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Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.
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Biomarcadores de Tumor/metabolismo , Vesículas Extracelulares/metabolismo , Leucemia Mieloide Aguda/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/genética , Antígenos CD/metabolismo , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Quinasas/metabolismo , Proteómica , Adulto JovenRESUMEN
Pluripotent stem cells (PSCs) can serve as an unlimited cell source for transplantation therapies for treating various devastating diseases, such as cardiovascular diseases, diabetes, and Parkinson's disease. However, PSC transplantation has some associated risks, including teratoma formation from the remaining undifferentiated PSCs. Thus, for successful clinical application, it is essential to ablate the proliferative PSCs before or after transplantation. In this study, neural stem cell-derived conditioned medium (NSC-CM) inhibited the proliferation of PSCs and PSC-derived neural precursor (NP) cells without influencing the potential of PSC-NP cells to differentiate into neurons in vitro and prevented teratoma growth in vivo. Moreover, we found that the NSC-CM remarkably decreased the expression levels of Oct4 and cyclin D1 that Oct4 directly binds to and increased the cleaved-caspase 3-positive cell death through the DNA damage response in PSCs and PSC-NPs. Interestingly, we found that NSCs distinctly secreted the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 proteins. These proteins suppressed not only the proliferation of PSCs in cell culture but also teratoma growth in mice transplanted with PSCs through inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 activity. Taken together, these results suggest that the TIMP proteins may improve the efficacy and safety of the PSC-based transplantation therapy.
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Células Madre Pluripotentes/metabolismo , Teratoma/terapia , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Animales , Humanos , Masculino , Ratones , Ratones Desnudos , Teratoma/patologíaRESUMEN
Owing to the role of exosome as a cargo for intercellular communication, especially in cancer metastasis, the evidence has been consistently accumulated that exosomes can be used as a noninvasive indicator of cancer. Consequently, several studies applying exosome have been proposed for cancer diagnostic methods such as ELISA assay. However, it has been still challenging to get reliable results due to the requirement of a labeling process and high concentration of exosome. Here, we demonstrate a label-free and highly sensitive classification method of exosome by combining surface-enhanced Raman scattering (SERS) and statistical pattern analysis. Unlike the conventional method to read different peak positions and amplitudes of a spectrum, whole SERS spectra of exosomes were analyzed by principal component analysis (PCA). By employing this pattern analysis, lung cancer cell derived exosomes were clearly distinguished from normal cell derived exosomes by 95.3% sensitivity and 97.3% specificity. Moreover, by analyzing the PCA result, we could suggest that this difference was induced by 11 different points in SERS signals from lung cancer cell derived exosomes. This result paved the way for new real-time diagnosis and classification of lung cancer by using exosome as a cancer marker.
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Biomarcadores de Tumor/análisis , Exosomas/química , Neoplasias Pulmonares/diagnóstico , Exosomas/patología , Humanos , Análisis de Componente Principal , Espectrometría Raman , Propiedades de SuperficieRESUMEN
Somatic cells were directly converted to functional neurons through the use of a combination of transcription factors, including Ascl1, Brn2, and Myt1l. However, a major limitation is the lack of a reliable source of cell-replacement therapy for neurological diseases. Here, we show that a combination of the transcription factors Ascl1 and Nurr1 (AN) and neurotrophic factors including SHH and FGF8b directly reprogrammed embryonic mouse fibroblasts to induced neuronal (iN) cells: pan-neuronal cells and dopaminergic (DA) neurons under our systematic cell culture conditions. Reprogrammed cells showed the morphological properties of neuronal cells. Additionally, cells were analyzed using various markers, including Tuj1 and Map2 for neuronal cells and Lmx1a, Th, Aadc and Vmat2 for DA neurons in our immunostaining and reverse transcription (RT)-PCR experiments. We found that a combination of transcription factors and neurotrophic factors could directly reprogram fibroblasts to neuronal cells including DA neurons. Various types of reprogrammed cells are promising cell sources for cell-based therapy of neurological disorders like Parkinson's disease and spinal cord injury.
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Reprogramación Celular/fisiología , Neuronas Dopaminérgicas/fisiología , Fibroblastos/fisiología , Células-Madre Neurales/fisiología , Animales , Humanos , Ratones , Ratones Endogámicos BALB C , Neuronas/fisiología , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/fisiologíaRESUMEN
BACKGROUND: Adolescence is a critical period for establishing healthy eating habits and weight management, essential for preventing obesity and promoting overall health. This study investigates the impact of mukbang and cookbang-popular online broadcasts in Korea that feature excessive consumption of food-on the dietary habits and body image perception of Korean adolescents. With digital media, especially platforms like YouTube, becoming an integral part of daily life, these broadcasts have the potential to significantly influence adolescent health behaviors. METHODS: Employing data from the 18th Korea Youth Risk Behavior Web-based Survey (2022), this descriptive survey research explores the relationship between watching mukbang and cookbang and various health-related factors among adolescents. The survey's comprehensive dataset provided a unique opportunity to examine this association in a population that is increasingly exposed to digital media content. The analysis focused on the frequency of watching mukbang and cookbang, their impact on eating habits, body mass index (BMI), body shape perception, and body image distortion among adolescents. RESULTS: The results revealed a significant engagement with mukbang and cookbang among adolescents, with notable gender differences in viewing habits and effects. Increased frequency of viewing was associated with negative impacts on eating habits and body image perception. Furthermore, psychological factors such as stress levels and sleep quality emerged as significant predictors of the frequency of watching these broadcasts. CONCLUSIONS: This study highlights the need for further investigation into the causal relationships between mukbang and cookbang viewership and adolescent health outcomes. The findings suggest the importance of developing targeted interventions to mitigate the negative influences of such content on adolescents' eating habits and body perceptions. Given the widespread popularity of these broadcasts, it is crucial to address their potential health implications through public health strategies, educational content, and policy development aimed at promoting healthier lifestyles among adolescents.
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Imagen Corporal , Índice de Masa Corporal , Conducta Alimentaria , Humanos , Adolescente , Femenino , Masculino , Imagen Corporal/psicología , República de Corea , Conducta Alimentaria/psicología , Conducta del Adolescente/psicología , Encuestas y Cuestionarios , Conductas Relacionadas con la Salud , Medios de Comunicación Sociales , TelevisiónRESUMEN
PURPOSE: This study aimed to investigate the influence of uncertainty-related factors on the health behavior of individuals with coronary artery disease (CAD) based on Mishel's uncertainty in illness theory (UIT). METHODS: We conducted a cross-sectional study and path analysis to investigate uncertainty and factors related to health behavior. The study participants were 228 CAD patients who visited the outpatient cardiology department between September 2020 and June 2021. We used SPSS 25.0 and AMOS 25.0 software to analyze the data. RESULTS: The final model demonstrated a good fit with the data. Eleven of the twelve paths were significant. Uncertainty positively affected danger and negatively affected self-efficacy and opportunity. Danger had a positive effect on perceived risk. Opportunity positively affected social support, self-efficacy, perceived benefit and intention, whereas it negatively affected perceived risk. Social support, self-efficacy, perceived benefit and intention had a positive effect on health behavior. We found that perceived benefit and intention had the most significant direct effects, whereas self-efficacy indirectly affected the relationship between uncertainty and health behavior. CONCLUSION: The path model is suitable for predicting the health behavior of CAD patients who experience uncertainty. When patients experience uncertainty, interventions to increase their self-efficacy are required first. Additionally, we need to develop programs that quickly shift to appraisal uncertainty as an opportunity, increase perceived benefits of health behavior, and improve intentions.
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Enfermedad de la Arteria Coronaria , Conductas Relacionadas con la Salud , Autoeficacia , Apoyo Social , Humanos , Incertidumbre , Masculino , Femenino , Enfermedad de la Arteria Coronaria/psicología , Enfermedad de la Arteria Coronaria/patología , Persona de Mediana Edad , Estudios Transversales , Anciano , Encuestas y Cuestionarios , Intención , AdultoRESUMEN
This research examines the low rate of co-administration of influenza and COVID-19 vaccines among seniors aged 65 and older in Korea, despite recommendations from authorities and academia worldwide. The study aimed to understand the influence of general characteristics and health beliefs on the vaccination choices of seniors, who were categorized into four groups based on their vaccination status: influenza only, COVID-19 only, both, or neither. A total of 400 participants, aged 65 and above, were selected through proportional stratified random sampling from five major Korean regions for a survey conducted between November 24th and December 15th, 2023. The results indicated no significant differences in general characteristics across these groups. However, regarding the health beliefs showed significant differences in perceived susceptibility and self-efficacy between the influenza-only and co-administration groups. Higher levels of perceived susceptibility and self-efficacy were associated with choosing co-administration. Contrary to previous studies focusing on safety concerns as a primary factor in vaccine hesitancy, this study highlights the role of individual health-related beliefs, particularly perceived susceptibility and self-efficacy, as critical in influencing the decision for co-administration among the elderly in Korea.
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Vacunas contra la COVID-19 , COVID-19 , Vacunas contra la Influenza , Gripe Humana , Humanos , Anciano , Vacunas contra la Influenza/administración & dosificación , Masculino , Femenino , Gripe Humana/prevención & control , República de Corea , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Anciano de 80 o más Años , Vacunación/psicología , Vacunación/estadística & datos numéricos , Vacilación a la Vacunación/estadística & datos numéricos , Vacilación a la Vacunación/psicología , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Autoeficacia , SARS-CoV-2/inmunología , Toma de DecisionesRESUMEN
Rheumatic diseases are known to be associated with the development of metabolic syndrome, which increases mortality rates due to cardiovascular complications. Although a variety of self-management programs for rheumatic diseases have been developed, few have concentrated on metabolic syndrome. This study aimed to develop and verify a blended (a mixture of telephone and online interventions) metabolic syndrome self-management program. The program was developed in four stages: analysis to identify program contents, website design, website development, and validity testing. A quasi-experimental nonequivalent control group, pretest-posttest design was adopted to verify the program effectiveness in 54 patients with rheumatic disease. The program was initially implemented via telephone for 4 weeks and then self-administered via a web-based platform for 20 weeks. Indices of metabolic syndrome and self-management and quality of life scores were measured as outcome variables. Data were collected three times: before intervention, after 4 weeks of telephone interventions, and after 20 weeks of online self-interventions. The devised program had a significant overall effect on metabolic syndrome indices, metabolic syndrome-related self-management behaviors, and quality of life. Detailed analysis showed the program effectively reduced body mass index, waist circumference, systolic blood pressure, and blood glucose levels and improved metabolic syndrome self-management behaviors. Based on our findings, it can be expected that the use of this program may retard or prevent the progression of metabolic syndrome by improving some metabolic syndrome indices and metabolic syndrome-related self-management behaviors, which are key components of care in rheumatic disease patients with metabolic syndrome. This web-based program appears to be beneficial in public health care settings because it is cost-effective, readily available, and may provide long-term support.
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AIMS AND OBJECTIVES: To identify cancer-related symptom clusters, to explore their inter-relationships and to examine the effects of single symptoms and the synergistic effects of symptom clusters on functional performance using path analysis by structural equation modelling in patients with various types of cancer. BACKGROUND: Recent studies suggest that cancer patients frequently experience three or more concurrent related symptoms and that this clustering of symptoms is likely to have negative synergistic impacts on outcomes, because of the complicated dynamics of clusters. DESIGN: A cross-sectional design. METHODS: One hundred and ten patients with various types of cancer were recruited as in- and out-patients at a University Hospital in Incheon, South Korea. Data collection was performed using a questionnaire and by direct interview. Pain, insomnia, fatigue, depression and functional performance were measured. RESULTS: The developed model was composed of antecedents, symptom clusters and outcomes. Of the symptoms often encountered as clusters in cancer patients, insomnia, depression and fatigue were found to have significant single (direct) effects on functional performance. Seven symptom clusters were identified between pain and functional performance, three between insomnia and functional performance and one between depression and functional performance. These single symptoms and symptom clusters were found to have significant synergistic effects on functional performance and to explain 24% of functional performance variance. CONCLUSIONS: Multiple cancer-related symptom clusters may occur and the dynamics within symptom clusters is complicated. Our findings provide sound evidence regarding the importance of assessing and managing clusters of symptoms simultaneously rather than focusing on single symptoms. RELEVANCE TO CLINICAL PRACTICE: A comprehensive understanding of symptom clusters in cancer patients would help establish valid diagnostic symptom cluster entities and aid the development of subjective/objective phenotypic criteria for symptom cluster based diagnoses and of nursing care protocols for managing symptom clusters.
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Neoplasias/epidemiología , Adulto , Anciano , Análisis por Conglomerados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Neoplasias/patología , República de Corea/epidemiologíaRESUMEN
Depression may have a negative impact on health behaviors during crisis situations, such as the COVID-19 pandemic. Accordingly, the present study aimed to investigate the effects of depression felt by nursing students on their infectious disease response. A total of 241 nursing students from two nursing colleges in Chungcheong Province was convenience sampled between 2 and 12 December 2020. The tools used in the study were the Patient Health Questionnaire-9 Korean version, Fear of COVID-19 Scale, COVID-19-related risk perceptions, and COVID-19 behavior changes. The depression group showed higher fear scores and lower behavioral change scores than the non-depression group. Such findings indicated that the depression group did not actively perform COVID-19-related preventive behaviors. With respect to the influencing factors of depression, depression scores were 2.28 times higher among sophomores than seniors; fear scores were 1.09 times higher in the depression group than the non-depression group; and behavioral change scores were 0.87 times lower in the depression group than the non-depression group. Based on the findings in the present study, it is necessary to screen nursing students with depression during disaster crisis situations, such as the COVID-19 pandemic, and provide active psychological support to such students for their mental health care.
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COVID-19 , Estudiantes de Enfermería , Ansiedad/epidemiología , COVID-19/epidemiología , Estudios Transversales , Depresión/epidemiología , Miedo/psicología , Humanos , Pandemias , SARS-CoV-2 , Estudiantes de Enfermería/psicologíaRESUMEN
This study investigated the long-term effects of an aging suit experience on the attitudes and behaviors of nursing college students toward the elderly. The aging suit experience was an activity in which participants indirectly experienced aging by performing various activities while wearing a specially designed experience suit, and 65 nursing department sophomores were selected in this study; they responded to structured questionnaires regarding their attitude and behavior toward the elderly at five time points-before the program, immediately after the program, after sharing about the experience with others, one month following the program's completion, and three months following the program's conclusion. Their attitude toward the elderly changed negatively immediately after the experience, followed by a more positive attitude after sharing about the experience with others that was maintained afterward. Subjects' behavior toward the elderly also improved after the experience and was maintained at three months after the program's conclusion. The students' attitudes and behaviors toward the elderly were positively correlated. The demonstrated long-term effects of the aging suit experience in improving nursing students' attitudes and behavior toward the elderly in this study suggest that the experience can be applied to geriatric nursing education.
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Actitud del Personal de Salud , Bachillerato en Enfermería , Enfermería Geriátrica , Estudiantes de Enfermería , Adulto , Envejecimiento , Competencia Clínica , Bachillerato en Enfermería/métodos , Femenino , Enfermería Geriátrica/educación , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Estudiantes de Enfermería/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Tumor-treating fields (TTFields) is an emerging non-invasive cancer-treatment modality using alternating electric fields with low intensities and an intermediate range of frequency. TTFields affects an extensive range of charged and polarizable cellular factors known to be involved in cell division. However, it causes side-effects, such as DNA damage and apoptosis, in healthy cells. OBJECTIVE: To investigate whether thymidine can have an effect on the DNA damage and apoptosis, we arrested the cell cycle of human glioblastoma cells (U373) at G1/S phase by using thymidine and then exposed these cells to TTFields. METHODS: Cancer cell lines and normal cell (HaCaT) were arrested by thymidine double block method. Cells were seeded into the gap of between the insulated wires. The exposed in alternative electric fields at 120 kHz, 1.2 V/cm. They were counted the cell numbers and analyzed for cancer malignant such as colony formation, Annexin V/PI staining, γH2AX and RT-PCR. RESULTS: The colony-forming ability and DNA damage of the control cells without thymidine treatment were significantly decreased, and the expression levels of BRCA1, PCNA, CDC25C, and MAD2 were distinctly increased. Interestingly, however, cells treated with thymidine did not change the colony formation, apoptosis, DNA damage, or gene expression pattern. CONCLUSIONS: These results demonstrated that thymidine can inhibit the TTFields-caused DNA damage and apoptosis, suggesting that combining TTFields and conventional treatments, such as chemotherapy, may enhance prognosis and decrease side effects compared with those of TTFields or conventional treatments alone.
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Apoptosis/genética , Daño del ADN/genética , Glioblastoma/terapia , Magnetoterapia , Apoptosis/efectos de la radiación , Proteína BRCA1/genética , Línea Celular Tumoral , Daño del ADN/efectos de la radiación , Campos Electromagnéticos/efectos adversos , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Glioblastoma/genética , Glioblastoma/patología , Humanos , Proteínas Mad2/genética , Antígeno Nuclear de Célula en Proliferación/genética , Timidina/farmacología , Fosfatasas cdc25/genéticaRESUMEN
The authors have noticed an inadvertent error in our article, ''Patterns of Multimorbidity in Adults: An Association Rules Analysis Using the Korea Health Panel" [...].
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PURPOSE: The purpose of this study was to develop and compare the prediction model for suicide attempts by Korean adolescents using logistic regression and decision tree analysis. METHODS: This study utilized secondary data drawn from the 2019 Youth Health Risk Behavior web-based survey. A total of 20 items were selected as the explanatory variables (5 of sociodemographic characteristics, 10 of health-related behaviors, and 5 of psychosocial characteristics). For data analysis, descriptive statistics and logistic regression with complex samples and decision tree analysis were performed using IBM SPSS ver. 25.0 and Stata ver. 16.0. RESULTS: A total of 1,731 participants (3.0%) out of 57,303 responded that they had attempted suicide. The most significant predictors of suicide attempts as determined using the logistic regression model were experience of sadness and hopelessness, substance abuse, and violent victimization. Girls who have experience of sadness and hopelessness, and experience of substance abuse have been identified as the most vulnerable group in suicide attempts in the decision tree model. CONCLUSION: Experiences of sadness and hopelessness, experiences of substance abuse, and experiences of violent victimization are the common major predictors of suicide attempts in both logistic regression and decision tree models, and the predict rates of both models were similar. We suggest to provide programs considering combination of high-risk predictors for adolescents to prevent suicide attempt.
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Conducta del Adolescente , Árboles de Decisión , Intento de Suicidio/psicología , Adolescente , Depresión/patología , Femenino , Humanos , Internet , Modelos Logísticos , Masculino , Factores de Riesgo , Aislamiento Social , Estrés Psicológico , Trastornos Relacionados con Sustancias/patología , Ideación Suicida , Encuestas y CuestionariosRESUMEN
No specific markers have been identified to detect non-small cell lung cancer (NSCLC) cell-derived exosomes circulating in the blood. Here, we report a new biomarker that distinguishes between cancer and non-cancer cell-derived exosomes. Exosomes isolated from patient plasmas at various pathological stages of NSCLC, NSCLC cell lines, and human pulmonary alveolar epithelial cells isolated using size exclusion chromatography were characterized. The GRIP and coiled-coil domain-containing 2 (GCC2) protein, involved in endosome-to-Golgi transport, was identified by proteomics analysis of NSCLC cell line-derived exosomes. GCC2 protein levels in the exosomes derived from early-stage NSCLC patients were higher than those from healthy controls. Receiver operating characteristic curve analysis revealed the diagnostic sensitivity and specificity of exosomal GCC2 to be 90% and 75%, respectively. A high area under the curve, 0.844, confirmed that GCC2 levels could effectively distinguish between the exosomes. These results demonstrate GCC2 as a promising early diagnostic biomarker for NSCLC.
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Isolation of pure extracellular vesicles (EVs), especially from blood, has been a major challenge in the field of EV research. The presence of lipoproteins and soluble proteins often hinders the isolation of high purity EVs upon utilization of conventional separation methods. To circumvent such problems, we designed a single-step dual size-exclusion chromatography (dSEC) column for effective isolation of highly pure EVs from bone marrow derived human plasma. With an aim to select appropriate column design parameters, we analyzed the physiochemical properties of the major substances in bone marrow derived plasma, which include EVs, lipoproteins, and soluble proteins. Based on these findings, we devised a novel dSEC column with two different types of porous beads sequentially stacked each other for efficient separation of EVs from other contaminants. The newly developed dSEC columns exhibited better performance in isolating highly pure EVs from AML plasma in comparison to conventional isolation methods.
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Médula Ósea/química , Cromatografía en Gel/métodos , Diseño de Equipo/métodos , Vesículas Extracelulares/química , Plasma/química , Apolipoproteínas B/análisis , Apolipoproteínas B/aislamiento & purificación , LDL-Colesterol/aislamiento & purificación , Cromatografía en Gel/instrumentación , Diseño de Equipo/instrumentación , Células HL-60 , Humanos , Plasma/citología , Células THP-1 , Tetraspanina 30/análisis , Tetraspanina 30/aislamiento & purificaciónRESUMEN
In this study, we constructed a structural equation model (SEM) for predicting the quality of life (QOL) in elderly Koreans with chronic musculoskeletal pain (CMP) and examined the differences between sexes. Data were earlier collected in a prior study of 307 participants (101 men and 206 women) with CMP, aged 65 years and above, who used geriatric welfare centers located in two cities. The effects of pain, functional limitation, perceived health status, pain coping, and social support on the QOL were estimated with a multigroup SEM. For both men and women, the results show sequential causality from pain to functional limitation, perceived health status, and QOL. However, the relationships among pain, pain coping, functional limitation, and QOL differ between men and women. The multigroup SEM provides a better understanding of the sex differences in the QOL of elderly with CMP. The results suggest that in order to improve QOL among the elderly with CMP, a customized strategy should be applied that takes into account differences between the sexes.
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Dolor Musculoesquelético/fisiopatología , Calidad de Vida , Factores Sexuales , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , República de CoreaRESUMEN
This study aimed to identify the prevalence and patterns of multimorbidity among Korean adults. A descriptive study design was used. Of 11,232 adults aged 18 and older extracted from the 2014 Korean Health Panel Survey, 7118 had one or more chronic conditions. The chronic conditions code uses the Korean Standard Classification of Diseases. Association rule analysis and network analysis were conducted to identify patterns of multimorbidity among 4922 participants with multimorbidity. The prevalence of multimorbidity in the overall population was 34.8%, with a higher prevalence among women (40.8%) than men (28.6%). Hypertension had the highest prevalence in both men and women. In men, diabetes mellitus and hypertension yielded the highest probability of comorbidity (10.04%). In women, polyarthrosis and hypertension yielded the highest probability of comorbidity (12.51%). The results of the network analysis in four groups divided according to gender and age showed different characteristics for each group. Public health practitioners should adopt an integrated approach to manage multimorbidity rather than an individual disease-specific approach, along with different strategies according to age and gender groups.
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Multimorbilidad/tendencias , Adolescente , Adulto , Enfermedad Crónica , Comorbilidad , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , República de Corea/epidemiologíaRESUMEN
Cancer stem cells (CSCs) have been implicated in the growth and progression of several types of human cancer. The technology to derive and establish CSCs in vitro could be a critical tool for understanding cancer and developing new therapeutic targets. In this study, we derived expandable CD15+ induced CSCs (iCSCs) from immortalised 293FT human epithelial cells by co-culture with human bone marrow-derived mesenchymal stem cells (BM-MSCs) as feeder cells in vitro. The iCSCs converted through an epithelial-mesenchymal transition program acquired mesenchymal traits, the expression of stem cell markers, and epigenetic changes. Moreover, the iCSCs not only efficiently formed tumorspheres in vitro but also initiated tumours in immunocompromised mice injected with only 10 of the iCSCs. Furthermore, we showed that the expression of the chemokine CXCL12 and its receptor CXCR4 by the iCSCs resulted in the activation of the Fut4 gene through CXCR4/ERK/ELK-1-signalling pathways and the maintenance of the iCSCs in the undifferentiated state through CXCR4/AKT/STAT3-signalling. These findings suggest that immortalised 293FT cells may acquire potential oncogenicity through molecular and cellular alteration processes in microenvironments using BM-MSCs, and could represent a valuable in vitro model as a cancer stem cell surrogate for studying the pathophysiological properties of CSCs.
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Quimiocina CXCL12/metabolismo , Células Madre Neoplásicas/patología , Receptores CXCR4/metabolismo , Transducción de Señal , Animales , Carcinogénesis , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células HEK293 , Humanos , Ratones , Proteína Elk-1 con Dominio ets/metabolismoRESUMEN
Lung cancer has a high mortality rate, but an early diagnosis can contribute to a favorable prognosis. A liquid biopsy that captures and detects tumor-related biomarkers in body fluids has great potential for early-stage diagnosis. Exosomes, nanosized extracellular vesicles found in blood, have been proposed as promising biomarkers for liquid biopsy. Here, we demonstrate an accurate diagnosis of early-stage lung cancer, using deep learning-based surface-enhanced Raman spectroscopy (SERS) of the exosomes. Our approach was to explore the features of cell exosomes through deep learning and figure out the similarity in human plasma exosomes, without learning insufficient human data. The deep learning model was trained with SERS signals of exosomes derived from normal and lung cancer cell lines and could classify them with an accuracy of 95%. In 43 patients, including stage I and II cancer patients, the deep learning model predicted that plasma exosomes of 90.7% patients had higher similarity to lung cancer cell exosomes than the average of the healthy controls. Such similarity was proportional to the progression of cancer. Notably, the model predicted lung cancer with an area under the curve (AUC) of 0.912 for the whole cohort and stage I patients with an AUC of 0.910. These results suggest the great potential of the combination of exosome analysis and deep learning as a method for early-stage liquid biopsy of lung cancer.