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The museum system is exposed to a high risk of seismic hazards. However, it is difficult to carry out seismic hazard prevention to protect cultural relics in collections due to the lack of real data and diverse types of seismic hazards. To address this problem, we developed a deep-learning-based multi-source feature-fusion method to assess the data on seismic damage caused by collected cultural relics. Firstly, a multi-source data-processing strategy was developed according to the needs of seismic impact analysis of the cultural relics in the collection, and a seismic event-ontology model of cultural relics was constructed. Additionally, a seismic damage data-classification acquisition method and empirical calculation model were designed. Secondly, we proposed a deep learning-based multi-source feature-fusion matching method for cultural relics. By constructing a damage state assessment model of cultural relics using superpixel map convolutional fusion and an automatic data-matching model, the quality and processing efficiency of seismic damage data of the cultural relics in the collection were improved. Finally, we formed a dataset oriented to the seismic damage risk analysis of the cultural relics in the collection. The experimental results show that the accuracy of this method reaches 93.6%, and the accuracy of cultural relics label matching is as high as 82.6% compared with many kinds of earthquake damage state assessment models. This method can provide more accurate and efficient data support, along with a scientific basis for subsequent research on the impact analysis of seismic damage to cultural relics in collections.
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A pH/temperature bi-responsive gallic acid magnetic imprinted polymer (PTBG-MIP) was synthesized on a Fe3O4@SiO2@KH570 carrier using methacrylic acid (MAA), p-Vinylphenylboronic acid (p-VPBA), and N-isopropyl-acrylamide (NIPAAm) as complex functional monomers. The density functional theory (DFT) was employed to optimize the molar ratio of multi-functional monomers-template complex, which proved to be an effective tool for predicting complex configuration based on electrostatic potential (ESP) analysis and the lowest binding energy. DFT calculation and analysis determined the optimized molar ratio of 2:1:1:1 for GA-MAA-NIPAAm-p-VPBA, which showed good agreement with experimental results. The PTBG-MIP-4 obtained under the optimized conditions exhibited high pH- and temperature- dependence in rebinding the template, displaying a maximum adsorption capacity (Qe) of 62.26 mg g-1 and a highest selection factor (α) of 5.217. Additionally, the PTBG-MIP-4 exhibited exceptional physicochemical properties encompassing magnetization characteristics, morphology, surface sites distribution, and adsorption performance. The application efficiency of this imprinted composite in the extraction and purification of gallic acid from Galla chinensis was remarkably demonstrated.
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Medicamentos Herbarios Chinos , Ácido Gálico , Taninos , Temperatura , Acrilamidas/química , Adsorción , Productos Biológicos/química , Productos Biológicos/síntesis química , Medicamentos Herbarios Chinos/química , Ácido Gálico/química , Ácido Gálico/aislamiento & purificación , Concentración de Iones de Hidrógeno , Impresión Molecular/métodos , Polímeros Impresos Molecularmente/química , Polímeros/química , Polímeros/síntesis química , Dióxido de Silicio/química , Extracción en Fase Sólida/métodos , Taninos/químicaRESUMEN
Pancreatic ß-cell failure by WFS1 deficiency is manifested in individuals with wolfram syndrome (WS). The lack of a suitable human model in WS has impeded progress in the development of new treatments. Here, human pluripotent stem cell derived pancreatic islets (SC-islets) harboring WFS1 deficiency and mouse model of ß cell specific Wfs1 knockout were applied to model ß-cell failure in WS. We charted a high-resolution roadmap with single-cell RNA-seq (scRNA-seq) to investigate pathogenesis for WS ß-cell failure, revealing two distinct cellular fates along pseudotime trajectory: maturation and stress branches. WFS1 deficiency disrupted ß-cell fate trajectory toward maturation and directed it towards stress trajectory, ultimately leading to ß-cell failure. Notably, further investigation of the stress trajectory identified activated integrated stress response (ISR) as a crucial mechanism underlying WS ß-cell failure, characterized by aberrant eIF2 signaling in WFS1-deficient SC-islets, along with elevated expression of genes in regulating stress granule formation. Significantly, we demonstrated that ISRIB, an ISR inhibitor, efficiently reversed ß-cell failure in WFS1-deficient SC-islets. We further validated therapeutic efficacy in vivo with ß-cell specific Wfs1 knockout mice. Altogether, our study provides novel insights into WS pathogenesis and offers a strategy targeting ISR to treat WS diabetes.
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Células Secretoras de Insulina , Síndrome de Wolfram , Ratones , Animales , Humanos , Síndrome de Wolfram/genética , Síndrome de Wolfram/metabolismo , Síndrome de Wolfram/patología , Células Secretoras de Insulina/metabolismo , Ratones NoqueadosRESUMEN
A [BMIM]PF6 ion liquid (IL)-assisted synthesis of a rutin imprinted monolith (RIM) was carried out in an in-situ polymerization method. Bi-functional monomers and a ternary porogen containing IL was used for the RIM preparation and a L9(33) orthogonal factor design performed. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and N2 adsorption method was for structural characterization of the RIMs. The monolith was directly used as stationary phase in liquid chromatography to test the retention selectivity, adsorption capacity and extraction application. The optimized porogen consists of 900 µL DMF, 144 µL ACN and 216 µL IL. The monolith RIM-13 obtained under the optimized conditions possessed improved adsorption performance, with a dynamic adsorption capacity of 6.695 mg/g, an imprinting efficiency of 4.841 and a selectivity α value of 4.821. Additionally, this monolith had also higher specific surface area, pore volume and permeability than that obtained without IL and the homogeneity of the imprint sites could be improved by using IL. When the RIM-13 was applied to the separation and purification of rutin from tartary buckwheat, a rutin product with a purity higher than 92 % can be obtained by one cycle. This molecular imprint solid-phase extraction (MI-SPE) is of potency to be applied to preparative-scale separation of other natural products.
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Líquidos Iónicos , Impresión Molecular , Rutina/química , Líquidos Iónicos/química , Espectroscopía Infrarroja por Transformada de Fourier , Impresión Molecular/métodos , Cromatografía Liquida , Extracción en Fase Sólida/métodos , Adsorción , Cromatografía Líquida de Alta PresiónRESUMEN
Dysregulated neurite outgrowth and synapse formation underlie many psychiatric disorders, which are also manifested by wolfram syndrome (WS). Whether and how the causative gene WFS1 deficiency affects synapse formation remain elusive. By mirroring human brain development with cerebral organoids, WFS1-deficient cerebral organoids not only recapitulate the neuronal loss in WS patients, but also exhibit significantly impaired synapse formation and function associated with reduced astrocytes. WFS1 deficiency in neurons autonomously delays neuronal differentiation with altered expressions of genes associated with psychiatric disorders, and impairs neurite outgrowth and synapse formation with elevated cytosolic calcium. Intriguingly, WFS1 deficiency in astrocytes decreases the expression of glutamate transporter EAAT2 by NF-κB activation and induces excessive glutamate. When co-cultured with wildtype neurons, WFS1-deficient astrocytes lead to impaired neurite outgrowth and increased cytosolic calcium in neurons. Importantly, disrupted synapse formation and function in WFS1-deficient cerebral organoids and impaired neurite outgrowth affected by WFS1-deficient astrocytes are efficiently reversed with Riluzole treatment, by restoring EAAT2 expression in astrocytes. Furthermore, Riluzole rescues the depressive-like behavior in the forced swimming test and the impaired recognition and spatial memory in the novel object test and water maze test in Wfs1 conditional knockout mice. Altogether, our study provides novel insights into how WFS1 deficiency affects synapse formation and function, and offers a strategy to treat this disease.
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Células Madre Embrionarias Humanas , Síndrome de Wolfram , Animales , Ratones , Humanos , Síndrome de Wolfram/tratamiento farmacológico , Síndrome de Wolfram/genética , Síndrome de Wolfram/metabolismo , Riluzol/farmacología , Riluzol/metabolismo , Calcio/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Neuronas/metabolismo , Ratones Noqueados , Sinapsis/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Surgical patients with depleted skeletal muscle mass tend to have a worse outcome. Whether perioperative change of urea to creatinine ratio (CUCR) can reflect muscle wasting and predict postoperative complications have not been investigated. This study aimed to evaluate the relationship of perioperative CUCR with postoperative complications and skeletal muscle wasting in pancreatic cancer patients undergoing pancreatoduodenectomy (PD). METHODS AND STUDY DESIGN: Pancreatic cancer patients undergoing PD were included retrospectively. The association between postoperative complications and perioperative CUCR as well as other nutritional biomarkers was analyzed. In a subset of patients with serial CT scans, the correlation of the CUCR and the changes of CT-derived skeletal muscle area (SMA) were tested. Furthermore, the capacity of complication prediction of CUCR and CT-derived parameter were compared in these patients. RESULTS: A total of 321 surgical patients were included. Univariable and multivariable logistic regression demonstrated CUCR was a strong predictor for complications in these patients, independent of age, BMI and comorbidity. Patients with CUCR above the median have higher complication rate (p=0.007) and longer postoperative days to discharge (p=0.017). In a subset patients with both pre- and postoperative digital abdominal CT scans, spearman correlation analysis shown both L3 muscle area and L4-psoas area were significantly correlated with CUCR (R2=0.64, p<0.05; R2=0.62, p<0.05, respectively). CONCLUSIONS: Perioperative CUCR is an independent predictor for postoperative complications in pancreatic cancer patients undergoing PD. Elevated CUCR is a reflection of skeletal muscle wasting in postoperative surgical patients.
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Neoplasias Pancreáticas , Pancreaticoduodenectomía , Creatinina , Humanos , Músculo Esquelético , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , UreaRESUMEN
AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.
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Empalme Alternativo , Proteínas Argonautas/metabolismo , ARN Helicasas DEAD-box/metabolismo , Transporte Activo de Núcleo Celular , Núcleo Celular/metabolismo , Células HeLa , Humanos , Unión Proteica , ARN Bicatenario/genética , Proteína 2 para la Supervivencia de la Neurona Motora/genéticaRESUMEN
Riverine runoff is a significant transport pathway for microplastics (MPs) discharged from land-based sources to marine environments where MPs accumulate. Knowledge of riverine MP-associated biofilms will improve the understanding of the fate and potential effects of MPs in marine environments. This study aimed to characterize the microbial biofilms colonizing MPs in the riverine water of the Pearl River Delta, China, and identify the seasonal, geographical and environmental influences on MP-associated communities. We sampled MPs and the surrounding surface water from eight outlets in three seasons and analyzed their microbial communities by Illumina sequencing of the 16S rRNA gene libraries. Across all sampling seasons and locations, abundant MP-colonizing taxa belonged to the phylum Proteobacteria, which suggested initial biofilm development on those MPs. The structure and composition of MP-attached microbial communities varied with respect to season and location, and the microbial diversity of the MP-associated biofilm communities decreased in June compared with that in the April and November sampling events. Opportunistic pathogens of the genus Acinetobacter were significantly enriched on the MP surfaces for all sampling events. Among the 15 environmental variables examined, the main drivers of MP-associated biofilm community composition included IC, alkalinity, TOC, TDS, Cl-, NO3-, NO2- and pH. This study provides an insight into the environmental factors that shape microbial biofilm colonization on MPs in estuary environments and a further understanding of the structure, diversity and ecological roles of MP-associated communities.
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Microplásticos , Contaminantes Químicos del Agua , Biopelículas , China , Monitoreo del Ambiente , Plásticos , ARN Ribosómico 16S , Ríos , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Body composition has been shown closely related to the outcome in surgical patients. The aim of the present study was to investigate whether preoperative skeletal muscle condition and postoperative nutrition would affect major complications in patients underwent pancreaticoduodenectomy (PD). METHODS: This retrospective study included 265 patients underwent PD. Body composition data was extracted from the L3 level of the preoperative CT scan. Univariable and multivariable regression analyses were performed to investigate correlations between body composition data and postoperative complications. Furthermore, a subgroup analysis was conducted to explore the relationship between postoperative nutrition strategy and the outcome. RESULTS: Of all the 265 patients, major complications occurred in 81 patients (30.6%). Cutoff values for skeletal muscle depletion were defined by ROC curve analysis from postoperative complications in skeletal muscle index (SMI) (male 47.32 cm2/m2 and female 40.65 cm2/m2). Univariable analysis and multivariable regression revealed age (OR 1.49, 95% CI 1.22-1.83, p = 0.026), SMI (OR 0.77, 95% CI 0.51-0.94, p = 0.015) and skeletal muscle density (SMD) (OR 0.85, 95% CI 0.64-1.03, p = 0.029) were independent predictors for major complications. Subgroup analysis showed the initial parenteral nutrition time (IPNT) (OR 1.89, 95% CI 1.43-2.49, p = 0.032) and average protein delivery (APD) (OR 0.76, 95% CI 0.53-0.89, p = 0.021) were significantly associated with major complications in patients with lower SMI. CONCLUSIONS: Preoperative skeletal muscle index and density were independently associated with major complications in patients underwent PD. In patients with lower SMI, early parenteral nutrition and higher protein delivery were related to better outcome.
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Pancreaticoduodenectomía , Sarcopenia , Composición Corporal , Femenino , Humanos , Masculino , Músculo Esquelético/patología , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Sarcopenia/etiología , Sarcopenia/patologíaRESUMEN
[This corrects the article DOI: 10.3389/fgene.2019.00778.].
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Purpose: Fungal keratitis (FK) is an eye disease that can lead to blindness and has a high incidence worldwide. At present, there is no effective treatment for this disease. There are innate immune response mechanisms that protect against fungal infections. One example is C-type lectin receptors (CLRs), which can identify fungal invaders and trigger signal transduction pathways and cellular responses to eliminate pathogens. However, previous studies have focused mostly on single-receptor factors, and a systematic analysis of the genetic factors underlying the pathogenesis of FK has not been conducted. This study aimed to investigate the molecular mechanisms of FK in terms of genomics and to further elucidate its pathogenesis. Methods: We performed a transcriptome analysis of a mouse model of FK using RNA sequencing to obtain the relevant gene expression profiles and to identify differentially expressed genes, signaling pathways, and regulatory networks of the key genetic factors in the pathogenesis of murine FK. Results: Several genes that are significantly associated with FK and serve as markers of FK, such as the inflammatory cytokine genes IL1B, IL6, IL10, IL23, and TNF, were identified. The mRNA and protein expression patterns of IL-1ß, IL-6, and TNF-α in the corneas of mice with FK were validated by quantitative RT-PCR and Luminex multiplex assay technology. The Wnt, cGMP-PKG, and Hippo signaling pathways were significantly enriched during fungal infection of mouse corneas. Conclusions: Our study may help to elucidate the mechanisms of FK pathogenesis and to identify additional candidate drug targets for the treatment of FK.
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Córnea/metabolismo , Infecciones Fúngicas del Ojo/genética , Regulación de la Expresión Génica , Queratitis/genética , RNA-Seq/métodos , Transcriptoma/genética , Animales , Córnea/patología , Modelos Animales de Enfermedad , Infecciones Fúngicas del Ojo/metabolismo , Infecciones Fúngicas del Ojo/patología , Perfilación de la Expresión Génica , Queratitis/metabolismo , Queratitis/patología , Ratones Endogámicos C57BL , Secuenciación del ExomaRESUMEN
Praja2 (Pja2), a member of the growing family of mammalian RING E3 ubiquitin ligases, is reportedly involved in not only several types of cancer but also neurological diseases and disorders, but the genetic mechanism underlying the regulation of Pja2 in the nervous system remains unclear. To study the cellular and molecular functions of Pja2 in mouse hippocampal neuronal cells (MHNCs), we used gain- and loss-of-function manipulations of Pja2 in HT-22 cells and tested their regulatory effects on three Alzheimer's disease (AD) genes and cell proliferation. The results revealed that the expression of AD markers, including amyloid beta precursor protein (App), microtubule-associated protein tau (Mapt), and gamma-secretase activating protein (Gsap), could be inhibited by Pja2 overexpression and activated by Pja2 knockdown. In addition, HT-22 cell proliferation was enhanced by Pja2 upregulation and suppressed by its downregulation. We also evaluated and quantified the targets that responded to the enforced expression of Pja2 by RNA-Seq, and the results showed that purinergic receptor P2X, ligand-gated ion channel 3 and 7 (P2rx3 and P2rx7), which show different expression patterns in the critical calcium signaling pathway, mediated the regulatory effect of Pja2 in HT-22 cells. Functional studies indicated that Pja2 regulated HT-22 cells development and AD marker genes by inhibiting P2rx3 but promoting P2rx7, a gene downstream of P2rx3. In conclusion, our results provide new insights into the regulatory function of the Pja2 gene in MHNCs and thus underscore the potential relevance of this molecule to the pathophysiology of AD.
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Enfermedad de Alzheimer/enzimología , Proliferación Celular , Hipocampo/enzimología , Neuronas/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Línea Celular , Regulación de la Expresión Génica , Hipocampo/patología , Humanos , Ratones , Neuronas/patología , Proteínas/genética , Proteínas/metabolismo , Receptores Purinérgicos P2X3/genética , Receptores Purinérgicos P2X7/genética , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
14-3-3τ plays a critical role in tumorigenesis and metastasis of breast cancer and can be used as new drug target protein. Dicaffeoylquinic acids (DCQAs), natural products, have antioxidant, antimicrobial, and anti-inflammatory activities. In this study, the anticancer effects of DCQAs on breast cancer cells MCF-7, MDA-MB-231 cell lines and mechanism in triple negative breast cancer (TNBC) were investigated. First, we screened for DCQAs that could bind to 14-3-3τ and had a significant inhibitory effect on breast cancer cells. MTT, colony formation, transwell migration, and flow cytometric assays revealed that 1,3-DCQA was the best one of 14-3-3τ binding protein from DCQAs against breast cancer cell proliferation and metastasis but safe for normal cells. Through molecular docking simulation, overexpression and knockdown assays, we confirmed that 14-3-3τ was one of 1,3-DCQA target protein. Eukaryotic transcriptome sequencing and western blot analysis demonstrated that 1,3-DCQA binds to 14-3-3τ to prevent breast cancer proliferation and metastasis via Jak/PI3K/Akt and Raf/ERK pathway, which promote IL6 and CSF3 expression raised by CREB (CREBBP, CREB5) and induced cell apoptosis via Bad/Bax/caspase 9 signaling pathway. Our results provided evidence that 1,3-DCQA can be used as a novel lead compound against breast cancer by inhibition of 14-3-3 protein.
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Proteínas 14-3-3/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Interleucina-6/metabolismo , Janus Quinasa 2/metabolismo , Ácido Quínico/análogos & derivados , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Cinamatos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/genética , Janus Quinasa 2/genética , Modelos Moleculares , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Conformación Proteica , Ácido Quínico/farmacologíaRESUMEN
Mouse Nsmce1 gene is the homolog of non-structural maintenance of chromosomes element 1 (NSE1) that is mainly involved in maintenance of genome integrity, DNA damage response, and DNA repair. Defective DNA repair may cause neurological disorders such as Alzheimer's disease (AD). So far, there is no direct evidence for the correlation between Nsmce1 and AD. In order to explore the function of Nsmce1 in the regulation of nervous system, we have overexpressed or knocked down Nsmce1 in the mouse hippocampal neuronal cells (MHNCs) HT-22 and detected its regulation of AD marker genes as well as cell proliferation. The results showed that the expression of App, Bace2, and Mapt could be inhibited by Nsmce1 overexpression and activated by the knockdown of Nsmce1. Moreover, the HT-22 cell proliferation ability could be promoted by Nsmce1 overexpression and inhibited by knockdown of Nsmce1. Furthermore, we performed a transcriptomics study by RNA sequencing (RNA-seq) to evaluate and quantify the gene expression profiles in response to the overexpression of Nsmce1 in HT-22 cells. As a result, 224 significantly dysregulated genes including 83 upregulated and 141 downregulated genes were identified by the comparison of Nsmce1 /+ to WT cells, which were significantly enriched in several Gene Ontology (GO) terms and pathways. In addition, the complexity of the alternative splicing (AS) landscape was increased by Nsmce1 overexpression in HT-22 cells. Thousands of AS events were identified to be mainly involved in the pathway of ubiquitin-mediated proteolysis (UMP) as well as 3 neurodegenerative diseases including AD. The protein-protein interaction network was reconstructed to show top 10 essential genes regulated by Nsmce1. Our sequencing data is available in the Gene Expression Omnibus (GEO) database with accession number as GSE113436. These results may provide some evidence of molecular and cellular functions of Nsmce1 in MHNCs.
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Neuronas/metabolismo , Transcriptoma , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Línea Celular , Proliferación Celular , Hipocampo/citología , Ratones , Neuronas/fisiología , Regulación hacia Arriba , Proteínas tau/genética , Proteínas tau/metabolismoRESUMEN
Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer. It has neurotoxicity and exposure to it causes impairment of neurodevelopment, behavior and cognition. However, the molecular mechanisms responsible for the DEHP-induced neurotoxicity are not yet clearly defined. Tumor necrosis factor-induced protein 1 (TNFAIP1) was first discovered in umbilical vein endothelial cells and was further found to be important in the progress of Alzheimer's disease. Herein we explore the mechanism of TNFAIP1 in DEHP-induced neurotoxicity with the involvement of cyclic AMP response elements binding protein (CREB) signaling pathway in a mouse neuroblastoma cell line (N2a cells). We found that exposure to DEHP induced apoptosis and downregulated the expression of brain-derived neurotrophic factor (BDNF), synaptic proteins PSD 95 and synapsin-1 while upregulated the expression of TNFAIP1 and decreased the levels of phosphorylated Akt, CaMK â £, catalytic subunits of PKA and CREB in CREB signaling pathway. Knockdown of TNFAIP1 using TNFAIP1 small interfering RNA (siRNA) expression vector prevented DEHP from inhibiting CREB pathway, thus reduced apoptosis and restored expression of BDNF, PSD 95 and synapsin-1. Our data indicate that downregulation of TNFAIP1 prevents DEHP-induced neurotoxicity via activating CREB pathway. Therefore, TNFAIP1 is a potential target for relieving the DEHP-induced neurotoxicity and related neurological disorders.
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Proteínas Adaptadoras Transductoras de Señales/genética , Apoptosis/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Dietilhexil Ftalato/toxicidad , Síndromes de Neurotoxicidad/prevención & control , Plastificantes , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Animales , Línea Celular , Regulación hacia Abajo , Células Endoteliales/metabolismo , Células Endoteliales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Ratones , Neuroblastoma/patología , Síndromes de Neurotoxicidad/etiología , Ácidos Ftálicos , Plastificantes/toxicidadRESUMEN
Evidence from biochemical liver function index and histopathology analysis suggested that selenium could effectively repair the liver injury caused by beta-cypermethrin (ß-CYP). However, the molecular mechanism of selenium against liver injury induced by ß-CYP remains unclear. In the present study, dynamic changes in gene expression profiles before and after the treatment of Na2SeO3 in liver injury mice were analyzed by using RNA sequencing. As a result, several essential genes and pathways were identified to be significantly associated with this process. In particular, ten genes including Cyp2j11, Cyp2b10, Cyp3a13, Dhrs9, Socs2, Stat4, Gm13305, Cyp3a44, Retsat, and Cyp26b1 were significantly enriched in the functional categories related to retinol metabolism, linoleic acid metabolism, and Jak-STAT signaling pathway. Among them, the expression patterns of nine genes were validated by qRT-PCR, except for Cyp3a44. Furthermore, we have constructed the associated regulatory network based on the identified targets revealed by high throughput screening. Our study may provide insight into the molecular mechanism underlying the protective effect of selenium against liver injury induced by ß-CYP in mammals.
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Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Hígado/metabolismo , Selenio/farmacología , Transcriptoma , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Insecticidas/toxicidad , Quinasas Janus/genética , Quinasas Janus/metabolismo , Hígado/efectos de los fármacos , Ratones , Piretrinas/toxicidad , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Selenio/uso terapéuticoRESUMEN
Combination with genomic DNA is one of the important ways for microRNAs (miRNAs) to perform biological processes. However, because of lack of an experimental method, the identified genomic sites targeted by microRNA were only located in the promoter and enhancer regions. In this study, based on affinity purification of labeled biotin at the 3'-end of miRNAs, we established an efficiently experimental method to screen miRNA binding sequences in the whole genomic regions in vivo. Biotinylated miR-373 was used to test our approach in MCF-7 cells, and then Sanger and next-generation sequencing were used to screen miR-373 binding sequences. Our results demonstrated that the genomic fragments precipitated by miR-373 were located not only in promoter but also in intron, exon, and intergenic. Eleven potentially miR-373 targeting genes were selected for further study, and all of these genes were significantly regulated by miR-373. Furthermore, the targeting sequences located in E-cadherin, cold-shock domain-containing protein C2 (CSDC2), and PDE4D genes could interact with miR-373 in MCF-7 cells rather than HeLa cells, which is consistent with our data that these three genes can be regulated by miR-373 in MCF-7 cells while not in HeLa cells. On the whole, this is an efficient method to identify miRNA targeting sequences in the whole genome.
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The occurrence of microplastics (MPs) in the environment has been gaining widespread attention globally. MP-colonizing microorganisms are important links for MPs contamination in various ecosystems, but have not been well understood. To partially address this issue, the present study investigated biofilm formation by microorganisms originating from lake water on low-density polyethylene (LDPE) MPs using a cultivation approach and the surface-related effects on the MP-associated microbial communities using 16S rRNA high-throughput sequencing. With the addition of nonionic surfactants and UV-irradiation pretreatment that changed the surface properties of LDPE MPs, more microorganisms were colonized on LDPE surface. Microbial community analysis indicated that LDPE MPs were primarily colonized by the phyla Proteobacteria, Bacteroidetes and Firmicutes, and the surface roughness and hydrophobicity of MP were important factors shaping the LDPE MP-associated microbial community structure. Half of the top 20 most abundant genera colonizing on LDPE were found to be potential pathogens, e.g., plant pathogens Agrobacterium, nosocomial pathogens Chryseobacterium and fish pathogens Flavobacterium. This study demonstrated rapid bacterial colonization of LDPE MPs in lake water microcosms, the role of MPs as transfer vectors for harmful microorganisms in lake water, and provided a first glimpse into the effect of surface properties on LDPE MP-associated biofilm communities.
Asunto(s)
Bacteroidetes/crecimiento & desarrollo , Firmicutes/crecimiento & desarrollo , Nanopartículas/microbiología , Polietileno/química , Proteobacteria/crecimiento & desarrollo , Bacteroidetes/clasificación , Bacteroidetes/genética , Biopelículas/crecimiento & desarrollo , Ecosistema , Firmicutes/clasificación , Firmicutes/genética , Interacciones Hidrofóbicas e Hidrofílicas , Lagos/microbiología , Proteobacteria/clasificación , Proteobacteria/genética , ARN Ribosómico 16S/genéticaRESUMEN
Although many of the genetic loci associated with breast cancer risk have been reported, there is a lack of systematic analysis of regulatory networks composed of different miRNAs and mRNAs on survival analysis in breast cancer. To reconstruct the microRNAs-genes regulatory network in breast cancer, we employed the expression data from The Cancer Genome Atlas (TCGA) related to five essential miRNAs including miR-21, miR-22, miR-210, miR-221, and miR-222, and their associated functional genomics data from the GEO database. Then, we performed an integration analysis to identify the essential target factors and interactions for the next survival analysis in breast cancer. Based on the results of our integrated analysis, we have identified significant common regulatory signatures including differentially expressed genes, enriched pathways, and transcriptional regulation such as interferon regulatory factors (IRFs) and signal transducer and activator of transcription 1 (STAT1). Finally, a reconstructed regulatory network of five miRNAs and 34 target factors was established and then applied to survival analysis in breast cancer. When we used expression data for individual miRNAs, only miR-21 and miR-22 were significantly associated with a survival change. However, we identified 45 significant miRNA-gene pairs that predict overall survival in breast cancer out of 170 one-on-one interactions in our reconstructed network covering all of five miRNAs, and several essential factors such as PSMB9, HLA-C, RARRES3, UBE2L6, and NMI. In our study, we reconstructed regulatory network of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. These results may provide new insights into regulatory network-based precision medicine for breast cancer.
Asunto(s)
Neoplasias de la Mama/genética , Carcinoma/genética , Redes Reguladoras de Genes , MicroARNs/genética , ARN Mensajero/genética , Neoplasias de la Mama/patología , Carcinoma/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/metabolismo , Invasividad Neoplásica , ARN Mensajero/metabolismo , Análisis de SupervivenciaRESUMEN
Proliferative diabetic retinopathy (PDR) is characterized by neovascularization on the surface of the retina or the optic disc, which is associated with environmental and genetic factors. However, its regulatory mechanism remains to be fully elucidated, particularly at a multiomics level. In the present study, a comprehensive analysis was performed of the gene expression profile of fibrovascular membranes (FVMs) associated with PDR, including an analysis of differentially expressed genes, functional enrichment, and regulation of transcription factors (TFs). As a result, novel marker genes of PDR were identified, including flavin containing monooxygenase 2. Furthermore, several common or specific genes, pathways and TFs have been recovered for active and inactive FVMs. In the present study, lymphoid enhancer binding factor 1 (LEF1) was identified as an upregulator in active and inactive FVMs, which is capable of activating or repressing target genes, including claudin 2, secreted phosphoprotein 1 (SPP1), and aristaless-like homeobox 4. It was demonstrated that the Wnt/ß-catenin effector LEF1 regulating SPP1 is potentially important in PDR. The results of the present study may provide novel insights into the molecular mechanisms underlying the pathophysiology of PDR.