ABSTRACT
OBJECTIVE: Bladder cancer (BC), as the most common malignant tumor of the urinary tract, has a complex biological behavior. Currently, there are still some limitations in the diagnosis and treatment of BC. Despite the great progress made in immunotherapy, there is still a lack of key genes for the diagnosis of BC. Therefore, it is particularly important to explore the differentially expressed genes (DEGs) and their effectiveness on prognosis of BC with different tumor microenvironment scores. METHODS: The gene expression dataset of BC was downloaded from the Cancer Genome Atlas (TCGA) database. The correlation between clinicopathological characteristics of patients and scores of immune and stromal components was analyzed. Patients were divided into high and low score groups according to their tumor microenvironment score (Immune score, Stromal score, ESTIMATE score). DEGs between high and low score groups were identified using R software and then subjected to enrichment analyses to assess their potential biological functions and signaling pathways. The protein-protein interaction (PPI) network was constructed using the STRING database to further identify hub genes. The expression levels of hub genes in BC were verified by TCGA database. Subsequently, the hub genes were evaluated for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS), and corresponding forest plots were created. RESULTS: A total of 2346 DEGs were obtained, including 1120 up-regulated genes and 1226 down-regulated genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses found DEGs were mainly enriched in cell migration and immune-related pathways. Meanwhile, The PPI network finally yielded top 10 hub genes with predictive value, which included actin beta (ACTB), interleukin 6 (IL-6), Jun proto-oncogene (JUN), CD4 molecule (CD4), heat shock protein 90 alpha family class A member 1 (HSP90AA1), protein tyrosine phosphatase receptor type C (PTPRC), tumor protein p53 (TP53), SRC proto-oncogene (SRC), fibronectin 1 (FN1), and tumor necrosis factor (TNF). Among them, CD4, PTPRC, and SRC were potential protective factors for BC. CONCLUSION: The top 10 hub genes (ACTB, IL-6, JUN, CD4, HSP90AA1, PTPRC, TP53, SRC, FN1, TNF) obtained based on tumor microenvironment scores all had potential predictive value. Elevated expression of protective factors (CD4, PTPRC, and SRC) indicates better survival outcome of BC subjects. Further exploration of the molecular developmental mechanisms of these hub genes will help to develop novel personalized therapies and improve BC prognosis.
Subject(s)
Biomarkers, Tumor , Databases, Genetic , Gene Expression Regulation, Neoplastic , Protein Interaction Maps , Tumor Microenvironment , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Prognosis , Protein Interaction Maps/genetics , Gene Expression Regulation, Neoplastic/genetics , Biomarkers, Tumor/genetics , Female , Gene Expression Profiling/methods , Male , Gene Regulatory Networks , Proto-Oncogene Mas , Computational Biology/methodsABSTRACT
Chinese medicinal materials (CMMs) are important strategic resource in China. The cultivation process of medicinal plants is the key link which directly affect the quality and efficacy. The literatures of CMMs cultivation were acquired from China National Knowledge Infrastructure (CNKI) database and State Intellectual Property Office (SIPO) patent database for the years between 2001 and 2021. All the articles found were subjected to bibliometric analysis. The development trends and key topics were analyzed and visualized by VOSviewer and CiteSpace software. The results indicate that ecological planting, under-forest economy, intercropping patterns and industrialization production are the research hotspots in this field; cultivation technology and nutritional fertilization technology are the main areas addressed in recent years. Therefore, the high-quality and sustainable development of CMMs cultivation should be examined in terms of theoretical approaches, technical innovation, multi-cooperation, and intellectual property protection.
ABSTRACT
Tumor metastasis and cancer recurrence are often a result of cell heterogeneity, where specific subpopulations of tumor cells may be resistant to radio- or chemotherapy. To investigate this physiological and phenotypic diversity, single-cell metabolomics provides a powerful approach at the chemical level, where distinct lipid profiles can be found in different tumor cells. Here, we established a highly sensitive platform using nanoflow liquid chromatography (nLC) combined with multinozzle emitter electrospray ionization mass spectrometry for more in-depth metabolomics profiling. Our platform identified 15 and 17 lipids from individual osteosarcoma (U2OS) and glioblastoma (GBM) cells when analyzing single-cell samples. Additionally, we used the functional single-cell selection (fSCS) pipeline to analyze the subpopulations of cells with a DNA damage response (DDR) in U2OS cells and fast migration in GBM cells. Specifically, we observed a down-regulation of polyunsaturated fatty acids (PUFAs) in U2OS cells undergoing DDR, such as fatty acids FA 20:3; O2 and FA 17:4; O3. Furthermore, ceramides (Cer 38:0; O3) and triglycerides (TG 36:0) were found to be down-regulated in fast-migrating GBM cells compared to the slow-migrating subpopulation. These findings suggest the potential roles of these metabolites and/or lipids in the cellular behavior of the subpopulations.
Subject(s)
Glioblastoma , Spectrometry, Mass, Electrospray Ionization , Humans , Chromatography, Liquid/methods , Spectrometry, Mass, Electrospray Ionization/methods , Metabolomics/methods , Fatty Acids, Unsaturated/metabolism , TriglyceridesABSTRACT
<p><b>OBJECTIVE</b>To study the relationships among magnetic resonance imaging (MRI), histological findings, and insulin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits.</p><p><b>METHODS</b>Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I.</p><p><b>RESULTS</b>At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific "line-like sign". The MRI findings of all femora in Group B were normal.</p><p><b>CONCLUSION</b>MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.</p>