fermion behaviors, giant magneto-resistance and so on. A fascinating type of rare earth hexaboride RB6 (R = Sm, Yb, Eu and Ce) belongs to a strongly correlated electron system (SCES), but shows unusual ambient-pressure and high-pressure behaviors beyond the phenomena mentioned above. Particularly, the recent discovery of the coexistence of an unusual metallic surface state and an insulating bulk state in SmB6, known to be a Kondo insulator decades ago, by theoretical calculations and many experimental measurements creates new interest for the investigation of the RB6. This significant progress encourages people to revisit the RB6 with an attempt to establish a new physics that links the SCES and the unusual metallic surface state which is a common feature of a topological insulator (TI). It is well known that pressure has the capability of tuning the electronic structure and modifying the ground state of solids, or even inducing a quantum phase transition which is one of the kernel issues in studies of SCESs. In this brief review, we will describe the progress in high pressure studies on the RB6 based on our knowledge and research interests, mainly focusing on the pressure-induced phenomena in YbB6 and SmB6, especially on the quantum phase transitions and their connections with the valence state of the rare earth ions. Moreover, some related high-pressure results obtained from CeB6 and EuB6 are also included. Finally, a summary is given in the conclusions and perspectives section.

9.
Nat Commun ; 15(1): 5470, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38937441

RESUMEN

Global warming has a severe impact on the flowering time and yield of crops. Histone modifications have been well-documented for their roles in enabling plant plasticity in ambient temperature. However, the factor modulating histone modifications and their involvement in habitat adaptation have remained elusive. In this study, through genome-wide pattern analysis and quantitative-trait-locus (QTL) mapping, we reveal that BrJMJ18 is a candidate gene for a QTL regulating thermotolerance in thermotolerant B. rapa subsp. chinensis var. parachinensis (or Caixin, abbreviated to Par). BrJMJ18 encodes an H3K36me2/3 Jumonji demethylase that remodels H3K36 methylation across the genome. We demonstrate that the BrJMJ18 allele from Par (BrJMJ18Par) influences flowering time and plant growth in a temperature-dependent manner via characterizing overexpression and CRISPR/Cas9 mutant plants. We further show that overexpression of BrJMJ18Par can modulate the expression of BrFLC3, one of the five BrFLC orthologs. Furthermore, ChIP-seq and transcriptome data reveal that BrJMJ18Par can regulate chlorophyll biosynthesis under high temperatures. We also demonstrate that three amino acid mutations may account for function differences in BrJMJ18 between subspecies. Based on these findings, we propose a working model in which an H3K36me2/3 demethylase, while not affecting agronomic traits under normal conditions, can enhance resilience under heat stress in Brassica rapa.


Asunto(s)
Brassica rapa , Flores , Regulación de la Expresión Génica de las Plantas , Histonas , Histona Demetilasas con Dominio de Jumonji , Proteínas de Plantas , Sitios de Carácter Cuantitativo , Brassica rapa/genética , Brassica rapa/metabolismo , Brassica rapa/crecimiento & desarrollo , Brassica rapa/fisiología , Flores/genética , Flores/crecimiento & desarrollo , Histonas/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Temperatura , Termotolerancia/genética , Metilación , Plantas Modificadas Genéticamente , Clorofila/metabolismo
10.
Adv Sci (Weinh) ; 11(5): e2305054, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38050864

RESUMEN

Topological superconductors have drawn significant interest from the scientific community due to the accompanying Majorana fermions. Here, the discovery of electronic structure and superconductivity (SC) in high-entropy ceramics Ti0.2 Zr0.2 Nb0.2 Mo0.2 Ta0.2 Cx (x = 1 and 0.8) combined with experiments and first-principles calculations is reported. The Ti0.2 Zr0.2 Nb0.2 Mo0.2 Ta0.2 Cx high-entropy ceramics show bulk type-II SC with Tc ≈ 4.00 K (x = 1) and 2.65 K (x = 0.8), respectively. The specific heat jump (∆C/γTc ) is equal to 1.45 (x = 1) and 1.52 (x = 0.8), close to the expected value of 1.43 for the BCS superconductor in the weak coupling limit. The high-pressure resistance measurements show a robust SC against high physical pressure in Ti0.2 Zr0.2 Nb0.2 Mo0.2 Ta0.2 C, with a slight Tc variation of 0.3 K within 82.5 GPa. Furthermore, the first-principles calculations indicate that the Dirac-like point exists in the electronic band structures of Ti0.2 Zr0.2 Nb0.2 Mo0.2 Ta0.2 C, which is potentially a topological superconductor. The Dirac-like point is mainly contributed by the d orbitals of transition metals M and the p orbitals of C. The high-entropy ceramics provide an excellent platform for the fabrication of novel quantum devices, and the study may spark significant future physics investigations in this intriguing material.

11.
Adv Ther ; 40(4): 1899-1912, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36737594

RESUMEN

BACKGROUND: Angina pectoris (AP) is the initial and the most common manifestation of coronary artery disease (CAD). Therefore, management and control of AP can help prevent further complications associated with CAD. However, there is under-reporting of angina symptoms in clinical practice, resulting in under-treatment and reduced quality of life (QoL). Prospective and standardized monitoring is needed to support timely and appropriate treatment. OBJECTIVES: To establish a large cohort of Chinese patients with AP and compare the effectiveness of different anti-angina regimens with the help of electronic patient-reported outcomes (e-PROs), using the Seattle Angina Questionnaire (SAQ) to assess health status. METHODS: The registry study (GREAT) is a multicenter, prospective, observational, cohort study. Patients diagnosed with AP will be enrolled from 10 hospitals and assessed based on the different anti-anginal regimens. Patients will be followed up every 3 months from baseline to 12 months to observe the difference in the therapeutic effectiveness of the drugs. Data will be collected in the form of e-PROs combined with on-site visit records. PLANNED OUTCOMES: The change in SAQ summary score (SAQ SS) at Month 12 from baseline will be the primary outcome. The secondary measures will include changes in SAQ SS at Months 3, 6, and 9 from baseline, changes in retest results of vascular stenosis imaging at Month 12 from baseline, and medication adherence based on the proportion of days covered. Safety data will be evaluated based on the incidence of adverse events (AEs). CONCLUSION: This study will evaluate the effectiveness of anti-anginal regimens using ePROs in real-world settings in China. The results from this study may provide a new perspective on treatment patterns and the effectiveness of different anti-anginal regimens for patients with AP. STUDY REGISTRATION NUMBER: NCT05050773.


Asunto(s)
Fármacos Cardiovasculares , Enfermedad de la Arteria Coronaria , Humanos , Calidad de Vida , Estudios de Cohortes , Estudios Prospectivos , Pueblos del Este de Asia , Resultado del Tratamiento , Angina de Pecho/diagnóstico , Angina de Pecho/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Fármacos Cardiovasculares/uso terapéutico , Medición de Resultados Informados por el Paciente , Estudios Multicéntricos como Asunto
12.
Cell Rep ; 42(8): 112938, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37552600

RESUMEN

Increasing plant resistance to Verticillium wilt (VW), which causes massive losses of Brassica rapa crops, is a challenge worldwide. However, few causal genes for VW resistance have been identified by forward genetic approaches, resulting in limited application in breeding. We combine a genome-wide association study in a natural population and quantitative trait locus mapping in an F2 population and identify that the MYB transcription factor BrMYB108 regulates plant resistance to VW. A 179 bp insertion in the BrMYB108 promoter alters its expression pattern during Verticillium longisporum (VL) infection. High BrMYB108 expression leads to high VL resistance, which is confirmed by disease resistance tests using BrMYB108 overexpression and loss-of-function mutants. Furthermore, we verify that BrMYB108 confers VL resistance by regulating reactive oxygen species (ROS) generation through binding to the promoters of respiratory burst oxidase genes (Rboh). A loss-of-function mutant of AtRbohF in Arabidopsis shows significant susceptibility to VL. Thus, BrMYB108 and its target ROS genes could be used as targets for genetic engineering for VL resistance of B. rapa.


Asunto(s)
Brassica rapa , Verticillium , Brassica rapa/genética , Especies Reactivas de Oxígeno , Verticillium/genética , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética
13.
Nat Commun ; 14(1): 3116, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37253725

RESUMEN

Here we report the first observation of the concurrent breakdown of the strange metal (SM) normal state and superconductivity at a pressure-induced quantum critical point in Ca10(Pt4As8)((Fe0.97Pt0.03)2As2)5 superconductor. We find that, upon suppressing the superconducting state, the power exponent (α) changes from 1 to 2, and the slope of the temperature-linear resistivity per FeAs layer (A□) gradually diminishes. At a critical pressure, A□ and superconducting transition temperature (Tc) go to zero concurrently, where a quantum phase transition from a superconducting state with a SM normal state to a non-superconducting Fermi liquid state occurs. Scaling analysis reveals that the change of A□ with Tc obeys the relation of Tc ~ (A□)0.5, similar to what is seen in other chemically doped unconventional superconductors. These results suggest that there is a simple but powerful organizational principle of connecting the SM normal state with the high-Tc superconductivity.

14.
Phys Rev Lett ; 108(19): 197001, 2012 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-23003077

RESUMEN

We report a finding of a pressure-induced quantum critical transition in K0.8Fe(x)Se2 (x = 1.7 and 1.78) superconductors through in situ high-pressure electrical transport and x-ray diffraction measurements in diamond anvil cells. Transitions from metallic Fermi liquid behavior to non-Fermi liquid behavior and from antiferromagnetism to paramagnetism are found in the pressure range of 9.2-10.3 GPa, in which superconductivity tends to disappear. The change around the quantum critical point from the coexisting antiferromagnetism state and the Fermi liquid behavior to the paramagnetism state and the non-Fermi liquid behavior in the iron-selenide superconductors demonstrates a unique mechanism for their quantum critical transition.

15.
Front Plant Sci ; 13: 918112, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35755702

RESUMEN

Leaf curling is an essential prerequisite for the formation of leafy heads in Chinese cabbage. However, the part or tissue that determines leaf curvature remains largely unclear. In this study, we first introduced the auxin-responsive marker DR5::GUS into the Chinese cabbage genome and visualized its expression during the farming season. We demonstrated that auxin response is adaxially/abaxially distributed in leaf veins. Together with the fact that leaf veins occupy considerable proportions of the Chinese cabbage leaf, we propose that leaf veins play a crucial supporting role as a framework for heading. Then, by combining analyses of QTL mapping and a time-course transcriptome from heading Chinese cabbage and non-heading pak choi during the farming season, we identified the auxin-related gene BrPIN5 as a strong candidate for leafy head formation. PIN5 displays an adaxial/abaxial expression pattern in leaf veins, similar to that of DR5::GUS, revealing an involvement of BrPIN5 in leafy head development. The association of BrPIN5 function with heading was further confirmed by its haplo-specificity to heading individuals in both a natural population and two segregating populations. We thus conclude that the adaxial/abaxial patterning of auxin and auxin genes in leaf veins functions in the formation of the leafy head in Chinese cabbage.

16.
Adv Mater ; 31(11): e1807240, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30614584

RESUMEN

The extraordinary superconductivity has been observed in a pressurized commercial niobium-titanium alloy. Its zero-resistance superconductivity persists from ambient pressure to the pressure as high as 261.7 GPa, a record-high pressure up to which a known superconducting state can continuously survive. Remarkably, at such an ultra-high pressure, although the ambient pressure volume is shrunk by 45% without structural phase transition, the superconducting transition temperature (TC ) increases to ≈19.1 K from ≈9.6 K, and the critical magnetic field (HC2 ) at 1.8 K has been enhanced to 19 T from 15.4 T. These results set new records for both the TC and the HC2 among all the known alloy superconductors composed of only transition metal elements. The remarkable high-pressure superconducting properties observed in the niobium-titanium alloy not only expand the knowledge on this important commercial superconductor but also are helpful for a better understanding on the superconducting mechanism.

17.
Sci Bull (Beijing) ; 62(12): 857-862, 2017 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-36659320

RESUMEN

One of the most strikingly universal features of the high-temperature superconductors is that the superconducting phase emerges in the close proximity of the antiferromagnetic phase, and the interplay between these two phases poses a long-standing challenge. It is commonly believed that, as the antiferromagnetic transition temperature is continuously suppressed to zero, there appears a quantum critical point, around which the existence of antiferromagnetic fluctuation is responsible for the development of the superconductivity. In contrast to this scenario, we report the observation of a bi-critical point identified at 2.88GPa and 26.02K in the pressurized high-quality single crystal Ca0.73La0.27FeAs2 by complementary in-situ high pressure measurements. At the critical pressure, we find that the antiferromagnetism suddenly disappears and superconductivity simultaneously emerges at almost the same temperature, and that the external magnetic field suppresses the superconducting transition temperature but hardly affects the antiferromagnetic transition temperature.

18.
Sci Bull (Beijing) ; 62(21): 1439-1444, 2017 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36659393

RESUMEN

SmB6 has been a well-known Kondo insulator for decades, but recently attracts extensive new attention as a candidate topological system. Studying SmB6 under pressure provides an opportunity to acquire the much-needed understanding about the effect of electron correlations on both the metallic surface state and bulk insulating state. Here we do so by studying the evolution of two transport gaps (low temperature gap El and high temperature gap Eh) associated with the Kondo effect by measuring the electrical resistivity under high pressure and low temperature (0.3 K) conditions. We associate the gaps with the bulk Kondo hybridization, and from their evolution with pressure we demonstrate an insulator-to-metal transition at ∼4 GPa. At the transition pressure, a large change in the Hall number and a divergence tendency of the electron-electron scattering coefficient provide evidence for a destruction of the Kondo entanglement in the ground state. Our results raise the new prospect for studying topological electronic states in quantum critical materials settings.

19.
J Phys Condens Matter ; 18(37): 8573-80, 2006 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-21690910

RESUMEN

Silane (SiH(4)) has been studied in a diamond anvil cell from 7-210 GPa by using optical reflection and absorption techniques at 300 K. The reflectivity and transmission measurements showed a dramatic change in the neighbourhood of 100 GPa. On the basis of reflectivity and absorption experimental data, the pressure dependence of the refractive index (n) of solid SiH(4) was derived, which was then used to determine the ratio of the molar refraction (R) to the molar volume (V). There is a large jump in the ratio R/V between 92 and 109 GPa. At 109 GPa and 1.6 eV, n(*)(SiH(4)) = 3.62 (the real part of refractive index) and R/V (SiH(4)) = 0.79, which are similar to the values for silicon at one atmosphere at the same energy. The results indicated that an insulator-semiconductor phase transition might have occurred in solid SiH(4) between 92 and 109 GPa. Comparing values of the real part of n, n(*), and the extinction coefficient k(*) with that of metals, we conclude that SiH(4) is not yet a metal at the maximum pressure investigated (210 GPa), suggesting that a higher pressure is needed for its metallization.

20.
Biomed Pharmacother ; 84: 237-243, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27662474

RESUMEN

Mnk kinase is required for the phosphorylation and activation of the eukaryotic initiation factor 4E (eIF4E), which regulates translation of proteins involve in important aspects of hepatocellular carcinoma (HCC). Here we investigated whether an antifungal agent, cercosporamide, which had been recently identified as a potent Mnk inhibitor, is active against HCC and angiogenesis. We showed that cercosporamide significantly inhibited growth and induced caspase-dependent apoptosis on numerous HCC cell lines, while sparing normal liver cells. In addition, cercosporamide impaired HCC angiogenesis via inhibiting HCC-endothelial cells (HCC-EC) capillary network formation, migration, proliferation and survival. Importantly, cercosporamide sensitized HCC cells to cisplatin in in vitro cell culture and in vivo HCC xenograft mouse model. Cercosporamide blocked the phosphorylation of eIF4E but not Erk or p38 in a dose- and time-dependent manner in HCC and HCC-EC cells, suggesting that suppression of eIF4E phosphorylation was the result of inhibition of Mnk but not Mnk upstream pathways. Overexpression of constitutively active eIF4E (S209D) but not the nonphosphorylatable eIF4E (S209A) abolished the inhibitory effects of cercosporamide in HepG2 cells. Altogether, our work demonstrates that cercosporamide acts as a Mnk inhibitor through blockage of eIF4E phosphorylation and selectively exhibits anti-HCC activities. Our work suggests that targeting MNK-eIF4E pathway represents a therapeutic strategy to overcome chemo-resistance for HCC treatment.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Benzofuranos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Factor 4E Eucariótico de Iniciación/metabolismo , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Neoplasias Hepáticas/tratamiento farmacológico , Neovascularización Patológica , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/patología , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Factor 4E Eucariótico de Iniciación/genética , Células Hep G2 , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/patología , Ratones SCID , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto
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