RESUMO
Lung cancer subtyping, particularly differentiating adenocarcinoma (ADC) from squamous cell carcinoma (SCC), is paramount for clinicians to develop effective treatment strategies. In this study, we aimed: (i) to discover volatile organic compound (VOC) biomarkers for precise diagnosis of ADC and SCC, (ii) to investigated the impact of risk factors on ADC and SCC prediction, and (iii) to explore the metabolic pathways of VOC biomarkers. Exhaled breath samples from patients with ADC (n= 149) and SCC (n= 94) were analyzed by gas chromatography-mass spectrometry. Both multivariate and univariate statistical analysis method were employed to identify VOC biomarkers. Support vector machine (SVM) prediction models were developed and validated based on these VOC biomarkers. The impact of risk factors on ADC and SCC prediction was investigated. A panel of 13 VOCs was found to differ significantly between ADC and SCC. Utilizing the SVM algorithm, the VOC biomarkers achieved a specificity of 90.48%, a sensitivity of 83.50%, and an area under the curve (AUC) value of 0.958 on the training set. On the validation set, these VOC biomarkers attained a predictive power of 85.71% for sensitivity and 73.08% for specificity, along with an AUC value of 0.875. Clinical risk factors exhibit certain predictive power on ADC and SCC prediction. Integrating these risk factors into the prediction model based on VOC biomarkers can enhance its predictive accuracy. This work indicates that exhaled breath holds the potential to precisely detect ADCs and SCCs. Considering clinical risk factors is essential when differentiating between these two subtypes.
Assuntos
Testes Respiratórios , Carcinoma de Células Escamosas , Expiração , Cromatografia Gasosa-Espectrometria de Massas , Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Testes Respiratórios/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Idoso , Biomarcadores Tumorais/análise , Adenocarcinoma de Pulmão/diagnóstico , Máquina de Vetores de Suporte , Diagnóstico DiferencialRESUMO
Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.
Assuntos
Endométrio , Hidrogéis , Plasma Rico em Plaquetas , Ratos Sprague-Dawley , Regeneração , Animais , Feminino , Endométrio/efeitos dos fármacos , Hidrogéis/química , Regeneração/efeitos dos fármacos , Ratos , Proliferação de Células/efeitos dos fármacos , Ácido Hialurônico/química , Álcool de Polivinil/química , Humanos , Ácidos Borônicos/química , Injeções , Aderências TeciduaisRESUMO
The prevalence of infertility caused by endometrial defects is steadily increasing, posing a significant challenge to women's reproductive health. In this study, injectable "homing-like" bioactive decellularized extracellular matrix short-fibers (DEFs) of porcine skin origin are innovatively designed for endometrial and fertility restoration. The DEFs can effectively bind to endometrial cells through noncovalent dipole interactions and release bioactive growth factors in situ. In vitro, the DEFs effectively attracted endometrial cells through the "homing-like" effect, enabling cell adhesion, spreading, and proliferation on their surface. Furthermore, the DEFs effectively facilitated the proliferation and angiogenesis of human primary endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), and inhibited fibrosis of pretreated HESCs. In vivo, the DEFs significantly accelerated endometrial restoration, angiogenesis, and receptivity. Notably, the deposition of endometrial collagen decreased from 41.19 ± 2.16% to 14.15 ± 1.70% with DEFs treatment. Most importantly, in endometrium-injured rats, the use of DEFs increased the live birth rate from 30% to an impressive 90%, and the number and development of live births close to normal rats. The injectable "homing-like" bioactive DEFs system can achieve efficient live births and intrauterine injection of DEFs provides a new promising clinical strategy for endometrial factor infertility.
Assuntos
Endométrio , Nascido Vivo , Feminino , Animais , Ratos , Suínos , Humanos , Modelos Animais de Doenças , Gravidez , Matriz Extracelular Descelularizada , Ratos Sprague-Dawley , Células Endoteliais da Veia Umbilical HumanaRESUMO
Clear cell renal cell carcinoma (ccRCC), the most common malignant subtype of renal cell carcinoma, is characterized by the accumulation of lipid droplets in the cytoplasm. RNASET2 is a protein coding gene with a low expression level in ovarian cancers, but it is overexpressed in poorly differentiated neuroendocrine carcinomas. There is a correlation between RNASET2 upregulation and triglyceride expression levels in human serum but is unknown whether such an association is a factor contributing to lipid accumulation in ccRCC. Herein, we show that RNASET2 expression levels in ccRCC tissues and cell lines are significantly higher than those in both normal adjacent tissues and renal tubular epithelial cells. Furthermore, its upregulation is associated with increases in ccRCC malignancy and declines in patient survival. We also show that an association exists between increases in both cytoplasmic lipid accumulation and HIF-2α transcription factor upregulation, and increases in both RNASET2 and triglyceride expression levels in ccRCC tissues. In addition, DGAT1 and DGAT2, two key enzymes involved in triglyceride synthesis, are highly expressed in ccRCC tissues. By contrast, RNASET2 knockdown inhibited their expression levels and lowered lipid droplet accumulation, as well as suppressing in vitro cell proliferation, cell invasion, and migration. In conclusion, our data suggest HIF2α upregulates RNASET2 transcription in ccRCC cells, which promotes both the synthesis of triglycerides and ccRCC migration. As such, RNASET2 may have the potential as a biomarker or target for the diagnosis and treatment of ccRCC.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Renais/metabolismo , Lipídeos , Ribonucleases/metabolismo , Proteínas Supressoras de Tumor/genética , Regulação para Cima/genéticaRESUMO
Candida albicans can form biofilm on biotic and abiotic surfaces of medical implants to cause superficial and systemic infections under specific condition. The formation of hyphae and matrix of C. albicans are considered as probable virulence factors. We assessed the inhibitory activities of 26 anthraquinones against C. albicans biofilm formation, which were substituted by different functional groups including hydroxyl groups, amino groups, carboxyl groups, alkyl groups, and glycoside groups at C1- or C2-position. Among them, anthraquinones without substituents at other positions but only an alkyl group attached to C2-position, namely 2-alkyl-anthraquinones were determined to have significant anti-biofilm activities. Furthermore, 2-ethylanthraquinone can significantly affect genes related to extracellular matrix (PMT6 and IFD6), and hyphal formation (HWP1, ECE1 and EFG1), leading to the disrupted formation of biofilm, by detail transcriptomics analysis. We believed that 2-ethylanthraquinone could inspire more discoveries of anti-biofilm agents against C. albicans.
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Candida albicans , Hifas , Antraquinonas/farmacologia , Antifúngicos/farmacologia , Biofilmes , Candida albicans/genética , Perfilação da Expressão Gênica , Hifas/genéticaRESUMO
Exhaled breath analysis has emerged as a promising non-invasive method for diagnosing lung cancer (LC), whereas reliable biomarkers are lacking. Herein, a standardized and systematic study was presented for LC diagnosis, classification and metabolism exploration. To improve the reliability of biomarkers, a validation group was included, and quality control for breath sampling and analysis, comprehensive pollutants analysis, and strict biomarker screening were performed. The performance of exhaled breath biomarkers was shown to be excellent in diagnosing LC even in early stages (stage I and II) with surpassing 0.930 area under the receiver operating characteristic (ROC) curve (AUC), 90% of sensitivity and 88% of specificity both in the discovery and validation analyses. Meanwhile, in these two groups, diagnosing subtypes of LC attained AUCs over 0.930 and reached 1.00 in the two subtypes of adenocarcinomas. It is demonstrated that the metabolism changes in LC are possibly related to lipid oxidation, gut microbial, cytochrome P450 and glutathione S-transferase, and glutathione pathways change in LC progression. Overall, the reliable biomarkers contribute to the clinical application of breath analysis in screening LC patients as well as those in early stages.
Assuntos
Biomarcadores Tumorais/análise , Testes Respiratórios/métodos , Expiração , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Área Sob a Curva , Estudos de Casos e Controles , Análise Discriminante , Poluentes Ambientais/análise , Feminino , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROC , Reprodutibilidade dos Testes , Compostos Orgânicos Voláteis/análiseRESUMO
Chronic fructose consumption and vitamin D deficiency (VDD) diet have been linked to the pandemic of metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). The metabolic mechanisms remain unclear. This study is to explore metabolic changes of mice fed with high fructose syrup and VDD diet in the biogenesis of MetS and NAFLD. C57BL/6J mice were treated with four conditions for 28 weeks: control (standard chow and sterile water), fructose drinking (FD, standard chow and 20 g/100 mL fructose in drinking water), VDD (standard chow with VD depleted and sterile water), and FD+VDD. Metabolites in the serum and liver of mice were analyzed by gas chromatography-mass spectrometry combined with trimethylsilyl derivatization. The histological results indicated that one-hit from long-term fructose drinking led to mild MetS, and a combination with VDD diet induced hepatic steatosis, inflammatory lesion, and interstitial fibrosis in mice, showing significant nonalcoholic steatohepatitis features. Metabolomics analysis showed significant changes in amino acids and short-chain organic acids in response to fructose drinking. VDD diet led to significant increase of hepatic fatty acids, which was consistent with the hepatic morphology of fat deposition. This work demonstrated a concert effect of FD and VDD in promoting MetS and NAFLD through changing in vivo metabolism and signaling pathways. And metabolomics analysis could provide early warnings for the biogenesis of MetS and NAFLD. Importantly, vitamin D supplementation in the diet can balance the metabolic disorders caused by excessive fructose intake.
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Frutose/administração & dosagem , Síndrome Metabólica/metabolismo , Metaboloma , Hepatopatia Gordurosa não Alcoólica/metabolismo , Deficiência de Vitamina D/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Most of the previous literature has focused on the positive effects of ethical leadership on organizations and employees, but some studies have unexpectedly found that ethical leadership is negatively related to employees' well-being at work. Based on the theory of workplace anxiety, this research explored whether ethical leadership can reduce employees' well-being at work by causing them to feel anxious about organizational citizenship behavior and whether organizational concern motivation moderates this mechanism. We collected 227 three-stage time-crossed data samples from 12 institutions in Hainan China, then tested our research hypotheses to confirm that ethical leadership has a negative impact on employees' well-being at work under certain conditions. We found that: (1) ethical leadership is significantly and positively correlated with the organizational citizenship anxiety perceived by employees, (2) organizational citizenship anxiety perceived by employees plays a completely mediating role between ethical leadership and employee well-being at work, and (3) organizational concern motivation not only negatively moderates the negative correlation between employees' organizational citizenship anxiety and well-being at work, but also further moderates the indirect negative effect of ethical leadership on employee well-being at work through organizational citizenship anxiety.
RESUMO
Accurate classification of adenocarcinoma (AC) and squamous cell carcinoma (SCC) in lung cancer is critical to physicians' clinical decision-making. Exhaled breath analysis provides a tremendous potential approach in non-invasive diagnosis of lung cancer but was rarely reported for lung cancer subtypes classification. In this paper, we firstly proposed a combined method, integrating K-nearest neighbor classifier (KNN), borderline2-synthetic minority over-sampling technique (borderlin2-SMOTE), and feature reduction methods, to investigate the ability of exhaled breath to distinguish AC from SCC patients. The classification performance of the proposed method was compared with the results of four classification algorithms under different combinations of borderline2-SMOTE and feature reduction methods. The result indicated that the KNN classifier combining borderline2-SMOTE and feature reduction methods was the most promising method to discriminate AC from SCC patients and obtained the highest mean area under the receiver operating characteristic curve (0.63) and mean geometric mean (58.50) when compared to others classifiers. The result revealed that the combined algorithm could improve the classification performance of lung cancer subtypes in breathomics and suggested that combining non-invasive exhaled breath analysis with multivariate analysis is a promising screening method for informing treatment options and facilitating individualized treatment of lung cancer subtypes patients.
Assuntos
Testes Respiratórios , Neoplasias Pulmonares/classificação , Adenocarcinoma/classificação , Adenocarcinoma/diagnóstico , Algoritmos , Testes Respiratórios/métodos , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/diagnóstico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Prognóstico , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Lung cancer is the most common cancer and the leading cause of cancer death in China, as well as in the world. Late diagnosis is the main obstacle to improving survival. Currently, early detection methods for lung cancer have many limitations, for example, low specificity, risk of radiation exposure and overdiagnosis. Exhaled breath analysis is one of the most promising non-invasive techniques for early detection of lung cancer. The aim of this study is to identify volatile organic compound (VOC) biomarkers in lung cancer and to construct a predictive model for lung cancer based on exhaled breath analysis. METHODS AND ANALYSIS: The study will recruit 389 lung cancer patients in one cancer centre and 389 healthy subjects in two lung cancer screening centres. Bio-VOC breath sampler and Tedlar bag will be used to collect breath samples. Gas chromatography-mass spectrometry coupled with solid phase microextraction technique will be used to analyse VOCs in exhaled breath. VOC biomarkers with statistical significance and showing abilities to discriminate lung cancer patients from healthy subjects will be selected for the construction of predictive model for lung cancer. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Sichuan Cancer Hospital on 6 April 2017 (No. SCCHEC-02-2017-011). The results of this study will be disseminated in presentations at academic conferences, publications in peer-reviewed journals and the news media. TRIAL REGISTRATION NUMBER: ChiCTR-DOD-17011134; Pre-results.