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1.
Curr Med Sci ; 44(3): 529-544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38809379

RESUMO

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.


Assuntos
Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Mapas de Interação de Proteínas , Trocadores de Sódio-Hidrogênio , Humanos , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Biologia Computacional/métodos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Mapas de Interação de Proteínas/genética , Linhagem Celular Tumoral , Prognóstico , Genes Supressores de Tumor , Proliferação de Células/genética , Redes Reguladoras de Genes , Ontologia Genética , Perfilação da Expressão Gênica/métodos , Movimento Celular/genética
2.
Org Biomol Chem ; 10(19): 3852-8, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22526353

RESUMO

A novel boron-containing π-conjugated compound has been synthesized by the introduction of electron-acceptors (dimesitylboron groups) at the 3,3'-positions of a carbazole dimer (electron-donor). The compound possesses excellent electrochemical properties and high fluorescence quantum yields. In addition, is a sensitive fluorescence sensor with remarkable colour changes and the results could be confirmed through theoretical calculations of the compounds and [(n)Bu(4)N](+)(2)[·(F)(2)](2-). Our studies indicate that could be used as an excellent optoelectronic material in OLED devices and a ratiometric fluorescent chemosensor.

3.
Curr Med Sci ; 42(2): 357-372, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35325407

RESUMO

OBJECTIVE: Gastric cancer (GC) is a deadly cancer and a challenging public health problem globally. This study aimed to analyze potential genes associated with pathogenesis and prognosis of gastric cancer. METHODS: This work selected the overlapping differentially expressed genes (DEGs) in GC from four datasets, the GSE29272, GSE29998, GSE54129 and GSE118916 Gene Expression Omnibus databases. These DEGs were used to carry out comprehensive bioinformatic analysis to analyze the related functions and pathways enriched, the relative expression levels and immune infiltrates, the prognostic characteristics and the interaction network. RESULTS: In total, 55 DEGs increased while 98 decreased in their expression levels. For those DEGs with increased expression, they were mostly concentrated on "focal adhesion" and "ECM-receptor interaction", whereas DEGs with decreased expression were mostly associated with "gastric acid secretion" and "drug metabolism cytochrome P450". MCODE and ClueGO results were then integrated to screen 10 hub genes, which were FN1, COL1A1, COL3A1, BGN, TIMP1, COL1A2, LUM, VCAN, COL5A2 and SPP1. Survival analysis revealed that higher expression of the ten hub genes significantly predicted lower overall survival of GC patients. TIMP1 was most significantly related to neutrophils, CD8+ T cells, as well as dendritic cells, while LUM was most significantly related to macrophages. CONCLUSION: Immunohistochemistry results and functional testing showed that the expression of COL5A2 was elevated in GC and that it might be a key gene in GC tumorigenesis.


Assuntos
Neoplasias Gástricas , Linfócitos T CD8-Positivos/patologia , Carcinogênese , Biologia Computacional/métodos , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
4.
Artigo em Inglês | MEDLINE | ID: mdl-22459937

RESUMO

A novel A-π-D-π-D-π-A type compound, containing two benzothiazole rings as electron acceptors and two N-ethylcarbazole groups as electron donors, (E)-1,2-bis(3-(benzothiazol-2-yl)-9-ethylcarbazol-6-yl)ethene (BBECE), was synthesized and characterized by elemental analysis, NMR, MS and thermogravimetric analysis. Electrochemical property of compound BBECE was studied by cyclic voltammetry analysis. The absorption and emission spectra of BBECE was experimentally determined in several solvents and simultaneously computed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculated absorption and emission wavelengths are coincident with the measured data. The lowest-lying absorption spectra can be mainly attributed to intramolecular charge transfer (ICT), and the fluorescence spectra can be mainly described as originating from an excited state with intramolecular charge transfer (ICT) character. The molecular orbitals (HOMO and LUMO), the ionization potential (IP), the electron affinity (EA) and reorganization energy of compound BBECE were also investigated using density functional theory (DFT). The results show that compound BBECE exhibited excellent thermal stability and electrochemical stability as well as high fluorescence quantum yield, indicating its potential applications as an excellent optoelectronic material in optical fields.


Assuntos
Benzotiazóis/química , Carbazóis/química , Benzotiazóis/síntese química , Carbazóis/síntese química , Dimerização , Elétrons , Fluorescência , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Teoria Quântica , Espectrometria de Fluorescência , Espectrofotometria
5.
Chem Commun (Camb) ; 48(68): 8586-8, 2012 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-22814790

RESUMO

Nanoparticles of a novel boron-based carbazole derivative have been reported. They exhibit efficient green fluorescence, aggregation induced ratiometric fluorescence change and green/blue fluorescent switching to sense VOCs.

6.
Artigo em Inglês | MEDLINE | ID: mdl-21943713

RESUMO

Two novel pyrazoline derivatives, named 2,8-bis(1,3-diphenyl-pyrazoline-5-yl)dibenzofuran (A) and 2,8-bis(1-(4-bromophenyl)-3-phenyl-pyrazoline-5-yl)dibenzofuran (B), were synthesized and characterized by elemental analysis, NMR, MS and thermogravimetric analysis. The absorption and emission spectra of them were determined by experimental methods in different polar solvents and were computed using the density functional theory (DFT) and the time-dependent density functional theory (TDDFT) at the same time. The calculated absorption and emission wavelengths are in good agreement with the experimental data. The fluorescence quantum yields and fluorescence lifetimes of them in different polar solvents were studied by means of steady state and time resolved fluorescence. The calculated reorganization energy for hole and electron indicates that the two compounds are in favor of hole transport than electron transport. The results show the two compounds present high fluorescence quantum yields and excellent thermal stability. It makes them of great interest as novel fluorescent probes and optoelectronic materials.


Assuntos
Benzofuranos/química , Pirazóis/química , Benzofuranos/síntese química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Químicos , Modelos Moleculares , Pirazóis/síntese química , Teoria Quântica , Termogravimetria
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