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1.
Small ; : e2403737, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949018

RESUMEN

In next-generation neuromorphic computing applications, the primary challenge lies in achieving energy-efficient and reliable memristors while minimizing their energy consumption to a level comparable to that of biological synapses. In this work, hexagonal boron nitride (h-BN)-based metal-insulator-semiconductor (MIS) memristors operating is presented at the attojoule-level tailored for high-performance artificial neural networks. The memristors benefit from a wafer-scale uniform h-BN resistive switching medium grown directly on a highly doped Si wafer using metal-organic chemical vapor deposition (MOCVD), resulting in outstanding reliability and low variability. Notably, the h-BN-based memristors exhibit exceptionally low energy consumption of attojoule levels, coupled with fast switching speed. The switching mechanisms are systematically substantiated by electrical and nano-structural analysis, confirming that the h-BN layer facilitates the resistive switching with extremely low high resistance states (HRS) and the native SiOx on Si contributes to suppressing excessive current, enabling attojoule-level energy consumption. Furthermore, the formation of atomic-scale conductive filaments leads to remarkably fast response times within the nanosecond range, and allows for the attainment of multi-resistance states, making these memristors well-suited for next-generation neuromorphic applications. The h-BN-based MIS memristors hold the potential to revolutionize energy consumption limitations in neuromorphic devices, bridging the gap between artificial and biological synapses.

2.
Medicina (Kaunas) ; 60(5)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38792996

RESUMEN

Stroke often results in sensory deficits, muscular weakness, and diminished postural control, thereby restricting mobility and functional capabilities. It is important to promote neuroplasticity by implementing task-oriented exercises that induce changes in patients. Therefore, this study aimed to investigate the effects of rehabilitation robot training on physical function, functional recovery, and activities of daily living (ADLs) in patients with subacute stroke. The study participants were patients with subacute stroke receiving treatment at Hospitals A and B. They were selected as research subjects based on selection and exclusion criteria. The experimental group received rehabilitation robot training in sessions of 30 min, five times weekly, for a total of 20 sessions over four weeks. Conversely, the control group underwent standard rehabilitation equipment training with an identical frequency, duration, and number of sessions. Measurements were taken before and after the training period to assess changes in physical function, functional recovery, and activities of daily living using tools such as the MMT, BBS, FBG, FAC, FIM, and MBI. The results were as follows: in the within-group comparison, the rehabilitation robot training group showed significant differences in MMT, BBS, FBG, FAC, FIM, and MBI (p < 0.05), while the control group showed significant differences in FIM (p < 0.05). Statistically significant differences were observed in the time, group, and time × group interaction effects among the MMT, static seated FBG, dynamic seated FBG, FIM, and MBI (p < 0.05). Based on these results, rehabilitation robotic training resulted in significant improvements in physical function, functional recovery, and activities of daily living in patients with subacute stroke. Based on these findings, providing a basic protocol for a rehabilitation program that applies rehabilitation robot training to patients with subacute stroke may offer more effective treatment and outcomes in the future.


Asunto(s)
Actividades Cotidianas , Recuperación de la Función , Robótica , Rehabilitación de Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Femenino , Masculino , Robótica/métodos , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/fisiopatología , Terapia por Ejercicio/métodos , Terapia por Ejercicio/instrumentación , Resultado del Tratamiento
3.
BMC Cancer ; 23(1): 1014, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37864152

RESUMEN

BACKGROUND: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision. METHODS: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews. DISCUSSION: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.


Asunto(s)
Neoplasias Ováricas , Radiocirugia , Femenino , Humanos , Carcinoma Epitelial de Ovario/radioterapia , Ensayos Clínicos Fase III como Asunto , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/etiología , Neoplasias Ováricas/radioterapia , Neoplasias Ováricas/etiología , Estudios Prospectivos , Radiocirugia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Nivel de Atención
4.
Langmuir ; 39(38): 13546-13559, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37706471

RESUMEN

Amphiphilic block copolymer micelles can mimic the ability of natural lung surfactant to reduce the air-water interfacial tension close to zero and prevent the Laplace pressure-induced alveolar collapse. In this work, we investigated the air-water interfacial behaviors of polymer micelles derived from eight different poly(ethylene glycol) (PEG)-based block copolymers having different hydrophobic block chemistries to elucidate the effect of the core block chemistry on the surface mechanics of the block copolymer micelles. Aqueous micelles of about 30 nm in hydrodynamic diameter were prepared from the PEG-based block copolymers via equilibration-nanoprecipitation (ENP) and spread on the water surface using water as the spreading medium. Surface pressure-area isotherm and quantitative Brewster angle microscopy (QBAM) measurements were performed to investigate how the micelle/monolayer structures change during lateral compression of the monolayer; widely varying structural behaviors were observed, including the wrinkling/collapse of micelle monolayers and deformation and/or the desorption of individual micelles. By bivariate correlation regression analysis of surface pressure-area isotherm data, it was found that the rigidity and hydrophobicity of the hydrophobic core domain, which are quantified by glass-transition temperature (Tg) and water contact angle (θ) measurements, respectively, are coupled factors that need to be taken into account concurrently in order to control the surface mechanical properties of polymer micelle monolayers; micelles having rigid and strongly hydrophobic cores exhibited high surface pressure and a high compressibility modulus under high compression. High surface pressure and a high compressibility modulus were also found to be correlated with the formation of wrinkles in the micelle monolayer (visualized by Brewster angle microscopy (BAM)). From this study, we conclude that polymer micelles based on hydrophobic block materials having higher Tg and θ are more suitable for surfactant replacement therapy applications that require the therapeutic surfactant to produce a high surface pressure and modulus at the alveolar air-water interface.

5.
Soft Matter ; 19(47): 9269-9281, 2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38009013

RESUMEN

In the pursuit of the development of a first-in-kind polymer lung surfactant (PLS) therapeutic whose effects are biophysical in nature, a comprehensive understanding of the factors affecting the air-water surface mechanical behavior of water-spread block copolymer micelles is desired. To this end, we explore the effect of temperature on the surface mechanical behavior of two different micelle core chemistries, poly(styrene) (PS) and poly(tert-butyl methacrylate) (PtBMA), each having poly(ethylene glycol) (PEG) as the hydrophilic block. The behavior is characterized using surface pressure-area isotherms and quantitative Brewster angle microscopy. The results indicate that the temperature has a significant effect on the micelle structure at the interface and this effect is related to the core Tg as well as the core interfacial tension properties. When temperature is higher than the core Tg for PS-PEG, the spherical micelle core rearranges to form an oblate-like structure which increases its interfacial area. The structural rearrangement changes the mechanism by which the film produces high surface pressure. For PtBMA-PEG, which has a lower interfacial tension with water and air compared to PS, the core domains spread at the interface when the mobility is sufficiently high such that a PtBMA film is formed under high compression. The implications of these changes on PLS efficacy are discussed highlighting the importance of core Tg characterization for polymer nanoparticle applications.

6.
BMC Public Health ; 23(1): 1776, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700251

RESUMEN

BACKGROUND: There have been many prediction studies for imported infectious diseases, employing air-travel volume or the importation risk (IR) index, which is the product of travel-volume and disease burden in the source countries, as major predictors. However, there is a lack of studies validating the predictability of the variables especially for infectious diseases that have rarely been reported. In this study, we analyzed the prediction performance of the IR index and air-travel volume to predict disease importation. METHODS: Rabies and African trypanosomiasis were used as target diseases. The list of rabies and African trypanosomiasis importation events, annual air-travel volume between two specific countries, and incidence of rabies and African trypanosomiasis in the source countries were obtained from various databases. RESULTS: Logistic regression analysis showed that IR index was significantly associated with rabies importation risk (p value < 0.001), but the association with African trypanosomiasis was not significant (p value = 0.923). The univariable logistic regression models showed reasonable prediction performance for rabies (area under curve for Receiver operating characteristic [AUC] = 0.734) but poor performance for African trypanosomiasis (AUC = 0.641). CONCLUSIONS: Our study found that the IR index cannot be generally applicable for predicting rare importation events. However, it showed the potential utility of the IR index by suggesting acceptable performance in rabies models. Further studies are recommended to explore the generalizability of the IR index's applicability and to propose disease-specific prediction models.


Asunto(s)
Enfermedades Transmisibles Importadas , Rabia , Humanos , Enfermedades Transmisibles Importadas/epidemiología , Rabia/epidemiología , Costo de Enfermedad , Bases de Datos Factuales , Factores de Riesgo
7.
J Korean Med Sci ; 38(38): e293, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37750367

RESUMEN

BACKGROUND: In vitro fertilization-embryo transfer (IVF-ET), an expensive option for infertile couples, started to be fully covered by the National Health Insurance (NHI) from October 2017 in South Korea. We investigated the association between woman's socioeconomic status (SES) and abortive outcomes in pregnancies after IVF-ET in the setting of universal coverage of the treatment. METHODS: Using the NHI database in South Korea, we conducted a retrospective cohort study of all women who achieved clinical pregnancy after ET between October 2017 and February 2019. A total of 44,038 clinical pregnancy episodes of 29,847 women who underwent ET were analyzed. We used employment status, income in percentiles, and living in the Seoul capital area as indicators of SES. Relative risks (RRs) for abortive pregnancy outcomes were calculated for each socioeconomic stratum, using log-binomial regression models included woman's age, body mass index, fasting blood glucose, fresh ET, month of ET, and history of smoking. RESULTS: While most pregnancy outcomes were live births (n = 30,783, 69.9%), 11,215 (25.5%) cycles ended with abortion or early pregnancy loss, 1,779 (4.0%) cycles were ectopic pregnancy, 45 (0.1%) were coded as molar pregnancy, and 224 (0.5%) were fetal death in utero or stillbirth. The risk of overall abortive outcomes was higher when a woman was unemployed (adjusted RR, 1.08; 95% confidence interval [CI], 1.05-1.11) or living in a non-Seoul capital area (1.11; 95% CI, 1.08-1.14). The association between relative income level and abortive outcomes was close to null. Living outside Seoul capital area was associated with the greater risk of abortive outcomes especially in younger women. CONCLUSION: Unemployment and living in non-capital areas were associated with a higher risk of abortive outcomes among pregnancies after ET, even in the setting of universal coverage of IVF-ET. This suggests potential impact of socioeconomic position on the IVF-ET pregnancy.


Asunto(s)
Aborto Espontáneo , Fertilización In Vitro , Embarazo , Femenino , Humanos , Cobertura Universal del Seguro de Salud , Estudios Retrospectivos , Transferencia de Embrión , Resultado del Embarazo , Índice de Embarazo , Nacimiento Vivo , Aborto Espontáneo/epidemiología , Clase Social
8.
J Transl Med ; 20(1): 104, 2022 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-35216600

RESUMEN

BACKGROUND: Graft-versus-host disease (GvHD) is a critical complication after allogeneic hematopoietic stem cell transplantation (HSCT). The immunosuppressants given to patients undergoing allogeneic HSCT disturb the microbiome and the host immune system, potentially leading to dysbiosis and inflammation, and may affect immune function and bone marrow transplantation. The intestinal microbiome is a target for the development of novel therapies for GvHD. Lactobacillus species are widely used supplements to induce production of antimicrobial and anti-inflammatory factors. METHODS: We determined the effect of the combination of Lactobacillus acidophilus and FK506 on GvHD following major histocompatibility complex-mismatched bone marrow transplantation. RESULTS: The combination treatment suppressed IFN-γ and IL-17-producing T cell differentiation, but increased Foxp3+Treg differentiation and IL-10 production. Also, the combination treatment and combination treated-induced Treg cells modulated the proliferation of murine alloreactive T cells in vitro. Additionally, the combination treatment upregulated Treg-related genes-Nt5e, Foxp3, Ikzf2, Nrp1 and Itgb8-in murine CD4+-T cells. The combination treatment also alleviated GvHD clinically and histopathologically by controlling the effector T cell and Treg balance in vivo. Moreover, the combination treatment decreased Th17 differentiation significantly and significantly upregulated Foxp3 and IL-10 expression in peripheral blood mononuclear cells from healthy controls and liver transplantation (LT) patients. CONCLUSIONS: Therefore, the combination of L. acidophilus and FK506 is effective and safe for patients undergoing allogeneic hematopoietic stem cell transplantation.


Asunto(s)
Enfermedad Injerto contra Huésped , Linfocitos T Reguladores , Enfermedad Aguda , Animales , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Lactobacillus acidophilus , Leucocitos Mononucleares , Ratones , Ratones Endogámicos C57BL , Tacrolimus/farmacología , Tacrolimus/uso terapéutico
9.
Biomacromolecules ; 23(6): 2471-2484, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35580262

RESUMEN

We have recently discovered that pulmonary administration of nanoparticles (micelles) formed by amphiphilic poly(styrene-block-ethylene glycol) (PS-PEG) block copolymers has the potential to treat a lung disorder involving lung surfactant (LS) dysfunction (called acute respiratory distress syndrome (ARDS)), as PS-PEG nanoparticles are capable of reducing the surface tension of alveolar fluid, while they are resistant to deactivation caused by plasma proteins/inflammation products unlike natural LS. Herein, we report studies of the clearance pathways and kinetics of PS-PEG nanoparticles from the lung, which are essential for designing further preclinical IND-enabling studies. Using fluorescently labeled PS-PEG nanoparticles, we found that, following pharyngeal aspiration in mice, the retention of these nanoparticles in the lungs extends over 2 weeks, while their transport into other (secondary) organs is relatively insignificant. An analysis based on a multicompartmental pharmacokinetic model suggests a biphasic mechanism involving a fast mucociliary escalator process through the conducting airways and much slower alveolar clearance processes by the action of macrophages and also via direct translocation into the circulation. An excessive dose of PS-PEG nanoparticles led to prolonged retention in the lungs due to saturation of the alveolar clearance capacity.


Asunto(s)
Polietilenglicoles , Polímeros , Animales , Pulmón , Ratones , Micelas , Polietilenglicoles/farmacocinética , Tensoactivos
10.
Soft Matter ; 18(21): 4146-4155, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35583260

RESUMEN

This study investigates the nanostructure of complex coacervate core hydrogels (C3Gs) with varying compositions of cationic charged groups (i.e., ammonium and guanidinium) using small-angle X-ray/neutron scattering (SAX/NS). C3Gs were prepared by stoichiometric mixing of two oppositely charged ABA triblock copolymers in aqueous solvents, in which A end-blocks were functionalized with either sulfonate groups or a mixture of ammonium and guanidinium groups. Comprehensive small-angle X-ray/neutron scattering (SAX/NS) analysis elucidated the dependence of C3Gs structures on the fraction of guanidinium groups in the cationic end-block (x) and salt concentration (cs). As x increases, the polymer volume fraction in the cores, and interfacial tension (γcore) and salt resistance (c*) of the coacervate cores increase, which is attributed to the greater hydrophobicity and non-electrostatic association. Furthermore, we observed that the salt dependence of the interfacial tension follows γcore ∼ (1 - cs/c*)3/2 in all series of x. The results show that the variation of the ionic group provides a powerful method to control the salt-responsiveness of C3Gs as stimuli-responsive materials.

11.
Macromol Rapid Commun ; 43(12): e2100618, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34738689

RESUMEN

ABC triblock copolymers composed of hydrophobic poly(ε-caprolactone) (PCL), zwitterionic poly(carboxybetaine methacrylate) midblock, and P(PEGMA-UPy0.15 ) containing supramolecular ureidopyrimidinone moieties, poly(ε-caprolactone-block-carboxybetaine methacrylate-block-[poly(ethylene glycol) methyl ether methacrylate-co-(α-methacryloyl-ω-(6-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)hexylcarbamoyloxy)poly(ethylene glycol))]), are investigated to achieve multifunctional antifreeze hydrogels. The PCL and P(PEGMA-UPy0.15 ) blocks induce the formation of physical network with a hierarchical nanostructure comprising hydrophobic PCL cores and supramolecular junctions, respectively. The super-hydrophilic nature of polyzwitterion midblocks and the confinement effect of the supramolecular junctions enhance the antifreeze performance, where the majority of water molecules remains supercooled below sub-zero temperature. The hydrogel relaxation characterized over a wide range of timescale reveals that the facile dynamics of the supramolecular junctions lead to the self-healing and injectability of the hydrogels. In conjunction with the biodegradable PCL cores, the antifreeze and rheological characteristics of the triblock copolymer hydrogels provide significant potential to use for cryo-preservable and bio-injectable drug storage and delivery.


Asunto(s)
Hidrogeles , Poliésteres , Hidrogeles/química , Metacrilatos , Poliésteres/química , Polietilenglicoles/química , Polímeros/química
12.
BMC Public Health ; 22(1): 1766, 2022 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-36115935

RESUMEN

BACKGROUND: Although a growing body of evidence suggests air pollution is associated with low serum vitamin D status, few studies have reported whether obesity status affects this relationship. The aim of this study was to identify associations between ambient air pollution exposure, obesity, and serum vitamin D status in the general population of South Korea. METHODS: This study was conducted in a cross-sectional design. A total of 30,242 Korean adults from a nationwide general population survey were included for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and carbon monoxide (CO). We measured serum 25-hydroxyvitamin D concentration to assess vitamin D status for each participant. Multiple linear and logistic regression analyses were performed to identify associations between ambient air pollution and vitamin D status in each subgroup according to body mass index level. RESULTS: The annual average concentrations of PM10, NO2, and CO were significantly associated with a lower serum vitamin D concentration and higher risk of vitamin D deficiency. The results show a significant association between serum vitamin D status and PM10 exposure in obese subgroup. Based on the gender, females with obesity showed more strong association (negative) between different air pollutants and low serum vitamin D concentration and a higher risk of vitamin D deficiency. However, this pattern was not observed in men. CONCLUSIONS: This study provides the first evidence that women with obesity may be more vulnerable to vitamin D deficiency in the context of persistent exposure to air pollution.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Deficiencia de Vitamina D , Adulto , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Monóxido de Carbono/análisis , Estudios Transversales , Femenino , Humanos , Masculino , Dióxido de Nitrógeno/análisis , Obesidad/complicaciones , Obesidad/epidemiología , Material Particulado/efectos adversos , Material Particulado/análisis , Vitamina D , Vitaminas/análisis
13.
PLoS Comput Biol ; 16(10): e1007940, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33095769

RESUMEN

Availability of genome sequence, molecular, and clinical phenotype data for large patient cohorts generated by recent technological advances provides an opportunity to dissect the genetic architecture of complex diseases at system level. However, previous analyses of such data have largely focused on the co-localization of SNPs associated with clinical and expression traits, each identified from genome-wide association studies and expression quantitative trait locus mapping. Thus, their description of the molecular mechanisms behind the SNPs influencing clinical phenotypes was limited to the single gene linked to the co-localized SNP. Here we introduce PerturbNet, a statistical framework for learning gene networks that modulate the influence of genetic variants on phenotypes, using genetic variants as naturally occurring perturbation of a biological system. PerturbNet uses a probabilistic graphical model to directly model the cascade of perturbation from genetic variants to the gene network to the phenotype network along with the networks at each layer of the biological system. PerturbNet learns the entire model by solving a single optimization problem with an efficient algorithm that can analyze human genome-wide data within a few hours. PerturbNet inference procedures extract a detailed description of how the gene network modulates the genetic effects on phenotypes. Using simulated and asthma data, we demonstrate that PerturbNet improves statistical power for detecting disease-linked SNPs and identifies gene networks and network modules mediating the SNP effects on traits, providing deeper insights into the underlying molecular mechanisms.


Asunto(s)
Redes Reguladoras de Genes/genética , Genómica/métodos , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Algoritmos , Genoma Humano/genética , Estudio de Asociación del Genoma Completo , Humanos , Aprendizaje Automático , Modelos Genéticos , Sitios de Carácter Cuantitativo
14.
Biochem Biophys Res Commun ; 521(1): 15-18, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31640857

RESUMEN

To investigate whether earthworm cellulases contribute to the innate immune system, the responsiveness of cellulase activity and mRNA expression to bacterial challenge was examined by zymography and RNA sequencing. A zymographic analysis revealed that the activity levels of earthworm cellulases were upregulated in response to either a bacterial (Bacillus subtilis or Escherichia coli) or LPS challenge. After the challenge, significant increases in cellulase 1 and cellulase 2 activity levels were observed within 8-16 and 16-24 h, respectively. In the coelomic fluid, both activities were significantly upregulated at 8 h post-injection with B. subtilis. Based on RNA sequencing, cellulase-related mRNAs encoding beta-1,4-endoglucanases were upregulated by 3-fold within 6 h after B. subtilis injection. Our results clearly demonstrated that earthworm cellulases are upregulated by bacterial challenge at the mRNA and protein levels. These results support the view that earthworm cellulases act as inducible humoral effectors of innate immunity against bacterial infection.


Asunto(s)
Bacillus subtilis/metabolismo , Celulasas/inmunología , Escherichia coli/metabolismo , Inmunidad Innata/inmunología , Oligoquetos/enzimología , ARN Mensajero/genética , Animales , Secuencia de Bases , Celulasas/metabolismo , Oligoquetos/metabolismo , Oligoquetos/microbiología , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN , Regulación hacia Arriba
15.
J Transl Med ; 18(1): 483, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33317573

RESUMEN

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting. METHODS: We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysis. RESULTS: We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3 + Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset. CONCLUSIONS: Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Células Supresoras de Origen Mieloide , Enfermedad Aguda , Animales , Enfermedad Injerto contra Huésped/terapia , Inmunidad , Ratones , Ratones Endogámicos C57BL , Linfocitos T Reguladores , Células Th17
16.
J Transl Med ; 18(1): 225, 2020 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-32505218

RESUMEN

BACKGROUND: Fibrosis is the formation of excess connective tissue in an organ or tissue during a reparative or reactive process. Graft-versus-host disease (GvHD) is a medical complication of allogeneic tissue transplantation with transplanted donor T cell-mediated inflammatory response; it is characterized by a severe immune response with fibrosis in the final stage of the inflammatory process. T helper 17 cells play a critical role in the pathogenesis of GvHD. Fingolimod (FTY720), an analogue of sphingosine-1-phosphate (S1P), is an effective immunosuppressive agent in experimental transplantation models. METHODS: In this study, we evaluated the effects of FTY720 as a treatment for an animal GvHD model with inflammation and fibrosis. The splenocytes, lymph nodes, blood, tissues from Syngeneic mice and GvHD-induced mice treated vehicle or FTY720 were compared using flow cytometry, hematological analyses, histologic analyses. RESULTS: FTY720 reduced clinical scores based on the following five clinical parameters: weight loss, posture, activity, fur texture, and skin integrity. FACS data showed that T lymphocyte numbers increased in mesenteric lymph nodes and decreased in splenocytes of FTY720-treated mice. Tissue analysis showed that FTY720 reduced skin, intestinal inflammation, and fibrotic markers. FTY720 dramatically decreased α-smooth muscle actin, connective tissue growth factor, and fibronectin protein levels in keloid skin fibroblasts. CONCLUSIONS: Thus, FTY720 suppressed migration of pathogenic T cells to target organs, reducing inflammation. FTY720 also inhibited fibrogenesis marker expression in vitro and in vivo. Together, these results suggest that FTY720 prevents GvHD progression via immunosuppression of TH17 and simultaneously acts an anti-fibrotic agent.


Asunto(s)
Clorhidrato de Fingolimod , Enfermedad Injerto contra Huésped , Animales , Fibrosis , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Inmunosupresores/farmacología , Ratones , Ratones Endogámicos C57BL , Glicoles de Propileno/farmacología
17.
J Theor Biol ; 496: 110249, 2020 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-32197958

RESUMEN

Human walking consists of two major sequential events (i.e., single- and double-support phases). Although there have been many studies relating to basic principles of the each stage, how the two distinct but continuous phases interact with each other remains to be clarified. We examined the change in walking strategy with varying walking speed on a local reference frame with telescoping and tangential axes; we expect that the telescoping directional dynamics at the end of a single-support phase change with walking speed to facilitate the modulation of the push-off work during a double-support phase. The telescoping directional force and power are calculated using two methods: model simulation and kinematic configuration. The empirical walking data for eight healthy young subjects and the corresponding model parameters obtained from a data-fit optimization were used to investigate the changing trend of each factor (i.e., force and power) with the increase in speed. The resulting force at the end of the single-support phase significantly increased with the walking speed for both methods, whereas the resulting power remained nearly unchanged and was close to zero for the entire range of walking speeds. This result implies that the positive amount of the telescoping directional force at the end of the single-support phase may be a certain type of preparation for the double-support phase, which can contribute to a larger push-off.


Asunto(s)
Marcha , Velocidad al Caminar , Fenómenos Biomecánicos , Humanos , Pierna , Caminata
18.
Proc Natl Acad Sci U S A ; 114(16): 4082-4086, 2017 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-28373575

RESUMEN

Graphene epitaxy on the Si face of a SiC wafer offers monolayer graphene with unique crystal orientation at the wafer-scale. However, due to carrier scattering near vicinal steps and excess bilayer stripes, the size of electrically uniform domains is limited to the width of the terraces extending up to a few microns. Nevertheless, the origin of carrier scattering at the SiC vicinal steps has not been clarified so far. A layer-resolved graphene transfer (LRGT) technique enables exfoliation of the epitaxial graphene formed on SiC wafers and transfer to flat Si wafers, which prepares crystallographically single-crystalline monolayer graphene. Because the LRGT flattens the deformed graphene at the terrace edges and permits an access to the graphene formed at the side wall of vicinal steps, components that affect the mobility of graphene formed near the vicinal steps of SiC could be individually investigated. Here, we reveal that the graphene formed at the side walls of step edges is pristine, and scattering near the steps is mainly attributed by the deformation of graphene at step edges of vicinalized SiC while partially from stripes of bilayer graphene. This study suggests that the two-step LRGT can prepare electrically single-domain graphene at the wafer-scale by removing the major possible sources of electrical degradation.

19.
J Transl Med ; 17(1): 84, 2019 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-30876479

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. METHODS: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). RESULTS: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. CONCLUSIONS: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.


Asunto(s)
Artritis Experimental/enzimología , Artritis Experimental/patología , Osteogénesis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/antagonistas & inhibidores , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Citocinas/metabolismo , Imidazoles/farmacología , Imidazoles/uso terapéutico , Indoles/farmacología , Indoles/uso terapéutico , Inflamación/patología , Mediadores de Inflamación/metabolismo , Masculino , Ratones Endogámicos DBA , Necrosis , Osteogénesis/efectos de los fármacos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Linfocitos T/efectos de los fármacos
20.
Opt Express ; 27(4): A206-A215, 2019 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-30876136

RESUMEN

Photoelectrochemical (PEC) water splitting is one of the most promising hydrogen production methods because of its high efficiency, renewable resources and harmless by-products. Gallium nitride (GaN) is suitable for PEC water splitting because it has excellent stability in electrolyte and band gap energy which straddles the redox potential of water (Vredox = 1.23 V). These characteristics allow this material to split water stably without external bias. However, the stability of GaN is still not sufficient for practical applications. In this study, we investigated the properties of GaN photoelectrodes with aluminum oxide (Al2O3) thin film as a protection layer for increasing stability. In a long-term stability test, Al2O3-coated GaN showed more stable photocurrent than that of bare GaN. The total hydrogen production amount was also improved in Al2O3-coated samples than bare GaN. These results indicate that the Al2O3 protection layer significantly enhances stability and hydrogen production.

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