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1.
Respir Res ; 25(1): 101, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38403646

RESUMEN

BACKGROUND: Although some studies have indicated that Psoriasis could contribute to the risk of idiopathic pulmonary fibrosis (IPF), no study has reported a clear causal association between them. Our aim was to explore the potential relationship between Psoriasis and IPF using Mendelian randomization (MR) design. METHODS: To explore a causal association between Psoriasis and IPF, we used genetic instruments from the largest available genome-wide association study (GWAS) of European ancestry, including psoriasis (5314 cases, 457,619 controls) and IPF (1028 cases, 196,986 controls). Our main analyses were conducted by inverse-variance weighted (IVW) method with random-effects model, with the other complementary four analyses: weighted median method, weighted mode, multivariable MR and MR-Egger approach. RESULTS: The results of IVW methods demonstrated that genetically predicted psoriasis was significantly associated with higher odds of IPF, with an odds ratio (OR) of 1.09 (95%CI, 1.01-1.18; P = 0.02). Weighted median method, weighted mode and multivariable MR also demonstrated directionally similar results (P < 0.05), while the MR-Egger regression did not reveal the impact of psoriasis on IPF (OR = 1.09, 95%CI, 0.98-1.21; P = 0.11). In addition, both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between psoriasis and IPF. CONCLUSIONS: Our study provided potential evidence between genetically predicted psoriasis and IPF, which suggests that understanding the mutual risk factors between psoriasis and IPF can facilitate the clinical management of both diseases.


Asunto(s)
Fibrosis Pulmonar Idiopática , Psoriasis , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/epidemiología , Fibrosis Pulmonar Idiopática/genética , Nonoxinol , Psoriasis/diagnóstico , Psoriasis/epidemiología , Psoriasis/genética
2.
Proc Natl Acad Sci U S A ; 106(38): 16108-13, 2009 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-19805266

RESUMEN

Recent experiments have demonstrated that plastic strains in nanocrystalline aluminum and gold films with grain sizes on the order of 50 nm are partially recoverable. To reveal the mechanisms behind such strain recovery, we perform large scale molecular dynamics simulations of plastic deformation in nanocrystalline aluminum with mean grain sizes of 10, 20, and 30 nm. Our results indicate that the inhomogeneous deformation in a polycrystalline environment results in significant residual stresses in the nanocrystals. Upon unloading, these internal residual stresses cause strain recovery via competitive deformation mechanisms including dislocation reverse motion/annihilation and grain-boundary sliding/diffusion. By tracking the evolution of each individual deformation mechanism during strain recovery, we quantify the fractional contributions by grain-boundary and dislocation deformation mechanisms to the overall recovered strain. Our analysis shows that, even under strain rates as high as those in molecular dynamics simulations, grain-boundary-mediated processes play important roles in the deformation of nanocrystalline aluminum.


Asunto(s)
Aluminio/química , Nanoestructuras/química , Plásticos/química , Cristalización , Modelos Químicos , Nanotecnología/métodos , Propiedades de Superficie , Termodinámica
3.
Phys Rev E Stat Nonlin Soft Matter Phys ; 77(3 Pt 1): 031910, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18517425

RESUMEN

We develop a physical model to describe the kinetic behavior in cell-adhesion molecules. Unbinding of noncovalent biological bonds is assumed to occur by both bond dissociation and bond rupture. Such a decomposition of debonding processes is a space decomposition of the debonding events. Dissociation under thermal fluctuation is nondirectional in a three-dimensional space, and its energy barrier to escape is not influenced by a tensile force, but the microstates that could lead to dissociation are changed by the tensile force; rupture happens along the tensile force direction. An applied force effectively lowers the energy barrier to escape along the loading direction. The lifetime of the biological bond, due to the two concurrent off rates, may grow with increasing tensile force to a moderate amount and then decrease with further increasing load. We hypothesize that a catch-to-slip bond transition is a generic feature in biological bonds. The model also predicts that catch bonds in a more flexible molecular structure have longer lifetimes and need less force to be fully activated.


Asunto(s)
Biofisica/métodos , Adhesión Celular , Dimerización , Elasticidad , Entropía , Calor , Cinética , Ligandos , Modelos Estadísticos , Modelos Teóricos , Conformación Molecular , Selectina-P , Polímeros/química , Estrés Mecánico , Resistencia a la Tracción
4.
Macromol Biosci ; 17(4)2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27762492

RESUMEN

Stimuli-responsive nanocarriers with the ability to respond to tumorous heterogeneity have been extensively developed for drug delivery. However, the premature release during blood circulation and insufficient intracellular drug release are still a significant issue. Herein, three disulfide bonds are introduced into the amphiphilic poly(ethylene glycol)-polycaprolactone copolymer blocks to form triple-sensitive cleavable polymeric nanocarrier (tri-PESC NPs) to improve its sensitivity to narrow glutathione (GSH) concentration. The tri-PESC NPs keep intact during blood circulation due to the limited cleaving of triple-disulfide bonds, whereas the loaded drug is efficiently released at tumor cells with the increased concentration of GSH. In vitro studies of doxorubicin-loaded tri-PESC NPs show that the nanocarriers achieve sufficient drug release in cancerous cells and inhibit the tumor cells growth, though they only bring minimum damage to normal cells. Therefore, the tri-PESC NPs with triple-sensitive cleavable bonds hold great promise to improve the therapeutic index in cancer therapy.


Asunto(s)
Preparaciones de Acción Retardada/farmacología , Portadores de Fármacos/química , Nanopartículas/química , Poliésteres/química , Polietilenglicoles/química , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Doxorrubicina/farmacología , Endocitosis/efectos de los fármacos , Células HEK293 , Células Hep G2 , Humanos , Espacio Intracelular/metabolismo , Microscopía Confocal , Nanopartículas/ultraestructura , Oxidación-Reducción , Tamaño de la Partícula , Poliésteres/síntesis química , Polietilenglicoles/síntesis química , Espectroscopía de Protones por Resonancia Magnética , Electricidad Estática
5.
Sci Rep ; 5: 10537, 2015 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-26022892

RESUMEN

It is generally observed that the existence of geometrical discontinuity like notches in materials will lead to strength weakening, as a resultant of local stress concentration. By comparing the influence of notches to the strength of three typical materials, aluminum alloys with intermediate tensile ductility, metallic glasses with no tensile ductility, and brittle ceramics, we observed strengthening in aluminum alloys and metallic glasses: Tensile strength of the net section in circumferentially notched cylinders increases with the constraint quantified by the ratio of notch depth over notch root radius; in contrast, the ceramic exhibit notch weakening. The strengthening in the former two is due to resultant deformation transition: Shear failure occurs in intact samples while samples with deep notches break in normal mode fracture. No such deformation transition was observed in the ceramic, and stress concentration leads to its notch weakening. The experimental results are confirmed by theoretical analyses and numerical simulation. The results reported here suggest that the conventional criterion to use brittleness and/or ductility to differentiate notch strengthening or weakening is not physically sound. Notch strengthening or weakening relies on the existence of failure mode transition and materials exhibiting shear failure while subjected to tension will notch strengthen.


Asunto(s)
Aleaciones/química , Cerámica/química , Resistencia a la Tracción , Ensayo de Materiales , Estrés Mecánico
6.
ACS Nano ; 9(10): 9912-21, 2015 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-26448362

RESUMEN

The functionalized lipid shell of hybrid nanoparticles plays an important role for improving their biocompatibility and in vivo stability. Yet few efforts have been made to critically examine the shell structure of nanoparticles and its effect on cell-particle interaction. Here we develop a microfluidic chip allowing for the synthesis of structurally well-defined lipid-polymer nanoparticles of the same sizes, but covered with either lipid-monolayer-shell (MPs, monolayer nanoparticles) or lipid-bilayer-shell (BPs, bilayer nanoparticles). Atomic force microscope and atomistic simulations reveal that MPs have a lower flexibility than BPs, resulting in a more efficient cellular uptake and thus anticancer effect than BPs do. This flexibility-regulated cell-particle interaction may have important implications for designing drug nanocarriers.


Asunto(s)
Portadores de Fármacos/química , Membrana Dobles de Lípidos/química , Microfluídica/métodos , Nanopartículas/química , Nanotecnología/métodos , Polímeros/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Cuello del Útero/efectos de los fármacos , Cuello del Útero/patología , Portadores de Fármacos/metabolismo , Femenino , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Membrana Dobles de Lípidos/metabolismo , Ratones , Simulación de Dinámica Molecular , Nanopartículas/metabolismo , Nanopartículas/ultraestructura , Polímeros/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología
7.
Adv Mater ; 27(8): 1402-7, 2015 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-25529120

RESUMEN

Core-shell nanoparticles (NPs) with lipid shells and varying water content and rigidity but with the same chemical composition, size, and surface properties are assembled using a microfluidic platform. Rigidity can dramatically alter the cellular uptake efficiency, with more-rigid NPs able to pass more easily through cell membranes. The mechanism accounting for this rigidity-dependent cellular uptake is revealed through atomistic-level simulations.


Asunto(s)
Ácido Láctico/química , Ácido Láctico/metabolismo , Lípidos/química , Fenómenos Mecánicos , Nanopartículas , Ácido Poliglicólico/química , Ácido Poliglicólico/metabolismo , Transporte Biológico , Células HeLa , Humanos , Conformación Molecular , Simulación de Dinámica Molecular , Copolímero de Ácido Poliláctico-Ácido Poliglicólico
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