Data mining of The Cancer Genome Atlas (TCGA) data has significantly facilitated cancer genome research and provided unprecedented opportunities for cancer researchers. However, existing web ...applications for DNA methylation analysis does not adequately address the need of experimental biologists, and many additional functions are often required.
To facilitate DNA methylation analysis, we present the SMART (Shiny Methylation Analysis Resource Tool) App, a user-friendly and easy-to-use web application for comprehensively analyzing the DNA methylation data of TCGA project. The SMART App integrates multi-omics and clinical data with DNA methylation and provides key interactive and customized functions including CpG visualization, pan-cancer methylation profile, differential methylation analysis, correlation analysis and survival analysis for users to analyze the DNA methylation in diverse cancer types in a multi-dimensional manner.
The SMART App serves as a new approach for users, especially wet-bench scientists with no programming background, to analyze the scientific big data and facilitate data mining. The SMART App is available at http://www.bioinfo-zs.com/smartapp.
An organocatalytic asymmetric formal 3+2 cycloaddition of isatin-derived 3-indolylmethanol with 3-methyl-2-vinylindole has been established, leading to highly stereoselective construction of a ...spirocyclopentabindole-1,3'-oxindole scaffold with the concomitant creation of three contiguous stereogenic centers (72-99% yield, all >95 : 5 dr, 90-98% ee), one of which is an all-carbon quaternary stereogenic center.
Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Novel molecules are urgently required for the diagnosis and prognosis of LUSC. ...Here, we conducted our data mining analysis for LUSC by integrating the differentially expressed genes acquired from Gene Expression Omnibus (GEO) database by comparing tumor tissues versus normal tissues (GSE8569, GSE21933, GSE33479, GSE33532, GSE40275, GSE62113, GSE74706) into The Cancer Genome Atlas (TCGA) database which includes 502 tumors and 49 adjacent non-tumor lung tissues. We identified intersections of 129 genes (91 up-regulated and 38 down-regulated) between GEO data and TCGA data. Based on these genes, we conducted our downstream analysis including functional enrichment analysis, protein-protein interaction, competing endogenous RNA (ceRNA) network and survival analysis. This study may provide more insight into the transcriptomic and functional features of LUSC through integrative analysis of GEO and TCGA data and suggests therapeutic targets and biomarkers for LUSC.
Predicting lung adenocarcinoma (LUAD) risk is crucial in determining further treatment strategies. Molecular biomarkers may improve risk stratification for LUAD.
We analyzed the gene expression ...profiles of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We initially used three distinct algorithms (sigFeature, random forest, and univariate Cox regression) to evaluate each gene's prognostic relevance. Survival related genes were then fitted into the least absolute shrinkage and selection operator (LASSO) model to build a risk prediction model for LUAD. After 100,000 times of calculation and model construction, a 16-gene-based prediction model capable of classifying LUAD patients into high-risk and low-risk groups was successfully built.
Using a combined strategy, we initially identified 2472 significant survival-related genes. Functional enrichment analysis demonstrated these genes' relevance to tumor initiation and progression. Using the LASSO method, we successfully built a reliable risk prediction model. The risk model was validated in two external sets and an independent set. The expression of these 16 genes was highly correlated with patients' risk. High-risk group patients witnessed poorer recurrence-free survival (RFS) and overall survival (OS) compared to low-risk group patients. Moreover, stratification analysis and decision curve analysis (DCA) confirmed the independence and potential translational value of this predictive tool. We also built a nomogram comprising risk model and stage to predict OS for LUAD patients.
Our risk model may serve as a practical and reliable prognosis predictive tool for LUAD and could provide novel insights into the understanding of the molecular mechanism of this disease.
A series of novel oxime-containing pyrazole derivatives were synthesized and characterized by IR,
1H NMR, HRMS spectroscopy, and X-ray analysis. A dose- and time-dependent inhibition of proliferation ...was observed in A549 lung cancer cell after compounds treatment. Hoechst 33258 staining assay and Western blot analysis of LC3-II level showed that the inhibition against A549 cell growth might be attributed to apoptosis and autophagy.
A series of novel oxime-containing pyrazole derivatives were synthesized by the reaction of ethyl 3-phenyl-1
H-pyrazole-5-carboxylate derivatives and 2-bromo-1-phenylethanone followed by the reaction with hydroxylamine hydrochloride. The structures were determined by IR,
1H NMR, HRMS, and X-ray analysis. A dose- and time-dependent inhibition of proliferation was observed in A549 lung cancer cell after compound treatment. Inhibition of growth was mainly attributed to the autophagy induction.
In our country, the Yellow River Basin ecological protection and development are put forward under the background of high quality. Among the 14 large-scale coal bases in our country, 9 coal bases are ...located in the Yellow River Basin, and the Shenfu-Dongsheng Coalfield, which is currently the largest under development, is located here. The region is in the process of coal mining, and the movement of overlying strata will cause the stress redistribution and coal seam in overlying aquifers also due to the effect of pore water pressure along the seepage of rock fracture and damage of overlying aquifer, so in the same formation, stress and the coupled action of seepage flow will produce mutual influence. This article through the early stage of the theoretical results discussed the application of numerical simulation method for simulating 2301 face, and the effect of stress on seepage is concluded. It is proved that the numerical simulation analysis has an important reference value for the coupling problem of stress and seepage. At the same time, the protective mining of aquifers is the basic condition for the surface ecological protection of the area, and it also provides a theoretical basis for the restoration of the ecological environment in the coal mining areas of the Yellow River Basin.
TGFB2-OT1 (TGFB2 overlapping transcript 1) is a newly discovered long noncoding RNA (lncRNA) derived from the 3′UTR of TGFB2. It can regulate autophagy in vascular endothelial cells (VECs). However, ...the mechanisms of TGFB2-OT1 action are unclear, and whether it is involved in VECs dysfunction needs investigation. Here, the level of TGFB2-OT1 was markedly increased by lipopolysaccharide and oxidized low-density lipoprotein, 2 VECs inflammation triggers. A chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) significantly decreased TGFB2-OT1 levels and inhibited the effect of LPS and oxLDL. The NUPR1 level was upregulated by the 2 inflammation inducers and modulated the TGFB2-OT1 level by promoting the expression of TIA1, responsible for TGFB2-OT1 processing. We focused on how TGFB2-OT1 regulated autophagy and inflammation. Use of miRNA chip assay, TGFB2-OT1 overexpression technology and 3BDO revealed that TGFB2-OT1 regulated the levels of 3 microRNAs, MIR3960, MIR4488 and MIR4459. Further studies confirmed that TGFB2-OT1 acted as a competing endogenous RNA, bound to MIR3960, MIR4488 and MIR4459, then regulated the expression of the miRNA targets CERS1 (ceramide synthase 1), NAT8L (N-acetyltransferase 8-like GCN5-related, putative), and LARP1 (La ribonucleoprotein domain family, member 1). CERS1 and NAT8L participate in autophagy by affecting mitochondrial function. TGFB2-OT1 increased the LARP1 level, which promoted SQSTM1 (sequestosome 1) expression, NFKB RELA and CASP1 activation, and then production of IL6, IL8 and IL1B in VECs. Thus, NUPR1 and TIA1 may control the level of TGFB2-OT1, and TGFB2-OT1 bound to MIR3960, MIR4488 and MIR4459, which targeted CERS1, NAT8L, and LARP1, respectively, the key proteins involved in autophagy and inflammation.
Abstract Objectives Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. ...Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133+ CXCR4+ cells in esophageal squamous cell carcinoma. Methods Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan–Meier and Cox regression. Results Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4+ cells (CD133+ CXCR4+ and CD133− CXCR4+ ) showed high invasive potential and CD133+ CXCR4+ cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival ( P < .01). Conclusions Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets.
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