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Neoplasias da Mama , Recidiva Local de Neoplasia , Humanos , Feminino , Estudos Retrospectivos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , China , Adulto , Antineoplásicos Hormonais/uso terapêutico , IdosoRESUMO
Exosomal miRNAs have vital functions in mediating intercellular communication as well as tumor occurrence and development. Thus, our research was aimed at exploring the regulatory mechanisms of exosomal miR-130b-3p/DEP domain containing 1 (DEPDC1)/transforming growth factor-ß (TGF-ß) signaling pathway in non-small cell lung cancer (NSCLC). Here we indicated that exosomal miR-130b-3p expression decreased in the serum of NSCLC patients, and it was of significant diagnostic value. Moreover, elevated miR-130b-3p levels suppressed the proliferation and migration of NSCLC cells, and enhanced their apoptosis. Conversely, miR-130b-3p down-regulation led to an opposite effect. As the upstream of DEPDC1, miR-130b-3p directly bound to 3'UTR in DEPDC1 to regulate its expression. DEPDC1 levels affected the proliferation, migration, and apoptosis of NSCLC cells via TGF-ß signaling pathway. Exosomal miR-130b-3p was highly expressed in BEAS-2B cells, besides, BEAS-2B cells transferred exosomal miR-130b-3p to NSCLC cells. Finally, exosomal miR-130b-3p suppressed NSCLC cell growth and migration, promoted their apoptosis via TGF-ß signaling pathway by decreasing DEPDC1 expression, and suppressed epithelial-mesenchymal transition (EMT) in NSCLC cells. In conclusion, exosomal miR-130b-3p has the potential to be a predictive biomarker for NSCLC, thereby stimulating the exploration of diagnostic and therapeutic approaches targeting NSCLC.
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Apoptose , Carcinoma Pulmonar de Células não Pequenas , Movimento Celular , Proliferação de Células , Exossomos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , MicroRNAs , Transdução de Sinais , Fator de Crescimento Transformador beta , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Apoptose/genética , Exossomos/metabolismo , Exossomos/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Masculino , Feminino , Metástase Neoplásica , Pessoa de Meia-IdadeRESUMO
Hypoxia exerts a profound influence on the tumor microenvironment and immune response, shaping treatment outcomes and prognosis. Utilizing consistency clustering, we discerned two hypoxia subtypes in OPSCC bulk sequencing data from GEO. Key modules within OPSCC were identified through weighted gene correlation network analysis (WGCNA). Core modules underwent CIBERSORT immune infiltration analysis and GSEA functional enrichment. Univariate Cox and LASSO analyses were employed to construct prognostic models for seven hypoxia-related genes. Further investigation into clinical characteristics, the immune microenvironment, and TIDE algorithm prediction for immunotherapy response was conducted in high- and low-risk groups. scRNA-seq data were visually represented through TSNE clustering, employing the scissors algorithm to map hypoxia phenotypes. Interactions among cellular subpopulations were explored using the Cellchat package, with additional assessments of metabolic and transcriptional activities. Integration with clinical data unveiled a prevalence of HPV-positive patients in the low hypoxia and low-risk groups. Immunohistochemical validation demonstrated low TDO2 expression in HPV-positive (P16-positive) patients. Our prediction suggested that HPV16 E7 promotes HIF-1α inhibition, leading to reduced glycolytic activity, ultimately contributing to better prognosis and treatment sensitivity. The scissors algorithm effectively segregated epithelial cells and fibroblasts into distinct clusters based on hypoxia characteristics. Cellular communication analysis illuminated significant crosstalk among hypoxia-associated epithelial, fibroblast, and endothelial cells, potentially fostering tumor proliferation and metastasis.
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Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Comunicação Celular , Hipóxia/genética , Hipóxia/metabolismo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , MasculinoRESUMO
Objectives: We conducted an assessment to explore potential associations of the dietary oxidative balance score (DOBS), cardiovascular disease (CVD), with all-cause mortality among older adults, while also exploring the potential moderating effect of DOBS on the relationship between CVD and mortality. Methods: This study included 9059 older adults (≥60 years) from NHANES 2003-2014. Determination of DOBS involves scoring the combination of 16 nutrients, comprising 2 pro-oxidants and 14 anti-oxidants. Cox regression analysis was used to assess the individual associations of CVD and DOBS status with all-cause mortality. Additional evaluations were conducted to assess the combined impact of CVD and DOBS status on mortality, and the interaction were estimated. Sensitivity analyses were performed by excluding participants who died within two years. Results: The findings demonstrated a significant association between pro-oxidant diet (lower DOBS) or CVD and elevated mortality risk among older adults. It is also suggested that older adults with CVD and pro-oxidant diet exhibit the highest risk of all-cause mortality (HR = 1.96, 95% CI: 1.64-2.34), compared to individuals without CVD who follow an antioxidant-rich diet. Further stratified analysis based on CVD status revealed a different pattern in the correlation between pro-oxidant diet and all-cause mortality risk (P for interaction = 0.015). The results of sensitivity analysis were consistent. Conclusions: The lower levels of DOBS and/or CVD were significantly associated with an increased risk of all-cause mortality in older adults. Notably, we also identified a significant interaction between DOBS and CVD affecting all-cause mortality.
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Doenças Cardiovasculares , Dieta , Inquéritos Nutricionais , Humanos , Doenças Cardiovasculares/mortalidade , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Antioxidantes/metabolismo , Idoso de 80 Anos ou mais , Estresse Oxidativo , Fatores de RiscoRESUMO
Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets. Meanwhile, the summary receiver operating characteristic (sROC) curve analysis result showed that DEPDC1 had a high diagnostic value in NSCLC (AUC = 0.96, 95% CI: 0.94-0.98; diagnostic odds ratio = 99.08, 95%CI: 31.91-307.65; sensitivity = 0.89, 95%CI: 0.81-0.94; specificity = 0.92, 95%CI: 0.86-0.96; positive predictive value = 0.94, 95%CI: 0.89-0.98; negative predictive value = 0.78, 95%CI: 0.67-0.90; positive likelihood ratio = 11.77, 95%CI: 6.11-22.68; and negative likelihood ratio = 0.12, 95%CI: 0.06-0.22). Subsequently, quantitative real-time PCR (qRT-PCR) and western blotting indicated that DEPDC1 was high expressed in NSCLC cells. According to the in vitro MTS and apoptotic assays, downregulated DEPDC1 expression targeting P53 signaling pathway inhibited the proliferation of NSCLC cells while promoting apoptosis of NSCLC cells. Moreover, DEPDC1 was significantly correlated with immune cell infiltrating levels in NSCLC based on TCGA data, which were primarily associated with T cells CD4 memory activated, macrophages M1, B cells memory, mast cells resting, T cells regulatory, monocytes, and T cells CD4 memory resting. Compared with the group with high expression of DEPDC1, the group with low expression level had higher scores for immune checkpoint inhibitors (ICIs) treatment. GSEA confirmed that DEPDC1 was involved in gene expression and tumor-related signaling pathways. Finally, DEPDC1 and its associated immune-related genes were shown to be enriched in 'receptor ligand activity', 'external side of plasma membrane', 'regulation of innate immune response', and 'Epstein-Barr virus infection' pathways. The present study demonstrates that DEPDC1 may contribute to NSCLC tumorigenesis and can be applied as the biomarker for diagnosis and immunology.
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Carcinoma Pulmonar de Células não Pequenas , Infecções por Vírus Epstein-Barr , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Herpesvirus Humano 4/metabolismo , Transdução de Sinais , Proteínas de Neoplasias/genética , Proteínas Ativadoras de GTPase/metabolismoRESUMO
BACKGROUND: Intra-abdominal infections are frequently associated with acute respiratory distress syndrome, which significantly affects patient prognosis. However, little is known about the specific risk factors of acute respiratory distress syndrome in sepsis caused by intra-abdominal infections. METHODS: This retrospective study included adult patients with intra-abdominal sepsis admitted to the intensive care unit of a tertiary teaching hospital in China between June 2017 and June 2022. Patients were categorized based on the presence or absence of acute respiratory distress syndrome. Data, including vital signs, laboratory values, and severity scores collected within 24 hours of sepsis diagnosis, as well as outcomes within 90 days, were analyzed. Multivariable logistic regression was used to identify independent risk factors associated with acute respiratory distress syndrome. RESULTS: A total of 738 patients were included, of whom 218 (29.5%) developed acute respiratory distress syndrome. Patients with acute respiratory distress syndrome were younger, had a higher body mass index and disease severity scores, and exhibited higher proportions of septic shock and hospital-acquired intra-abdominal infections. The mortalities in the intensive care unit and at 28 and 90 days were higher in the acute respiratory distress syndrome group. In the multivariate logistic regression model, age under 65 years (odds ratio [95% confidence interval]: 1.571 [1.093-2.259]), elevated body mass index (2.070 [1.382-3.101] for overweight, 6.994 [3.207-15.255]) for obesity, septic shock (2.043 [1.400-2.980]), procalcitonin (1.009 [1.004-1.015]), hospital-acquired intra-abdominal infections (2.528[1.373-4.657]), and source of intra-abdominal infections (2.170 [1.140-4.128] for biliary tract infection, 0.443 [0.217-0.904] for gastroduodenal perforation) were independently associated with acute respiratory distress syndrome. CONCLUSION: In patients with intra-abdominal sepsis, age under 65 years, higher body mass index and procalcitonin, septic shock, hospital-acquired intra-abdominal infections, and biliary tract infection were risk factors for acute respiratory distress syndrome.
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Infecções Intra-Abdominais , Síndrome do Desconforto Respiratório , Sepse , Choque Séptico , Adulto , Humanos , Idoso , Choque Séptico/complicações , Estudos Retrospectivos , Pró-Calcitonina , Sepse/complicações , Fatores de Risco , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Unidades de Terapia Intensiva , Hospitais de Ensino , Infecções Intra-Abdominais/complicações , Infecções Intra-Abdominais/diagnósticoRESUMO
INTRODUCTION: Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. OBJECTIVE: The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. METHODS: MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. RESULTS: A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. CONCLUSION: LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Estudos Transversais , Aceitação pelo Paciente de Cuidados de Saúde , Fármacos Anti-HIV/uso terapêuticoRESUMO
Diesel exhaust has long been of health concern due to established toxicity including carcinogenicity in humans. However, the precise components of diesel engine emissions that drive carcinogenesis are still unclear. Limited work has suggested that nitrated polycyclic aromatic hydrocarbons (NPAHs) such as 1-nitropyrene and 2-nitrofluorene may be more abundant in diesel exhaust. The present study aimed to examine whether urinary amino metabolites of these NPAHs were associated with high levels of diesel engine emissions and urinary mutagenicity in a group of highly exposed workers including both smokers and nonsmokers. Spot urine samples were collected immediately following a standard work shift from each of the 54 diesel engine testers and 55 non-tester controls for the analysis of five amino metabolites of NPAHs, and cotinine (a biomarker of tobacco smoke exposure) using liquid chromatography-mass spectrometry. An overnight urine sample was collected in a subgroup of non-smoking participants for mutagenicity analysis using strain YG1041 in the Salmonella (Ames) mutagenicity assay. Personal exposure to fine particles (PM2.5) and more-diesel-specific constituents (elemental carbon and soot) was assessed for the engine testers by measuring breathing-zone concentrations repeatedly over several full work shifts. Results showed that it was 12.8 times more likely to detect 1-aminopyrene and 2.9 times more likely to detect 2-aminofluorene in the engine testers than in unexposed controls. Urinary concentrations of 1-aminopyrene were significantly higher in engine testers (p < 0.001), and strongly correlated with soot and elemental carbon exposure as well as mutagenicity tested in strain YG1041 with metabolic activation (p < 0.001). Smoking did not affect 1-aminopyrene concentrations and 1-aminopyrene relationships with diesel exposure. In contrast, both engine emissions and smoking affected 2-aminofluorene concentrations. The results confirm that urinary 1-aminopyrene may serve as an exposure biomarker for diesel engine emissions and associated mutagenicity.
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Mutagênicos , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Mutagênicos/toxicidade , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Fuligem/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Nitratos/análise , Biomarcadores/urinaRESUMO
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Adenocarcinoma de Pulmão/genética , Ásia Oriental/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: With the changes in social and medical environments and people's health needs, the nursing core competency should be updated and developed promptly. This study aimed to explore the core competencies of nurses in Chinese tertiary hospitals under the new health development strategy. METHODS: Descriptive qualitative research was conducted using qualitative content analysis. 20 clinical nurses and nursing managers from 11 different provinces and cities were interviewed via purposive sampling. RESULTS: Data analysis revealed 27 competencies, which were grouped into three major categories according to the onion model. These categories were motivation and traits (responsibility, enterprise, etc.), professional philosophy and values (professionalism, career perception, etc.), and knowledge and skills (clinical nursing competency, leadership and management competency, etc.). CONCLUSION: Based on the onion model, core competencies for nurses in Chinese tertiary hospitals were established, revealing three layers of core competencies and giving a theoretical reference for nursing managers to conduct competency training courses based on the competency levels.
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Targeting the tumor microenvironment is increasingly recognized as an effective treatment of advanced lung adenocarcinoma (LUAD). However, few studies have addressed the efficacy of immunotherapy for LUAD. Here, a novel method for predicting immunotherapy efficacy has been proposed, which combines single-cell and bulk sequencing to characterize the immune microenvironment and metabolic profile of LUAD. TCGA bulk dataset was used to cluster two immune subtypes: C1 with "cold" tumor characteristics and C2 with "hot" tumor characteristics, with different prognosis. The Scissor algorithm, which is based on these two immune subtypes, identified GSE131907 single cell dataset into two groups of epithelial cells, labeled as Scissor_C1 and Scissor_C2. The enrichment revealed that Scissor_C1 was characterized by hypoxia, and a hypoxic microenvironment is a potential inducing factor for tumor invasion, metastasis, and immune therapy non-response. Furthermore, single cell analysis was performed to investigate the molecular mechanism of hypoxic microenvironment-induced invasion, metastasis, and immune therapy non-response in LUAD. Notably, Scissor_C1 cells significantly interacted with T cells and cancer-associated fibroblasts (CAF), and exhibited epithelial-mesenchymal transition and immunosuppressive features. CellChat analysis revealed that a hypoxic microenvironment in Scissor_C1elevated TGFß signaling and induced ANGPTL4 and SEMA3C secretion. Interaction with endothelial cells with ANGPTL4, which increases vascular permeability and achieves distant metastasis across the vascular endothelium. Additionally, interaction of tumor-associated macrophages (TAM) and Scissor_C1 via the EREG/EFGR pathway induces tyrosine kinase inhibitor drug-resistance in patients with LAUD. Thereafter, a subgroup of CAF cells that exhibited same features as those of Scissor_C1 that exert immunosuppressive functions in the tumor microenvironment were identified. Moreover, the key genes (EPHB2 and COL1A1) in the Scissor_C1 gene network were explored and their expressions were verified using immunohistochemistry. Finally, the metabolism dysfunction in cells crosstalk was determined, which is characterized by glutamine secretion by TAM and uptake by Scissor_C1 via SLC38A2 transporter, which may induce glutamine addiction in LUAD cells. Overall, single-cell sequencing clarifies how the tumor microenvironment affects immunotherapy efficacy via molecular mechanisms and biological processes, whereas bulk sequencing explains immunotherapy efficacy based on clinical information.
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BACKGROUND: We previously found that occupational exposure to diesel engine exhaust (DEE) was associated with alterations to 19 biomarkers that potentially reflect the mechanisms of carcinogenesis. Whether DEE is associated with biological alterations at concentrations under existing or recommended occupational exposure limits (OELs) is unclear. METHODS: In a cross-sectional study of 54 factory workers exposed long-term to DEE and 55 unexposed controls, we reanalysed the 19 previously identified biomarkers. Multivariable linear regression was used to compare biomarker levels between DEE-exposed versus unexposed subjects and to assess elemental carbon (EC) exposure-response relationships, adjusted for age and smoking status. We analysed each biomarker at EC concentrations below the US Mine Safety and Health Administration (MSHA) OEL (<106 µg/m3), below the European Union (EU) OEL (<50 µg/m3) and below the American Conference of Governmental Industrial Hygienists (ACGIH) recommendation (<20 µg/m3). RESULTS: Below the MSHA OEL, 17 biomarkers were altered between DEE-exposed workers and unexposed controls. Below the EU OEL, DEE-exposed workers had elevated lymphocytes (p=9E-03, false discovery rate (FDR)=0.04), CD4+ count (p=0.02, FDR=0.05), CD8+ count (p=5E-03, FDR=0.03) and miR-92a-3p (p=0.02, FDR=0.05), and nasal turbinate gene expression (first principal component: p=1E-06, FDR=2E-05), as well as decreased C-reactive protein (p=0.02, FDR=0.05), macrophage inflammatory protein-1ß (p=0.04, FDR=0.09), miR-423-3p (p=0.04, FDR=0.09) and miR-122-5p (p=2E-03, FDR=0.02). Even at EC concentrations under the ACGIH recommendation, we found some evidence of exposure-response relationships for miR-423-3p (ptrend=0.01, FDR=0.19) and gene expression (ptrend=0.02, FDR=0.19). CONCLUSIONS: DEE exposure under existing or recommended OELs may be associated with biomarkers reflective of cancer-related processes, including inflammatory/immune response.
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Poluentes Ocupacionais do Ar , MicroRNAs , Exposição Ocupacional , Humanos , Emissões de Veículos/análise , Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Ocupacionais do Ar/análise , Estudos Transversais , União Europeia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Biomarcadores/análiseRESUMO
Diesel engine exhaust (DEE) is an established lung carcinogen, but the biological mechanisms of diesel-induced lung carcinogenesis are not well understood. MicroRNAs (miRNAs) are small noncoding RNAs that play a potentially important role in regulating gene expression related to lung cancer. We conducted a cross-sectional molecular epidemiology study to evaluate whether serum levels of miRNAs are altered in healthy workers occupationally exposed to DEE compared to unexposed controls. We conducted a two-stage study, first measuring 405 miRNAs in a pilot study of six DEE-exposed workers exposed and six controls. In the second stage, 44 selected miRNAs were measured using the Fireplex circulating miRNA assay that profiles miRNAs directly from biofluids of 45 workers exposed to a range of DEE (Elemental Carbon (EC), median, range: 47.7, 6.1-79.7 µg/m3 ) and 46 controls. The relationship between exposure to DEE and EC with miRNA levels was analyzed using linear regression adjusted for potential confounders. Serum levels of four miRNAs were significantly lower (miR-191-5p, miR-93-5p, miR-423-3p, miR-122-5p) and one miRNA was significantly higher (miR-92a-3p) in DEE exposed workers compared to controls. Of these miRNAs, miR-191-5p (ptrend = .001, FDR = 0.04) and miR-93-5p (ptrend = .009, FDR = 0.18) showed evidence of an inverse exposure-response with increasing EC levels. Our findings suggest that occupational exposure to DEE may affect circulating miRNAs implicated in biological processes related to carcinogenesis, including immune function.
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Poluentes Ocupacionais do Ar , MicroRNAs , Exposição Ocupacional , Humanos , MicroRNAs/genética , Poluentes Ocupacionais do Ar/toxicidade , Poluentes Ocupacionais do Ar/análise , Emissões de Veículos/toxicidade , Emissões de Veículos/análise , Epidemiologia Molecular , Estudos Transversais , Projetos Piloto , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , CarcinogêneseRESUMO
BACKGROUND: A blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. METHODS: Adult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18-64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. RESULTS: Of the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. CONCLUSION: Elderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.
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Coagulação Intravascular Disseminada , Sepse , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/etiologia , Fibrinogênio/análiseRESUMO
ADGRD1 (GPR133), an adhesion G protein-coupled receptor (GPCR), has been linked to cancer. However, the prognostic value and regulatory function within non-small-cell lung cancer (NSCLC) is still unclear. This work adopted various bioinformatics methods, including publicly available databases as well as real-time PCR (RT-PCR), for detecting ADGRD1 expression level and investigating the correlation between ADGRD1 expression level and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), immune infiltrating cells, immune-related genes, and targeted regulation mechanisms in NSCLC. According to the results, ADGRD1 expression decreased within NSCLC, which might be the factor predicting prognosis of NSCLC. Meanwhile, ADGRD1 showed significant correlation with TMB and MSI, respectively, as well as immune cell infiltrating levels in lung adenocarcinoma (LUAD), which were primarily linked to macrophage M1, mast cell resting, T cell CD4 memory activated, and T cell CD4 memory resting and were associated with mast cell activated and mast cell resting in lung squamous cell carcinoma (LUSC). The most promising upstream regulation pathways of ADGRD1 were likely miR-142-5p, miR-93-5p, and miR-17-5p, which were overexpressed and associated with poor prognosis in NSCLC. ADGRD1 and immune-related genes correlated with ADGRD1 were shown to be enriched in "positive regulation of leukocyte activation," "external side of plasma membrane," "receptor ligand activity," and "cytokine-cytokine receptor interaction" pathways. ADGRD1 expression and regulation may be critical in determining NSCLC prognosis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Receptores Acoplados a Proteínas G , Humanos , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Instabilidade de Microssatélites , Prognóstico , Receptores Acoplados a Proteínas G/genéticaRESUMO
The application of radiogenomics in oncology has great prospects in precision medicine. Radiogenomics combines large volumes of radiomic features from medical digital images, genetic data from high-throughput sequencing, and clinical-epidemiological data into mathematical modelling. The amalgamation of radiomics and genomics provides an approach to better study the molecular mechanism of tumour pathogenesis, as well as new evidence-supporting strategies to identify the characteristics of cancer patients, make clinical decisions by predicting prognosis, and improve the development of individualized treatment guidance. In this review, we summarized recent research on radiogenomics applications in solid cancers and presented the challenges impeding the adoption of radiomics in clinical practice. More standard guidelines are required to normalize radiomics into reproducible and convincible analyses and develop it as a mature field.
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Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Neoplasias/radioterapia , Genômica/métodos , OncologiaRESUMO
Background: Biological agents used to treat moderate-to-severe plaque psoriasis have been associated with Candida infection and other serious infections. It is, however, necessary to verify whether biologic agents increase the risk of Candida infection and serious infections and whether these risks vary among biologics. Methods: PubMed, EMBASE, and Cochrane Library were searched for eligible randomized controlled trials (RCTs) from their inception to December 2021. Results from individual RCT were pooled using Peto's method with a fixed-effects model, and I 2 was calculated to assess the heterogeneity. A Cochrane collaboration tool was used to examine bias risk, and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were used to assess the quality of evidence. Results: This study included 48 published articles with data from 52 RCTs involving 27297 participants. The anti-interleukin (IL)-17 agents (95% confidence interval (CI) = 1.54-3.45, P < 0.0001) and anti-IL-12/23 agents (95% CI = 1.69-3.83, P < 0.0001) were associated with an increased risk of Candida infection compared with placebos, but there was no difference in Candida infection risk between anti-IL-17 agents and tumor necrosis factor inhibitors (TNFi) (95% CI = 0.92-3.07, P=0.09). There was no evidence that the biological agents increased the risk of serious infections in adult psoriasis (95% CI = 0.93-2.06, P=0.11) or that the biologics differed in the risk of serious infections. Conclusions: Our results indicated that anti-IL-17 agents, especially secukinumab, were associated with the increased risk of Candida infection. The clinically used biological agents did not increase the risk of serious infections.
Assuntos
Produtos Biológicos , Candidíase , Psoríase , Adulto , Anticorpos Monoclonais/uso terapêutico , Fatores Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Candidíase/induzido quimicamente , Candidíase/tratamento farmacológico , Humanos , Psoríase/induzido quimicamente , Psoríase/complicações , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Fator de Necrose TumoralRESUMO
We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.
Assuntos
Exposição Ocupacional , Albumina Sérica Humana , Antioxidantes , Humanos , Espectrometria de Massas/métodos , Exposição Ocupacional/análise , Emissões de Veículos/toxicidadeRESUMO
Background: LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was competitive endogenous RNA (ceRNA) involved in various molecular processes for metastasis development in lung cancer. Single nucleotide polymorphisms (SNPs) in MALAT1 gene might be predictive markers for lung cancer. In our study, we selected rs619586 and rs3200401 in MALAT1 gene to explore their effects on lung cancer susceptibility. Methods: The case-control study included 444 lung cancer cases and 460 healthy controls. Genotyping was performed by Taqman allelic discrimination method. Logistic regression, Student t-test, and Chi-square test (χ2 ) were used to analyze the data. Results: The findings of the study showed that rs3200401 was significantly associated with the risk of non-small cell lung cancer (NSCLC) and lung squamous cell carcinoma (LUSC). Compared with homozygous CC genotype, CT heterozygous genotype decreased risk of NSCLC (Pa = 0.034) and LUSC (Pa = 0.025). In addition, no statistical association was detected between rs619586 and lung cancer susceptibility. The interactions between genes and cigarette smoking were discovered via crossover analysis. However, there were no remarkable gene-environment interactions in additive and multiplicative model. Conclusion: Rs3200401 in lncRNA MALAT1 was associated with the susceptibility of non-small-cell lung cancer and lung squamous cell carcinoma. The gene-environmental (cigarette smoking) interactions were not notable.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , RNA Longo não Codificante , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , China/epidemiologia , Fumar Cigarros/efeitos adversos , Fumar Cigarros/genética , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genéticaRESUMO
There is no consensus on the role of bilirubin in acute ischemic stroke. Higher levels of serum bilirubin may provide a treatment advantage in oxidative-stress-mediated diseases but also may simply reflect the strength of the oxidative stress. As of 28 February 2022, the relevant studies were selected from four databases (PubMed, Web of science, Cochrane, and CNKI) through a retrieval strategy, and strict literature screening and quality evaluation were carried out. The dose-response relationship was fitted with a restricted cubic splines function. We found that the serum total bilirubin level and the direct bilirubin level were positively correlated with the severity of ischemic stroke. The direct bilirubin level was linearly correlated with the severity of stroke (P for non-linearity = 0.55), and the direct bilirubin increase of 1 µmol/L may be related to the 1% increase in the possibility of having moderate or severe ischemic stroke. High bilirubin levels are associated with stroke severity in patients with ischemic stroke and may serve as a marker of the intensity of initial oxidative stress.