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Porous materials, characterized by their controllable pore size, high specific surface area, and controlled space functionality, have become cross-scale structures with microenvironment effects and multiple functions and have gained tremendous attention in the fields of catalysis, energy storage, and biomedicine. They have evolved from initial nanopores to multiscale pore-cavity designs with yolk-shell, multishells, or asymmetric structures, such as bottle-shaped, multichambered, and branching architectures. Various synthesis strategies have been developed for the interfacial engineering of porous structures, including bottom-up approaches by using liquid-liquid or liquid-solid interfaces "templating" and top-down approaches toward chemical tailoring of polymers with different cross-linking degrees, as well as interface transformation using the Oswald ripening, Kirkendall effect, or atomic diffusion and rearrangement methods. These techniques permit the design of functional porous materials with diverse microenvironment effects, such as the pore size effect, pore enrichment effect, pore isolation and synergistic effect, and pore local field enhancement effect, for enhanced applications. In this review, we delve into the bottom-up and top-down interfacial-oriented synthesis approaches of porous structures with advanced structures and microenvironment effects. We also discuss the recent progress in the applications of these collaborative effects and structure-activity relationships in the areas of catalysis, energy storage, electrochemical conversion, and biomedicine. Finally, we outline the persisting obstacles and prospective avenues in terms of controlled synthesis and functionalization of porous engineering. The perspectives proposed in this paper may contribute to promote wider applications in various interdisciplinary fields within the confined dimensions of porous structures.
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Mesoporous materials endowed with a hollow structure offer ample opportunities due to their integrated functionalities; however, current approaches mainly rely on the recruitment of solid rigid templates, and feasible strategies with better simplicity and tunability remain infertile. Here, we report a novel emulsion-driven coassembly method for constructing a highly tailored hollow architecture in mesoporous carbon, which can be completely processed on oil-water liquid interfaces instead of a solid rigid template. Such a facile and flexible methodology relies on the subtle employment of a 1,3,5-trimethylbenzene (TMB) additive, which acts as both an emulsion template and a swelling agent, leading to a compatible integration of oil droplets and composite micelles. The solution-based assembly process also shows high controllability, endowing the hollow carbon mesostructure with a uniform morphology of hundreds of nanometers and tunable cavities from 0 to 130 nm in diameter and porosities (mesopore sizes 2.5-7.7 nm; surface area 179-355 m2 g-1). Because of the unique features in permeability, diffusion, and surface access, the hollow mesoporous carbon nanospheres exhibit excellent high rate and cycling performances for sodium-ion storage. Our study reveals a cooperative assembly on the liquid interface, which could provide an alternative toolbox for constructing delicate mesostructures and complex hierarchies toward advanced technologies.
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PURPOSE: To develop thrombus radiomics models based on dual-energy CT (DECT) for predicting etiologic cause of stroke. METHODS: We retrospectively enrolled patients with occlusion of the middle cerebral artery who underwent computed tomography (NCCT) and DECT angiography (DECTA). 70 keV virtual monoenergetic images (simulate conventional 120kVp CTA images) and iodine overlay maps (IOM) were reconstructed for analysis. Five logistic regression radiomics models for predicting cardioembolism (CE) were built based on the features extracted from NCCT, CTA and IOM images. From these, the best one was selected to integrate with clinical information for further construction of the combined model. The performance of the different models was evaluated and compared using ROC curve analysis, clinical decision curves (DCA), calibration curves and Delong test. RESULTS: Among all the radiomic models, model NCCT+IOM performed the best, with AUC = 0.95 significantly higher than model NCCT, model CTA, model IOM and model NCCT+CTA in the training set (AUC = 0.88, 0.78, 0.90,0.87, respectively, P < 0.05), and AUC = 0.92 in the testing set, significantly higher than model CTA (AUC = 0.71, P < 0.05). Smoking and NIHSS score were independent predictors of CE (P < 0.05). The combined model performed similarly to the model NCCT+IOM, with no statistically significant difference in AUC either in the training or test sets. (0.96 vs. 0.95; 0.94 vs. 0.92, both P > 0.05). CONCLUSION: Radiomics models constructed based on NCCT and IOM images can effectively determine the source of thrombus in stroke without relying on clinical information.
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Silicon (Si) is regarded as a promising anode material because of its outstanding theoretical capacity, abundant existence, and mature infrastructure, but it suffers from an inherent volume expansion problem. Herein, a facile, scalable, and cost-effective route to produce Si nanosheets (Si NSs) using a low-cost silica fume as the start materials is proposed. After coated with carbon, the as-prepared Si-NSs@C material delivers ultrahigh capability (2770 mAh g-1 at 0.1 C), high initial Coulombic efficiency (87.9%), and long cycling lifespan (100 cycles at 0.5 C with a capacity decay rate of 0.3% per cycle). Beyond proof of concept, this work demonstrates a Si-NSs based pouch cell with an impressive capacity retention of 70.9% after 400 cycles, making it more promising for practical application. Revealed by the theoretical simulation, kinetics analysis, and in situ thickness/pressure detection, it is found that the superior performance of Si-NSs is attributed to the improved diffusivity and reversibility of Li+ ions and low expansion.
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The encapsulation of functional colloidal nanoparticles (100â nm) into single-crystalline ZSM-5 zeolites, aiming to create uniform core-shell structures, is a highly sought-after yet formidable objective due to significant lattice mismatch and distinct crystallization properties. In this study, we demonstrate the fabrication of a core-shell structured single-crystal zeolite encompassing an Fe3O4 colloidal core via a novel confinement stepwise crystallization methodology. By engineering a confined nanocavity, anchoring nucleation sites, and executing stepwise crystallization, we have successfully encapsulated colloidal nanoparticles (CN) within single-crystal zeolites. These grafted sites, alongside the controlled crystallization process, compel the zeolite seed to nucleate and expand along the Fe3O4 colloidal nanoparticle surface, within a meticulously defined volume (1.5×107≤V≤1.3×108â nm3). Our strategy exhibits versatility and adaptability to an array of zeolites, including but not restricted to ZSM-5, NaA, ZSM-11, and TS-1 with polycrystalline zeolite shell. We highlight the uniformly structured magnetic-nucleus single-crystalline zeolite, which displays pronounced superparamagnetism (14â emu/g) and robust acidity (~0.83â mmol/g). This innovative material has been effectively utilized in a magnetically stabilized bed (MSB) reactor for the dehydration of ethanol, delivering an exceptional conversion rate (98 %), supreme ethylene selectivity (98 %), and superior catalytic endurance (in excess of 100â hours).
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Due to their uncontrollable assembly and crystallization process, the synthesis of mesoporous metal oxide single crystals remains a formidable challenge. Herein, we report the synthesis of single-crystal-like mesoporous Li2TiSiO5 by using soft micelles as templates. The key lies in the atomic-scale self-assembly and step-crystallization processes, which ensure the formation of single-crystal-like mesoporous Li2TiSiO5 microparticles via an oriented attachment growth mechanism under the confinement of an in-situ formed carbon matrix. The mesoporous Li2TiSiO5 anode achieves a superior rate capability (148 mAh g-1 at 5.0 A g-1) and outstanding long-term cycling stability (138 mAh g-1 after 3000 cycles at 2.0 A g-1) for lithium storage as a result of the ultrafast Li+ diffusion caused by penetrating mesochannels and nanosized crystal frameworks (5-10 nm). In comparison, bulk Li2TiSiO5 exhibits poor rate capability and cycle performance due to micron-scale diffusion lengths. This method is very simple and reproducible, heralding a new way of designing and synthesizing mesoporous single crystals with controllable frameworks and chemical functionalities.
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BACKGROUND: The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM). PATIENTS AND METHODS: Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed. RESULTS: The values of hemoglobin, beta-2 microglobulin (ß2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADCmean at a specific value (368.5×10-6 mm2/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10-6mm2/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P < 0.001). CONCLUSIONS: The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico por imagen , Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Estudios de Factibilidad , Carga Tumoral , Hibridación Fluorescente in SituRESUMEN
Mesoporous materials with crystalline frameworks have been acknowledged as very attractive materials in various applications. Nevertheless, due to the cracking issue during crystallization and incompatible hydrolysis and assembly, the precise control for crystalline mesoscale membranes is quite infertile. Herein, we presented an ingenious stepwise monomicelle assembly route for the syntheses of highly ordered mesoporous crystalline TiO2 membranes with delicately controlled mesophase, mesoporosity, and thickness. Such a process involves the preparation of monomicelle hydrogels and follows self-assembly by stepwise solvent evaporation, which enables the sensitive hydrolysis of TiO2 oligomers and dilatory micelle assembly to be united. In consequence, the fabricated mesoporous TiO2 membranes exhibit a broad flexibility, including tunable ordered mesophases (worm-like, hexagonal p6mm to body-centered cubic Im3Ì m), controlled mesopore sizes (3.0-8.0 nm), and anatase grain sizes (2.3-8.4 nm). Besides, such mesostructured crystalline TiO2 membranes can be extended to diverse substrates (Ti, Ag, Si, FTO) with tailored thickness. The great mesoporosity of the in situ fabricated mesoscopic membranes also affords excellent pseudocapacitive behavior for sodium ion storage. This study underscores a novel pathway for balancing the interaction of precursors and micelles, which could have implications for synthesizing crystalline mesostructures in higher controllability.
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Multi-chambered architectures have attracted much attention due to the ability to establish multifunctional partitions in different chambers, but manipulating the chamber numbers and coupling multi-functionality within the multi-chambered mesoporous nanoparticle remains a challenge. Herein, we propose a nanodroplet remodeling strategy for the synthesis of hierarchical multi-chambered mesoporous silica nanoparticles with tunable architectures. Typically, the dual-chambered nanoparticles with a high surface area of ~469 m2 g-1 present two interconnected cavities like a calabash. Furthermore, based on this nanodroplet remodeling strategy, multiple species (magnetic, catalytic, optic, etc.) can be separately anchored in different chamber without obvious mutual-crosstalk. We design a dual-chambered mesoporous nanoreactors with spatial isolation of Au and Pd active-sites for the cascade synthesis of 2-phenylindole from 1-nitro-2-(phenylethynyl)benzene. Due to the efficient mass transfer of reactants and intermediates in the dual-chambered structure, the selectivity of the target product reaches to ~76.5%, far exceeding that of single-chambered nanoreactors (~41.3%).
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A sulfhydryl monomicelles interfacial assembly strategy is presented for the synthesis of fully exposed single-atom-layer Pt clusters on 2D mesoporous TiO2 (SAL-Pt@mTiO2 ) nanosheets. This synthesis features the introduction of the sulfhydryl group in monomicelles to finely realize the controllable co-assembly process of Pt precursors within ordered mesostructures. The resultant SAL-Pt@mTiO2 shows uniform SAL Pt clusters (≈1.2â nm) anchored in ultrathin 2D nanosheets (≈7â nm) with a high surface area (139â m2 g-1 ), a large pore size (≈25â nm) and a high dispersion (≈99 %). Moreover, this strategy is universal for the synthesis of other SAL metal clusters (Pd and Au) on 2D mTiO2 with high exposure and accessibility. When used as a catalyst for hydrogenation of 4-nitrostyrene, the SAL-Pt@mTiO2 shows a high catalytic activity (TOF up to 2424â h-1 ), 100 % selectivity for 4-aminostyrene, good stability, and anti-resistance to thiourea poisoning under relatively mild conditions (25 °C, 10â bar).
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Purpose: This study aimed to investigate the relationship between gut microbiota (GM) and serum metabolism using antineoplastic Fufangchangtai (FFCT) as the model prescription in the treatment of colorectal cancer (CRC). Methods: Tumor-bearing mice and normal mice were administered different doses of FFCT. The tumor volume of tumor-bearing mice was observed. The levels of CD4+ and CD8+ T cells in the blood, spleen, and tumor of mice were determined using a flow cytometer. The bacterial microbiota in stool samples from mice and the serum metabolomics of FFCT-treated mice and fecal microbiota transplantation mice were detected using 16s RNA sequencing and liquid chromatography-mass spectrometry (LC/MS), respectively. Results: The tumor volume of mice showed no significant decrease after FFCT intervention. The levels of CD4+ and CD8+T lymphocytes showed a significant increase under the intervention of FFCT. GM of colorectal tumor-bearing mice and healthy mice were determined, and the diversity and abundance of Firmicutes, Deferribacteres, Bacteroidetes, and Proteobacteria were significantly different between the two groups. Furthermore, we found that the levels of matrine, isogingerenone B, and armillaripin were significantly decreased in tumor-bearing mice after FFCT intervention, indicating that the tumor-induced dysbiosis of gut bacteria may affect the absorption and metabolism of FFCT. Under the intervention of FFCT, serum metabolism of mice transplanted with feces from CRC patients showed less metabolites related to FFCT than that from healthy people, indicating that GM could be a single factor affecting the metabolism of FFCT. Furthermore, we found that different doses of FFCT-treated mice had higher abundance of Roseburia, Turicibacter, and Flexispira than that in the non-intervention control group. Firmicutes and Bacteroidetes in FFCT-treated groups showed a similar trend compared to the healthy group, indicating that FFCT might correct the intestinal microenvironment by modulating gut microbiota in colorectal tumor-bearing mice. Conclusion: The dysbiosis of GM in tumor-bearing mice reduced the serum metabolites related to FFCT, and FFCT could correct the disordered GM of colorectal tumor-bearing mice to exert efficacy.
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Manipulating the super-assembly of polymeric building blocks still remains a great challenge due to their thermodynamic instability. Here, we report on a type of three-dimensional hierarchical core-satellite SiO2@monomicelle spherical superstructures via a previously unexplored monomicelle interfacial super-assembly route. Notably, in this superstructure, an ultrathin single layer of monomicelle subunits (~18 nm) appears in a typically hexagon-like regular discontinuous distribution (adjacent micelle distance of ~30 nm) on solid spherical interfaces (SiO2), which is difficult to achieve by conventional super-assembled methods. Besides, the number of the monomicelles on colloidal SiO2 interfaces can be quantitatively controlled (from 76 to 180). This quantitative control can be precisely manipulated by tuning the interparticle electrostatic interactions (the intermicellar electrostatic repulsion and electrostatic attractions between the monomicelle units and the SiO2 substrate). This monomicelle interfacial super-assembly strategy will enable a controllable way for building multiscale hierarchical regular micro- and/or macroscale materials and devices.
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As one of the most important parameters of the nanomotors' motion, precise speed control of enzyme-based nanomotors is highly desirable in many bioapplications. However, owing to the stable physiological environment, it is still very difficult to in situ manipulate the motion of the enzyme-based nanomotors. Herein, inspired by the brakes on vehicles, the near-infrared (NIR) "optical brakes" are introduced in the glucose-driven enzyme-based mesoporous nanomotors to realize remote speed regulation for the first time. The novel nanomotors are rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of the SiO2@Au core@shell nanospheres and the enzymes-modified periodic mesoporous organosilicas (PMOs). The nanomotor can be driven by the biofuel of glucose under the catalysis of enzymes (glucose oxidase/catalase) on the PMO domain. Meanwhile, the Au nanoshell at the SiO2@Au domain enables the generation of the local thermal gradient under the NIR light irradiation, driving the nanomotor by thermophoresis. Taking advantage of the unique Janus nanostructure, the directions of the driving force induced by enzyme catalysis and the thermophoretic force induced by NIR photothermal effect are opposite. Therefore, with the NIR optical speed regulators, the glucose-driven nanomotors can achieve remote speed manipulation from 3.46 to 6.49 µm/s (9.9-18.5 body-length/s) at the fixed glucose concentration, even after covering with a biological tissue. As a proof of concept, the cellar uptake of the such mesoporous nanomotors can be remotely regulated (57.5-109 µg/mg), which offers great potential for designing smart active drug delivery systems based on the mesoporous frameworks of this novel nanomotor.
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Nanoestructuras , Dióxido de Silicio , Sistemas de Liberación de Medicamentos , Glucosa , Glucosa Oxidasa , Nanoestructuras/química , Dióxido de Silicio/químicaRESUMEN
Streamlined architectures with a low fluid-resistance coefficient have been receiving great attention in various fields. However, it is still a great challenge to synthesize streamlined architecture with tunable surface curvature at the nanoscale. Herein, we report a facile interfacial dynamic migration strategy for the synthesis of streamlined mesoporous nanotadpoles with varied architectures. These tadpole-like nanoparticles possess a big streamlined head and a slender tail, which exhibit large inner cavities (75-170 nm), high surface areas (424-488 m2 g-1), and uniform mesopore sizes (2.4-3.2 nm). The head curvature of the streamlined mesoporous nanoparticles can be well-tuned from â¼2.96 × 10-2 to â¼5.56 × 10-2 nm-1, and the tail length can also be regulated from â¼30 to â¼650 nm. By selectively loading the Fe3O4 catalyst in the cavity of the streamlined silica nanotadpoles, the H2O2-driven mesoporous nanomotors were designed. The mesoporous nanomotors with optimized structural parameters exhibit outstanding directionality and a diffusion coefficient of 8.15 µm2 s-1.
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Nanopartículas , Dióxido de Silicio , Catálisis , Peróxido de Hidrógeno , PorosidadRESUMEN
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors with a poor prognosis. At present, the pathogenesis is not completely clear. Therefore, finding reliable prognostic indicators for CRC is of important clinical significance. In this study, bioinformatics methods were used to screen the prognostic immune-related lncRNAs of CRC, and a prognostic risk scoring model based on immune-related lncRNAs signatures were constructed to provide a basis for prognostic evaluation and immunotherapy of CRC patients. METHODS: The clinical information and RNA-seq data of CRC patients were obtained from The Cancer Genome Atlas (TCGA) database. The information of immune-related lncRNA was downloaded from the immunology database and analysis portal. The differentially expressed immune-related lncRNAs (IRLs) were screened by the edgeR package of R software. The prognostic value of IRLs was studied. Based on Cox regression analysis, a prognostic index (IRLPI) based on IRLs was established, and the relationship between the risk score and the clinicopathological characteristics of CRC was analyzed to determine the effectiveness of the risk score model as an independent prognostic factor. RESULTS: A total of 240 differentially expressed IRLs were identified between normal colorectal cancer tissues and normal colorectal cancer tissues, in which 8 were significantly associated with the survival of CRC patients (P < 0.05), including LINC00461, LINC01055, ELFN1-AS1, LMO7-AS1, CYP4A22-AS1, AC079612.1, LINC01351, and MIR31HG. And most of the lncRNAs related to survival were risk factors for the prognosis of CRC. The index established based on the 7 survival-related IRLs found to be highly accurate in monitoring CRC prognosis. Besides, IRLPI was significantly correlated with a variety of pathological factors and immune cell infiltration. CONCLUSION: Eight immune-related lncRNAs closely related to the prognosis of CRC patients were identified from the TCGA database. At the same time, an independent IRLPI was constructed, which may be helpful for clinicians to assess the prognosis of patients with CRC and to formulate individualized treatment plans.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment, which may influence its successful completion. The Huang-Qi-Gui-Zhi-Wu-Wu decoction (HQGZWWD) has been widely used to treat CIPN in China although the pharmacological mechanisms involved have not been clarified. Using the network pharmacology approach, this study investigated the potential pathogenesis of CIPN and the therapeutic mechanisms exerted by the HQGZWWD herbal formula in CIPN. The targets of HQGZWWD were identified using traditional Chinese medicine (TCM) databases (TCMSP and ETCM) and prediction platforms (PharmMapper and TargetNet), and the genes of CIPN were collected by DisGeNET, GeneCards, and literature search. The common target interaction network between herbal formula and diseases was constructed by using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal the mechanism and efficacy of HQGZWWD in the treatment of CIPN. A total of 153 CIPN-related genes were screened, and a protein-protein interaction (PPI) network with 96 nodes and 424 edges was constructed. Sixty-three active components were retrieved from HQGZWWD, with a herb-composite compound-target network including 748 nodes and 5448 edges. Forty-one targets belong to the above two networks. The analysis of network results and literature review shows that the main pathological processes of CIPN may be the inflammatory response and nerve injury, and HQGZWWD plays a therapeutic role in CIPN by regulating inflammatory response and repairing nerve injury, thus verifying the reliable efficacy of this herbal formula. In addition, we found two new potential therapeutic targets (CDK7 and GSTM2) warranting further investigation. This study fully illustrates that TCM has the characteristics of a multicompound, multitarget, and multipathway treatment, which is of great significance to study the curative effect of herbal formulations.
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Colorectal cancer, a malignant neoplasm that occurs in the colorectal mucosa, is one of the most common types of gastrointestinal cancer. Colorectal cancer has been studied extensively, but the molecular mechanisms of this malignancy have not been characterized. This study identified and verified core genes associated with colorectal cancer using integrated bioinformatics analysis. Three gene expression profiles (GSE15781, GSE110223, and GSE110224) were downloaded from the Gene Expression Omnibus (GEO) databases. A total of 87 common differentially expressed genes (DEGs) among GSE15781, GSE110223, and GSE110224 were identified, including 19 upregulated genes and 68 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for common DEGs using clusterProfiler. These common DEGs were significantly involved in cancer-associated functions and signaling pathways. Then, we constructed protein-protein interaction networks of these common DEGs using Cytoscape software, which resulted in the identification of the following 10 core genes: SST, PYY, CXCL1, CXCL8, CXCL3, ZG16, AQP8, CLCA4, MS4A12, and GUCA2A. Analysis using qRT-PCR has shown that SST, CXCL8, and MS4A12 were significant differentially expressed between colorectal cancer tissues and normal colorectal tissues (P < 0.05). Gene Expression Profiling Interactive Analysis (GEPIA) overall survival (OS) has shown that low expressions of AQP8, ZG16, CXCL3, and CXCL8 may predict poor survival outcome in colorectal cancer. In conclusion, the core genes identified in this study contributed to the understanding of the molecular mechanisms involved in colorectal cancer development and may be targets for early diagnosis, prevention, and treatment of colorectal cancer.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales , Transcriptoma/genética , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/mortalidad , Biología Computacional , Humanos , Mapas de Interacción de Proteínas/genéticaRESUMEN
Stroke is a neurological disease with high rates of mortality and disability. The pathogenesis of stroke is acute focal injury of the central nervous system, leading to impaired neural function. Ischemic stroke accounts for the majority of cases. At present, the exact molecular mechanism of ischemic stroke remains unclear. Studies have shown that long noncoding RNAs (lncRNAs) have an important regulatory role in biological processes, participating in the regulation of transcription and affecting the processing and splicing of mRNAs. Abnormal lncRNA expression is associated with various diseases, including diseases of the nervous system. To identify and verify the key lncRNAs in ischemic stroke, we downloaded gene expression data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) and obtain differentially expressed lncRNAs, miRNAs, and mRNAs by bioinformatics analysis. Cytoscape was used to reconstruct a lncRNA-miRNA-mRNA network on the basis of the competitive endogenous RNA theory. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the mRNAs regulated by lncRNAs in the lncRNA-miRNA-mRNA network. The resulting lncRNA-miRNA-mRNA network was composed of 91 lncRNA nodes, 70 mRNA nodes, 21 miRNA nodes, and 288 edges. GO analysis and KEGG pathway analysis have shown that 191 GO terms and 23 KEGG pathways were enriched. Finally, we found that four key lncRNAs were highly correlated with ischemic stroke and could be used as potential new targets for treatment.
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Accidente Cerebrovascular Isquémico , ARN Largo no Codificante , Biología Computacional , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica/genética , Marcadores Genéticos/genética , Humanos , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/metabolismo , ARN/genética , ARN/metabolismo , ARN Largo no Codificante/análisis , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transcriptoma/genéticaRESUMEN
INTRODUCTION: Exosomes are important mediators of intercellular communication. Previously, we characterized circulating exosomal miR-425-3p as a non-invasive prognostic marker for predicting clinical response to platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC). METHODS: Circulating exosomal miR-425-3p was validated by qRT-PCR in paired serum samples from NSCLC patients during the course of platinum-based chemotherapy. Cell coculture was performed to examine the effects of exosomal miR-425-3p on the sensitivity of recipient A549 cells to cisplatin. Using bioinformatics, ChIP and luciferase reporter assays, the transcription factor essential for miR-425-3p expression was identified. Autophagic activity in the recipient cells was determined by Western blot and fluorescence microscopy. RESULTS: Higher levels of exosomal miR-425-3p were found in serum samples from the patients in tolerance versus those at baseline. An upward trend in the expression of circulating exosomal miR-425-3p was revealed during chemotherapy. Furthermore, the expression of exosomal miR-425-3p could be induced by cisplatin in NSCLC cells. Exosomes isolated from either cisplatin-treated or cisplatin-resistant NSCLC cells conferred chemoresistance to sensitive A549 cells in a miR-425-3p-dependent manner. Cisplatin-induced c-Myc was found to directly bind the miR-425-3p promoter and transactivated its expression. Exosomal miR-425-3p facilitated autophagic activation in the recipient cells by targeting AKT1, eventually leading to chemoresistance. DISCUSSION: Our results suggest that apart from a prognostic marker of treatment response, exosomal miR-425-3p might be a potential dynamic biomarker to tailor cisplatin resistance in NSCLC patients during the treatment and represent a promising therapeutic target for therapy-resistant NSCLC.