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BACKGROUND: Stroke survivors face physical and cognitive challenges, leading to an increased dependency and a higher fall risk. We aimed to investigate the impact of poststroke disability and stroke type on fracture risk at various sites compared with matched controls. METHODS: This retrospective cohort study used data from the Korean National Health Insurance System database (2010-2018), including patients with stroke and 1:1 matched controls. Stroke survivors were grouped based on the presence and severity of their poststroke disability and stroke type. The primary outcome was a newly diagnosed fracture, analyzed by Cox proportional hazard regression analyses adjusting for potential confounders. RESULTS: Among 223â 358 stroke survivors (mean age, 64.8±10.9 years; 61.2% men), 16â 344 fractures occurred during a mean follow-up of 3.7±2.5 years. In matched controls (n=322â 161; mean age, 65.4±11.2 years; 61.3% men), 20â 398 fractures were identified. Stroke survivors had increased overall fracture risk compared with matched controls (adjusted hazard ratio [aHR], 1.40 [95% CI, 1.37-1.43]). Specifically, hip fracture risk was even greater in stroke survivors (incidence rate per 1000 person-years, 4.7 [95% CI, 4.5-4.8]; aHR, 2.42 [95% CI, 2.30-2.55]) than controls (incidence rate, 2.2 [95% CI, 2.1-2.3]). The risk of vertebral fractures (aHR, 1.29 [95% CI, 1.25-1.34]) and other fractures (aHR, 1.19 [95% CI, 1.15-1.23]) was also higher than that of the control group. Hip fracture risk was the highest among stroke survivors with severe poststroke disability (aHR, 4.82 [95% CI, 4.28-5.42]), although vertebral or other fracture risk was the highest among those with mild poststroke disability. No significant difference in fracture risk was found between hemorrhagic and ischemic stroke survivors when stratified by disability status. CONCLUSIONS: Our findings showed increased subsequent fracture risk among stroke survivors, particularly those with poststroke disability and for hip fracture. Bone health assessment and treatment should be emphasized as an essential part of stroke management.
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Accidente Cerebrovascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Estudios Retrospectivos , Sobrevivientes , República de Corea/epidemiología , Factores de Riesgo , Personas con Discapacidad , Fracturas Óseas/epidemiología , Fracturas Óseas/complicaciones , Fracturas de Cadera/epidemiología , Fracturas de Cadera/complicacionesRESUMEN
BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.
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Ansiedad , Depresión , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/epidemiología , República de Corea/epidemiología , Masculino , Femenino , Adulto , Esclerosis Múltiple/epidemiología , Persona de Mediana Edad , Ansiedad/epidemiología , Depresión/epidemiología , Estudios de Cohortes , Adulto Joven , Factores de RiesgoRESUMEN
INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1,492 patients with MS and 1,551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95% CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction = 0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with type 2 diabetes and a developing several cancers including esophageal cancer (EC). However, the association between MASLD and EC in diabetic patients has not been investigated. Therefore, we aimed to investigate the relation between MASLD and developing EC in diabetic patients. This was a population-based retrospective cohort study of data from the Korean National Health Insurance Service (NHIS). A total of 1,904,468 subjects diagnosed with diabetes who underwent NHIS-provided health checkups from 2009 to 2012 were included. We constructed a Cox proportional hazard model for the association of fatty liver index (FLI) and the risk of EC stratified by potential confounders. Over a mean follow-up duration of 6.9 years, the incidence of EC was higher in the high (≥60) FLI group compared to the low (<30) FLI group (14.4 vs. 13.7 event per 100,000 person-years). The risk of EC correlated with the degree of FLI, particularly in older (P = 0.002), female (P = 0.033), non-smoking (P = 0.002), and non-drinking patients (P = 0.025). Among obese patients, the risk of EC was not associated with FLI; however, the risk of EC was higher in the high FLI group in non-obese patients. Lean MASLD patients had the highest risk of EC (adjusted hazard ratio 1.78; 95% confidence interval, 1.5-2.13). MASLD was associated with an increased risk of EC in diabetic patients, and lean MASLD has the highest risk. Further studies are required to determine the causal relationship between MASLD and EC.
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Diabetes Mellitus Tipo 2 , Neoplasias Esofágicas , Modelos de Riesgos Proporcionales , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/etiología , Estudios Retrospectivos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , República de Corea/epidemiología , Factores de Riesgo , Incidencia , Adulto , Anciano , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Hígado Graso/etiologíaRESUMEN
BACKGROUND: This study aims to improve nursing students' ability to care for critically ill patients through education in extracorporeal membrane oxygenation (ECMO) nursing. METHODS: This study developed a virtual reality (VR) simulation program for the five-step ECMO nursing of the Analysis, Design, Development, Implement, and Evaluation (ADDIE) model and used an equivalent control group pre-test and post-test no-synchronized design to verify the effect. The participants of this study were fourth-year nursing students enrolled in nursing departments at three universities in Seoul, Gangwon, and Gyeonggi in South Korea; it included 66 participants, 33 in each of the experimental and control groups. The program consisted of pre-training, orientation, VR simulation, and debriefing. RESULTS: The interaction effect of the intervention and control groups with time points using the ECMO nursing VR simulation program was rejected due to no statistically significant difference in knowledge (F = 1.41, p = .251), confidence (F = 1.97, p = .144), and clinical reasoning capacity (F = 2.85, p = .061). However, learning immersion (t = 3.97, p < .001) and learning satisfaction (t = 4.25, p < .001) were statistically significantly higher in the experimental group than in the control group. CONCLUSION: VR simulation program for ECMO nursing developed in this study is a potential educational method that positively affects the learning immersion and learning satisfaction of nursing students.
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Bachillerato en Enfermería , Educación en Enfermería , Oxigenación por Membrana Extracorpórea , Estudiantes de Enfermería , Realidad Virtual , Humanos , Bachillerato en Enfermería/métodos , AprendizajeRESUMEN
BACKGROUND: We aimed to examine the association between smoking behavior change and risk of cardiovascular disease (CVD) incidence and mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: This study used nationwide data from the Korean National Health Insurance System and included 349,137 T2DM patients who smoked. Smoking behavior changes were defined with five groups: quitters, reducers I (≥ 50% reduction), reducers II (20-50% reduction), sustainers (± 20%), and increasers (≥ 20% increase) from the number of cigarettes/day at the baseline. RESULTS: During a median follow-up of 5.1 years, 6,514 cases of myocardial infarction (MI) (1.9%), 7,837 cases of ischemic stroke (IS) (2.2%), and 14,932 deaths (4.3%) were identified. Quitters had a significantly decreased risk of MI (adjusted hazard ratio [aHR] 0.80, 95% CI 0.75-0.86) and IS (aHR 0.80, 95% CI 0.75-0.85) compared to sustainers, whereas reducers did not have a significant association with the risk of MI (aHR 1.03, 95% CI 0.94-1.13) and IS (aHR 1.00, 95% CI 0.92-1.08) in reducer I. Quitters also had a lower all-cause and CVD mortality than sustainers. CONCLUSIONS: Smoking cessation was associated with decreased CVD incidence, and all-cause and CVD mortality among T2DM patients. However, smoking reduction was not associated with decreased risks for these.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Humanos , Incidencia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Fumar/efectos adversos , Fumar/epidemiología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiologíaRESUMEN
An electrochemical immunoassay based on the redox cycling method was presented using vertically paired electrodes (VPEs), which were fabricated using poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as an electrode material and parylene-C as a dielectric layer. For the application to immunoassays, different electrochemical properties of PEDOT:PSS were analyzed for the redox reaction of 3,3',5,5'-tetramethylbenzidine (TMB, the chromogenic substrate for enzyme-immunoassays) at different pH conditions, including the conductivity (σ), electron transfer rate constant (kapp), and double-layer capacitance (Cdl). The influencing factors on the sensitivity of redox cycling based on VPE based on PEDOT:PSS were analyzed for the redox reaction of TMB, such as the electrode gap and number of electrode pairs. Computer simulation was also performed for the redox cycling results based on VPEs, which had limitations in fabrication, such as VPEs with an electrode gap of less than 100 nm and more than five electrode pairs. Finally, the redox cycling based on VPE was applied to the medical diagnosis of human hepatitis-C virus (hHCV) using a commercial ELISA kit. The sensitivity of the redox cycling method for the medical diagnosis of hHCV was compared with conventional assay methods, such as TMB-based chromogenic detection, luminol-based chemiluminescence assay, and a rapid test kit (lateral flow immunoassay).
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Simulación por Computador , Humanos , Electrodos , Oxidación-Reducción , Inmunoensayo , Técnicas para InmunoenzimasRESUMEN
The assembly of metal nanoparticles and targets to be detected in a small light probe volume is essential for achieving sensitive in-solution surface-enhanced Raman spectroscopy (SERS). Such assemblies generally require either chemical linkers or templates to overcome the random diffusion of the colloids unless the aqueous sample is dried. Here, a facile method is reported to produce 3D multiscale assemblies of various colloids ranging from molecules and nanoparticles to microparticles for sensitive in-solution SERS detection without chemical linkers and templates by exploiting photothermally driven convective flow. The simulations suggest that colloids sub 100 nm in diameter can be assembled by photothermally driven convective flow regardless of density; the assembly of larger colloids up to several micrometers by convective flow is significant only if their density is close to that of water. Consistent with the simulation results, the authors confirm that the photothermally driven convective flow is mainly responsible for the observed coassembly of plasmonic gold nanorods with either smaller molecules or larger microparticles. It is further found that the coassembly with the plasmonic nanoantennae leads to dramatic Raman enhancements of molecules, microplastics, and microbes by up to fivefold of magnitude compared to those measured in solution without the coassembly.
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Nanopartículas del Metal , Plásticos , Coloides/química , Oro/química , Nanopartículas del Metal/química , Espectrometría Raman/métodosRESUMEN
In this study, parylene-C films from plasma deposition as well as thermal deposition were pyrolyzed to prepare a carbon electrode for application in electrochemical immunoassays. Plasma deposition could prepare parylene-C in a faster deposition rate and more precise control over the thickness in comparison with the conventional thermal deposition. To analyze the influence of the deposition method, the crystal and electronic structures of the pyrolyzed parylene-C films obtained via both deposition methods were compared using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. For application as a carbon electrode in immunoassays, the electrochemical properties of the pyrolyzed carbon films from two both deposition methods were analyzed, including the double layer capacitance (2.10 µF cm-2 for plasma deposition and 2.20 µF cm-2 for thermal deposition), the apparent electron transfer rate (approximately 1.1 × 10-3 cm s-1 for both methods), and the electrochemical window (approximately -1.0 â¼ 2.1 V for both methods). Finally, the applicability of the pyrolyzed carbon electrode from parylene-C was demonstrated for the diagnosis of human hepatitis-C using various amperometric methods, such as cyclic voltammetry, chronoamperometry, square-wave voltammetry and differential pulse voltammetry.
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Carbono , Pirólisis , Carbono/química , Electrodos , Humanos , Inmunoensayo , Polímeros , XilenosRESUMEN
A one-step immunoassay was developed for five types of food-poisoning-related bacteria using a switching peptide and antibodies isolated from unimmunized horse serum. The one-step immunoassay involves mixing samples and reagents in a homogeneous solution without any washing steps. In this work, a one-step immunoassay configuration was developed using isolated antibodies labelled with an organic fluorescence quencher and a switching-peptide labelled with a fluorescent dye. The fluorescence-labelled switching-peptide was bound to the antigen-binding site of the isolated antibodies before binding to the bacteria (no fluorescence signal), and the switching-peptide dissociated from the antibodies as soon as they bound to the bacteria (fluorescence signal turns on). By quantifying the generated fluorescence signal, the one-step immunoassay presented here allows microbial detection without any washing step.
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Anticuerpos , Transferencia Resonante de Energía de Fluorescencia , Inmunoensayo , Anticuerpos/química , Péptidos/química , BacteriasRESUMEN
Owing to their unique properties and biological activities, ionic liquids (ILs) have attracted research interest in pharmaceutics and medicine. Hypoxia-inducible factor (HIF)- 1α is an attractive cancer drug target involved in cancer malignancy in the hypoxic tumor microenvironment. Herein, we report the inhibitory activity of ILs on the HIF-1α pathway and their mechanism of action. Substitution of a dimethylamino group on pyridinium reduced hypoxia-induced HIF-1α activation. It selectively inhibited the viability of the human colon cancer cell line HCT116, compared to that of the normal fibroblast cell line WI-38. These activities were enhanced by increasing the alkyl chain length in the pyridinium. Under hypoxic conditions, dimethylaminopyridinium reduced the accumulation of HIF-1α and its target genes without affecting the HIF1A mRNA level in cancer cells. It suppressed the oxygen consumption rate and ATP production by directly inhibiting electron transfer chain complex I, which led to enhanced intracellular oxygen content and oxygen-dependent degradation of HIF-1α under hypoxia. These results indicate that dimethylaminopyridinium suppresses the mitochondria and HIF-1α-dependent glucose metabolic pathway in hypoxic cancer cells. This study provides insights into the anticancer activity of pyridinium-based ILs through the regulation of cancer metabolism, making them promising candidates for cancer treatment.
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Neoplasias del Colon , Líquidos Iónicos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Líquidos Iónicos/toxicidad , Hipoxia , Oxígeno , Microambiente TumoralRESUMEN
BACKGROUND: Education and training are needed for nursing students using artificial intelligence-based educational programs. However, few studies have assessed the effect of using chatbots in nursing education. OBJECTIVES: This study aimed to develop and examine the effect of an artificial intelligence chatbot educational program for promoting nursing skills related to electronic fetal monitoring in nursing college students during non-face-to-face classes during the COVID-19 pandemic. DESIGN: This quasi-experimental study used a nonequivalent control group non-synchronized pretest-posttest design. METHODS: The participants were 61 junior students from a nursing college located in G province of South Korea. Data were collected between November 3 and 16, 2021, and analyzed using independent t-tests. RESULTS: The experimental group-in which the artificial intelligence chatbot program was applied-did not show statistically significant differences in knowledge (t = -0.58, p = .567), clinical reasoning competency (t = 0.75, p = .455), confidence (t = 1.13, p = .264), and feedback satisfaction (t = 1.72, p = .090), compared with the control group; however, its participants' interest in education (t = 2.38, p = .020) and self-directed learning (t = 2.72, p = .006) were significantly higher than those in the control group. CONCLUSION: The findings of our study highlighted the potential of artificial intelligence chatbot programs as an educational assistance tool to promote nursing college students' interest in education and self-directed learning. Moreover, such programs can be effective in enhancing nursing students' skills in non-face-to face-situations caused by the ongoing COVID-19 pandemic.
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COVID-19 , Estudiantes de Enfermería , Humanos , Inteligencia Artificial , COVID-19/epidemiología , Pandemias , AprendizajeRESUMEN
Dynamics of release and cellular uptake of aqueous CO from CO-releasing molecules (CORMs) significantly affect signaling and cell viability. So far, it has been mainly observed by IR, UV-visible, and fluorescence techniques, which suffer from poor sensitivity and slow response time. Here, we show how to directly probe the mass transfer of aqueous CO from CORMs to cells using a fluidic chamber integrated with live cells and Raman reporters of large-area Au@Pd core-shell nanoparticle assembly to emulate a physiologically relevant microenvironment. We sensitively and directly detect CO release from trace CORMs of as low as 100 nM by measuring the Raman transitions of CO via rapid chemisorption onto the surface of the Au@Pd nanoparticles. By using our method, we successfully observe the dynamics of CO release from CORM-2 despite its very short half-life. We also reveal that the initial rate of CO release from CORM-3 is dramatically decreased by tens to hundreds of times when exposed to physiologically relevant pH variations from 7.4 to 2.5, which can be attributed to the acid hydrolysis of the CO ligand. CORM-2 tends to quickly release CO regardless of pH, probably because of its rapid cleavage into two monomeric Ru complexes by the co-solvent. The decrease in the initial rate at lower temperatures is more significant for CORM-3 than for CORM-2. Finally, we observe that the cellular uptake of aqueous CO from CORM-3 by lung cancer cells is approximately 2 times higher than that of normal lung cells.
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Monóxido de Carbono , Compuestos Organometálicos , Transporte Biológico , Supervivencia Celular , Humanos , AguaRESUMEN
Oral squamous cell carcinoma (OSCC) frequently invades nearby bone and bone involvement determines the prognosis of patients. Growth factors, stored in the bone matrix and released during bone destruction, are known as key components in the bone-tumor interaction. However, the coordination of growth factor signals and the precise mechanism of bone destruction in oral cancer are still unclear. In the study, we investigated the differential cytokine expression profile of oral cancer cells by TGF-ß treatment and the function of altered expression of cytokines on the osteoclast differentiation. We established TGFBR2-knockdown cells using small hairpin RNA. TGF-ß was treated to both TGFBR2 expressing and knockdown cells and the culture supernatants were analyzed using a cytokine array kit. We found that the TGF-ß inhibited IGFBP3 level and enhanced MMP9 level. We confirmed this regulation of IGFBP3 and MMP9 by TGF-ß using ELISA and zymography, respectively. IGFBP3 is known as to modulate the bioavailability of IGF1, which is abundant in the bone microenvironment and regulates osteoclast differentiation. Therefore, we further analyzed the function of IGFBP3 on osteoclastogenesis. Although IGFBP3 increased the viability of murine bone marrow macrophages, the osteoclast differentiation of these cells was blocked by IGFBP3 in a dose-dependent manner. These results revealed a novel pathway for the regulation of osteoclastogenesis by oral cancer cells, which may be a new therapeutic target for osteolysis induced by oral cancer infiltrating into the bone.
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Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Osteoclastos/metabolismo , Osteoclastos/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Línea Celular Tumoral , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos ICR , Neoplasias de la Boca/genética , Osteogénesis/genética , Osteogénesis/fisiología , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
Patients with oral squamous cell carcinoma (OSCC) bone invasion are surgically treated with bone resection, which results in severe physical and psychological damage. Here, we investigated the potential of fractalkine (CX3CL1), which is regulated by transforming growth factor (TGF-ß), as a novel biomarker for correct prediction and early detection of OSCC-associated bone invasion. TGF-ß knockdown and treatment with a TGF-ß-neutralizing antibody decreased the level of fractalkine in the culture media of HSC-2 and YD10B OSCC cells. Treatment with a fractalkine-neutralizing antibody reduced TGF-ß-stimulated invasion by HSC-2 and YD10B cells. Fractalkine treatment increased the viability, invasion, and uPA secretion of both OSCC cell lines. Furthermore, OSCC cell bone invasion was assessed following subcutaneous inoculation of wild-type or TGF-ß knockdown OSCC cells in mouse calvaria. TGF-ß knockdown prevented erosive bone invasion, reduced the number of osteoclasts at the tumor-bone interface, and downregulated fractalkine expression in mouse tumor tissues. Our results indicate that the production of fractalkine is stimulated by TGF-ß and mediates TGF-ß-induced cell invasion in several OSCC cell lines showing an erosive pattern of bone invasion. Fractalkine may be a useful predictive marker and therapeutic target for OSCC-induced bone destruction.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Biomarcadores , Línea Celular Tumoral , Quimiocina CX3CL1 , Humanos , Ratones , Invasividad Neoplásica , Carcinoma de Células Escamosas de Cabeza y Cuello , Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta1RESUMEN
The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1ß production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.
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MicroARNs , Daño por Reperfusión Miocárdica , Piroptosis , Trasplante de Células Madre , Células Madre , Animales , Humanos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , MicroARNs/genética , MicroARNs/farmacología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/terapia , Piroptosis/efectos de los fármacos , Piroptosis/genética , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Células Madre/metabolismo , Células Madre/patologíaRESUMEN
BACKGROUND/AIMS: Bone metastasis of cancer cells decreases patient survival and quality of life. Hybridization via the covalent coupling of two bioactive natural products is a useful strategy for developing more potent anticancer agents by enhancing their bioavailability and avoiding drug resistance. METHODS: The in vivo activities of artemisinin-daumone hybrid 15 (ARTD) were estimated in cancer cell-inoculated mice and ovariectomized mice. The viability, migration, and invasion of cancer cells were measured via MTT, wound-healing, and transwell invasion assays. ARTD-regulated transcription factors were detected with an RT2 profiler PCR array kit and Western blotting. Osteoclastogenesis and osteoclast activity were detected with tartrate-resistant acid phosphatase staining, a pit formation assay, gelatin zymography, and a cathepsin K ELISA assay. RESULTS: ARTD blocked cancer-associated osteolysis more potently than artemisinin in mice with intratibially inoculated breast cancer or lung cancer cells. ARTD inhibited the viability, migration, and invasion of breast and lung cancer cells in the absence or presence of transforming growth factor-ß1. ARTD treatment induced the expression of tumor suppressive activating transcription factor 3 and inhibited oncogenic E2F transcription factor 1 expression at the mRNA and protein levels. ARTD inhibited receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and bone resorbing activity by reducing the secreted levels of matrix metalloproteinase-9 and cathepsin K. Furthermore, ARTD prevented estrogen deficiency-induced bone loss in ovariectomized mice. CONCLUSION: ARTD may be a promising candidate for inhibiting cancer-induced bone destruction. The application of ARTD may be extended to patients with chemotherapy-induced ovarian failure or postmenopausal osteoporosis.
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Artemisininas/química , Conservadores de la Densidad Ósea/uso terapéutico , Ácidos Grasos/química , Osteólisis/prevención & control , Feromonas/química , Animales , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Huesos/diagnóstico por imagen , Huesos/patología , Catepsina K/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteólisis/etiología , Factor de Transcripción STAT3/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
Conventional optical components have been proposed to realize high-quality line focusing with uniform intensity distribution such as cylindrical lenses, segmented wedge-arrays, or a combination of prisms and spherical mirrors. Numerous factors such as the manufacturing tolerances or the need for precise alignment of conventional lenses cause wave front aberrations that impact the performance of optical systems. These aforementioned limitations affect the uniformity of the intensity distribution and the intercept factor of lenses. Here, we experimentally demonstrate an integrable planar dielectric cylindrical lens made of titanium dioxide for uniform line focusing and discuss the sensitivity of its performance to fabrication imperfections originating from non-ideal geometrical parameters. The lens has a numerical aperture of 0.247, an intercept factor of 0.85, and an efficiency of 79% at 800 nm.
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OBJECTIVE: Lymph node involvement is an important prognostic factor in patients with cervical cancer. However, the prognostic significance of lymph node response to chemoradiotherapy remains unclear. We retrospectively analyzed the relationship between residual lymph node status after definitive chemoradiotherapy and survival. METHODS: We enrolled 117 patients with node-positive cervical cancer. All patients were treated with definitive chemoradiotherapy in our institution, from 2006 to 2016. The median follow-up period was 41months (range, 6-128months). The criterion for a positive lymph node was defined as a maximum short axis diameter of ≥8mm on pretreatment magnetic resonance imaging (MRI)/computed tomography (CT) scans. Posttreatment pelvic MRI was obtained 3months after the completion of chemoradiotherapy. Residual primary tumor was defined as any residual lesion identified upon clinical examination and/or MRI. Residual lymph node was defined as any lymph node with a short axis diameter of ≥8mm posttreatment, according to MRI/CT. RESULTS: At follow-up, 3months after chemoradiotherapy, we observed residual primary tumor in 30 patients (25.6%), and residual lymph node in 31 patients (26.5%). The presence of residual lymph node was associated with worse overall survival according to multivariate analysis (hazard ratio, 3.04; 95% confidence interval, 1.43-6.44; p=0.004). In the 5-year time-dependent ROC analysis of survival prediction, the presence of residual lymph node showed an AUC value of 0.72. CONCLUSIONS: The presence of residual lymph node after chemoradiotherapy was associated with worse survival in patients with node-positive cervical cancer.
Asunto(s)
Adenocarcinoma/terapia , Carcinoma Adenoescamoso/terapia , Carcinoma de Células Escamosas/terapia , Ganglios Linfáticos/patología , Neoplasias del Cuello Uterino/terapia , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Adenoescamoso/diagnóstico por imagen , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Quimioradioterapia , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Pelvis , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
Plasmonic/metamaterial sensors are being investigated for their high sensitivity, fast response time, and high accuracy. We propose, characterize and experimentally realize subwavelength bilayer metamaterial sensors operating in the near-infrared domain. We measure the figure-of-merit (FOM) and the bulk sensitivity (S) of the two fundamental hybridized modes and demonstrate both numerically and experimentally that the magnetic dipolar mode, degenerate with the electric quadrupolar mode, has higher sensitivity to a variation of the refractive index compared to the electric dipolar mode. In addition, the hybridized system exhibits a four fold increase in the FOM compared to a standard dipolar plasmonic system.