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Spatially resolved transcriptomics (SRT) enable the comprehensive characterization of transcriptomic profiles in the context of tissue microenvironments. Unveiling spatial transcriptional heterogeneity needs to effectively incorporate spatial information accounting for the substantial spatial correlation of expression measurements. Here, we develop a computational method, SpaSRL (spatially aware self-representation learning), which flexibly enhances and decodes spatial transcriptional signals to simultaneously achieve spatial domain detection and spatial functional genes identification. This novel tunable spatially aware strategy of SpaSRL not only balances spatial and transcriptional coherence for the two tasks, but also can transfer spatial correlation constraint between them based on a unified model. In addition, this joint analysis by SpaSRL deciphers accurate and fine-grained tissue structures and ensures the effective extraction of biologically informative genes underlying spatial architecture. We verified the superiority of SpaSRL on spatial domain detection, spatial functional genes identification and data denoising using multiple SRT datasets obtained by different platforms and tissue sections. Our results illustrate SpaSRL's utility in flexible integration of spatial information and novel discovery of biological insights from spatial transcriptomic datasets.
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Perfilación de la Expresión Génica , Aprendizaje , TranscriptomaRESUMEN
MXenes, a class of two-dimensional transition metal carbides, nitrides, and carbonitrides, have garnered significant attention due to their remarkable potential for energy storage, electrocatalysis, and gas separation applications. The fabrication processes of MXene involve building up the MXene structure from constituent elements and the selective elimination of M-A bonds from the precursor MAX. However, considerable efforts are still required to design and develop efficient MXene-based technologies. This review article aims to briefly analyse the synthesis methods employed for MXene production, ranging from direct synthesis and conventional chemical wet etching approach to the more recent molten salt etching technique. The review highlights the advancements made in achieving precise control over the terminal groups, which is paramount for tailoring the properties of MXenes for specific applications. Furthermore, the potential of MXene-based materials for carbon capture applications, particularly in developing advanced adsorbents, is emphasized. The in-depth examination of MXene synthesis techniques and their implications for carbon capture applications provides a solid foundation for developing and optimizing these promising materials.
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OBJECTIVES: Cancer morbidity and mortality can be reduced if the cancer is detected early. Cell-free DNA (cfDNA) fragmentomics emerged as a novel epigenetic biomarker for early cancer detection, however, it is still at its infancy and requires technical improvement. We sought to apply a single-strand DNA sequencing technology, for measuring genetic and fragmentomic features of cfDNA and evaluate the performance in detecting multiple cancers. METHODS: Blood samples of 364 patients from six cancer types (colorectal, esophageal, gastric, liver, lung, and ovarian cancers) and 675 healthy individuals were included in this study. Circulating tumor DNA mutations, cfDNA fragmentomic features and a set of protein biomarkers were assayed. Sensitivity and specificity were reported by cancer types and stages. RESULTS: Circular Ligation Amplification and sequencing (CLAmp-seq), a single-strand DNA sequencing technology, yielded a population of ultra-short fragments (<100â¯bp) than double-strand DNA preparation protocols and reveals a more significant size difference between cancer and healthy cfDNA fragments (25.84â¯bp vs. 16.05â¯bp). Analysis of the subnucleosomal peaks in ultra-short cfDNA fragments indicates that these peaks are regulatory element "footprints" and correlates with gene expression and cancer stages. At 98â¯% specificity, a prediction model using ctDNA mutations alone showed an overall sensitivity of 46â¯%; sensitivity reaches 60â¯% when protein is added, sensitivity further increases to 66â¯% when fragmentomics is also integrated. More improvements observed for samples representing earlier cancer stages than later ones. CONCLUSIONS: These results suggest synergistic properties of protein, genetic and fragmentomics features in the identification of early-stage cancers.
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Ácidos Nucleicos Libres de Células , ADN Tumoral Circulante , Neoplasias , Humanos , Detección Precoz del Cáncer , Mutación , ADN Tumoral Circulante/genética , Neoplasias/diagnóstico , Neoplasias/genética , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.
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Aminoácidos , Neoplasias Colorrectales , Humanos , Triptófano , Sarcosina , Biomarcadores de Tumor/genética , Metabolómica , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , GlutamatosRESUMEN
BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).
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Adenoma , Neoplasias Colorrectales , Vesículas Extracelulares , MicroARNs , Humanos , Estudios Prospectivos , MicroARNs/genética , Adenoma/diagnóstico , Adenoma/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genéticaRESUMEN
We report a sub-terahertz scattering-type scanning near-field microscope (sub-THz s-SNOM) which uses a 6 mm long metallic tip driven by a quartz tuning fork as the near-field probe. Under continuous-wave illumination by a 94â GHz Gunn diode oscillator, terahertz near-field images are obtained by demodulating the scattered wave at both the fundamental and the second harmonic of the tuning fork oscillation frequency together with the atomic-force-microscope (AFM) image. The terahertz near-field image of a gold grating with a period of 2.3â µm obtained at the fundamental modulation frequency agrees well with the AFM image. The experimental relationship between the signal demodulated at the fundamental frequency and the tip-sample distance is well fitted with the coupled dipole model indicating that the scattered signal from the long probe is mainly contributed by the near-field interaction between the tip and the sample. This near-filed probe scheme using quartz tuning fork can adjust the tip length flexibly to match the wavelength over the entire terahertz frequency range and allows for operation in cryogenic environment.
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To satisfy the demand for broadband and high-sensitivity terahertz detectors, we designed and verified a broadband terahertz detector built with antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs). Eighteen pairs of dipole antennas with different center frequency from 0.24 to 7.4 THz are arrayed into a bow-tie pattern. The corresponding eighteen transistors have common a source and a drain but different gated channels coupled by the corresponding antennas. The photocurrents generated by each gated channel are combined in the drain as the output port. With incoherent terahertz radiation from a hot blackbody in a Fourier-transform spectrometer (FTS), the detector exhibits a continuous response spectrum from 0.2 to 2.0 THz at 298 K and from 0.2 to 4.0 THz at 77 K, respectively. The results agree well with simulations taking into account the silicon lens, antenna and blackbody radiation law. The sensitivity is characterized under coherent terahertz irradiation, the average noise-equivalent power (NEP) is about 188 p W/H z at 298 K and 19 p W/H z at 77 K from 0.2 to 1.1 THz, respectively. A maximum optical responsivity of 0.56 A/W and a minimum NEP of 7.0 p W/H z at 0.74 THz are achieved at 77 K. The blackbody response spectrum is divided by the blackbody radiation intensity to obtain a performance spectrum, which is calibrated by measuring coherence performance from 0.2 to 1.1 THz to evaluate detector performance at frequencies above 1.1 THz. At 298 K, the NEP is about 1.7 n W/H z at 2.0 THz. At 77 K, the NEP is about 3 n W/H z at 4.0 THz. For further improvements in sensitivity and bandwidth, high-bandwidth coupling components, smaller series resistance, smaller gate lengths and high-mobility materials need to be considered.
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The foundation for polarization-based terahertz applications is the acquisition of polarization information. To develop an all-electronic terahertz straightforward polarization detection system, in this paper, a terahertz polarization detector based on three antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs) on a single chip is designed and fabricated. The function of the direct polarization detector is proven by measuring the polarization angle of linearly polarized continuous-wave terahertz radiation at 216 GHz. The average deviation and maximum deviation of the measured polarization angle are 3.7 degrees and 10 degrees, respectively. The error comes mainly from the disturbance of the local terahertz field by the interference effect. Simulations locate the sources of interference and guide the further device design and packaging of such kind of direct polarization detectors.
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Gliomas are the most common and fatal primary brain tumors. Growing evidence suggests that long non-coding RNAs (lncRNAs) constitute novel and potential therapeutic targets for glioma. However, the biological role of glioblastoma down-regulated RNA (GLIDR) in glioma remains largely elusive. In the current study, we used quantitative real-time polymerase chain reaction (qRT-PCR) to detect GLIDR expression in glioma cells. Cell counting kit 8 (CCK-8) assay, colony formation assay, JC-1 staining, and flow cytometry were used to evaluate the role of GLIDR in proliferation and apoptosis of glioma cells. Western blotting was performed to assess the effect of GLIDR on the level of apoptosis-related proteins. In addition, bioinformatics prediction, RNA immunoprecipitation (RIP), RNA pull-down, and luciferase reporter gene assays were used to study the regulatory mechanisms of GLIDR in glioma. GLIDR was found to be highly expressed in glioma cells and silencing of GLIDR inhibited cell proliferation and promoted apoptosis. Functionally, GLIDR bound to miR-4677-3p that directly targeted membrane-associated guanylate kinase, WW, and PDZ domain-containing protein 2 (MAGI2). Our data showed that GLIDR affects the proliferation and apoptosis of glioma cells by targeting miR-4677-3p to regulate the expression of MAGI2. In conclusion, our study determined the oncogenic role of GLIDR in glioma, which may provide a new perspective for the treatment of glioma.
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Proteínas Adaptadoras Transductoras de Señales/genética , Guanilato-Quinasas/genética , MicroARNs/genética , Neuroglía/metabolismo , ARN Largo no Codificante/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/genética , Emparejamiento Base , Secuencia de Bases , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Guanilato-Quinasas/metabolismo , Humanos , MicroARNs/metabolismo , Neuroglía/patología , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de SeñalRESUMEN
Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF-κB pathways and enhanced the activity of nuclear factor E2-related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS-induced endotoxin death and had a protective effect on LPS-induced ALI. Our findings collectively indicated that RA has anti-inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.
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Lesión Pulmonar Aguda , Antiinflamatorios , Receptor Toll-Like 4 , Triterpenos/farmacología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Citocinas/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Transducción de Señal , Receptor Toll-Like 4/metabolismoRESUMEN
The aim of this study was to identify key genes related to the progression of colon adenocarcinoma (COAD), and to investigate the regulatory network of hub genes and transcription factors (TFs). Dataset GSE20916 including 44 normal colon, 55 adenoma, and 36 adenocarcinoma tissue samples was used to construct co-expression networks via weighted gene co-expression network. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the objective module were performed using the online Database for Annotation, Visualization and Integrated Discovery. Hub genes were identified by taking the intersection of differentially expressed genes between dataset GSE20916 and GSE39582 and validated using The Cancer Genome Atlas (TCGA) database. The correlations between microRNA (miRNA) and hub genes were analyzed using the online website StarBase. Cytoscape was used to establish a regulatory network of TF-miRNA-target gene. We found that the orange module was a key module related to the tumor progression in COAD. In datasets GSE20916 and GSE39582, a total of eight genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) were selected, which were closely related with patients' survivals in TCGA database and dataset GSE20916. COAD patients with higher expressions of each hub gene had a worse prognosis than those with lower expressions. A regulatory network of TF-miRNA-target gene with 144 TFs, 26 miRNAs, and 7 hub genes was established, including model KLF11-miR149-BGN, TCEAL6-miR29B2-COL1A1, and TCEAL6-miR29B2-COL1A2. In conclusion, during the progression of COAD, eight core genes (BGN, SULF1, COL1A1, FAP, THBS2, CTHRC1, COL5A2, and COL1A2) play vital roles. Regulatory networks of TF-miRNA-target gene can help to understand the disease progression and optimize treatment strategy.
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Adenocarcinoma/genética , Neoplasias del Colon/genética , Redes Reguladoras de Genes/genética , Factores de Transcripción/genética , Adenocarcinoma/patología , Biomarcadores de Tumor/genética , Colon/patología , Neoplasias del Colon/patología , Progresión de la Enfermedad , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Humanos , MicroARNs/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer-related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Current treatment modalities that include chemotherapy, radiotherapy and ablation are able to activate HSCs and remodel the tumor microenvironment. Growing evidence has demonstrated that the complex interaction between activated HSCs and tumor cells can facilitate cancer chemoresistance and metastasis. Therefore, therapeutic targeting of activated HSCs has emerged as a promising strategy to improve treatment outcomes for HCC. This review summarizes the molecular mechanisms of HSC activation triggered by treatment modalities, the function of activated HSCs in HCC, as well as the crosstalk between tumor cells and activated HSCs. Pathways of activated HSC reduction are discussed, including inhibition, apoptosis, and reversion to the inactivated state. Finally, we outline the progress and challenges of therapeutic approaches targeting activated HSCs in the development of HCC treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma Hepatocelular/terapia , Células Estrelladas Hepáticas/efectos de los fármacos , Neoplasias Hepáticas/terapia , Neovascularización Patológica/tratamiento farmacológico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Comunicación Celular/efectos de los fármacos , Comunicación Celular/inmunología , Comunicación Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Progresión de la Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/inmunología , Resistencia a Antineoplásicos/efectos de la radiación , Células Estrelladas Hepáticas/inmunología , Células Estrelladas Hepáticas/patología , Células Estrelladas Hepáticas/efectos de la radiación , Humanos , Hígado/irrigación sanguínea , Hígado/citología , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Terapia Molecular Dirigida/métodos , Neovascularización Patológica/etiología , Neovascularización Patológica/patología , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/métodos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Escape del Tumor/efectos de los fármacos , Escape del Tumor/inmunología , Escape del Tumor/efectos de la radiación , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de la radiaciónRESUMEN
Aiming at the requirement of passive terahertz imaging, we report a high-sensitivity terahertz detector based on an antenna-coupled AlGaN/GaN high-electron-mobility transistor (HEMT) at 77 K without using low-noise terahertz amplifier. The measured optical noise-equivalent power and the noise-equivalent temperature difference of the detector were about 0.3p W/H z and 370 mK in a 200 ms integration time over a bandwidth of 0.7 - 0.9 THz, respectively. By using this detector, we demonstrated passive terahertz imaging of room-temperature objects with signal-to-noise ratio up to 13 dB. Further improvement in the sensitivity may allow passive terahertz imaging using AlGaN/GaN-HEMT at room temperature.
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OBJECTIVES: In many malignant tumors, circRNAs play an important role. However, the biological role and clinical significance of circRNAs remain unclear. In this study, we investigated the effects of circ_0001946 on the progression of glioblastoma (GBM) and the molecular mechanism of circ_0001946. METHODS: Microarrays were applied to test the expression profiles of circRNAs and messenger RNAs (mRNAs). Coexpressed genes were identified by constructing differentially expressed circRNA-mRNA networks. The expression of circ_0001946, miR-671-5p, and cerebellar degeneration-related autoantigen 1 (CDR1) was detected by real-time quantitative PCR, and the protein expression of CDR1 was determined by western blotting. A dual-luciferase reporter assay was used to evaluate potential miR-671-5p target sites on circ_0001946 and CDR1. The proliferation, apoptosis, migration, and invasion of GBM cells were assessed by a colony formation assay, flow cytometry assay, transwell migration assay, and transwell invasion assay. Xenograft mouse models were used to determine the role of circ_0001946 in vivo. RESULTS: The expression of circ_0001946 and CDR1 was low and that of miR-671-5p was high in GBM cells. Circ_0001946 suppressed the expression of miR-671-5p, thus upregulating the expression of CDR1, the gene downstream of miR-671-5p. Circ_0001946 and CDR1 reduced proliferation, migration, and invasion and increased apoptosis in GBM cells, whereas miR-671-5p had an opposite effect. The xenograft mouse model and immunohistochemistry results indicated that circ_0001946 inhibited GBM growth as well as the expression of Ki67 in GBM cells. CONCLUSION: Our study confirmed that the circ_0001946/miR-671-5p/ CDR1 pathway modulates the development of GBM, and this pathway might be a promising target for the development of therapeutics for GBM.
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Autoantígenos/metabolismo , Neoplasias Encefálicas/patología , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/patología , MicroARNs/metabolismo , Proteínas del Tejido Nervioso/metabolismo , ARN Circular/metabolismo , Animales , Autoantígenos/genética , Neoplasias Encefálicas/genética , Progresión de la Enfermedad , Glioblastoma/genética , Xenoinjertos , Humanos , Ratones , MicroARNs/genética , Proteínas del Tejido Nervioso/genética , ARN Circular/genéticaRESUMEN
A series of novel 2-hydroxyphenyl substituted aminoacetamides was designed by molecular hybridization of the aminoacetamide scaffold and 2-hydroxyphenyl motif. The target compounds were synthesized and their fungicidal activities were evaluated. Some of the target compounds showed excellent antifungal activities against S. sclerotiorum and P. capsici. Significantly, compounds 5e displayed the most potent activity against S. sclerotiorum with EC50â¯=â¯2.89⯵g/mL, which was lower than that of commercial chlorothalonil. The systematic studies provided strong confidence that the hydroxyl group and the carbonyl group are crucial for the fungicidal activity. Molecular docking studies suggest that SDH enzyme could be one of the potential action targets of our compounds.
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Acetamidas/química , Antifúngicos/síntesis química , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Acetamidas/síntesis química , Acetamidas/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Ascomicetos/efectos de los fármacos , Sitios de Unión , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Relación Estructura-Actividad , Succinato Deshidrogenasa/antagonistas & inhibidores , Succinato Deshidrogenasa/metabolismoRESUMEN
Inflammation is a common pathogenesis in many diseases. Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has been considered to have good anti-inflammatory effects. In the present study, we investigated the anti-inflammatory effect of diethyl blechnic (DB), a novel compound isolated from Danshen, and its possible mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The results showed that DB can inhibit the LPS-induced pro-inflammatory cytokines release of prostaglandin E2 (PGE2) and mRNA expression of TNF-α, IL-6, and IL-1ß. In addition, the results of the flow cytometry assay and the fluorometric intracellular ROS kit assay indicated that DB reduced the generation of ROS in LPS-stimualted RAW264.7 cells. DB reversed the LPS-induced loss of the mitochondrial membrane potential (MMP). Furthermore, DB suppressed the LPS-stimulated increased expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and phosphorylation of TAK1, PI3K, and AKT. DB promoted NF-E2-related factor 2 (Nrf2) into the nucleus, increased the expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) and reduced the expression of Keap1. In summary, DB may inhibit LPS-induced inflammation, which mainly occurs through TLR4/MyD88 and oxidative stress signaling pathways in RAW264.7 cells.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Benzofuranos/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Animales , Antiinflamatorios/química , Antioxidantes/química , Benzofuranos/química , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Ratones , Estructura Molecular , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Plasmon in two-dimensional electron gas (2DEG) has long been considered as a promising active medium for terahertz emitters and detectors. However, the efficiency of terahertz plasmonic devices is severely limited by the high damping rate of plasma wave in solid state. In addition to the enhancement of plasmon lifetime by using 2DEGs with higher carrier mobility, engineering on the boundary condition and electromagnetic environment of plasmon cavity helps to preserve the plasmon states. Here we report on terahertz reflection spectroscopy of plasmon states in a grating-coupled AlGaN/GaN-2DEG plasmonic device at 7 K in equilibrium with ambient blackbody irradiation. Localized plasmon states and plasmon-polariton states were observed when the core plasmonic device is integrated with a silicon lens and when it is embedded in a terahertz Fabry-Pérot cavity, respectively. Simulation results including the reflection spectra and total reflection power agree well with the measured results. The Rabi splitting is found to be inversely proportional to the resonance frequency, and follows a linear relation with the square root of the sheet electron density. A normalized coupling ratio, ΩRω0≈0.13, is achieved between the Rabi splitting ΩR and the resonance frequency ω0. The coupling ratio could be further increased to allow for ultrastrong coupling between terahertz photons and plasmons.
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BACKGROUND: Negative lymph node (NLN) count has been reported to provide more accurate prognostic information than the N stage alone in patients with rectal cancer (RC). Since preoperative radiotherapy (Pre-RT) can significantly affect the LN status, it is unclear whether NLN count still has prognostic value count on survival of patients with RC who received Pre-RT. METHODS: In this study, clinicopathological characteristics, number of positive LNs and survival time were collected from Surveillance, Epidemiology, and End Results Program (SEER)-registered RC patients. Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. RESULTS: X-tile plots identified 9 (P < 0.001) as the optimal cutoff NLN value to divide the patients into high and low risk subsets in terms of cause specific survival (CSS). NLN count was validated as independently prognostic factor in univariate and multivariate analysis (P < 0.001). Subgroup analysis showed that NLN count was an independently prognostic factor for patients with stage ypII (P = 0.002) and ypIII (P < 0.001). CONCLUSIONS: Our results firmly demonstrated that NLN count provides accurate prognostic information for RC patients with Pre-RT.
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Adenocarcinoma Mucinoso/secundario , Adenocarcinoma/secundario , Carcinoma de Células en Anillo de Sello/secundario , Ganglios Linfáticos/patología , Radioterapia , Neoplasias del Recto/patología , Adenocarcinoma/radioterapia , Adenocarcinoma Mucinoso/radioterapia , Carcinoma de Células en Anillo de Sello/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Cuidados Preoperatorios , Pronóstico , Neoplasias del Recto/radioterapia , Programa de VERF , Tasa de SupervivenciaRESUMEN
MicroRNAs are increasingly reported as tumour suppressors that regulate gene expression after transcription. Our results demonstrated that miR-4295 is overexpression in glioma tissues and its level is significantly correlated with clinical stage. We also found that miR-4295 inhibited the cell G0/G1 arrest and apoptosis leading to promoted cell proliferation and activity. The murine modelling study revealed that female nude mice injected with U87/anti-miR-4295 exhibit subcutaneous tumours in the right groin. Compared with anti-NC, the tumour volume was significantly decreased in anti-miR-4295 treatment group. Furthermore, we confirmed miR-4295 mediates the expression of RUNX3 by targeting its 3'untranslation region. In addition, N-myc protein also could bind to the promoter of pri-miR-4295 and inhibit the expression of RUNX3 in glioma cells. These results validate a pathogenetic role of a miR-4295 in gliomas and establish a potentially regulatory and signalling pathway involving N-myc/miR-4295/RUNX3 in gliomas.
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Neoplasias Encefálicas/metabolismo , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Glioma/metabolismo , MicroARNs/genética , Proteínas Proto-Oncogénicas c-myc/fisiología , Regiones no Traducidas 3' , Animales , Apoptosis , Secuencia de Bases , Sitios de Unión , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Carcinogénesis/genética , Carcinogénesis/metabolismo , Línea Celular Tumoral , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/patología , Humanos , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Trasplante de Neoplasias , Interferencia de ARNRESUMEN
BACKGROUND: Chemoresistance is one of the most leading causes for tumor progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays a key role in the chemosensitivity of cancer cells. In the present study, emodin (1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in combination with cisplatin in T24 and J82 human bladder cancer cells. METHODS: Cell viability and apoptosis rate of different treatment groups were detected by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM). The expression of transporters was measured at both the transcription and translation levels using PCR and western blotting. In vitro findings were confirmed by in vivo experiments using tumor-bearing mice. The expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue was measured using immunohistochemistry and side effects of the emodin/cisplatin co-treatment were investigated by histological examination. RESULTS: Emodin increased the cellular ROS level and effectively enhanced the cisplatin-induced cytotoxicity of T24 and J82 human bladder cancer cells through decreasing glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance of T24 and J82 cells to cisplatin through suppressing the expression of MRP1. This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co-treatment increased the cell apoptosis and repressed the MRP1 expression in xenograft tumors, and without obvious systemic toxicity. CONCLUSIONS: This study revealed that emodin could increase the cisplatin-induced cytotoxicity against T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1 expression. We suggest that emodin could serve as an effective adjuvant agent for the cisplatin-based chemotherapy of bladder cancer.