RESUMEN

Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.

Asunto(s)

Biomarcadores , Lupus Eritematoso Sistémico , Rinitis Alérgica , Humanos , Lupus Eritematoso Sistémico/genética , Rinitis Alérgica/genética , Ontología de Genes , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Transducción de Señal , Redes Reguladoras de Genes , Biología Computacional/métodos

RESUMEN

Radionuclide diffusion will be influenced by numerous factors. Establishing a model that can elucidate the internal correlation between mesoscopic diffusion and the microscopic structure of bentonite can enhance the comprehension of radionuclide diffusion mechanisms. In this study, a light gradient boosting machine (LightGBM) was employed to predict the effective diffusion coefficients of HCrO4-, I-, and CoEDTA2- in bentonite. The model's hyperparameters were optimized using the particle swarm optimization (PSO) algorithm. Several correlated physical quantities, such as mesoscopic parameters (total porosity, rock capacity factor, and ion molar conductivity) and microscopic parameters (ionic radius and montmorillonite stacking number) were incorporated to develop a machine learning model that incorporated micro- and meso-scale features. The predictive performance of PSO-LightGBM was verified using diffusion experiments, which investigated the diffusion of HCrO4-, I-, and CoEDTA2- at compacted dry densities of 1200-1800 kg/m3 using a through-diffusion method. Spearman correlation and Shapley additive explanation analyses revealed that the compacted dry density, ionic diffusion coefficient in water, ionic radius, and total porosity were the top-four influencing factors among the 16 input features. Partial dependence plot analysis elucidated the relationship between the effective diffusion coefficient and each input feature. The analysis results were consistent with the experimental findings, demonstrating the reliability of machine learning. Due to the incorporation of multi-scale features, the PSO-LightGBM model demonstrated enhanced predictive accuracy, linking the microstructure of bentonite to radionuclide diffusion, and providing a comprehensive interpretation of the diffusion mechanism.

RESUMEN

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells. IMPLICATIONS: Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.

Asunto(s)

Proteínas Potenciadoras de Unión a CCAAT , Quimiocina CCL2 , Regiones Promotoras Genéticas , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Animales , Ratones , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Masculino , Línea Celular Tumoral , Femenino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Movimiento Celular , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Ratones Desnudos , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Apoptosis

RESUMEN

Background: Armeniaca sibirica seed kernel oil is rich in oleic acid and linoleic acid, thus holding potential value as a source of high-quality edible oils. However, some regulatory factors involved in fatty acids accumulation in A. sibirica seed kernels remain largely elusive. Thus, the aim of this study was to elucidate the regulatory mechanisms underlying fatty acids biosynthesis in A. sibirica developing seed kernels. Methods: Seed kernels from six plants from a single A. sibirica clone were taken at five different developmental stages (days 30, 41, 52, 63, and 73 after anthesis). Fatty acid composition in seed kernel oil was determined by gas chromatography-mass spectrometry (GC-MS). In addition, transcriptome analysis was conducted using second-generation sequencing (SGS) and single-molecule real-time sequencing (SMRT). Results: Rapid accumulation of fatty acids occurred throughout the different stages of seed kernels development, with oleic acid and linoleic acid as the main fatty acids. A total of 10,024, 9,803, 6,004, 6,719 and 9,688 unigenes were matched in the Nt, Nr, KOG, GO and KEGG databases, respectively. In the category lipid metabolism, 228 differentially expressed genes (DEGs) were annotated into 13 KEGG pathways. Specific unigenes encoding 12 key enzymes related to fatty acids biosynthesis were determined. Co-expression network analysis identified 11 transcription factors (TFs) and 13 long non-coding RNAs (lncRNAs) which putatively participate in the regulation of fatty acid biosynthesis. This study provides insights into the molecular regulatory mechanisms of fatty acids biosynthesis in A. sibirica developing seed kernels, and enabled the identification of novel candidate factors for future improvement of the production and quality of seed kernel oil by breeding.

Asunto(s)

Fitomejoramiento , Transcriptoma , Transcriptoma/genética , Semillas/genética , Ácidos Grasos/análisis , Ácido Linoleico/análisis , Aceites de Plantas/análisis , Ácidos Oléicos/análisis

RESUMEN

This study puts forward an efficient method for protein detection in virtue of the tremendous fluorescence enhancement property of 6-aza-2-thio-thymine protected gold nanoclusters (ATT-AuNCs). In-depth studies of the protein-induced photoluminescence enhancement mechanism illustrate the mechanism of the interaction between ATT-AuNCs and protein. This new-established probe enables feasible and sensitive quantification of the concentrations of total protein in real samples, such as human serum, human plasma, milk, and cell extracts. The results of this proposed method are in good agreement with those determined by the classical bicinchoninic acid method (BCA method).

RESUMEN

The development of simple yet powerful methods for monitoring enzyme activity is of great significance. Herein, a facile, convenient, cost-effective, and continuous fluorescent method for the detection of arginase and its inhibitor has been reported based on a host-guest interaction-controlled and enzymatic hydrolysis-controlled luminescent nanoswitch. The fluorescence intensity of 6-aza-2-thiothymine-stabilized gold nanoparticle (ATT-AuNP) is enhanced by l-arginine, owing to the formation of a supramolecular host-guest assembly between the guanidine group of l-arginine and ATT molecules capped on the AuNP surface. However, hydrolysis of l-arginine, catalyzed by arginase, leads to a decrease in the fluorescence intensity of l-arginine/ATT-AuNPs hybrids. Upon incorporation of the arginase inhibitor l-norvaline, the fluorescence of the ATT-AuNP-based detecting system is restored. The linear range of arginase activity determination is from 0.0625 to 1.15 U/mL and the limit of detection is 0.056 U/mL. The half-maximal inhibition value IC50 of l-norvaline is determined to be 5.6 mM. The practicability of this luminescent nanoswitch is validated by assaying the arginase activity in rat liver and monitoring the response of rat liver arginase to pharmacological agent. Compared to the existing fluorescent method of arginase activity assay, the approach demonstrated here does not involve any complicated technical manipulation, thereby greatly simplifying the detection steps. We propose that this AuNP-based luminescent nanoswitch would find wide applications in the field of life sciences and medicine.

Asunto(s)

Nanopartículas del Metal , Animales , Arginasa , Arginina , Oro , Hidrólisis , Luminiscencia , Ratas

RESUMEN

We herein report the intrinsic alkaline peroxidase-like activity exhibited by CuO nanoparticles when 3-(4-hydroxyphenyl)propionic acid was employed as a substrate. Based on this observation, a fluorometric assay method with a low detection limit of 0.81 µM was established for H2O2 determination under alkaline conditions. Notably, ammonia was found to inhibit the alkaline peroxidase-like activity of the CuO nanoparticles. Thus, a sensing platform for the determination of urea and urease was successfully constructed, with the limits of detection for urea and urease being 27 µM and 2.6 U L-1, respectively. This platform was then applied for the detection of urea in human urine and urease in soil, which yielded satisfactory results. These results suggest that it is possible to extend the catalytic potential of peroxidase and its mimetics from acidic and neutral conditions to include activity in alkaline media as well. Furthermore, this strategy is a novel method for the analysis of urea and urease. The assay developed in this work is facile, inexpensive, convenient, and highly selective and sensitive. Therefore, it is expected that this system can serve as a template for the development of similar enzyme nano-mimics.

RESUMEN

Dendrite-like cobalt selenide nanostructures were synthesized from cobalt and selenium powder precursors by a solvothermal method in anhydrous ethylenediamine. The as-prepared nanocrystalline cobalt selenide was found to possess peroxidase-like activity that could catalyze the reaction of peroxidase substrates in the presence of H2O2. A spectrophotometric method for uric acid (UA) determination was developed based on the nanocrystalline cobalt selenide-catalyzed coupling reaction between N-ethyl-N-(3-sulfopropyl)-3-methylaniline sodium salt and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Under optimum conditions, the absorbance was proportional to the concentration of UA over the range of 2.0-40 µM with a detection limit of 0.5 µM. The applicability of the proposed method has been validated by determination of UA in human serum samples with satisfactory results.

Asunto(s)

Cobalto/química , Nanopartículas del Metal/química , Espectrofotometría/métodos , Ácido Úrico/sangre , Ampirona/química , Análisis Químico de la Sangre/métodos , Catálisis , Humanos , Peróxido de Hidrógeno/química , Límite de Detección , Nanoestructuras/química , Peroxidasa , Peroxidasas/química , Peroxidasas/metabolismo

RESUMEN

In this work, bimetallic Bi/Pt nanoparticles in bovine serum albumin biomolecular scaffold (BSA-Bi/PtNPs) were synthesized through a facile and green method. As compared with BSA-PtNPs, the BSA-Bi/PtNPs possess enhanced peroxidase-like catalytic activity. Moreover, the BSA-Bi/PtNPs are stable in harsh conditions such as high temperature, extreme pH environments, and high ionic strength, as well as in common biological matrixes. These prominent advantages enable the BSA-Bi/PtNPs to be applied to a wide range of fields. Bioassays, such as serum glucose detection, extracellular hydrogen peroxide (H2O2) monitor, and cancer cells labeling, have been realized with satisfying results. The linear range of glucose determination was from 1 to 100 µM and the limit of detection (LOD) was 0.2 µM. The H2O2 released from each MCF-7 cell after stimulation was calculated to be 2.66 × 10-16 mol/s. By utilizing folic acid as a recognition element, tumor cell could be readily distinguished by BSA-Bi/PtNPs and the LOD for MCF-7 cell detection was 90 cells.

Asunto(s)

Bismuto , Nanopartículas del Metal , Peroxidasa/química , Platino (Metal) , Técnicas Biosensibles , Humanos , Peróxido de Hidrógeno , Límite de Detección , Células MCF-7 , Albúmina Sérica Bovina

RESUMEN

This paper reports a new and facile method for the synthesis of water-soluble thiolate-protected AuNCs via protein-ligand interaction. Using 3-mercaptopropionic acid (MPA) as a model ligand and bovine serum albumin (BSA) as a model protein, water-soluble AuNCs (BSA/MPA-AuNCs) with intense orange-yellow fluorescent emission (quantum yield=16%) are obtained. Results show that AuNCs produced with this method have hydrophobic interactions with BSA. The synthetic strategy is then successfully extended to produce water-soluble AuNCs protected by other thiolates. Moreover, a sensitive and eco-friendly sensing system is established for detection of the activity of inorganic pyrophosphatase (PPase), which relies on the selective coordination of Fe(3+)with BSA/MPA-AuNCs, the higher affinity between pyrophosphate (PPi) and Fe(3+), and the hydrolysis of PPi by PPase. A good linearity between the fluorescence intensity and PPase activity within the range from 0.1 to 3U/L is found, with a detection limit down to 0.07U/L. Additionally, the fluorescent assay developed here is utilized to assay the PPase activity in real biological samples and as well as to evaluate PPase inhibitor, illustrating the great potential for biological analysis.

Asunto(s)

Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Oro/química , Pirofosfatasa Inorgánica/metabolismo , Nanoestructuras/química , Ácido 3-Mercaptopropiónico/química , Animales , Bovinos , Difosfatos/metabolismo , Pruebas de Enzimas/métodos , Pirofosfatasa Inorgánica/análisis , Nanoestructuras/ultraestructura , Albúmina Sérica Bovina/química , Solubilidad , Espectrometría de Fluorescencia/métodos , Agua/química

RESUMEN

This work investigates the effect of reduction degree on graphene oxide (GO)-DNA interaction and the fluorescence quenching mechanism. Partial reduced graphene oxide (pRGO), which maintains well water-dispersibility, is synthesized using a mild reduction method by incubating GO suspension under alkaline condition at room temperature. The fluorescence quenching enhances with the restoration degree of sp(2) carbon bonds and follows the static quenching mechanism. The binding constant values imply that pRGO has much stronger affinity with ssDNA than GO. Utilizing this highly efficient nanoprobe, a universal sensing strategy is proposed for homogeneous detection of DNA. Compared with the reported GO-based DNA, this present strategy has obvious advantages such as requirement of low nanoprobe dosage, significantly reduced background, fast fluorescence quenching, and improved sensitivity. Even without any amplification process, the limit of detection can reach as low as 50 pM.

Asunto(s)

Técnicas Biosensibles , ADN/aislamiento & purificación , Nanoestructuras/química , Carbono/química , ADN/química , Colorantes Fluorescentes/química , Grafito/química , Óxidos/química