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BACKGROUND: This study aimed to explore the associations between household air pollution (HAP), measured by cooking fuel use, sensory impairments (SI), and their transitions in Chinese middle-aged and older adults. METHODS: Participants were recruited from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and were subsequently followed up until 2018. Data on SI were collected by self-reported hearing and vision impairments, which were divided into three categories: non-SI, single SI (hearing or vision impairment), and dual SI (DSI). Cooking fuels, including solid and clean fuels, are proxies for HAP. The transitions of cooking fuels and SI refer to the switching of the fuel type or SI status from baseline to follow-up. Cox proportional hazard regression models were used to explore associations, and hazard ratios (HRs) and 95% confidence intervals (CI) were used to evaluate the strength of the association. RESULTS: The prevalence of non-SI, single SI, and DSI was 59.6%, 31.8%, and 8.6%, respectively, among the 15,643 participants at baseline in this study. Over a median follow-up of 7.0 years, 5,223 worsening SI transitions were observed. In the fully adjusted model, solid fuel use for cooking was associated with a higher risk of worsening SI transitions, including from non-SI to single SI (HR = 1.08, 95% CI = 1.01-1.16) and from non-SI to DSI (HR = 1.26, 95% CI = 1.09-1.47), but not from single SI to DSI. In addition, compared to those who always used solid fuels, participants who switched from solid to clean fuel for cooking appeared to have attenuated the risk of worsening SI transitions. The statistical significance of the associations remained in the set of sensitivity analyses. CONCLUSION: Solid fuel use was associated with higher risks of worsening SI transitions, while converting the type of cooking fuel from solid to clean fuels may reduce the risk of worsening SI transitions. Our study suggests that tailored clean fuel interventions, especially in developing countries, should be implemented to prevent sensory impairments and hence reduce the burden of sensory impairment-related disability.
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Culinaria , Humanos , Persona de Mediana Edad , Anciano , Estudios de Cohortes , Factores de Riesgo , Estudios Longitudinales , Estudios Prospectivos , China/epidemiologíaRESUMEN
BACKGROUND: Anorexia of aging (AA) is a common geriatric syndrome that seriously endangers the health of older adults. Early identification of populations at risk of AAand the implementation of appropriate intervention measures hold significant public health importance. This study aimed to develop a nomogram for predicting the risk of AA among older people. METHODS: We conducted a cross-sectional study involving 2144 community-dwelling older adults to evaluate the AA using the Simplified Nutritional Appetite Questionnaire. We utilized the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis to select variables and develop a nomogram prediction model. The predictive performance of the nomogram was evaluated using the Receiver Operating Characteristic (ROC) curves, calibration curves, Decision Curve Analysis (DCA), and internal validation. RESULTS: The prevalence of AA among Chinese older adults was 21.7% (95%CI: 20.0%-23.5%). Age, sex, family economic level, smoking status, dysphagia, loneliness, depressive symptoms, living alone, health literacy, life satisfaction, and body mass index have been identified as predictive factors for AA among older people. The nomogram constructed based on these predictive factors showed an area under the curve (AUC) of 0.766 (95%CI: 0.742-0.791), indicating good calibration and discrimination ability. Additionally, the results obtained from the 10-fold cross-validation process confirmed the nomogram's good predictive capabilities. Furthermore, the DCA results showed that the nomogram has clinical utility. CONCLUSION: The nomogram constructed in this study serves as an effective tool for predicting anorexia of aging among community-dwelling older adults. Its implementation can help community healthcare workers evaluate the risk of AA in this population and identify high-risk groups.
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Anorexia , Nomogramas , Humanos , Masculino , Femenino , Anciano , Anorexia/epidemiología , Estudios Transversales , Anciano de 80 o más Años , Evaluación Geriátrica/métodos , Prevalencia , Envejecimiento/psicología , Encuestas y Cuestionarios/normas , China/epidemiología , Factores de Riesgo , Vida Independiente , Curva ROC , Persona de Mediana EdadRESUMEN
Countries worldwide have adopted environmental taxes to reduce pollution, making it essential for policymakers and researchers to understand their impact on corporate environmental investment. This study investigates the impact of China's environmental tax law on the environmental investment behavior of high-emission enterprises, using a Difference-in-Differences (DID) approach based on a quasi-natural experiment. The findings reveal that environmental taxes significantly incentivize these enterprises to increase their environmental investments, with the proportion of investment relative to total assets rising by approximately 82% compared to low-emission firms. This effect remains robust after controlling for various tests, including parallel trends, placebo tests, and Propensity Score Matching (PSM) tests, as well as excluding firms that never disclosed pollutant discharge tax payments or expected effects. Motivation analysis shows that high-emission enterprises are driven primarily by the goal of reducing pollution costs to engage in environmental governance. Mechanism analysis indicates that the implementation of environmental taxes strengthens corporate governance, further encouraging environmental governance activities. Cross-sectional analysis reveals that these effects are most pronounced in firms with high financing constraints, elevated operating costs, or low profitability. Additionally, environmental investment is found to enhance corporate productivity, net sales margins, and social evaluations. This study enhances the understanding of how environmental regulation influences corporate behavior, offering empirical evidence that environmental taxes foster sustainable practices and enhance corporate performance.
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The CRISPR-Cas systems have been widely used as genome editing tools, with type II and V systems typically introducing small indels, and type I system mediating long-range deletions. However, the precision of type I systems for large fragment deletion is still remained to be optimized. Here, we developed a compact Cascade-Cas3 Dvu I-C system with Cas11c for plant genome editing. The Dvu I-C system was efficient to introduce controllable large fragment deletion up to at least 20 kb using paired crRNAs. The paired-crRNAs design also improved the controllability of deletions for the type I-E system. Dvu I-C system was sensitive to spacer length and mismatch, which was benefit for target specificity. In addition, we showed that the Dvu I-C system was efficient for generating stable transgenic lines in maize and rice with the editing efficiency up to 86.67%. Overall, Dvu I-C system we developed here is powerful for achieving controllable large fragment deletions.
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Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , Plantas/genética , Genoma de Planta , Mutación INDELRESUMEN
OBJECTIVES: The development and validation of the specific health literacy assessment tool for older adults is the basis for conducting the research on health literacy among older adults. The existing health literacy assessment scale for older adults in Chinese mainland has some limitations, such as too many items and poor compliance during the survey. It is necessary to develop or introduce simplified assessment tools to support large-scale surveys in the future. This study aims to modify the brief health literacy assessment scale compiled by Taiwan scholars, and to conduct the test for the reliability, validity and the measurement equivalence across gender in the older population in mainland China. METHODS: From March to April 2021, 508 older adults from Jinan, Shandong Province, China were selected by cluster sampling method to conduct a questionnaire survey using the brief health literacy assessment scale and health-promoting lifestyle profile. After 4 weeks, 83 of them were selected for retesting. SPSS 25.0 statistical software was used for descriptive analysis, item analysis, exploratory factor analysis, correlation analysis, and reliability test, and Mplus 8.0 was used for confirmatory factor analysis and gender measurement equivalence test. RESULTS: Each item of the scale had good discrimination, and there were significant differences in the scores of each item between high score and low score groups (P<0.05), and the coefficient of correlation between the scores of each item and the total score was between 0.721 and 0.891. Exploratory factor analysis extracted a factor with a characteristic root greater than 1, and the cumulative variance interpretation amount was 67.94%. The confirmatory factor analysis showed that the single factor structure fit was good [χ2/df was 2.260, the Tucker-Lewis index was 0.973, the comparison fit index (CFI) was 0.982, and the root mean square error of approximation (RMSEA) was 0.071]. The multi-group confirmatory factor analysis results showed that the brief health literacy assessment scale's configural equivalence, weak equivalence, and strong equivalence models were all accepted. The comparison results of measurement equivalence models showed that the changes of RMSEA were less than 0.015, and the changes of CFI were less than 0.01, indicating that the brief health literacy assessment scale had measurement equivalence between different gender groups. Cronbach's α coefficient was 0.945, and the test-retest reliability was 0.946. The correlation coefficient between health literacy and health-promotion lifestyles was 0.557 (P<0.05). CONCLUSIONS: The brief health literacy assessment scale has good reliability, validity, and measurement equivalence across gender, and can be used as an effective measurement tool for the health literacy of the older people in Chinese mainland.
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Alfabetización en Salud , Humanos , Anciano , Reproducibilidad de los Resultados , Alfabetización en Salud/métodos , Psicometría , Encuestas y Cuestionarios , Pueblo Asiatico , China , Análisis FactorialRESUMEN
Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3) is a crucial oncogene in human lung cancer, whereas protein kinase C δ (PKCδ) acts as a tumor suppressor. In this study, we aimed to explore the regulation by PLOD3 on the expression of YAP1 to affect the progression of non-small cell lung cancer (NSCLC) via the PKCδ/CDK1/LIMD1 signaling pathway. We found that PLOD3, CDK1, and YAP1 were highly expressed, while LIMD1 was poorly expressed in NSCLC tissues. Mechanistic investigation demonstrated that silencing PLOD3 promoted the cleavage of PKCδ in a caspase-dependent manner to generate a catalytically active fragment cleaved PKCδ, enhanced phosphorylation levels of CDK1, and LIMD1 but suppressed nuclear translocation of YAP1. Furthermore, functional experimental results suggested that loss of PLOD3 led to increased phosphorylation levels of CDK1 and LIMD1 and downregulated YAP1, thereby suppressing the proliferation, colony formation, cell cycle entry, and resistance to apoptosis of NSCLC cells in vitro and inhibiting tumor growth in vivo. Taken together, these results show that PLOD3 silencing activates the PKCδ/CDK1/LIMD1 signaling pathway to prevent the progression of NSCLC, thus providing novel insight into molecular targets for treating NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/metabolismo , Apoptosis , Proteína Quinasa CDC2/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas con Dominio LIM , Neoplasias Pulmonares/metabolismo , Transducción de Señal , Proteínas Señalizadoras YAPRESUMEN
PURPOSE: This study aimed to examine the psychometric properties of the Chinese version of the modified Yale Food Addiction Scale 2.0 (C-mYFAS 2.0) and to analyze the prevalence of food addiction among Chinese college students and its relationship with resilience and social support. METHODS: A total of 1132 Chinese college students completed the C-mYFAS 2.0, BES, EAT-26, PHQ-9, GAD-7, TFEQ-18, CD-RISC-10, and PSSS. Confirmatory factor analysis was used to evaluate the factor structure of the C-mYFAS 2.0 and psychometric properties were assessed. Test-retest reliability was evaluated in a sub-sample (n = 62). Spearman correlation and logistic regression were used to examine the relationship between resilience, social support, and food addiction. RESULTS: The prevalence of food addiction according to the C-mYFAS 2.0 was 6.2%. Confirmatory factor analyses suggested a single-factor structure (comparative fit index = 0.961). The C-mYFAS 2.0 had good test-retest reliability and internal consistency (Kuder-Richardson's α = 0.824). Good convergent validity was indicated by correlations with binge eating, eating disorder symptoms, depressive symptoms, generalized anxiety symptoms, uncontrolled eating, emotional eating, and BMI (ps < 0.001). Appropriate divergent validity was reflected by no association with cognitive restraint. Finally, binge eating was significantly predicted by C-mYFAS 2.0, depressive symptoms, and eating disorder symptoms (ps < 0.001), confirming incremental validity. In addition, our study found that poorer resilience and social support were related to food addiction (ps < .001). CONCLUSIONS: The C-mYFAS 2.0 is a brief but reliable and valid screening instrument for food addiction among Chinese college students. In addition, we found that resilience and social support were negatively associated with food addiction. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.
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Adicción a la Comida , China/epidemiología , Estudios Transversales , Adicción a la Comida/psicología , Humanos , Prevalencia , Psicometría , Reproducibilidad de los Resultados , Apoyo Social , Encuestas y CuestionariosRESUMEN
Pluripotent stem cells (PSCs) are important models for analyzing cellular metabolism and individual development. As a hypoxia-inducible factor subunit, HIF-1α plays an important role in maintaining the pluripotency of PSCs under hypoxic conditions. However, the mechanisms underlying the self-renewal and pluripotency maintenance of human induced pluripotent stem cells (hiPSCs) via regulating HIF-1α largely remain elusive. In this study, we found that disrupting the expression of HIF-1α reduced self-renewal and pluripotency of hiPSCs. Additionally, HIF-1α-knockdown led to lower mitochondrial membrane potential (ΔΨm ) and higher reactive oxygen species production in hiPSCs. However, HIF-1α-overexpression increased ATP content in hiPSCs, while the role of HIF-1α-knockdown was opposite. The embryoid body (EB) and teratoma formation assays showed that HIF-1α-knockdown promoted endoderm differentiation and development in vitro and in vivo. In terms of the underlying molecular mechanisms, HIF-1α-knockdown inhibited the expression of Actl6a and histone H3K9ac acetylation (H3K9ac). Actl6a knockdown reduced the expression of H3K9ac and the pluripotency of hiPSCs, and also affected endoderm differentiation. These data suggest that hindering HIF-1α expression causes the changes in mitochondrial properties and metabolic disorders in hiPSCs. Furthermore, HIF-1α affects hiPSC pluripotency, and germ layer differentiation via Actl6a and histone acetylation.
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Actinas/metabolismo , Diferenciación Celular , Linaje de la Célula , Proteínas Cromosómicas no Histona/metabolismo , Proteínas de Unión al ADN/metabolismo , Histonas/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Células Madre Pluripotentes Inducidas/citología , Acetilación , Actinas/genética , Células Cultivadas , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Femenino , Histonas/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Madre Pluripotentes Inducidas/metabolismo , Procesamiento Proteico-PostraduccionalRESUMEN
PURPOSE: The aim of this study was to examine the association between eHealth literacy and health-related quality of life (HRQoL) and explore whether health-promoting behaviors mediate the association between eHealth literacy and HRQoL among Chinese older adults. METHODS: An anonymous cross-sectional survey was conducted among 2300 adults aged 60 or older from Jinan, China. The eHealth Literacy Scale, Short-Form Health-Promoting Lifestyle Profile, and Short-Form Health Survey (SF-12) were used to measure eHealth literacy, health-promoting behaviors, and HRQoL. Multivariate linear regression analyses were conducted to test the association between eHealth literacy, health-promoting behaviors, and HRQoL. The mediation analyses, composed of PROCESS analysis and bootstrapping method, were preformed to test both total (c), direct (c'), and indirect effects (a*b) of eHealth literacy on HRQOL through health-promoting behaviors. RESULTS: Regression analyses indicated that eHealth literacy (B = 0.487, p < 0.001) was significantly positively associated with health-promoting behaviors, and health-promoting behaviors (B = 0.257, p < 0.001) were associated with HRQoL. The mediation analyses indicated that eHealth literacy had a significant direct (c' = 0.183, p < 0.001) and indirect effect on older adults' HRQoL through health-promoting behaviors (a*b = 0.125, bootstrapped 95% confidence interval (CI) = 0.094-0.157). The indirect effect accounted for 40.6% of the total effect (c = 0.308, bootstrapped 95% CI 0.241-0.376) of eHealth literacy on HRQoL. CONCLUSIONS: Health-promoting behaviors mediated the association between eHealth literacy and HRQoL in Chinese older adults. The establishment of interventions focused on health-promoting behavior may be an effective way to help older adults with low eHealth literacy improve their HRQoL.
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Conductas Relacionadas con la Salud , Alfabetización en Salud , Promoción de la Salud , Calidad de Vida/psicología , Telemedicina , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cross-sectional and longitudinal studies have found that problematic mobile phone use, bedtime procrastination, sleep quality, and depressive symptoms are strongly associated. However, studies are inconsistent regarding whether problematic mobile phone use predicts depressive symptoms or vice versa, and sleep factors have been infrequently focused on in this regard. In addition, few studies have examined the longitudinal associations and directions of effects between these factors. Therefore, this study aims to explore the longitudinal relationship among problematic mobile phone use, bedtime procrastination, sleep quality, and depressive symptoms in college students. METHODS: Overall, 1181 college students completed questionnaires on problematic mobile phone use, bedtime procrastination, sleep quality, and depressive symptoms at two time points 12 months apart. A cross-lagged model was used to examine the longitudinal relationship between these factors. RESULTS: Cross-lagged analyses showed significant bidirectional relationships of problematic mobile phone use with bedtime procrastination and depressive symptoms. Additionally, there were also significant bidirectional relationships of sleep quality with bedtime procrastination and depressive symptoms. Problematic mobile phone use predicted subsequent sleep quality one-way, and bedtime procrastination predicted subsequent depressive symptoms one-way. CONCLUSIONS: This study further expands our understanding of the longitudinal and bidirectional relationships among problematic mobile phone use, bedtime procrastination, sleep quality and depressive symptoms and helps school mental health educators design targeted interventions to reduce problematic mobile phone use, sleep problems, and depressive symptoms among college students.
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Uso del Teléfono Celular , Procrastinación , China , Estudios Transversales , Depresión , Humanos , Sueño , EstudiantesRESUMEN
BACKGROUND: Social capital has been linked to health behaviours, but the underlying mechanism is unclear. Previous studies have found that health literacy played the role of a mediator in the relationships among social capital, individual physical activity and nutrition. But it is not clear whether eHealth literacy mediates the impact of social capital on health behaviours. Therefore, our research aimed to explore the relationships among social capital (structural and cognitive social capital), eHealth literacy, and the health behaviours of elderly people, and to analyse the mediating effect of eHealth literacy, while providing a theoretical basis for a health behaviour intervention for elderly people. METHODS: From January to February 2019, we conducted a cross-sectional survey of 1201 Chinese people aged over 60 years using the Chinese Shortened Social Capital Scale (contains two subscales of structural social capital and cognitive social capital), eHealth Literacy Scale, and Health-Promoting Lifestyle Profile. We used structural equation modelling to test a hypothetical mediation model. RESULTS: The mean scores of social capital was 72.07 (SD = 13.03), 17.24 (SD = 9.34) for eHealth literacy, and 112.23 (SD = 23.25) for health behaviours. Social capital and eHealth literacy were significantly correlated with health behaviours, and social capital and structural social capital were significantly correlated with eHealth literacy. Lastly, eHealth literacy mediated the relationship between structural social capital and health behaviours. CONCLUSIONS: eHealth literacy was an important mediating factor for elderly people's structural social capital and health behaviours. Therefore, social capital and eHealth literacy must be considered when designing and implementing health behaviour intervention programmes for elderly people.
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Alfabetización en Salud , Capital Social , Telemedicina , Anciano , China , Estudios Transversales , Conductas Relacionadas con la Salud , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: During the COVID-19 pandemic, the internet has significantly spread information, providing people with knowledge and advice about health protection regarding COVID-19. While a previous study demonstrated that health and eHealth literacy are related to COVID-19 prevention behaviors, few studies have focused on the relationship between health literacy, eHealth literacy, and COVID-19-related health behaviors. The latter includes not only preventative behaviors but also conventional health behaviors. OBJECTIVE: The objective of this study was to develop and verify a COVID-19-related health behavior questionnaire, explore its status and structure, and examine the associations between these behaviors and participants' health literacy and eHealth literacy. METHODS: A snowball sampling method was adopted to recruit participants to complete anonymous cross-sectional questionnaire surveys online that assessed sociodemographic information, self-reported coronavirus knowledge, health literacy, eHealth literacy, and COVID-19-related health behaviors. RESULTS: Of 1873 college students who were recruited, 781 (41.7%) had adequate health literacy; the mean eHealth literacy score was 30.16 (SD 6.31). The COVID-19-related health behavior questionnaire presented a two-factor structure-COVID-19-specific precautionary behaviors and conventional health behaviors-with satisfactory fit indices and internal consistency (Cronbach α=.79). The mean score of COVID-19-related health behaviors was 53.77 (SD 8.03), and scores differed significantly (P<.05) with respect to residence, college year, academic major, family economic level, self-reported health status, having a family member or friend infected with coronavirus, and health literacy level. Linear regression analysis showed that health literacy and eHealth literacy were positively associated with COVID-19-specific precautionary behaviors (ßhealth literacy=.149, ßeHealth literacy=.368; P<.001) and conventional health behaviors (ßhealth literacy=.219, ßeHealth literacy=.277; P<.001). CONCLUSIONS: The COVID-19-related health behavior questionnaire was a valid and reliable measure for assessing health behaviors during the pandemic. College students with higher health literacy and eHealth literacy can more actively adopt COVID-19-related health behaviors. Additionally, compared to health literacy, eHealth literacy is more closely related to COVID-19-related health behaviors. Public intervention measures based on health and eHealth literacy are required to promote COVID-19-related health behaviors during the pandemic, which may be helpful to reduce the risk of COVID-19 infection among college students.
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COVID-19/epidemiología , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Alfabetización en Salud/estadística & datos numéricos , Telemedicina/métodos , Adolescente , Adulto , Pueblo Asiatico/estadística & datos numéricos , COVID-19/prevención & control , China/epidemiología , Estudios Transversales , Humanos , Internet , Masculino , Pandemias , SARS-CoV-2/aislamiento & purificación , Factores Sociales , Estudiantes , Encuestas y Cuestionarios , Universidades , Adulto JovenRESUMEN
This study aimed to explore the underlying mechanism of linc01014 in oesophagus cancer gefitinib resistance. Gefitinib-resistant oesophagus squamous cell carcinoma (ESCC gefitinibR) cell lines were constructed by using different gefitinib treatment in FLO-1, KYAE-1, TE-8 and TE-5 cell lines and confirmed by MTS50 and proliferation assays. Expression of linc01014 was overexpressed/silenced in FLO-1 cells followed by gefitinib treatment, and then, the apoptosis-associated markers Bax and Bcl-2, and PI3KCA in PI3K signalling pathway were determined using Western blotting. MST50 and morphology analyses showed that ESCC gefitinibR cell lines presented obvious gefitinib resistance than their parental ESCC cell lines. ESCC gefitinibR cell lines showed significantly higher proliferation abilities than their parental ESCC cell lines after treating with gefitinib. Overexpression of linc01014 significantly inhibited the apoptosis of FLO-1 cells induced by gefitinib and silencing linc01014 obviously promoted the apoptosis of FLO-1 cells induced by gefitinib. Silencing linc01014 could significantly increase the gefitinib chemotherapy sensitivity of oesophagus cancer via PI3K-AKT-mTOR signalling pathway.
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Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/metabolismo , Neoplasias Esofágicas/genética , Gefitinib/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Forma de la Célula/efectos de los fármacos , Forma de la Célula/genética , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.
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Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Factores de Transcripción de la Familia Snail/genética , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Línea Celular , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Femenino , Perfilación de la Expresión Génica , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Estadificación de Neoplasias , Trasplante de Neoplasias , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Activación TranscripcionalRESUMEN
A large body of evidence indicates that microRNAs play a critical role in tumor initiation and progression by negatively regulating oncogenes or tumor suppressor genes. Here, we report that the expression of miR-200a was notably downregulated in 45 renal cell carcinoma (RCC) samples. Restoration of miR-200a suppressed cell proliferation, migration, and invasion in two RCC cell lines. Furthermore, we used an epithelial-to-mesenchymal transition PCR array to explore the putative target genes of miR-200a. By performing quantitative real-time PCR, ELISA, and luciferase reporter assays, transforming growth factor beta2 (TGFB2) was validated as a direct target gene of miR-200a. Moreover, siRNA-mediated knockdown of TGFB2 partially phenocopied the effect of miR-200a overexpression. These results suggest that miR-200a suppresses RCC development via directly targeting TGFB2, indicating that miR-200a may present a novel target for diagnostic and therapeutic strategies in RCC.
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Carcinoma de Células Renales/genética , Proliferación Celular/genética , MicroARNs/genética , Factor de Crecimiento Transformador beta2/biosíntesis , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , MicroARNs/biosíntesis , Invasividad Neoplásica/genética , ARN Interferente Pequeño/genética , Factor de Crecimiento Transformador beta2/genéticaRESUMEN
MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in human cancers. Increasing evidence shows that deregulation of miRNAs contributes to the development and progression of human non-small cell lung cancer (NSCLC). Here, we identified miR-186 as a tumor suppressor in NSCLC, which was decreased in NSCLC. Overexpression of miR-186 significantly inhibited proliferation, migration, and invasion of NSCLC cells. In addition, Rho-associated protein kinase 1 (ROCK1) was identified as a target of miR-186 in NSCLC cells. Restoration of ROCK1 remarkably reversed the tumor-suppressive effects of miR-186 on cell proliferation, migration, and invasion in NSCLC cells. Furthermore, ROCK1 was inversely correlated with miR-186 expression in NSCLC. Collectively, our data indicate that miR-186 functions as tumor suppressor in NSCLC by targeting ROCK1.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Proliferación Celular , Neoplasias Pulmonares/genética , MicroARNs/genética , Quinasas Asociadas a rho/genética , Regiones no Traducidas 3'/genética , Secuencia de Bases , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mutación , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Ácido Nucleico , Quinasas Asociadas a rho/metabolismoRESUMEN
The adipose stromal vascular fraction (SVF) contains abundant mesenchymal stem cell populations that have a limited ability to self-renew and differentiate. Male mouse adipose SVF cells were dedifferentiated by reprogramming factors (c-Myc, Oct4, Sox2, and Klf4) to form embryonic stem cell-like cells (ESCLCs), which upgraded their limited differentiation potential. The ESCLCs were induced to differentiate toward epiblast-like cells (EpiLCs) and primordial germ cell-like cells (PGCLCs) by culturing in media supplied with activin A and BMP-4, respectively. The derived ESCLCs possess embryonic stem cell features and can automatically form embryonic bodies. After culture in EpiLC induction medium for 2-3 days, ESCLCs formed flattened epithelial structures that were different from their original water drop-like colonies, and the expression of pluripotency-related genes decreased. When the cells that had been cultured in EpiLC induction medium for 2 days were isolated and cultured in PGCLC induction medium for 4-6 days, they formed typical water drop-like colonies again. Moreover, expression of the pluripotency-related genes and the primordial germ cell (PGC) specification-related genes increased. During progression from ESCLCs toward EpiLCs and PGCLCs, the levels of histone methylases H3K9me2 and H3K27me3 kept changing, which resembled those seen in PGC specification. The derived PGCLCs expressed SSEA-1, Blimp-1, and Stella. Furthermore, methylation of Igf2r and Snrpn was retained, but H19 and Kcnq1ot1 methylation levels were slightly reduced compared to non-PGCLCs, suggesting that the derived PGCLCs may have initiated the process of imprint erasure.
Asunto(s)
Tejido Adiposo/citología , Células Germinativas/citología , Células del Estroma/citología , Animales , Desdiferenciación Celular/efectos de los fármacos , Células Cultivadas , Reprogramación Celular/efectos de los fármacos , Proteínas Cromosómicas no Histona , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Células Germinativas/efectos de los fármacos , Células Germinativas/metabolismo , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/metabolismo , Factor 4 Similar a Kruppel , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/farmacologíaRESUMEN
Lung cancer is one of the most deadly human cancers and continues to be a major unsolved health problem worldwide. Here, we evaluate the function of Pbx1 in the proliferation of non-small-cell lung cancer (NSCLC). In contrast with its known proliferative function, we found that Pbx1 inhibits the proliferation of lung cancer cells. In particular, Pbx1-specific RNA interference resulted in increased proliferation in lung cancer cells. In addition, histone H3 phosphorylation was also increased following inhibition of Pbx1 expression. In contrast, Pbx1 overexpression repressed the proliferation of lung cancer cells and inhibited DNA synthesis. Collectively, our data indicate that Pbx1 inhibits proliferation in lung cancer cells, suggesting a complex role for Pbx1 in modulating the proliferation of cancer cells and making this protein a potential new target for lung cancer therapy.
RESUMEN
OBJECTIVES: Frailty is a common geriatric syndrome in older adults; however, its relationship with digital factors is underexplored. This study aimed to examine the association between digital skills, eHealth literacy, and frailty to provide insights for developing frailty interventions in the digital age. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Data were collected from a cross-sectional survey of older adults aged ≥60 years in China. METHODS: We used a digital skills questionnaire, the eHealth Literacy Scale, and the Tilburg Frailty Indicator to measure digital skill, eHealth literacy, and frailty, respectively. Linear regression and logistic models were established to explore the association between digital skill, eHealth literacy, and frailty. Finally, we used a structural equation model and the Karlson-Holm-Breen method to test the mediation. RESULTS: A total of 2144 older adults were included in this study. The rates of adequate digital skill, adequate eHealth literacy, and frailty were 4.1%, 11.9%, and 38.3%, respectively. Digital skill (ß = -0.108; 95% CI, -0.151 to -0.065) and eHealth literacy (ß = -0.153; 95% CI, -0.195 to -0.112) were negatively associated with frailty score (P < .05), and adequate digital skill (odds ratio, 0.367; 95% CI, 0.170-0.793) and adequate eHealth literacy (odds ratio, 0.455; 95% CI, 0.298-0.694) were associated with a lower prevalence of frailty. eHealth literacy had a mediating effect on the association between digital skills and frailty. CONCLUSIONS AND IMPLICATIONS: Better digital skill and eHealth literacy are associated with a lower prevalence of frailty among older adults. The association between digital skill and frailty was found to be completely mediated by eHealth literacy.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The underlying mechanisms of diabetic kidney disease (DKD) and effective treatment strategies remain unclear. DKD progression is closely associated with abnormal iron metabolism and ferroptosis in vivo. Leeches, used in traditional Chinese medicine for promoting blood circulation and resolving blood stasis, are utilized to treat diabetes and its associated complications. Leeches effectively antagonize oxidative stress injury and exert protective effects on renal function. However, whether leeches can inhibit ferroptosis by modulating oxidative stress and iron metabolism remains unclear. AIM OF THE STUDY: To investigate the therapeutic potential of leech granules in DKD and, specifically, their effects on ferroptosis. MATERIALS AND METHODS: We used a mouse model of DKD. The mice were treated with leech granules via gavage. Component identification and analysis of leech granules were performed using UPLC-MS, and efficacy was assessed by histopathology and analysis of blood glucose, lipids, and renal function. Additionally, the pharmacological mechanisms of leech granules were explored via proteomics, immunohistochemical staining, western blotting, and cell culture. RESULTS: Proteomic analysis showed that iron metabolism was dysregulated and ferroptosis increased in DKD mice. Leech granules significantly reduced iron accumulation and renal pathological damage, decreased ROS levels, upregulated GSH levels, and inhibited ferroptosis in the kidneys of DKD mice. Furthermore, in vitro cellular experiments demonstrated that leech granules could inhibit erastin-induced ferroptosis and protect renal cells. CONCLUSIONS: The regulation of renal iron metabolism and inhibition of ferroptosis mediates the therapeutic effect of leech granules on DKD. Leech granules represent a promising approach for DKD treatment.