RESUMO
This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2-4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1ß, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1ß, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1ß and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1ß, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified "wire-meshing cylindrical board" model effectively overcomes the limitations of the traditional "jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.
Assuntos
Astenopia , Síndromes do Olho Seco , Ratos , Animais , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Astenopia/metabolismo , Ratos Wistar , Síndromes do Olho Seco/metabolismo , Lágrimas/metabolismo , Fluoresceína/metabolismo , Interleucina-1beta/metabolismo , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant tumors worldwide. Finding effective prognostic markers and therapeutic targets is of great significance for controlling metastasis and invasion clinically. METHODS: The open copy-number aberrations and gene expression datasets were analysed, and the data of 102 LUAD patients was used for further validation. The cell proliferation, colony formation, migration, invasion assays and mice tumor models were used to detect the function of SEC61G. The epidermal growth factor receptor (EGFR) pathway was also detected to find the mechanism of Sec61γ. RESULTS: Based on the open datasets, we found that the high level of SEC61G mRNA may drive LUAD metastasis. Furthermore, the overexpression of Sec61γ protein was significantly associated with poor prognosis and greater tumor cell proliferation and metastasis. The SEC61G knockdown could inhibit the EGFR pathway, including STAT3, AKT and PI3K, which can be reversed by Sec61γ overexpression and epithelial growth factor (EGF) supplement. CONCLUSIONS: Sec61γ promoted the proliferation, metastasis, and invasion of LUAD through EGFR pathways. Sec61γ might be a potential target for the treatment of LUAD metastases.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Animais , Camundongos , Linhagem Celular Tumoral , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proliferação de Células/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
RNA-sequencing enables accurate and low-cost transcriptome-wide detection. However, expression estimates vary as reference genomes and gene annotations are updated, confounding existing expression-based prognostic signatures. Herein, prognostic 9-gene pair signature (GPS) was applied to 197 patients with stage I lung adenocarcinoma derived from previous and latest data from The Cancer Genome Atlas (TCGA) processed with different reference genomes and annotations. For 9-GPS, 6.6% of patients exhibited discordant risk classifications between the two TCGA versions. Similar results were observed for other prognostic signatures, including IRGPI, 15-gene and ORACLE. We found that conflicting annotations for gene length and overlap were the major cause of their discordant risk classification. Therefore, we constructed a prognostic 40-GPS based on stable genes across GENCODE v20-v30 and validated it using public data of 471 stage I samples (log-rank P < 0.0010). Risk classification was still stable in RNA-sequencing data processed with the newest GENCODE v32 versus GENCODE v20-v30. Specifically, 40-GPS could predict survival for 30 stage I samples with formalin-fixed paraffin-embedded tissues (log-rank P = 0.0177). In conclusion, this method overcomes the vulnerability of existing prognostic signatures due to reference genome and annotation updates. 40-GPS may offer individualized clinical applications due to its prognostic accuracy and classification stability.
Assuntos
Adenocarcinoma/patologia , Perfilação da Expressão Gênica , Neoplasias Pulmonares/patologia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Formaldeído , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Anotação de Sequência Molecular , Inclusão em Parafina , Prognóstico , Análise de Sequência de RNA/métodos , Fixação de Tecidos , TranscriptomaRESUMO
Surface water pollution has always posed a serious challenge to water quality management. Improving water quality management requires figuring out how to comprehend water quality conditions scientifically and effectively as well as quantitatively identify regional pollution sources. In this study, Xianghai Lake, a typical lake-type wetland on the Northeast China Plain, was taken as the research area. Based on a geographic information system (GIS) method and 11 water quality parameters, the single-factor evaluation and comprehensive water quality index (WQI) methods were used to comprehensively evaluate the water quality of the lake-type wetland in the level period. Four key water quality parameters were determined by the principal component analysis (PCA) method, and more convenient comprehensive water quality evaluation models, the minimum WQI considering weights (WQImin-w) and the minimum WQI without considering weights (WQImin-nw) were established. The multiple statistical method and the absolute principal component score-multiple liner regression (APCS-MLR) model were combined to analyse the lake pollution sources based on the spatial changes in pollutants. The findings demonstrated that the WQImin-nw model's water quality evaluation outcome was more accurate when weights were not taken into account. The WQImin-nw model can be used as a simple and convenient way to comprehend the variations in water quality in wetlands of lakes and reservoirs. It was concluded that the comprehensive water quality in the study area was at a "medium" level, and CODMn was the main limiting factor. Nonpoint source pollution (such as agricultural planting and livestock breeding) was the most important factor affecting the water quality of Xianghai Lake (with a comprehensive contribution rate of 31.65%). The comprehensive contribution rates of sediment endogenous and geological sources, phytoplankton and other plants, and water diversion and other hydrodynamic impacts accounted for 25.12%, 19.65%, and 23.58% of the total impact, respectively. This study can provide a scientific method for water quality assessment and management of lake wetlands, and an effective support for migration of migratory birds, habitat protection and grain production security.
Assuntos
Poluentes Químicos da Água , Qualidade da Água , Áreas Alagadas , Lagos , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Melhoramento Vegetal , Poluição da Água/análise , ChinaRESUMO
BASP1 is involved in signal transduction and cytoskeleton formation and plays a tumor-promoting or tumor-suppressing role in cancers. We found BASP1 was overexpressed in lung adenocarcinoma tissues and promoted the proliferation and migration of lung adenocarcinoma cells. The mechanism may be related to inhibition of cell apoptosis and abnormal activation of the Wnt/ß-catenin pathway and epithelial-mesenchymal transformation. BASP1 is associated with poor prognosis in lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão/genética , Biologia Computacional/métodos , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Repressoras/metabolismo , Progressão da Doença , Humanos , Prognóstico , TransfecçãoRESUMO
BACKGROUND/AIMS: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. METHODS: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. RESULTS: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. CONCLUSION: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.
Assuntos
Regulação para Baixo/efeitos dos fármacos , Neoplasias Pulmonares/terapia , Porfirinas/uso terapêutico , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Terapia por Ultrassom , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Porfirinas/farmacocinética , Porfirinas/farmacologia , Proteína Serina-Treonina Quinases de Interação com Receptores/análise , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Terapia por Ultrassom/métodosRESUMO
Background: Brain metastasis (BM) is a prevalent form of metastasis in lung adenocarcinoma (LUAD), necessitating investigations into the underlying mechanisms. Interleukin 34 (IL-34) and its receptors, macrophage colony-stimulating factor-1 receptor (CSF-IR), Syndecan-1 (SDC-1), and protein-tyrosine phosphatase zeta receptor (PTPRZ1), are known to play pivotal roles in the metastasis of malignant tumors, thereby holding promise as potential biomarkers for studying BM in LUAD. Methods: We performed immunohistochemistry to analyze the expression of IL-34, CSF-1R, SDC-1, and PTPRZ1 in 10 pairs of LUAD primary tissues and BMs, along with 96 unpaired primary tissues and 68 unpaired BMs. Subsequently, we evaluated the association between protein expression and the occurrence of BM. Furthermore, Kaplan-Meier survival curve analysis was conducted on both network and clinical data to explore the association between protein expression and patient prognosis and survival. Results: At the protein level, the expression of IL-34 and its receptors showed significant variation between paired primary tumors and BMs in 10 LUAD patients. The levels of IL-34, CSF-1R, and SDC-1 expression are typically elevated in brain metastatic lesions of LUAD compared to primary LUAD tumors. Furthermore, patients with high CSF-1R expression in primary LUAD are at a greater risk of developing brain metastases. High expression of IL-34 and CSF-1R in primary LUAD lesions indicated poor disease-free survival (DFS) and overall survival (OS), while high expression of SDC-1 indicated poor OS. Cox multivariate analysis further revealed that CSF-1R and IL-34+CSF-1R positivity independently affected LUAD OS. These findings were further substantiated in unpaired samples. Conclusions: Our results indicate significant alterations in the expression of IL-34 and its receptors, CSF-1R and SDC-1, between LUAD primary lesions and BMs, with increased expression observed in BMs. LUAD patients with positive CSF-1R expression in primary lesions exhibited a higher likelihood of developing BM, and high expression of IL-34, CSF-1R, and SDC-1 correlated with poor prognosis. These findings contribute novel insights towards identifying potential treatment or diagnostic targets for metastatic LUAD.
RESUMO
Background: RBM10 is commonly mutated in lung adenocarcinoma (LUAD). However, its role in the pathogenesis of LUAD remains undefined. EGFR-mutant LUAD represents a distinct subset of non-small cell lung cancer (NSCLC). The function of RBM10 in tumor pathogenesis is supposed to differ between EGFR-mutant and EGFR-wt LUAD. This study aimed to interrogate the prevalence of RBM10 mutation in a large cohort of Chinese patients with LUAD and investigate the association of RBM10 mutation with clinical and molecular characteristics of EGFR-mutant and EGFR-wt LUAD. Methods: Tumor sequencing data from 2848 Chinese patients with LUAD were retrospectively reviewed and analyzed. The prevalence of RBM10 was also compared with other three cohorts: OrigMed (n = 1222), MSKCC (n = 1267), and TCGA (n = 566). The associations of RBM10 mutation with clinical and molecular characteristics were assessed. An external cohort of 182 patients with LUAD who received PD-1 inhibitor were used to investigate the association of RBM10 mutation with clinical outcomes upon immunotherapy. Results: Our cohort showed a higher prevalence of RBM10 in EGFR-mutant LUAD than in EGFR-wt LUAD (14.8 % vs. 6.5 %, p < 0.001). The enrichment of RBM10 mutations in EGFR-mutant LUAD was also seen in another Chinese cohort (OrigMed: 14.9 % vs. 7.8 %, p < 0.001), but not in the two western cohorts (MSKCC: 7.4 % vs. 9.5 %, p = 0.272; TCGA: 8.1 % vs. 6.7 %, p = 0.624). RBM10 mutations co-occurred more frequently with EGFR L858R mutations (23.7 %) than with other types of EGFR mutations (19 del: 7.7 %; other: 7.1 % in others, p < 0.001). In EGFR-mutant LUAD, RBM10 mutations were more commonly found in stage I (18.2 %) and II (21.8 %) vs. stage III (9.4 %) and IV (11.3 %) tumors (p < 0.001). The proportion of PD-L1 positive expression in EGFR-mutant LUAD with concomitant RBM10 mutation was not different from that those without RBM10 mutations (41.8 % vs. 47.9 %, p = 0.566). In contrast, RBM10 mutation occurred more frequently in EGFR-wt LUAD at stage II-IV (stage II: 12.0 %, stage III: 8.7 %, stage IV: 6.6 %) than at stage I (2.8 %). EGFR-wt LUAD with concomitant RBM10 mutations had higher proportions of PD-L1 expression positivity (78.9 % vs. 61.9 %, p = 0.014) and higher tumor mutational load (8.97 vs. 2.99 muts/Mb, p < 0.001) than those without. Patients with EGFR-wt LUAD who also harbored RBM10 loss of function (LOF) mutations had a longer median PFS upon immunotherapy than those with RBM10 non-LOF mutations (7.15 m vs. 2.60 m, HR = 4.83 [1.30-17.94], p = 0.010). Conclusion: We comprehensively investigated RBM10 mutations in a Chinese cohort with LUAD. Compared to western cohorts, a significant enrichment of RBM10 mutations in EGFR-mutant LUAD compared to EGFR-wildtype LUAD in the Chinese population. RBM10 mutation shows different associations with clinical and molecular characteristics between EGFR-mutant and EGFR-wt LUAD, suggesting a divergent mechanism between these two subsets via which RBM10 deficiency contribute to tumor pathogenesis. The findings contribute to our understanding of the molecular landscape of LUAD and highlight the importance of considering population-specific factors in cancer genomics research.
RESUMO
Anthropogenic activities have dramatically altered land use/land cover (LULC), leading to ecosystem service (ES) degradation and further ecological risks. Ecological risks are particularly serious in ecologically fragile regions because trade-offs between economic development and ecological protection are prominent. Thus, ways in which to assess the response of ecological risks to LULC change under each development scenario in ecologically fragile regions remain challenging. In this study, future LUCC and its impact on ESs under four development scenarios in 2040 in western Jilin Province were predicted using a patch-generating land use simulation model and the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model. Ecological risk was assessed based on future LUCC possibilities, and potential ES degradation and potential drivers of ecological risks were explored using a geographic detector. The results showed that the cropland development scenario (CDS) would experience large-scale urbanization and cropland expansion. Carbon storage (CS), habitat quality (HQ), and water purification (WP) degraded the most under the CDS, and grain yield (GY) and water yield (WY) degraded the most under the ecological protection scenario (EPS). The LUCC probability under the CDS (14.37 %) was the highest, while the LUCC probability under the comprehensive development scenario (CPDS) (8.68 %) was the lowest. The risk of WP degradation was greatest under the CDS, but the risk of soil retention (SR) degradation was greatest under the natural development scenario (NDS), EPS, and CPDS. Ecological risk coverage was the largest (98.04 %), and ecological risks were the highest (0.21) under the CDS, while those under the EPS were the opposite. Distance to roads and population density had a higher impact on ecological risks than other drivers. Further attention should be given to the ecological networks and pattern establishment in urbanized regions. This study will contribute to risk prevention and sustainable urban and agricultural development.
RESUMO
Atherosclerosis (AS) is the pathologic basis of various cardiovascular and cerebrovascular events, with a high degree of heterogeneity among different arterial beds. However, mechanistic differences between arterial beds remain unexplored. The aim of this study was to explore key genes and potential mechanistic differences between AS in different arterial beds through bioinformatics analysis. Carotid atherosclerosis (CAS), femoral atherosclerosis (FAS), infrapopliteal atherosclerosis (IPAS), abdominal aortic atherosclerosis (AAS), and AS-specific differentially expressed genes (DEGs) were screened from the GSE100927 and GSE57691 datasets. Immune infiltration analysis was used to identify AS immune cell infiltration differences. Unsupervised cluster analysis of AS samples from different regions based on macrophage polarization gene expression profiles. Weighted gene co-expression network analysis (WGCNA) was performed to identify the most relevant module genes with AS. Hub genes were then screened by LASSO regression, SVM-REF, and single-gene differential analysis, and a nomogram was constructed to predict the risk of AS development. The results showed that differential expression analysis identified 5, 4, 121, and 62 CAS, FAS, IPAS, AAS-specific DEGs, and 42 AS-common DEGs, respectively. Immune infiltration analysis demonstrated that the degree of macrophage and mast cell enrichment differed significantly in different regions of AS. The CAS, FAS, IPAS, and AAS could be distinguished into two different biologically functional and stable molecular clusters based on macrophage polarization gene expression profiles, especially for cardiomyopathy and glycolipid metabolic processes. Hub genes for 6 AS (ADAP2, CSF3R, FABP5, ITGAX, MYOC, and SPP1), 4 IPAS (CLECL1, DIO2, F2RL2, and GUCY1A2), and 3 AAS (RPL21, RPL26, and RPL10A) were obtained based on module gene, gender stratification, machine learning algorithms, and single-gene difference analysis, respectively, and these genes were effective in differentiating between different regions of AS. This study demonstrates that there are similarities and heterogeneities in the pathogenesis of AS between different arterial beds.
Assuntos
Doenças da Aorta , Aterosclerose , Doenças das Artérias Carótidas , Humanos , Aterosclerose/genética , Artérias , Algoritmos , Proteínas de Ligação a Ácido GraxoRESUMO
RNA-binding motif protein 10 (RBM10), one of the members of the RNA-binding protein (RBP) family, has a tumor suppressor role in multiple cancers. However, the functional role of RBM10 in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we observed that RBM10 is significantly downregulated in LUAD tissues compared with normal tissues. Low RBM10 expression is significantly associated with poor outcome of LUAD patients. In vitro and in vivo experiments show that RBM10 inhibits cell proliferation, metastasis and EMT progression in LUAD. Mechanistically, we demonstrate that RBM10 interacts with ß-catenin interacting protein 1 (CTNNBIP1) and positively regulates its expression, disrupting the binding of ß-catenin to the transcription factor TCF/LEF, thereby inactivating the Wnt/ß-catenin pathway. In conclusion, this is the first study reporting the role of RBM10 in suppressing LUAD progression at least via partly inactivating the Wnt/ß-catenin pathway, which provides new insights into the tumorigenesis and metastasis of LUAD. Thus, RBM10 may be a promising new therapeutic target or clinical biomarker for LUAD therapy in the future.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Ligação a RNA/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
With the advancement of tumor subtype-specific treatments, precise histopathologic distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is of significant clinical importance. Nevertheless, the current markers are insufficiently precise in poorly differentiated tissue. This study aimed to establish a histology-specific immunomarker combination to subclassify non-small cell lung cancer (NSCLC) specimens. Based on previous work, we assessed the differential expression of anterior gradient 2 (AGR2) and keratin 5 (KRT5) in ADC and SCC by analyzing public datasets and postoperative specimens. Subsequently, we established a train set (n = 188) and a validation set (n = 42) comprised of NSCLC surgical specimens for training and verifying the subtype-identification capabilities of the two biomarkers separately and in combination, and contrasted the diagnostic utility of AGR2-KRT5 with that of the classic immunomarker combination, TTF1-P40. Differential expression of the two genes was statistically significant in ADC and SCC samples, both at the mRNA and protein levels. The specificity and sensitivity of AGR2 to detect ADC in the training set were 97.0% and 94.4%, while the sensitivity and specificity of KRT5 to determine SCC were 93.9% and 98.9%, respectively. The accuracies of AGR2-KRT5 in ADC, SCC, and across all samples were 93.3%, 92.0% and 92.6% respectively. In the validation cohort, the predictive accuracy of AGR2-KRT5 was up to 100% for ADC and 86.7% for SCC. Compared with TTF1-P40 in ADC samples, AGR2-KRT5 had 8.4% higher accuracy. In summary, the AGR2-KRT5 immunomarker combination reliably distinguished SCC from ADC, and was more accurate than TTF1-P40 in ADC.
RESUMO
Non-small cell lung cancer (NSCLC) is one type of the most common cancers, which results in the major death worldwide. This study focuses on the understanding of the molecular mechanism of lncRNA NR2F2-AS1 and its regulation on epithelial-mesenchymal transition (EMT) in the development of NSCLC. Expressions of lncRNA NR2F2-AS1, miR-545-5p, c-Met, biliverdin reductase (BVR), ATF-2 and EMT-related markers in NSCLC tissues and cells were measured by western blotting and RT-qPCR assays. The impact of lncRNA NR2F2-AS1 and miR-545-5p on the cell proliferation, migration, invasion and EMT were analyzed by CCK-8, colony formation, wound healing and transwell assays. The interactions among lncRNA NR2F2-AS1, miR-545-5p and c-Met predicted by bioinformatic analysis were evaluated through dual luciferase reporter assay and fluorescence in situ hybridization (FISH). After generating tumor xenografts, immunohistochemistry was utilized to measure the expression of Ki-67 and EMT-related proteins in vivo. Our results showed that lncRNA NR2F2-AS1, c-Met, BVR and ATF-2 were overexpressed while miR-545-5p was silenced in NSCLC tissues and cells. Silencing of lncRNA NR2F2-AS1 or upregulating miR-545-5p significantly inhibited the cell proliferation, migration, invasion and EMT process. The EMT process could be inhibited by suppressing c-Met/BVR/ATF-2 axis. The tumor xenograft experiments demonstrated that the tumor growth and EMT process were significantly inhibited by silencing lncRNA NR2F2-AS1 or overexpression of miR-545-5p in vivo. LncRNA NR2F2-AS1 promoted the NSCLC development through suppressing miR-545-5p to activate EMT process through c-Met/BVR/ATF-2 axis. Our study indicated that lncRNA NR2F2-AS1 and miR-545-5p could be used as potential therapeutic targets to improve NSCLC treatment.
RESUMO
Superadsorbent hydrogel was prepared from lignin and montmorillonite for Cu(II) ions removal, and the chemical structure and morphology of the hydrogel were characterized by FT-IR, XRD, SEM and XPS. The swelling kinetics of the prepared hydrogel was investigated, and the result showed that the swelling process fit the Schott second-order dynamic equation. The influences of pH, contact time, Na+ concentration, and initial Cu(II) ion concentration on adsorption were studied, and the maximum adsorption value was 1.17â¯mmol/g, and the adsorption was rapid during the initial 5â¯h period, and copper ions adsorption on the superadsorbent hydrogel is a favorable process. The results also indicated that the adsorption kinetics was in accordance with the pseudo-second-order kinetic model and the adsorption isotherm conformed to the Freundlich model. FT-IR and XPS analysis revealed that the adsorption behavior was mainly due to ion exchange. The desorption ratios of copper ions from the superadsorbent were >0.8, and the regeneration efficiency was >80% after five cycles reuse, and the results show the excellent desorption performance and reusability of the prepared hydrogel.