RESUMEN
Tetracoordinated organoboron dyes exhibiting strong fluorescence in either solution or the solid state are currently receiving much attraction in view of their photovoltaic, optoelectronic, and biological applications. Herein, a series of aromatic-ring-fused BOPPY dyes have been developed by one-pot condensation of formylated isoindoles or indoles and pyridinylhydrazine followed by subsequent borylation coordination. The facile synthesis provides excellent diversity of these unsymmetrical α-benzo- and ß-benzothiophene-fused BOPPY dyes with intriguing photophysical properties owing to their rigid and planar structure and extended π-conjugation while containing a reactive site. They display intense green to orange fluorescence in solution and red-to-near-infrared emission in the solid state, with high fluorescence quantum yields up to 92 and 21%, respectively, relatively large Stokes shifts, and excellent photostability. Furthermore, two representative benzo-fused BOPPY probes with morpholine or benzenesulfonamide groups were developed and used to selectively "light up" the subcellular organelles such as lysosomes and endoplasmic reticulum under ultralow concentration, respectively.
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Colorantes Fluorescentes , Indoles , Colorantes Fluorescentes/química , Ionóforos , Oxidación-Reducción , Morfolinas , IsoindolesRESUMEN
Objective: This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1- (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis. Methods: Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer. Results: PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. Conclusions: LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.
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Antígeno CD146/metabolismo , Neoplasias Colorrectales , Neoplasias Hepáticas , MicroARNs , Netrina-1/metabolismo , ARN Largo no Codificante , Actinas/metabolismo , Animales , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Metástasis de la Neoplasia , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
A new class of tailor-made push-pull isoindole fluorophores has been synthesized through the combination of Suzuki coupling and Knoevenagel reactions. The efficient synthetic strategy rendered the isoindole scaffold as the π-bridge and the isolation spacer and provided dyes bearing various types of electron donors and electron acceptors for manipulating their energy gaps and tuning their absorptions and emissions. Most of the N-alkylated isoindole dyes showed aggregation-induced emission behaviors suitable for bioimaging and nice solid-state emission with maxima up to 851 nm.
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Colorantes Fluorescentes , IsoindolesRESUMEN
Pancreatic carcinoma (PC) is one of the most common and deadly human malignancies worldwide. LncRNAs play significant roles in the occurrence and development of various cancers. LncRNA SNHG11 (SNHG11) has been found to display high expression in serum of PC patients, which implies that dysregulated SNHG11 may be related to the development of PC. However, there is still a knowledge gap concerning the specific function and molecular mechanism of SNHG11 in PC. After conducting experiments with constructed models in vitro or in vivo, we found that exosomal SNHG11 promoted cell proliferation, migration, and angiogenesis but impeded cell apoptosis in PC in vitro, and additionally, it facilitated tumor growth in vivo. Exosome-mediated SNHG11 regulated the expression of VEGFA through sponging miR-324-3p. Rescue assays validated that the inhibitory effect of SNHG11 depletion on cell proliferation, migration, and angiogenesis could be reversed by miR-324-3p downregulation or VEGFA upregulation, and the promoting effect of SNHG11 silence on cell apoptosis could be rescued by transfection of miR-324-3p inhibitor or pcDNA3.1-VEGFA. To conclude, exosomal-mediated SNHG11 could regulate PC progression via miR-324-3p/VEGFA axis. Our findings may provide a novel insight for understanding PC, which might contribute to the development of potential PC biomarker.
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Exosomas/metabolismo , MicroARNs/metabolismo , Neovascularización Patológica , Neoplasias Pancreáticas/metabolismo , ARN Largo no Codificante/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Exosomas/genética , Exosomas/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genética , Neoplasias PancreáticasRESUMEN
Organic small-molecule fluorescent chromophores have become essential to modern chemical, biological, and materials related investigations. Herein, a straightforward synthesis and subsequent borylation were presented to form a novel family of bisBF2-anchoring acyl-pyridinylhydrazine, which we named BOAPH. The chromophore enjoys outstanding structural diversities owing to varied acyl chlorides and N-heteroarenylhydrazides. These resultant BOAPH dyes are confirmed by NMR, HRMS, and single-crystal X-ray structure analysis. Their spectroscopic properties were studied, and most of the strong absorbance and bright fluorescence with maximum wavelengths centered in the range of 400 and 650 nm. More importantly, they exhibit promising fluorescence quantum yields up to 0.79 in solution and solid states, good photostability, and large Stokes shifts. Furthermore, a respective BOAPH dye with a para-dimethylaminophenyl group exhibited the interesting ability of ultrafast staining and two-photon imaging, which can specifically label lipid droplets of living cells immediately without the need for incubation.
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Colorantes Fluorescentes , Fotones , Fluorescencia , IonóforosRESUMEN
A new family of N2O-type hydrazine-containing bipyrrole boron complexes has been developed via a one-pot condensation of formylisoindole, hydrazine, and various organoboronic acids. Because of the conformation-restricted coplanar structure and the axial-substituted aryl groups, these novel dyes show deep-red absorption, bright near-infrared (NIR) fluorescence in both solution and solid states, and good solubility in organic solvents. The derivative with pyridinium ions also has been synthesized as an NIR mitochondrially targetable fluorescent probe.
RESUMEN
Conjugated molecules with coplanar strong donor and acceptor (D-A) units have been widely used in the design of near-infrared (NIR) photothermal agents to increase an absorption band through intramolecular charge transfer and to control intramolecular motions in aggregated states. However, such conjugated D-A systems have strong dipolar moments and intermolecular interactions, which may inhibit other channels of photothermal conversion and are often susceptible to nucleophiles, especially in the presence of light irradiation. Now, we report a molecular guideline to develop novel NIR organic photothermal nanoagents based on conjugated boron dipyrromethene (BODIPY) oligomers. This oligomerization is helpful not only for their tunable NIR absorptions in the ground state with distinctly redshifted absorption maxima up to 1002 nm and high extinction coefficients but also for their highly efficient photothermal conversion because of the possible motion of the BODIPY motifs around the ethene linked group in the excited state. These oligomers were fabricated as ultra-photostable nanoagents for multiple imaging-guided phototherapies, which efficiently accumulated in tumors, and gave complete tumor ablation with NIR laser irradiation. This strategy of "ground-state conjugation, excited-state rotation" provides a novel guideline to develop advanced theranostic molecules with NIR absorption.
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Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Fármacos Fotosensibilizantes/farmacología , Nanomedicina Teranóstica , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Compuestos de Boro/síntesis química , Compuestos de Boro/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Teoría Funcional de la Densidad , Rayos Infrarrojos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Desnudos , Estructura Molecular , Nanopartículas/química , Imagen Óptica , Tamaño de la Partícula , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Propiedades de SuperficieRESUMEN
A new family of pyrrolyl-acylhydrazones anchored with two BF2 units, named BOAPY, have been developed as BODIPY-like and unsymmetrical bis(BF2) chromophores via a simple one-pot reaction. The easily accessible scaffold enjoys excellent diversity due to the structural versatilities of 2-formylpyrroles and acylhydrazines. BOAPYs exhibit good molar absorption coefficients, large Stokes shifts, and excellent chemical stability. More importantly, most of them display excellent fluorescence quantum yields both in solution and the solid state (up to 0.88 and 0.64, respectively).
RESUMEN
Anoikis is a form of apoptosis which occurs when anchorage-dependent cells either show loss of adhesion or inappropriate adhesion. Only a few cancer cells that detach from the primary site of the tumor acquire the ability to resist anoikis and form metastasis. The mechanism underlying the resistance of colorectal cancer (CRC) cells to anoikis remains unclear. Interleukin-8 (alternatively known as CXCL8) is associated with CRC angiogenesis and progression. Here, we found that a high abundance of CXCL8 or TOPK strongly correlated with poor overall and disease-free survival of 186 patients with CRC. A combination of high CXCL8 and high TOPK expressions had the worst prognosis. We showed that CXCL8 expression was negatively correlated with anoikis in CRC cells. CXCL8 treatment enhanced the resistance of CRC cells to apoptosis, which was accompanied by the increase of TOPK, and the activation of AKT and ERK. Moreover, we demonstrated that the inhibition of either ERK or AKT by specific chemical inhibitors attenuated the CXCL8-mediated resistance to anoikis. Treatment with AKT inhibitor abolished the effects of CXCL8 on TOPK expression, suggesting that TOPK was downstream of AKT in the process of anoikis. Taken together, we demonstrated that CXCL8 is strongly implicated in the resistance of CRC cells to anoikis, and that the AKT, TOPK and ERK pathway may be a potential therapeutic target for CRC.
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Anoicis , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Interleucina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Femenino , Técnica del Anticuerpo Fluorescente , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Clasificación del Tumor , Invasividad Neoplásica , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Células Tumorales Cultivadas , Adulto JovenRESUMEN
Liver metastases represent the major cause of death in patients with colorectal cancer (CRC). Recent studies have suggested that the chemotactic responses of tumor cells are necessary for metastatic spread to the liver, and CCL20 and CXCL8 have a strong association with CRC metastasis. The aim of our study was to identify the mechanisms by which CCL20 and CXCL8 synergize to promote metastatic progression and evaluated their potential as prognostic markers for CRC patients. The abilities of CCL20 and CXCL8 to promote CRC cell progression and epithelial-mesenchymal transition(EMT)phenotype were analyzed in vitro. Possible signaling pathways were investigated with specific pathway inhibitors and small interfering RNA (siRNA). 213 Patients with CRC who underwent surgery were enrolled for analysis of CCL20, CXCL8 and E-cadherin expressions in tumor tissues. Prognostic factors were then identified. CCL20 or CXCL8 alone was not sufficient to induce complete EMT in CRC cells, but both of them could coordinately induce EMT-like phenotype that was required to maintain CRC cell proliferation, migration and invasion. PI3K/AKT-ERK1/2 pathway crosstalk was demonstrated to be responsible for this process. Coexpression of CCL20 and CXCL8 was negatively correlated with E-cadherin expression in human CRC tissues. CRC patients with coexpression of CCL20 and CXCL8 were more likely to develop liver metastases and both coexpression was an independent high-risk factor for a most poor prognosis. CCL20 and CXCL8 synergize to promote CRC metastatic progression by coordinated induction of EMT via PI3K/AKT-ERK1/2 signaling axis. Detection of both coexpressions can be used to predict clinical outcomes in CRC patients.