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1.
Opt Express ; 31(25): 42637-42650, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38087633

RESUMEN

In the context of optical fiber humidity sensing, the long-term stability of sensors in high humidity and dew environments such as bathrooms or marine climates remains a challenge, especially since many humidity sensitive materials are water soluble. In this study, we use methyldiethanolamine, pentaerythritol triacrylate and Eosin Y to form a liquid-solid structure humidity sensitive component, the outermost layer is coated with PDMS passivating layer to ensure the stability and durability of the humidity sensor under the conditions of dew and high humidity. The liquid microcavity of the sensor consists of methyldiethanolamine-pentaerythritol triacrylate composite solution, and the sensitivity is several times higher than that of the liquid-free cavity sensor. The sensitivity of the sensor to temperature is verified (0.43 nm/°C and 0.30 nm/°C, respectively) and temperature crosstalk is compensated using a matrix. The compact structure allows for ultra-fast response (602 ms) and recovery time (349 ms). Our work provides a promising platform for efficient and practical humidity and other gas monitoring systems.

2.
Opt Lett ; 48(19): 5177-5180, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37773414

RESUMEN

We propose and experimentally demonstrate a balloon-like optical fiber sensor with an anti-resonance mechanism for the simultaneous measurement of displacement and temperature. The sensor consists of a hollow-core fiber spliced between two single-mode fibers and bent into a balloon-like shape. The balloon-like structure not only increases the contrast of the spectral lines but also improves the displacement sensitivity. Theoretical and experimental results show that the incidence angle of light varies with the change in displacement, resulting in the variation of spectral intensity based on the anti-resonance mechanism. In addition, the temperature change causes the wavelength drift of the spectrum. Thus, by separately demodulating the intensity and wavelength of this sensor, it is possible to measure displacement and temperature simultaneously. The sensitivity of the displacement and temperature of the sensor is 0.043 dB/µm and 20.94 pm/°C, respectively. The proposed optical fiber sensor has a compact structure and simple preparation, making it an ideal choice for simultaneous measurement of displacement and temperature in the fields of micro-manufacturing and structural monitoring in the future.

3.
Opt Lett ; 48(10): 2591-2594, 2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37186716

RESUMEN

In this Letter, we show stable suspension and directional manipulation of microdroplets on a liquid surface employing simple-mode fiber with a Gaussian beam at 1480-nm wavelength using the photothermal effect. The intensity of the light field generated by the single-mode fiber is used to generate droplets of different numbers and sizes. In addition, the effect of the heat generated at different heights from the liquid surface is discussed through numerical simulation. In this work, the optical fiber is not only free to move at any angle, solving the difficulty that a certain working distance is needed to generate microdroplets on free space, it can also allow the continuous generation and directional manipulation of multiple microdroplets, which is of tremendous scientific relevance and application value in promoting the development and cross-fertilization of life sciences and other interdisciplinary fields.

4.
Environ Res ; 237(Pt 2): 116939, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37611781

RESUMEN

The UV/sulfite system is a promising source of •SO4- and/or •OH, but its application is largely limited by the use of UV light due to its high cost and high energy consumption. Graphite carbon nitride (g-C3N5), as a new photocatalytic material, has better visible light absorption capacity and narrower band gap than g-C3N4, which is expected to activate sulfite under visible light to solve this problem. Herein, a novel FeS2/CN heterojunction material based on g-C3N5 was constructed by hydrothermal in-situ synthesis method and successfully activated sulfite, which was confirmed by tetracycline degradation experiments in water. Under optimized conditions, the degradation rate of TC in 1 h reached 96%. The experimental results revealed that the FeS2/CN heterostructure enhances the absorption of visible light and inhibits the recombination of carriers, enabling more electrons and holes to be utilized. Holes play a major role in the degradation reaction, promote the sulfite chain reaction, and effectively regulate the cycle of Fe2+ and Fe3+ in the solution. Iron ion leaching is negligible and the degradation reaction remains stable at pH 5-9.

5.
Sensors (Basel) ; 23(20)2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37896612

RESUMEN

An optical fiber sensor for the simultaneous measurement of microdisplacement and temperature based on balloon-shaped single-mode fibers cascaded with a fiber Bragg grating with two core-offset joints is proposed. The interference between the core mode and cladding mode is caused by the stimulation of the cladding mode by the core-offset joints' structure. The cladding of the core has a distinct refractive index, which causes optical path differences and interference. The balloon-shaped structure realizes mode selection by bending. As the displacement increases, the radius of the balloon-shaped interferometer changes, resulting in a change in the interference fringes of the interferometer, while the Bragg wavelength of the fiber grating remains unchanged. Temperature changes will cause the interference fringes of the interferometer and the Bragg wavelength of the fiber grating to shift. The proposed optical fiber sensor allows for the simultaneous measurement of microdisplacement and temperature. The results of the experiment indicate that the sensitivity of the interferometer to microdisplacement is 0.306 nm/µm in the sensing range of 0 to 200 µm and that the temperature sensitivity is 0.165 nm/°C, respectively. The proposed curvature sensor has the advantages of a compact structure, extensive spectrum of dynamic measurement, high sensitivity, and simple preparation, and has a wide range of potential applications in the fields of structural safety monitoring, aviation industry, and resource exploration.

6.
Int J Mol Sci ; 24(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37372960

RESUMEN

Lysophosphatidic acid receptors (LPARs) are six G-protein-coupled receptors that mediate LPA signaling to promote tumorigenesis and therapy resistance in many cancer subtypes, including breast cancer. Individual-receptor-targeted monotherapies are under investigation, but receptor agonism or antagonism effects within the tumor microenvironment following treatment are minimally understood. In this study, we used three large, independent breast cancer patient cohorts (TCGA, METABRIC, and GSE96058) and single-cell RNA-sequencing data to show that increased tumor LPAR1, LPAR4, and LPAR6 expression correlated with a less aggressive phenotype, while high LPAR2 expression was particularly associated with increased tumor grade and mutational burden and decreased survival. Through gene set enrichment analysis, it was determined that cell cycling pathways were enriched in tumors with low LPAR1, LPAR4, and LPAR6 expression and high LPAR2 expression. LPAR levels were lower in tumors over normal breast tissue for LPAR1, LPAR3, LPAR4, and LPAR6, while the opposite was observed for LPAR2 and LPAR5. LPAR1 and LPAR4 were highest in cancer-associated fibroblasts, while LPAR6 was highest in endothelial cells, and LPAR2 was highest in cancer epithelial cells. Tumors high in LPAR5 and LPAR6 had the highest cytolytic activity scores, indicating decreased immune system evasion. Overall, our findings suggest that potential compensatory signaling via competing receptors must be considered in LPAR inhibitor therapy.


Asunto(s)
Neoplasias de la Mama , Receptores del Ácido Lisofosfatídico , Humanos , Femenino , Receptores del Ácido Lisofosfatídico/genética , Receptores del Ácido Lisofosfatídico/metabolismo , Neoplasias de la Mama/genética , Microambiente Tumoral/genética , Células Endoteliales/metabolismo , Transducción de Señal , Lisofosfolípidos/metabolismo
7.
Opt Lett ; 46(13): 3017-3020, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34197368

RESUMEN

We propose and demonstrate an optical trap on the basis of a normal single-mode fiber (SMF), which is used to trap two particles in the axial direction at the same time without contact based on mode division multiplexing technology. We design and manufacture a tapered fiber probe. The LP11 mode beam is excited by docking a normal SMF to a 980 nm SMF with a 2 µm offset. Then the beams of LP01 and LP11 are both transmitted in the fiber. To converge the LP11 mode beam, a SMF with a tapered end is used to produce a cage for trapping the first microparticle. This particle acts as a lens to converge the LP01 mode beam to trap the second microparticle. We verify the feasibility of trapping two particles simultaneously through simulation. With this function, the proposed optical trap is easier to manipulate different individual particles for comparison and testing, which can promote the development of the biological, biophysical, colloidal, and soft matter fields.

8.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34575976

RESUMEN

Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. HCMV proteins and DNA are detected in tumors and metastases, suggesting an association with increased invasion. We investigated HCMV infection in human breast cancer cell lines compared to fibroblasts, a component of tumors, and the role of platelet-derived growth factor receptor-α (PDGFRα). HCMV productively infected HEL299 fibroblasts and, to a lesser extent, Hs578T breast cancer cells. Infection of another triple-negative cell line, MDA-MB-231, and also MCF-7 cells, was extremely low. These disparate infection rates correlated with expression of PDGFRA, which facilitates HCMV uptake. Increasing PDGFRA expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased PDGFRA expression, potentially attenuating signaling through this receptor. HCMV infection of fibroblasts promoted the secretion of proinflammatory factors, whereas an overall decreased secretion of inflammatory factors was observed in infected Hs578T cells. We conclude that HCMV infection in tumors will preferentially target tumor-associated fibroblasts and breast cancer cells expressing PDGFRα. HCMV infection in the tumor microenvironment, rather than cancer cells, will increase the inflammatory milieu that could enhance metastasis involving lysophosphatidate.


Asunto(s)
Neoplasias de la Mama/genética , Infecciones por Citomegalovirus/genética , Lisofosfolípidos/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Neoplasias de la Mama/virología , Citomegalovirus/patogenicidad , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/patología , Infecciones por Citomegalovirus/virología , Femenino , Fibroblastos/patología , Fibroblastos/virología , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Lisofosfolípidos/metabolismo , Células MCF-7 , Metástasis de la Neoplasia/genética , Transducción de Señal/genética , Microambiente Tumoral/genética , Internalización del Virus
9.
FASEB J ; 33(2): 1899-1910, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30192654

RESUMEN

Lysophosphatidate (LPA) signaling through 6 receptors is regulated by the balance of LPA production by autotaxin (ATX) vs. LPA degradation by lipid phosphate phosphatases (LPPs). LPA promotes an inflammatory cycle by increasing the synthesis of cyclooxygenase-2 and multiple inflammatory cytokines that stimulate further ATX production. We aimed to determine whether the anti-inflammatory glucocorticoid (GC) dexamethasone (Dex) functions partly by decreasing the ATX-LPA inflammatory cycle in adipose tissue, a major site of ATX secretion. Treatment of human adipose tissue with 10-1000 nM Dex decreased ATX secretion, increased LPP1 expression, and decreased mRNA expressions of IL-6, TNF-α, peroxisome proliferator-activated receptor (PPAR)-γ, and adiponectin. Cotreatment with rosiglitazone (an insulin sensitizer), insulin, or both abolished Dex-induced decreases in ATX and adiponectin secretion, but did not reverse Dex-induced decreases in secretions of 20 inflammatory cytokines and chemokines. Dex-treated mice exhibited lower ATX activity in plasma, brain, and adipose tissue; decreased mRNA levels for LPA and sphingosine 1-phosphate (S1P) receptors in brain; and decreased plasma concentrations of LPA and S1P. Our results establish a novel mechanism for the anti-inflammatory effects of Dex through decreased signaling by the ATX-LPA-inflammatory axis. The GC action in adipose tissue has implications for the pathogenesis of insulin resistance and obesity in metabolic syndrome and breast cancer treatment.-Meng, G., Tang, X., Yang, Z., Zhao, Y., Curtis, J. M., McMullen, T. P. W., Brindley, D. N. Dexamethasone decreases the autotaxin-lysophosphatidate-inflammatory axis in adipose tissue: implications for the metabolic syndrome and breast cancer.


Asunto(s)
Tejido Adiposo/metabolismo , Dexametasona/farmacología , Lisofosfolípidos/sangre , Neoplasias Mamarias Experimentales/sangre , Síndrome Metabólico/sangre , Proteínas de Neoplasias/sangre , Hidrolasas Diéster Fosfóricas/sangre , Transducción de Señal/efectos de los fármacos , Tejido Adiposo/patología , Animales , Femenino , Humanos , Inflamación , Neoplasias Mamarias Experimentales/patología , Síndrome Metabólico/patología , Ratones , Ratones Endogámicos BALB C
10.
Int J Mol Sci ; 21(16)2020 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-32824846

RESUMEN

Autotaxin (ATX) is a secreted enzyme that produces lysophosphatidate (LPA), which signals through six G-protein coupled receptors, promoting tumor growth, metastasis, and survival from chemotherapy and radiotherapy. Many cancer cells produce ATX, but breast cancer cells express little ATX. In breast tumors, ATX is produced by tumor-associated stroma. Breast tumors are also surrounded by adipose tissue, which is a major bodily source of ATX. In mice, a high-fat diet increases adipocyte ATX production. ATX production in obesity is also increased because of low-level inflammation in the expanded adipose tissue. This increased ATX secretion and consequent LPA signaling is associated with decreased adiponectin production, which results in adverse metabolic profiles and glucose homeostasis. Increased ATX production by inflamed adipose tissue may explain the obesity-breast cancer association. Breast tumors produce inflammatory mediators that stimulate ATX transcription in tumor-adjacent adipose tissue. This drives a feedforward inflammatory cycle since increased LPA signaling increases production of more inflammatory mediators and cyclooxygenase-2. Inhibiting ATX activity, which has implications in breast cancer adjuvant treatments, attenuates this cycle. Targeting ATX activity and LPA signaling may potentially increase chemotherapy and radiotherapy efficacy, and decrease radiation-induced fibrosis morbidity independently of breast cancer type because most ATX is not derived from breast cancer cells.


Asunto(s)
Neoplasias de la Mama/metabolismo , Lisofosfolípidos/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Transducción de Señal , Tejido Adiposo/metabolismo , Animales , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Dexametasona/uso terapéutico , Femenino , Humanos
11.
Opt Express ; 27(4): A92-A116, 2019 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-30876006

RESUMEN

This paper reports on accurate calculations of backscattering properties of transported and soot-contaminated dust at triple wavelengths (0.355, 0.532, and 1.064 µm, respectively) by using the invariant imbedding T-matrix method. The changes of backscattering ratios from bare to soot-contaminated dust were systematically investigated by employing super-spheroidal dust and fractal soot models. The impacts of morphology change and soot absorptivity on backscattering ratios of soot-contaminated dust were clarified. In addition, it was found that adhesion has a large impact on the backscattering ratios. However, the results of non-contact soot-contaminated dust appear to be closer to observations than those of contact mixing.

12.
Opt Express ; 27(9): 12414-12423, 2019 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-31052781

RESUMEN

Although optical tweezers function well for the majority of transparent particles, the absorbing particles experience a considerably high absorption force that can destroy the stable optical traps. Photophoretic force is an alternative mechanism that can be used to trap the absorbing particles. The major difficulty that is associated with the utilization of photophoretic forces for trapping strongly absorbing particles in liquids is the presence of considerable absorption on the illuminated side; a positive photophoretic force is usually induced, thereby pushing away the absorbing particles from the high-intensity region of the laser source. Here, we demonstrate a novel principle for the optical trapping and manipulation of strongly absorbing particles by harnessing strong Δα-type photophoretic forces while suppressing their stochastic nature in pure liquid glycerol using a normal divergent Gaussian beam and a Bessel-like beam. Further, our approach expands the optical manipulation of strong absorbing particles to liquid media and provides position control over the trapped particles, including the optical transportation and pinpoint positioning of the 3-µm objects over a distance of a millimeter.

13.
Opt Lett ; 44(21): 5165-5168, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31674957

RESUMEN

We propose and demonstrate a simple approach for noncontact, three-dimensional, and stable trapping of a single nanoparticle with a super-low incident laser power (0.7 mW) via the single-fiber optical tweezers. We splice a section of single-mode fiber and a section of multimode fiber to construct a Bessel-like beam, which produces narrow output laser beams. We integrate a high-refractive-index glass microsphere on the tip of the multimode fiber to focus the narrow output laser beams. The focused beams provide a nanoscale optical trap for a single nanoparticle (polystyrene sphere, diameter of 200 nm). This optical fiber probe has the advantages of high laser transmission efficiency, high spatial resolution, and minimum joule heating. The proposed approach extends the application potential of fiber-based optical manipulations, such as nanoparticle sorting, single-cell organelle analysis, and bio-sensing.

14.
Opt Lett ; 43(12): 2784-2786, 2018 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-29905688

RESUMEN

We proposed and experimentally demonstrated 3-dimensional dark traps for low refractive index bio-cells using a single optical fiber Bessel beam. The Bessel beam was produced by concatenating single-mode fiber and a step index multimode fiber, which was then focused by a high refractive index glass microsphere integrated on the fiber end facet. The focused Bessel beam provided two dark fields along the axial direction, where stable trapping of low refractive index bio-cells was realized in a high refractive index liquid bath. The all-fiber and seamlessly integrated structure of the proposed scheme can find ample potential as a micro-optical probe in in situ characterization and manipulation of multiple bio-cells with refractive indices lower than that of the liquid bath.


Asunto(s)
Tecnología de Fibra Óptica/métodos , Imagenología Tridimensional , Fibras Ópticas , Pinzas Ópticas , Refractometría/métodos , Fenómenos Físicos
15.
Phys Rev Lett ; 121(13): 133901, 2018 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-30312072

RESUMEN

We demonstrate a new principle of the laser-induced hammer-hit vibration of a micron-sized black sphere in liquid glycerol with a single divergent Gaussian beam. The light-induced Δα-photophoretic force, which is significantly improved by the vibrating speed of the microparticle, is responsible for both the pushing and pulling force of the hammer-hit vibration. Our approach expands the optical manipulation of microparticle hammer-hit vibration to a liquid medium and provides full control over the trapped particles, including the adjustment of the vibration frequency, amplitude, and position.

16.
FASEB J ; 31(9): 4064-4077, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28539367

RESUMEN

We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy. To test this hypothesis, we exposed rat and human adipose tissue to radiation doses (0.25-5 Gy) that were expected during radiotherapy. This exposure increased mRNA levels for ATX, cyclooxygenase-2, IL-1ß, IL-6, IL-10, TNF-α, and LPA1 and LPA2 receptors by 1.8- to 5.1-fold after 4 to 48 h. There were also 1.5- to 2.5-fold increases in the secretion of ATX and 14 inflammatory mediators after irradiating at 1 Gy. Inhibition of the radiation-induced activation of NF-κB, cyclooxygenase-2, poly (ADP-ribose) polymerase-1, or ataxia telangiectasia and Rad3-related protein blocked inflammatory responses to γ-radiation. Consequently, collateral damage to adipose tissue during radiotherapy could establish a comprehensive wound-healing response that involves increased signaling by LPA, cyclooxygenase-2, and other inflammatory mediators that could decrease the efficacy of further radiotherapy or chemotherapy.-Meng, G., Tang, X., Yang, Z., Benesch, M. G. K., Marshall, A., Murray, D., Hemmings, D. G., Wuest, F., McMullen, T. P. W., Brindley, D. N. Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/radioterapia , Regulación Enzimológica de la Expresión Génica/efectos de la radiación , Hidrolasas Diéster Fosfóricas/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de la radiación , Animales , Línea Celular Tumoral , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Humanos , Hidrolasas Diéster Fosfóricas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores del Ácido Lisofosfatídico/genética , Receptores del Ácido Lisofosfatídico/metabolismo
17.
Appl Opt ; 57(29): 8573-8577, 2018 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-30461924

RESUMEN

A method to estimate the Stark levels of the rare-earth ions doped in a laser medium from the measured emission and absorption cross-sections is proposed. The method is based on the McCumber theory, which can calculate the emission/absorption cross-sections from the given Stark levels. By fitting the calculated emission/absorption spectra to the measured ones through a numerical optimization process, the Stark levels of the RE ions can be determined. As examples, the Stark levels of the laser-emission-related manifolds of Er3+ and Yb3+ ions in a gain fiber and two doped glasses have been determined by the proposed method. The data were then used to analyze the temperature-dependent population of the Stark levels. This method avoids the difficulties in direct measurement of the Stark levels in a cryogenic temperature environment. It is important to the evaluation of the thermal load, distribution, and design of the thermal management system of high-power fiber lasers and amplifiers.

18.
Appl Opt ; 57(7): 1541-1547, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29521999

RESUMEN

Thermal effects are critical constraints for developing high-power Er/Yb-codoped fiber amplifiers (EYDFAs), especially those with an auxiliary Yb-band cavity. In this paper, we developed a numerical model to investigate the temperature-dependent effects on EYDFAs with an Yb-band cavity with consideration of thermal-induced cross-section changes. Our results show that the quantum-defect-induced heat affects the performance of the EYDFA, and its effect varies with the resonant wavelength of the Yb-band cavity. There is a finite applicable resonant wavelength range limited by thermal damage. So, it is important to take into account the thermal effect during the design of such EYDFAs in order to optimize their performance and determine the heat dissipation systems.

19.
J Lipid Res ; 58(12): 2348-2364, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28986436

RESUMEN

Lipin-1 is a Mg2+-dependent phosphatidic acid phosphatase (PAP) that in mice is necessary for normal glycerolipid biosynthesis, controlling adipocyte metabolism, and adipogenic differentiation. Mice carrying inactivating mutations in the Lpin1 gene display the characteristic features of human familial lipodystrophy. Very little is known about the roles of lipin-1 in human adipocyte physiology. Apparently, fat distribution and weight is normal in humans carrying LPIN1 inactivating mutations, but a detailed analysis of adipose tissue appearance and functions in these patients has not been available so far. In this study, we performed a systematic histopathological, biochemical, and gene expression analysis of adipose tissue biopsies from human patients harboring LPIN1 biallelic inactivating mutations and affected by recurrent episodes of severe rhabdomyolysis. We also explored the adipogenic differentiation potential of human mesenchymal cell populations derived from lipin-1 defective patients. White adipose tissue from human LPIN1 mutant patients displayed a dramatic decrease in lipin-1 protein levels and PAP activity, with a concomitant moderate reduction of adipocyte size. Nevertheless, the adipose tissue develops without obvious histological signs of lipodystrophy and with normal qualitative composition of storage lipids. The increased expression of key adipogenic determinants such as SREBP1, PPARG, and PGC1A shows that specific compensatory phenomena can be activated in vivo in human adipocytes with deficiency of functional lipin-1.


Asunto(s)
Adipocitos/metabolismo , Tejido Adiposo Blanco/metabolismo , Mutación , Fosfatidato Fosfatasa/genética , Rabdomiólisis/genética , Adipocitos/citología , Tejido Adiposo Blanco/citología , Adolescente , Alelos , Distribución de la Grasa Corporal , Peso Corporal , Estudios de Casos y Controles , Diferenciación Celular , Niño , Preescolar , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , PPAR gamma/genética , PPAR gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Fosfatidato Fosfatasa/deficiencia , Rabdomiólisis/metabolismo , Rabdomiólisis/patología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo
20.
Mol Cancer ; 16(1): 36, 2017 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-28178994

RESUMEN

BACKGROUND: We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. METHODS: In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. RESULTS: Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1ß, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80+ macrophages and CD31+ blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence or absence of lysophosphatidate. CONCLUSION: These results contribute a new dimension for understanding the anti-inflammatory effects of tetracyclines, which make them potential candidates for adjuvant therapy of cancers and other inflammatory diseases.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Doxiciclina/farmacología , Inflamación/metabolismo , Inflamación/patología , Lisofosfolípidos/sangre , FN-kappa B/metabolismo , Animales , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Citocinas/sangre , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Fosforilación , Transporte de Proteínas , Carga Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
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