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1.
New Phytol ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38887135

RESUMEN

Bamboo, a renewable resource with rapid growth and an impressive height-to-diameter ratio, faces mechanical instability due to its slender structure. Despite this, bamboo maintains its posture without breaking in its battle against environmental and gravitational forces. But what drives this motor function in bamboo? This study subjected Moso bamboo (Phyllostachys edulis) to gravitational stimulation, compelling it to grow at a 45° angle instead of upright. Remarkably, the artificially inclined bamboo exhibited astonishing shape control and adjustment capabilities. The growth strain was detected at both macroscopic and microscopic levels, providing evidence for the presence of internal stress, namely growth stress. The high longitudinal tensile stress on the upper side, along with a significant asymmetry in stress distribution in tilted bamboo, plays a pivotal role in maintaining its mechanical stability. Drawing upon experimental findings, it can be deduced that the growth stress primarily originates from the broad layers of fiber cells. Bamboo could potentially regulate the magnitude of growth stress by modifying the number of fiber cell layers during its maturation process. Additionally, the microfibril angle and lignin disposition may decisively influence the generation of growth stress.

2.
ACS Appl Mater Interfaces ; 16(4): 4818-4826, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38232354

RESUMEN

Aqueous electrolytes have become a research hotspot because of their high safety and low cost, while the inevitable ionization phenomenon of water in aqueous solution leads to the existence of competitive ions (H+) except the active ions. In this article, we take aqueous Na base electrolyte as an example to clear the ion competition behavior by modeling, simulating together with experimental verification. First, the reaction tendency of the two ions (Na+ and H+) is obtained by calculating the Gibbs energy change of the reaction. Furthermore, the properties of electrolytes with different concentrations including transportation are obtained by modeling. After that, relevant experiments are also proceeded to verify the simulation results. Then, the ion competition behavior is analyzed by in situ observation by controlling the constant concentration of Na+: the high concentration of Na+ can reduce the proportion of H+ and reduce the competitiveness of H+; a high concentration of Na+ causes the increased viscosity and reduces the ion diffusion. Based on this, the correlation between ion competitiveness and ion ratio is also confirmed by keeping the concentration of Na+ unchanged and adjusting the concentration of H+ (adjusting pH). The influence of the ion competition phenomenon (Na+ and H+) is the reaction characteristics of the substance itself and the ratio of ion concentration. Finally, the electrochemical performance is further verified in 3,4,9,10-perylene tetracarboxylic dianhydride (PTCDI) symmetric cells and in full-cells with vanadium phosphate sodium (NVP) as the cathode and PTCDI as the anode.

3.
Small ; 20(14): e2307388, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38059741

RESUMEN

The application of metal batteries is seriously affected by active ions transport and deposition stability during operation. This article takes water-based Zn metal electrodes as an example to analyze the factors that affect ion distribution and the impact of ion distribution on electrodeposition morphology through electrochemical model simulation calculation, in situ observation and electrochemical experiment: 1) high concentration will reduce the concentration polarization and the overpotential; 2) The passage of active ions through channels are facilitated by small anion (Cl-) rather than bigger one (SO4 2-), which means small deposition overpotential; 3) The transportability-reaction properties of cations (Zn2+, Li+, Na+ and H+) depends on their concentration, solvent coordination structure, and the energy changes during redox reactions. Based on the diffusion and reaction properties, a Li+ coupled Zn2+ electrolyte is designed to achieve the rapid transportation of doped ions to cover uneven growth sites and maintain a stable interface for the steady deposition of active Zn2+, guiding the interface design for high stability metal batteries in addition to the traditional addition of organic solvents.

4.
Nat Mater ; 23(1): 52-57, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38052935

RESUMEN

Although metallic nanostructures have been attracting tremendous research interest in nanoscience and nanotechnologies, it is known that environmental attacks, such as surface oxidation, can easily initiate cracking on the surface of metals, thus deteriorating their overall functional/structural properties1-3. In sharp contrast, here we report that severely oxidized metallic glass nanotubes can attain an ultrahigh recoverable elastic strain of up to ~14% at room temperature, which outperform bulk metallic glasses, metallic glass nanowires and many other superelastic metals hitherto reported. Through in situ experiments and atomistic simulations, we reveal that the physical mechanisms underpinning the observed superelasticity can be attributed to the formation of a percolating oxide network in metallic glass nanotubes, which not only restricts atomic-scale plastic events during loading but also leads to the recovery of elastic rigidity on unloading. Our discovery implies that oxidation in low-dimensional metallic glasses can result in unique properties for applications in nanodevices.

5.
Polymers (Basel) ; 14(13)2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35808694

RESUMEN

Bamboo is recognized as a potential and sustainable green material. The longitudinal-splitting and shear strengths of bamboo are weak but critical to its utilizations. To discuss the different shear performances of bamboo, the shear strength and behaviors of bamboo culm were investigated by four test methods: the tensile-shear, step-shear, cross-shear, and short-beam-shear methods. Then, the different shear performance and mechanisms were discussed. Results indicated that the shear strength was significantly different in the four test methods and was highest in the step-shear-test method but lowest in the tensile-shear-test method. Moreover, the typical load-displacement curves were different across the shear methods but were similar to the curves of the respective loading modes. The axially aligned fiber bundles played an important role in all the shear performances. In the tensile-shear method, specimens fractured at the interface of the bamboo-fiber bundles. However, compress-shear behaviors were a combination of compression and shear. Then, the cross-shear method, in compress-shear, was lower than that of the step-shear method because of oval-shaped bamboo culm sections of different thickness. In the short-beam shear method, the behaviors and shearing characteristics were like bending with the fiber bundle pulled out.

6.
J Int Med Res ; 49(6): 3000605211018592, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34082605

RESUMEN

OBJECTIVE: To explore the neddylation pathway, found to be highly activated in various cancers, as a potential therapeutic target in endometrial carcinoma, one of the three most frequent malignant tumours in the female reproductive system. METHODS: Data from The Cancer Genome Atlas were analysed using online servers. Expression levels of key neddylation genes were validated by reverse-transcription polymerase chain reaction and western blots of tumour and adjacent tissues. Underlying mechanisms and the effects on cell activities of the neddylation pathway-specific inhibitor, MLN4924, were investigated in endometrial cancer cell lines. RESULTS: Key neddylation enzymes, ubiquitin conjugating enzyme E2 M (UBC12), ubiquitin conjugating enzyme E2 F (UBE2F), ring-box 1 (RBX1) and ring finger protein 7 (RBX2), were significantly overexpressed in endometrial carcinoma tissues versus normal tissues, but only UBE2F and RBX2 positively correlated with patient survival. MLN4924 significantly suppressed proliferation and colony formation in EC cells by inducing DNA re-replication, cell cycle arrest and apoptosis. Mechanism study revealed that MLN4924 induced the accumulation of cullin-RING ligase substrates in vitro. CONCLUSIONS: The neddylation pathway was identified to play an important role in endometrial cancer. The neddylation specific inhibitor, MLN4924, may be a potential therapeutic drug for endometrial carcinoma.


Asunto(s)
Neoplasias Endometriales , Ubiquitinas , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Ciclopentanos/farmacología , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Femenino , Humanos , Proteína NEDD8/genética , Pirimidinas , Ubiquitinas/genética
7.
ACS Omega ; 5(26): 15931-15935, 2020 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-32656413

RESUMEN

Drag reduction performance was studied with a rotating disk instrument in the laboratory, and experiments show that there is an initial rapid growth stage and stability stage for drag reduction ratio change. The higher the rotational speed, the larger the initial drag reduction ratio is; the larger the concentration, the shorter the drag reduction stabilization time is. Under high concentration and high speed, the drag reduction onset time is short. Because of the shear degradation, the Reynolds number should be taken into account during use. Through a comparison of diesel properties after adding agents with national standard, it is confirmed that drag reduction agents could be used in this pipeline.

8.
Cell Mol Immunol ; 15(6): 618-629, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28287112

RESUMEN

Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis. Pharmacological modulation of GR by its agonist (dexamethasone, Dex) protects IMH mice against inflammatory injury. Mechanistically, GR signaling suppresses HIF1α and HIF1α-dependent glycolysis in MDSCs and thus promotes the immune suppressive activity of MDSCs. Our studies reveal a role of GR-HIF1α in regulating the metabolism and function of MDSCs and further implicate MDSC GR signaling as a potential therapeutic target in hepatic diseases that are driven by innate immune cell-mediated systemic inflammation.


Asunto(s)
Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Supresoras de Origen Mieloide/metabolismo , Receptores de Glucocorticoides/metabolismo , Animales , Dexametasona/farmacología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Inmunidad Innata , Inflamación/patología , Lipopolisacáridos , Hígado/lesiones , Hígado/patología , Ratones Endogámicos C57BL , Mifepristona/farmacología , Transducción de Señal/efectos de los fármacos
9.
Proc Natl Acad Sci U S A ; 112(9): E957-65, 2015 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-25730867

RESUMEN

The differentiation of naive CD4(+) T cells into distinct lineages plays critical roles in mediating adaptive immunity or maintaining immune tolerance. In addition to being a first line of defense, the innate immune system also actively instructs adaptive immunity through antigen presentation and immunoregulatory cytokine production. Here we found that sirtuin 1 (SIRT1), a type III histone deacetylase, plays an essential role in mediating proinflammatory signaling in dendritic cells (DCs), consequentially modulating the balance of proinflammatory T helper type 1 (TH1) cells and antiinflammatory Foxp3(+) regulatory T cells (T(reg) cells). Genetic deletion of SIRT1 in DCs restrained the generation of T(reg) cells while driving TH1 development, resulting in an enhanced T-cell-mediated inflammation against microbial responses. Beyond this finding, SIRT1 signaled through a hypoxia-inducible factor-1 alpha (HIF1α)-dependent pathway, orchestrating the reciprocal TH1 and T(reg) lineage commitment through DC-derived IL-12 and TGF-ß1. Our studies implicates a DC-based SIRT1-HIF1α metabolic checkpoint in controlling T-cell lineage specification.


Asunto(s)
Células Dendríticas/inmunología , Subunidad alfa del Factor 1 Inducible por Hipoxia/inmunología , Interleucina-12/inmunología , Sirtuina 1/inmunología , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Factor de Crecimiento Transformador beta1/inmunología , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Línea Celular , Células Dendríticas/citología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Interleucina-12/genética , Ratones , Ratones Noqueados , Transducción de Señal/genética , Transducción de Señal/inmunología , Sirtuina 1/genética , Linfocitos T Reguladores/citología , Células TH1/citología , Factor de Crecimiento Transformador beta1/genética
10.
Mol Cell Biol ; 35(3): 598-609, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25452304

RESUMEN

While cyclosporine (CsA) inhibits calcineurin and is highly effective in prolonging rejection for transplantation patients, the immunological mechanisms remain unknown. Herein, the role of calcineurin signaling was investigated in a mouse allogeneic skin transplantation model. The calcineurin inhibitor CsA significantly ameliorated allograft rejection. In CsA-treated allograft recipient mice, CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) were functional suppressive immune modulators that resulted in fewer gamma interferon (IFN-γ)-producing CD8(+) T cells and CD4(+) T cells (T(H)1 T helper cells) and more interleukin 4 (IL-4)-producing CD4(+) T cells (T(H2)) and prolonged allogeneic skin graft survival. Importantly, the expression of NFATc1 is significantly diminished in the CsA-induced MDSCs. Blocking NFAT (nuclear factor of activated T cells) with VIVIT phenocopied the CsA effects in MDSCs and increased the suppressive activities and recruitment of CD11b(+) Gr1(+) MDSCs in allograft recipient mice. Mechanistically, CsA treatment enhanced the expression of indoleamine 2,3-dioxygenase (IDO) and the suppressive activities of MDSCs in allograft recipients. Inhibition of IDO nearly completely recovered the increased MDSC suppressive activities and the effects on T cell differentiation. The results of this study indicate that MDSCs are an essential component in controlling allograft survival following CsA or VIVIT treatment, validating the calcineurin-NFAT-IDO signaling axis as a potential therapeutic target in transplantation.


Asunto(s)
Calcineurina/farmacología , Diferenciación Celular/efectos de los fármacos , Células Mieloides/inmunología , Factores de Transcripción NFATC/metabolismo , Oligopéptidos/farmacología , Aloinjertos/efectos de los fármacos , Aloinjertos/inmunología , Animales , Presentación de Antígeno/inmunología , Calcineurina/inmunología , Diferenciación Celular/inmunología , Ciclosporina/farmacología , Supervivencia de Injerto/inmunología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Células Mieloides/metabolismo , Factores de Transcripción NFATC/efectos de los fármacos
11.
J Leukoc Biol ; 96(5): 675-84, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24948701

RESUMEN

Whereas GCs have been demonstrated to be beneficial for transplantation patients, the pharmacological mechanisms remain unknown. Herein, the role of GR signaling was investigated via a pharmacological approach in a murine allogeneic skin transplantation model. The GC Dex, a representative GC, significantly relieved allograft rejection. In Dex-treated allograft recipient mice, CD11b(+)Gr1(+) MDSCs prolonged graft survival and acted as functional suppressive immune modulators that resulted in fewer IFN-γ-producing Th1 cells and a greater number of IL-4-producing Th2 cells. In agreement, Dex-treated MDSCs promoted reciprocal differentiation between Th1 and Th2 in vivo. Importantly, the GR is required in the Dex-induced MDSC effects. The blocking of GR with RU486 significantly diminished the expression of CXCR2 and the recruitment of CD11b(+)Gr1(+) MDSCs, thereby recovering the increased MDSC-suppressive activity induced by Dex. Mechanistically, Dex treatment induced MDSC iNOS expression and NO production. Pharmacologic inhibition of iNOS completely eliminated the MDSC-suppressive function and the effects on T cell differentiation. This study shows MDSCs to be an essential component in the prolongation of allograft survival following Dex or RU486 treatment, validating the GC-GR-NO signaling axis as a potential therapeutic target in transplantation.


Asunto(s)
Aloinjertos/efectos de los fármacos , Aloinjertos/metabolismo , Dexametasona/farmacología , Supervivencia de Injerto/efectos de los fármacos , Células Mieloides/efectos de los fármacos , Células Mieloides/metabolismo , Óxido Nítrico/metabolismo , Animales , Antígenos de Superficie/metabolismo , Antígeno CD11b/metabolismo , Diferenciación Celular/efectos de los fármacos , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Supervivencia de Injerto/inmunología , Inmunofenotipificación , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Ratones , Células Mieloides/inmunología , Óxido Nítrico/biosíntesis , Fenotipo , Receptores de Superficie Celular/metabolismo , Trasplante de Piel , Bazo/citología , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo
12.
Immunology ; 2014 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-24835113

RESUMEN

T lymphocytes are a central component, and play an important role in controlling immunity and immunological diseases. Recent studies have shown that T cell metabolism is highly dynamic and has a tremendous impact on the modulation of T lymphocyte immunity. Specific metabolic pathways meet energy and biosynthetic requirements that can support specific T cell functional activities in immunity and immunological diseases. This review summarizes the recent progresses about the modulatory role of cell metabolism in T cell development, differentiation, activation and function in immunity. These might provide new opportunities to modulate the immune responses and treat clinical immunological diseases. This article is protected by copyright. All rights reserved.

13.
J Immunol ; 192(7): 3068-79, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24567529

RESUMEN

Although FTY720 may alter migration and homing of lymphocytes via sphingosine-1-phosphate (S1P) receptors, our recent studies indicated that FTY720 directly controls the differentiation of Th1 cells to regulatory T cells (Tregs) by targeting S1P1. However, the pharmacological function of FTY720 in immunological hepatic injury remains unknown. In this study, the role and regulatory signaling pathway of S1P receptor were investigated using a pharmacological approach in immune-mediated hepatic injury (IMH). In the context of IMH, FTY720 significantly ameliorated mortality and hepatic pathology. In FTY720-treated mice, recruited CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) mediate protection against IMH and are functional suppressive immune modulators that result in fewer IFN-γ-producing Th1 cells and more Foxp3(+) Tregs. In agreement, FTY720-treated MDSCs promote the reciprocal differentiation between Th1 cells and Tregs in vitro and in vivo. Mechanistically, FTY720 treatment induced inducible NO synthase expression and NO production in MDSCs. Pharmacologic inhibition of inducible NO synthase completely eliminates MDSC suppressive function and eradicates their inducible effects on T cell differentiation. Finally, the mTOR inhibitor, rapamycin, photocopies the effects of FTY720 on MDSCs, implicating mTOR as a downstream effector of S1P1 signaling. This study identifies MDSCs as an essential component that provides protection against IMH following FTY720 or rapamycin treatment, validating the S1P1-mTOR signaling axis as a potential therapeutic target in hepatic injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Hígado/inmunología , Células Mieloides/inmunología , Receptores de Lisoesfingolípidos/inmunología , Animales , Antígeno CD11b/inmunología , Antígeno CD11b/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Femenino , Clorhidrato de Fingolimod , Immunoblotting , Inmunosupresores/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células Mieloides/efectos de los fármacos , Células Mieloides/metabolismo , Óxido Nítrico/inmunología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Glicoles de Propileno/farmacología , Interferencia de ARN , Receptores de Quimiocina/inmunología , Receptores de Quimiocina/metabolismo , Receptores de Lisoesfingolípidos/antagonistas & inhibidores , Receptores de Lisoesfingolípidos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sirolimus/farmacología , Esfingosina/análogos & derivados , Esfingosina/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/inmunología , Serina-Treonina Quinasas TOR/metabolismo , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células TH1/metabolismo , omega-N-Metilarginina/farmacología
14.
J Leukoc Biol ; 95(6): 961-70, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24569105

RESUMEN

The mTOR pathway integrates diverse environmental inputs, including immune signals and metabolic cues, to direct the innate and adaptive immune responses. MDSCs are a heterogeneous cell population that plays a crucial regulatory effect in immune-related diseases. However, whether mTOR signaling affects the functions of MDSCs remains largely unknown. Here, we show that mTOR signaling is a pivotal negative determinant of MDSC recruitment in IMH disease. In the context of IMH, inhibition of mTOR with rapamycin in CD11b⁺Gr1⁺ MDSCs mediates protection against IMH and serves as a functional, suppressive immune modulator that results in increased CD11b⁺Gr1⁺Ly6C(high) MDSC recruitment to inflammatory sites. In agreement with this, mTOR down-regulation promotes CD11b⁺Gr1⁺Ly6C(high) MDSC migration in vitro and in vivo. Mechanistically, mTOR activity down-regulation in MDSCs induced iNOS expression and NO production. Pharmacologic inhibition of iNOS completely eliminated MDSC recruitment. This study identifies MDSCs as an essential component for protection against IMH following rapamycin treatment. Rapamycin treatment or mTOR inhibition promotes CD11b⁺Gr1⁺Ly6C(high) MDSC recruitment and is critically required for protection against hepatic injury. This study further validates the targeting of mTOR signaling as a potential therapeutic approach to IMH-related diseases.


Asunto(s)
Antígenos Ly/análisis , Antígeno CD11b/análisis , Hepatopatías/inmunología , Células Mieloides/fisiología , Receptores de Quimiocina/análisis , Serina-Treonina Quinasas TOR/fisiología , Animales , Movimiento Celular/efectos de los fármacos , Tolerancia Inmunológica , Ratones , Células Mieloides/inmunología , Óxido Nítrico/biosíntesis , Transducción de Señal/fisiología , Sirolimus/farmacología
15.
J Cell Physiol ; 229(1): 17-26, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23804073

RESUMEN

The mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase which has a central role in the regulation of cell growth and metabolism. In the study of the mTOR signaling pathway, tuberous sclerosis complex (TSC) 1/2 complex is identified as a critical regulator of mTOR activity. TSC1/2 plays important roles for immune cell homeostasis and differentiation by negative control of mTOR signaling pathway. TSC1/2-mTOR pathway is proving to be a central point in regulating immune function of diverse immune cells. In this review, we discuss the function of TSC1/2-mTOR to direct the innate and adaptive immune cell development and function. Furthermore, we focus on the role of TSC1/2-mTOR signaling pathway in immune cell mediated diseases, especially autoimmunity.


Asunto(s)
Inmunidad Innata , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Proliferación Celular , Humanos , Fosforilación , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/genética
16.
Cancer Res ; 74(3): 727-37, 2014 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-24351289

RESUMEN

Myeloid-derived suppressor cells (MDSC) display an immature phenotype that may assume a classically activated (M1) or alternatively activated phenotype (M2) in tumors. In this study, we investigated metabolic mechanisms underlying the differentiation of MDSCs into M1 or M2 myeloid lineage and their effect on cancer pathophysiology. We found that SIRT1 deficiency in MDSCs directs a specific switch to M1 lineage when cells enter the periphery from bone marrow, decreasing the suppressive function in favor of a proinflammatory M1 phenotype associated with tumor cell attack. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against tumors. Our results define the essential nature of a SIRT1-mTOR/HIF-1α glycolytic pathway in determining MDSC differentiation, with implications for metabolic reprogramming as a cancer therapeutic approach.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Mieloides/inmunología , Células Mieloides/metabolismo , Neoplasias/genética , Neoplasias/inmunología , Sirtuina 1/genética , Animales , Diferenciación Celular/genética , Modelos Animales de Enfermedad , Glucólisis/genética , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Melanoma Experimental , Redes y Vías Metabólicas , Ratones , Ratones Noqueados , Células Mieloides/citología , Neoplasias/metabolismo , Neoplasias/patología , Sirtuina 1/deficiencia , Bazo/citología , Bazo/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Carga Tumoral/genética , Carga Tumoral/inmunología
17.
J Immunol ; 191(5): 2680-90, 2013 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-23904165

RESUMEN

Neutrophils are critically involved in host defense and inflammatory injury. However, intrinsic signaling mechanisms controlling neutrophil recruitment and activities are poorly defined. In this article, we showed that protein kinase AKT1 (also known as PKBα) is the dominant isoform expressed in neutrophils and is downregulated upon bacterial infection and neutrophil activation. AKT1 deficiency resulted in severe disease progression accompanied by recruitment of neutrophils and enhanced bactericidal activity in the acute inflammatory lung injury (ALI) and the Staphylococcus aureus infection mouse models. Moreover, the depletion of neutrophils efficiently reversed the aggravated inflammatory response, but adoptive transfer of AKT1(-/-) neutrophils could potentiate the inflammatory immunity, indicating an intrinsic effect of the neutrophil in modulating inflammation in AKT1(-/-) mice. In the ALI model, the infiltration of neutrophils into the inflammatory site was associated with enhanced migration capacity, whereas inflammatory stimuli could promote neutrophil apoptosis. In accordance with these findings, neutralization of CXCR2 attenuated neutrophil infiltration and delayed the occurrence of inflammation. Finally, the enhanced bactericidal activity and inflammatory immunity of AKT-deficient neutrophils were mediated by a STAT1-dependent, but not a mammalian target of rapamycin-dependent, pathway. Thus, our findings indicated that the AKT1-STAT1 signaling axis negatively regulates neutrophil recruitment and activation in ALI and S. aureus infection in mice.


Asunto(s)
Inflamación/inmunología , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Proteínas Proto-Oncogénicas c-akt/inmunología , Infecciones Estafilocócicas/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Immunoblotting , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Activación Neutrófila/inmunología , Neutrófilos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/inmunología
18.
Immunology ; 140(2): 143-52, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23692658

RESUMEN

The critical roles of kinase AKT in tumour cell proliferation, apoptosis and protein synthesis have been widely recognized. But AKT also plays an important role in immune modulation. Recent studies have confirmed that kinase AKT can regulate the development and functions of innate immune cells (neutrophil, macrophage and dendritic cell). Studies have shown that different isoforms of kinase AKT have different effects in regulating immunity-related diseases, mainly through the mammalian target of rapamycin-dependent or -independent pathways. The purpose of this review is to illustrate the immune modulating effects of kinase AKT on innate immune cell development, survival and function.


Asunto(s)
Inmunidad Innata/fisiología , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal/inmunología , Animales , Diferenciación Celular , Humanos
19.
Langmuir ; 29(22): 6687-96, 2013 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-23509875

RESUMEN

With a simple protocol, we synthesize a novel mesoporous silica nanocomposite shuttle that can reversibly transfer between an organic phase and water in response to the pH, due to the switchable surface hydrophobicity/hydrophilicity. Our synthesis protocol allows the phase transfer ability to be tuned in a controllable fashion. This nanocomposite shuttle exhibits a good ability to load various cargoes such as Pd(OAc)2, Pd nanoparticles, and organic molecules. The built-in properties of the nanocomposite shuttle lay the foundations for many innovative applications. As a proof of concept, we successfully demonstrate its application in separating and recycling Pd nanoparticle catalysts. The composite shuttle can take Pd nanoparticles to an organic phase for catalyzing hydrogenation of olefins and come back to an aqueous phase at the end of reaction, making in situ separation and recycling of nanocatalysts possible. This pH-driven round trip for catalysis can be repeated several times. Our investigations not only supply a novel nanocomposite shuttle with controllable properties but also open an innovative avenue to in situ separation and recycling of nanocatalysts, which can address the obstacles of the conventional methods such as centrifugation and filtration.


Asunto(s)
Alquenos/química , Nanocompuestos/química , Paladio/química , Dióxido de Silicio/química , Catálisis , Concentración de Iones de Hidrógeno , Hidrogenación , Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , Agua
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