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Graphene nanoscroll (GNS) is an important 1D tubular form of graphene-derivative materials, which has garnered widely attention. However, conventional fabrication methods commonly suffer from complex processing and time-consuming. Herein, with graphene oxide (GO) as a precursor, the study puts forward a facile air-plasma synthesis strategy to fabricate 3D graphene nanoscroll-nanosheet aerogels (GSSA). It is demonstrated that without using any chemical additives, a highly efficient reduction-exfoliation-scrolling process can be achieved all-in-one at room temperature within 1 s. The GNSs "grew" from 2D graphene sheets and firmly cross-linked them together, and they not only provide a shortcut path for electron transport but also act as intrinsic spacers to prevent restacking of graphene sheets. When using as an electrode material for capacitive deionization (CDI), GSSA exhibits excellent merits of salt-removal performance. These findings open a new pathway to large-scale synthesis of high-quality and high-purity GNS-based materials with promising applications in CDI and beyond.
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We investigated absorption and field enhancements of shallow nanocavities on top of high-aspect-ratio dielectric pillars in the infrared range. The structure includes a high-aspect-ratio nanopillar array of high refractive index, with nano-cavities on top of the pillars, and a metal plane at the bottom. The enhancement factor of electric field intensity reaches 3180 in the nanocavities and peak absorption reaches 99%. We also investigated the finite-size effect of the presented structure to simulate real experiments. Due to its narrow absorption bandwidth 3.5 nm, it can work as a refractive index sensor with sensitivity 297.5 nm/RIU and figure of merit 85. This paves the way to directly control light field at the nanoscales in the infrared light range. The investigated nanostructure will find applications in multifunctional photonics devices such as chips for culturing cells, refractive index sensors, biosensors of single molecule detection and nonlinear sensors.
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Metasurfaces exhibit unique optical properties that depend on the ratio of their refractive index and that of their surroundings. As such, they are effective for sensing global changes in refractive index based on the shifts of resonances in their reflectivity spectra. However, when used as a biosensor, the metasurface can be exposed to a spatial distribution of biomolecules that brings about gradients in refractive index along the plane of the metasurface. Such gradients produce complex global reflectivity spectrum but with distinct optical enhancements in localized areas along the metasurface. Here, we propose a unique sensing paradigm that images and maps out the optical enhancements that are correlated with the spatial distribution of the refractive index. Moreover, we designed a metasurface whose resonances can be tuned to detect a range of refractive indices. Our metasurface consists of silicon nanopillars with a cylindrical nanotrench at their centers and a metal plane at the base. To assess its feasibility, we performed numerical simulations to show that the design effectively produces the desired reflectivity spectrum with resonances in the near-infrared. Using an incident light tuned to one of its resonances, our simulations further show that the field enhancements are correlated with the spatial mapping of the gradients of refractive indices along the metasurface.
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In recent years, carbon dots (CDs) with red-emitting wavelengths have received increasing attention in cancer therapy and imaging. Here, we reported a multi-functional CD based platform combining bimodal magnetic resonance/fluorescence (MR/FL) imaging and chemodynamic therapy (CDT) for in vivo imaging of tumor tissues and efficient anticancer treatment. The red-emitting CDs were synthesized via a one-step solvothermal method with p-phenylenediamine as the carbon source. Ethylenediaminetetraacetic acid (EDTA) was covalently coupled to the surface of CDs and then complexed with Fe2+ and Gd3+ to obtain functionalized red CDs (CDs@EDTA@Gd@Fe). CDs@EDTA@Gd@Fe exhibited bright and stable fluorescence and strong T1-weighted MR imaging (MRI) contrast. Moreover, the CDs@EDTA@Gd@Fe showed an excellent anticancer effect both in vitro and in vivo via a Fenton reaction-based CDT by releasing Fe2+ in the tumor. Our study offers a promising strategy for developing multi-functional CDs for cancer theranostics.
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Carbono/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Imagem Óptica/métodos , Nanomedicina Teranóstica/métodos , Células A549 , HumanosRESUMO
Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. New anticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.623, r 2 = 0.987, r pred 2 = 0.857) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.960, r pred 2 = 0.899) were used to establish the model, and the structure-activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future.
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Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Histona Desmetilases/antagonistas & inibidores , Estilbenos/química , Sítios de Ligação , Simulação de Dinâmica Molecular , Ligação Proteica , Relação Quantitativa Estrutura-AtividadeRESUMO
Metasurfaces are investigated intensively for biophotonics applications due to their resonant wavelength flexibly tuned in the near infrared region specially matching biological tissues. Here, we present numerically a metasurface structure combining dielectric resonance with surface plasmon mode of a metal plane, which is a perfect absorber with a narrow linewidth 10 nm wide and quality factor 120 in the near infrared regime. As a sensor, its bulk sensitivity and bulk figure of merit reach respectively 840 nm/RIU and 84/RIU, while its surface sensitivity and surface figure of merit are respectively 1 and 0.1/nm. For different types of adsorbate layers with the same thickness of 8 nm, its surface sensitivity and figure of merit are respectively 32.3 and 3.2/RIU. The enhanced electric field is concentrated on top of dielectric patch ends and in the patch ends simultaneously. Results show that the presented structure has high surface (and bulk) sensing capability in sensing applications due to its narrow linewidth and deep modulation depth. This could pave a new route toward dielectric-metal metasurface in biosensing applications, such as early disease detections and designs of neural stem cell sensing platforms.
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Proanthocyanidins, including polymers with both low and high degrees of polymerization, are the focus of intensive research worldwide due to their high antioxidant activity, medicinal applications, and pharmacological properties. However, the nutritional value of these compounds is limited because they readily form complexes with proteins, polysaccharides, and metal ions when consumed. In this study, we examined the effects of proanthocyanidins with different degrees of polymerization on white mice. Twenty-four male white mice were randomly divided into three groups of eight mice each and fed proanthocyanidins with a low degree of polymerization or a high degree of polymerization or a distilled water control via oral gavage over a 56-day period. We examined the effects of these proanthocyanidins on digestive enzyme activity and nutrient absorption. Compared to the control group, the group fed high-polymer proanthocyanidins exhibited a significant reduction in net body mass, total food intake, food utility rate, amylase activity, protease activity, and major nutrient digestibility (p < 0.05), while the group fed low-polymerization proanthocyanidins only exhibited significant reductions in total food intake, α-amylase activity, and apparent digestibility of calcium and zinc (p < 0.05). Therefore, proanthocyanidins with a high degree of polymerization had a greater effect on digestive enzyme activity and nutrient absorption than did those with a low degree of polymerization. This study lays the foundation for elucidating the relationship between procyanidin polymerization and nutrient uptake, with the aim of reducing or eliminating the antinutritional effects of polyphenols.
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Amilases/metabolismo , Peptídeo Hidrolases/metabolismo , Proantocianidinas/administração & dosagem , Proantocianidinas/química , Absorção Fisiológica/efeitos dos fármacos , Animais , Índice de Massa Corporal , Ingestão de Alimentos/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Polimerização , Proantocianidinas/farmacologia , Distribuição Aleatória , Ratos WistarRESUMO
PURPOSE: To investigate the function of LINC01170 in the progression of endometrial carcinoma and its underlying mechanism. METHODS: The expression profiles and prognostic data of endometrial carcinoma were downloaded by GDC (genomic data commons) analysis tools. Differentially expressed long noncoding (lnc)RNAs were analyzed by the edgeR (empirical analysis of digital gene expression data in R) package. LncRNAs that were related to prognosis of endometrial carcinoma were calculated by the survival function. Moreover, the PHEAT map package was introduced to edit heatmaps of differentially expressed lncRNAs. Human endometrial carcinoma cell lines (Ishikawa, ECC and HEC-IA) were cultured. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expressions of lncRNAs and related genes. Cell proliferation was detected by MTT, and cell cycle and apoptosis were detected by flow cytometry. Additionally, Western blot was used to detect protein expressions of relative genes. RESULTS: Results showed that LINC01170 was a non-coding RNA. LINC01170 was overexpressed in endometrial carcinoma, which was a risk factor for prognosis of this disease. LINC01170 expressions in carcinoma and para-cancerous tissues of 50 patients with endometrial carcinoma were detected by qRT-PCR and found that the expression level of LINC01170 in endometrial carcinoma was remarkably increased than that of para-cancerous tissues. Moreover, the expression level of LINC01170 in advanced endometrial carcinoma was remarkably higher than that of early-stage disease. After interfering with LINC01170, the proliferation of both the Ishikawa and HEC-1A cells were remarkably decreased, and cell cycle was arrested at the G0/G1 phase. Meanwhile, apoptosis results showed a remarkable apoptosis rate after interfering with LINC01170. Western blot results also demonstrated the decreased activity of AKT pathway and phosphorylated expression of AKT protein after LINC01170 knockdown. In addition, expressions of CDK2, CDK4 and Bcl-2 were decreased after LINC01170 knockdown. CONCLUSIONS: LINC01170 promotes the progression of endometrial carcinoma through stimulating proliferation, cell cycle transition and inhibiting apoptosis of endometrial carcinoma cells via AKT pathway.
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Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Adulto , Idoso , Apoptose , Biomarcadores Tumorais/genética , Ciclo Celular , Proliferação de Células , Progressão da Doença , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Focal adhesion kinase (FAK) is an important drug target that plays a fundamental role in mediating signal transduction system. We report herein the discovery of a novel class of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton with improved potency toward FAK. All of the 17 new synthesized compounds were assayed for the anticancer activities against four cancer cells, HepG2, Hela, SW116 and BGC823. Because of the combination of 1,4-benzodioxan, 1,3,4-oxadiazole and piperazine ring, most of them exhibited remarkable antitumor activities. Notably, compound 5m showed the most potent biological activities (IC50=5.78µM for HepG2, and IC50=47.15µM for SW1116), and its anti-FAK inhibitory activity (IC50=0.78µM) was also the best. Computational docking studies also showed that compound 5m has interaction with FAK key residues in the active site.
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Dioxanos/farmacologia , Quinase 1 de Adesão Focal/antagonistas & inibidores , Oxidiazóis/farmacologia , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Tionas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dioxanos/síntese química , Dioxanos/química , Ensaios Enzimáticos , Humanos , Simulação de Acoplamento Molecular , Oxidiazóis/síntese química , Oxidiazóis/química , Piperazinas/síntese química , Piperazinas/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Tionas/síntese química , Tionas/químicaRESUMO
Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2 promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhibition and anticancer. Among them, compound 7t showed most powerful selective inhibitory and antiproliferative activity (IC50=0.09µM for COX-2, IC50=48.20µM for COX-1, IC50=0.36µM against HeLa cells), comparable to the control positive compound Celecoxib (0.31µM, 43.37µM, 7.79µM). Cancer cell apoptosis assay were performed and results indicated that compound 7t effectively fuels HeLa cells apoptosis in a dose and time-dependent manner. Moreover, 7t could significantly suppress cancer cell adhesion, migration and invasion which were essential process of cancer metastasis. Docking simulations results was further indicated that compound 7t could bind well to the COX-2 active site and guided a reasonable design of selective COX-2 inhibitor with anticancer activities in future.
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Cumarínicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Sulfonamidas/farmacologia , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/síntese química , Cumarínicos/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/químicaRESUMO
We propose an ultranarrow bandwidth perfect infrared absorber consisting of a metal periodic structured surface with nanoslits, a spacer dielectric, and a metal back plate. Its bandwidth and aborption are respectively about 8 nm and 95%. The thickness of the nanobars and the spacer, and the width of the nanoslits are primary factors determining the absorption performance. This structure not only has narrow bandwidth but also can obtain the giant electric field enhancement in the tiny volume of the nanoslits. Operated as a refractive index sensor, this structure has figure of merit as high as 25. It has potential in biomedical and sensing applications.
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We have investigated numerically the narrowband absorption property of a metal-dielectric-metal based structure which includes a top metallic nanoring arrays, a metal backed plate, and a middle dielectric spacer. Its absorption is up to 90% with linewidth narrower than 10 nm. This can be explained in terms of surface lattice resonance of the periodic structure. The spectrum with the sharp absorption dip, i.e. the lattice resonance, strongly depends on the refractive index of media surrounding the nanorings. This feature can be explored to devise a refractive index sensor, of which the bulk sensitivity factor is one order larger than that based on gap resonance mode, while the surface sensitivity factor can be two times larger. The proposed narrowband absorber has potential in applications of plasmonic biosensors.
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Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.33 µM; COX-1 IC50=68.49 µM) relative to the reference drugs celecoxib (IC50=0.052 µM). Docking simulation was performed to position compound 48 into the COX-2 active site and the result showed that compound 48 could bind well at the COX-2 active site and it indicated that compound 48 could be a potent and selective COX-2 inhibitor.
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Antineoplásicos/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Fármacos , Modelos Moleculares , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/síntese química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células MCF-7 , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/químicaRESUMO
New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure-activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays. Among the compounds, compound 3i exhibited the most potent inhibitory activity with IC50 values of 0.21 µM inhibiting MMP-2 and 1.87 µM inhibiting MMP-9, comparable to the control positive compound CMT-1 (1.26 µM, 2.52 µM). Docking simulation was performed to position compound 3i into the MMP-2 active site to determine the probable binding pose. Docking simulation was further performed to position compound 3i into the MMP-2 active site to determine the probable binding model the 3D-QSAR models were built for reasonable design of MMP-2/MMP-9 inhibitors at present and in future.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Pirazóis/farmacologia , Relação Quantitativa Estrutura-Atividade , Sulfonamidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inibidores de Metaloproteinases de Matriz/síntese química , Inibidores de Metaloproteinases de Matriz/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirazóis/química , Sulfonamidas/síntese química , Sulfonamidas/químicaRESUMO
A novel array of slits design combining the nano-slit grating and dielectric-metal is proposed to obtain giant and tunable electric field enhancement in the terahertz regime. The maximum amplitude of electric field is more than 6000 times larger than that of the incident electric field. It is found that the enhancement depends primarily on the stripe and nano-slits width of grating, as well as the thickness of spacer layer. This property is particularly beneficial for the realization of ultra-sensitive nanoparticles detection and nonlinear optics in the terahertz range, such as the second harmonic generation (SHG).
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Twenty four pyrazoline derivatives modified from Celecoxib were designed and synthesized as bi-inhibitor of COX-2 and B-Raf. They were evaluated for their COX-1/COX-2/B-Raf inhibitory and anti-proliferation activities. Compound A3 displayed the most potent activity against COX-2 and HeLa cell line (IC50=0.008 µM; GI50=19.86 µM) and showed superb COX-1/COX-2 selectivity (>500), being more potent and selective than positive control Celecoxib or 5-fluorouracil. Compounds A5 and B5 were introduced best B-Raf inhibitory activities (IC50=0.15 µM and 0.12 µM, respectively). Compound A4 retained superb bioactivity against COX-2 and HeLa cell line (IC50=0.015 µM; GI50=23.82 µM) and displayed moderate B-Raf inhibitory activity (IC50=3.84 µM). Docking simulation was conducted to give binding patterns. QSAR models were built using bioactivity data and optimized conformations to provide a future modification of COX-2/B-Raf inhibitors.
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Inibidores de Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Pirazóis/química , Sítios de Ligação , Celecoxib , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Feminino , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas B-raf/metabolismo , Pirazóis/síntese química , Pirazóis/farmacologia , Relação Quantitativa Estrutura-Atividade , Sulfonamidas/química , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologiaRESUMO
Endometrial cancer (EC) is one of the predominant tumors of the female reproductive system. In this current study, we investigated the functions and related mechanisms of NAP1L1/DDX5 in EC. This retrospective study analyzed the medical records of EC patients, collected tissue samples for NAP1L1 and DDX5 staining, and conducted survival analysis using the Kaplan-Meier method. To evaluate the impact of NAP1L1 and/or DDX5 on cellular processes in EC cells, several techniques were employed. These included CCK-8 assay, wound healing assay, Transwell assay, as well as overexpression or knockdown of target gene expression. Additionally, ChIP, dual luciferase reporter gene, Co-IP assay were utilized to confirm the interaction between NAP1L1, EP300 and DDX5. Furthermore, qRT-PCR, western blot and Co-IP assay were performed to analyze the modulation of NAP1L1/DDX5 in Wnt/ß-catenin. NAP1L1 and DDX5 expression were upregulated in EC tissues, and correlated with poor prognosis. NAP1L1/DDX5 promoted EC cell proliferation, migration and invasion. NAP1L1 promotes acetylation and transcription by recruiting EP300 to the DDX5 promoter. DDX5 could activate Wnt/ß-catenin signal by binding to ß-catenin. In animal models, knockdown of NAP1L1 inhibits EC tumor growth and lung metastasis. To sum up, our study demonstrated that NAP1L1 promoted the malignant phenotypes of EC cells via recruiting EP300 to promote DDX5 acetylation, thus activating the Wnt/ß-catenin signaling pathway. Implications: Our research findings indicate that targeting the NAP1L1/EP300/DX5 axis might be a new potential treatment option for endometrial cancer.
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The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55-0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067-2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51-0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542-0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34-0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.
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Neoplasias Ovarianas , RNA Longo não Codificante , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Transdução de Sinais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Activation of the NOTCH signaling pathway is associated with tumorigenesis. The aim of this study was to investigate NOTCH pathway gene functions and regulatory mechanisms in ovarian cancer (OC). METHODS: We conducted a bioinformatics analysis of publicly available datasets in order to identify potential NOTCH-related mechanisms, associated genes, biological pathways, and their relation to immune function. RESULTS: Significant differential expression of the NOTCH pathway genes DLL1, DLL3, DLL4, HES1, HEY1, JAG1, NOTCH2, NOTCH3, and NOTCH4 was observed between OC samples and normal controls. Low expression of DLL4 and of NOTCH4 in OC patients was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p <0.001 and p = 0.036, respectively), while high expression of NOTCH3 was associated with race (p = 0.039) and age (p = 0.044). JAG2 and NOTCH1 expression were significantly associated with progression-free interval (PFI) (p = 0.011 and p = 0.039, respectively). DLL1 (Hazard Ratio (HR): 2.096; 95% CI: 1.522-2.886, p < 0.001) and NOTCH1 (HR: 0.711; 95% CI: 0.514-0.983, p = 0.039) expression were independently associated with PFI in multivariate analysis. DLL1, DLL3, JAG1, JAG2, NOTCH3 and NOTCH4 expression could significantly differentiate OC from non-cancer samples. Genes associated with the NOTCH pathway were mainly enriched in five signaling pathways: the NOTCH signaling pathway, breast cancer, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. The expression of NOTCH pathway genes was significantly associated with immune cell infiltration. CONCLUSIONS: NOTCH pathway genes appear to play an important role in the progression of OC by regulating immune cells, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. JAG2 and NOTCH1 are potential biomarkers and therapeutic targets for the treatment of OC.
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Relevância Clínica , Neoplasias Ovarianas , Gravidez , Humanos , Feminino , Transdução de Sinais/genética , Neoplasias Ovarianas/genética , Proteínas de Membrana/genética , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Background: Endocrine disruption is an important factor in the development of endometrial cancer. Expression of miR-149-3p is observed in some cancer types, while its role in uterine corpus endometrial carcinoma (UCEC) is unclear. Methods: The clinical and genomic data and prognostic information on UCEC were obtained for patients from the TCGA database. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between clinical characteristics and miR-149-3p expression. Kaplan-Meier survival curve analysis was used to study the influence of miR-149-3p expression and miR-149-3p target genes on the prognosis of UCEC patients. The TargetScan, PicTar, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the involvement of miR-149-3p target genes in function. Immune infiltration analysis was used to analyze the functional involvement of miR-149-3p. QRT-PCR was used to validate the expression of miR-149-3p in UCEC cell lines. Results: High expression of miR-149-3p in UCEC was significantly associated with age (P < 0.001), histological type (P < 0.001), histological grade (P < 0.001), tumor invasion (P=0.014), and radiation therapy (P=0.011). High miR-149-3p expression predicted poorer overall survival (OS) (HR: 2.56; 95% CI: 1.64-4.00; P < 0.001), progression-free interval (PFI) (HR: 1.85; 95% CI: 1.29-2.65; P=0.001), and disease-specific survival (DSS) (HR: 2.33; 95% CI: 1.37-3.99; P=0.002). Low expressions of miR-149-3p target genes, including ADCYAP1R1, CGNL1, CHST3, CYGB, DNAH9, ESR1, HHIP, HIC1, HOXD11, IGF1, INMT, LSP1, MTMR10, NFIC, PLCE1, RARA, SNTN, SPRYD3, and ZBTB7A, were associated with poor OS in UCEC. MiR-149-3p may be involved in the occurrence and development of UCEC via pathways including PI3K-Akt signaling pathway, Ras signaling pathway, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and MAPK signaling pathway. miR-149-3p may inhibit the function of CD8 T cells, cytotoxic cells, eosinophils, iDC, mast cells, neutrophils, NK CD56bright cells, NK CD56dim cells, pDC, T cells, T helper cells, TFH, Th17 cells, and Treg. miR-149-3p was significantly upregulated in UCEC cell lines compared with endometriotic stromal cells. Conclusion: High expression of miR-149-3p was significantly associated with poor survival in UCEC patients. It may be a promising biomarker of prognosis and response to immunotherapy for UCEC patients.