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1.
Heliyon ; 10(18): e37739, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39318795

ABSTRACT

Lung adenocarcinoma (LUAD) remains a challenge within the realm of non-small cell lung cancer (NSCLC), demanding innovative diagnostic and therapeutic solutions. In this study, we systematically detected the correlation between the expression of hypoxia-induced factor 1A (HIF1A) and the clinical characteristics of LUAD, alongside lung squamous cell carcinoma (LUSC). Our bioinformatic analysis reveals that HIF1A mRNA expression is significantly upregulated in both LUAD and LUSC samples compared to non-tumorous lung tissues. The overexpression is positively correlated with increased copy number variation and negatively associated with promoter methylation. However, meta-analysis and survival analyses revealed a pronounced association between elevated HIF1A expression and poor clinical outcome specifically within the LUAD subset, with no such correlation evident in LUSC. Additionally, we explored the interplay between HIF1A expression, leukocyte infiltration, and the presence of immunosuppressive markers, revealing HIF1A's suppressive role in cytotoxicity against cancer cells. Furthermore, we performed in silico prediction to explore the correlations between HIF1A and its interacting proteins, associated pathways, glycolysis, and m6A modification, and the feasibility of targeting HIF1A with specific drugs. In summary, our study revealed the prognostic significance and therapeutic potential of HIF1A in LUAD.

2.
J Chemother ; : 1-12, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221698

ABSTRACT

Colorectal cancer (CRC) is the second leading cause of cancer death, and about 10% of all malignancies are CRC. Cancer stem cells are considered main culprits in CRC treatment resistance and disease recurrence. This study explored the effects of tripartite motif containing 24 (TRIM24) and zinc finger protein, X-linked (ZFX) on CRC cell stemness and 5-FU resistance. A 5-FU-resistant cell line (HT29-5-FU) was constructed for functional analysis of CRC 5-FU-resistant cells. qRT-PCR and western blot (WB) were employed to analyze mRNA and protein levels of ZFX in 5-FU resistant cells and sensitive cells. WB was also utilized to analyze the surface markers of stem cells in each group. CCK-8 assay determined the IC50 values of different cell groups treated with 5-FU. The sphere-forming ability of cells in each group was determined using tumor sphere assay. Dual-luciferase reporter gene assay validated binding of ZFX to TRIM24. ZFX was highly expressed in HT29-5-FU cells. Silencing ZFX significantly reduced the 5-FU resistance and IC50 value of HT29-5-FU cells, and the surface markers and cell sphere-forming ability of stem cells were also significantly reduced. The function of HT29 cells was opposite when ZFX was overexpressed. In CRC cells, TRIM24 was an upstream transcription factor of ZFX, and they interacted with each other. TRIM24 activated the expression of ZFX to influence the stemness and 5-FU resistance of cells. The TRIM24/ZFX regulatory axis affected the stemness of CRC cells and their sensitivity to 5-FU, providing potential drug targets for novel therapeutic avenues for CRC.

3.
Ann Hepatol ; 27(4): 100701, 2022.
Article in English | MEDLINE | ID: mdl-35351639

ABSTRACT

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) ranks third on the list of the leading cause for cancer death globally. The treatment of HCC patients is unsatisfactory. However, the traditional Chinese medicine Chebulae Fructus has potential efficacy in the treatment of HCC. MATERIALS AND METHODS: We mined the active ingredients of Chebulae Fructus and its main targets from the Traditional Chinese Medicine Systems Pharmacology database. HCC-related datasets were downloaded from The Cancer Genome Atlas database and differentially expressed genes (DEGs) in HCC were obtained by differential expression analysis. Top10 small molecule compounds capable of reversing HCC pathology were screened by the Connectivity Map database based on DEGs. Ellipticine, an extract of Chebulae Fructus, had the potential to reverse HCC pathology. Protein-Protein Interaction (PPI) networks of DEGs in HCC were constructed using STRING. Eighteen potential targets of Chebulae Fructus for the treatment of HCC were obtained by taking intersection of DEGs in HCC with targets corresponding to the active constituents of Chebulae Fructus. In addition, MTT assay was also employed to examine the effect of ellipticine on HCC cell viability. RESULTS: It has been shown that ellipticine and ellagic acid have antitumor activity. Random Walk with Restart analysis of PPI networks was performed using potential targets as seeds, and the genes with the top 50 affinity coefficients were selected to construct a drug-active constituent-gene interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key genes involved in the treatment of HCC with Chebulae Fructus demonstrated that these genes were mainly enriched in signaling pathways related to tumor metabolism such as cAMP signaling pathway and Ras signaling pathway. Finally, it was verified by MTT assay that proliferation of HCC cells could be remarkably hindered. CONCLUSIONS: We excavated ellipticine, a key active constituent of Chebulae Fructus, by network pharmacology, and elucidated the signaling pathways involved in Chebulae Fructus, providing a theoretical basis for the use of Chebulae Fructus for HCC clinical application.


Subject(s)
Carcinoma, Hepatocellular , Ellipticines , Liver Neoplasms , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Computational Biology , Gene Expression Profiling , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Network Pharmacology , Plant Extracts , Protein Interaction Maps , Terminalia
4.
ACS Appl Mater Interfaces ; 13(48): 57521-57531, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34793675

ABSTRACT

MXene aerogels with a porous microstructure are a promising electromagnetic interference (EMI) shielding material due to its low density and excellent electrical conductivity, which has attracted widespread attention. Compared with traditional EMI shielding materials that rely on reflection as the primary mechanism, MXene aerogels with absorption as the dominant mechanism have greater potential for development as a novel EMI shielding material because of its ability to reduce environmental contamination from reflected electromagnetic (EM) waves from materials. In this study, a novel Ti3C2Tx MXene/PEDOT:PSS hybrid aerogel was presented by freeze-drying and thermal annealing using few-layered Ti3C2Tx MXene and the conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS). PEDOT:PSS not only improved the gelling ability of Ti3C2Tx but also successfully established a conductive bridge between MXene nanosheets. The experimental results demonstrated that the hybrid aerogel exhibited an obvious porous microstructure, which was beneficial for the multiple scattering of EM waves within the materials. The EMI shielding effectiveness and specific shielding effectiveness reached up to 59 dB and 10,841 dB·cm2·g-1, respectively, while the SER/SET ratio value was only 0.05, indicating superior wave absorption performance. Furthermore, the good impedance matching, due to the electrical conductance loss and polarization loss effect of the composites, plays a critical role in their excellent wave absorption and EMI shielding performance. Therefore, this work provides a practical approach for designing and fabricating lightweight absorption-dominated EMI shielding materials.

5.
Polymers (Basel) ; 8(8)2016 Aug 17.
Article in English | MEDLINE | ID: mdl-30974582

ABSTRACT

Carbon nanotube (CNT) coatings were utilized to enhance the interfacial properties of carbon fiber (CF)/epoxy(EP) composites by ultrasonically assisted electrophoretic deposition (EPD). A characterization of the CF surface properties was done before and after coating (surface chemistry, surface morphologies, and surface energy). The result shows that oxygenated groups concentrations of the CF surfaces experienced significant increases from 12.11% to 24.78%. Moreover, the uniform and homogeneous CNT films were tightly attached on the surface of CF, and the surface wettability of CF is significant improved by enhanced surface free energy when introduced ultrasonic during the EPD process. In addition, the interlaminar shear strength (ILSS) and water absorption of CF/EP composite were measured. Scanning electron microscopy (SEM) revealed that the fracture mechanisms of the new interface layer formed by depositing CNTs on the CF surface contributed to the enhancement of the mechanical performance of the epoxy. This means that the efficient method to improve interfacial performance of composites has shown great commercial application potential.

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