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1.
Artículo en Inglés | MEDLINE | ID: mdl-38551418

RESUMEN

Objective: To investigate the influence of the dyadic coping model on anxiety and depression levels and treatment compliance in glaucoma patients. Methods: According to the random number table method, 80 glaucoma patients were assigned into an observation group and a control group, with 40 cases in each group are recruited from January 2021 to February 2022. Both groups received routine preoperative glaucoma care; in addition, the observation group received a 10-week dyadic coping model intervention. The dyadic coping model is a therapeutic approach that involves the collaborative efforts of both patients and their close partners or caregivers to cope with stressors and challenges related to the perioperative period. The baseline data questionnaires were collected before the intervention, and the outcome was evaluated 10 weeks later using the Anxiety and Depression Self-Rating Scale and the Treatment Compliance Scale. Results: After intervention, the treatment compliance of glaucoma in the observation group was significantly better than that in the control group, and the anxiety and depression level in the observation group was significantly lower than that in the control group (P < .05). Conclusion: The dyadic coping model intervention for glaucoma patients can successfully increase treatment compliance and lower anxiety and depression levels.

2.
Appl Opt ; 61(12): 3480-3485, 2022 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-35471445

RESUMEN

X-ray backlighting is been widely used today in dynamic phenomena observation. By applying proper synchronizing techniques, the in-situ data of the intensity distribution of the fragments in laser-driven shock-loaded aluminum were obtained for a particular moment using x-ray backlighting imaging. The image resolution was better than 40 µm in this context by introducing a pinhole. In order to obtain the areal mass of the fragments, a set of reference Al step wedges with certain thicknesses was employed. Furthermore, a novel, to the best of our knowledge, calibration method is introduced to calibrate the x-ray intensity distribution. It was effective to decrease the non-uniformity influence of the x-ray intensity with this calibration method by simulating a light field. After calibration, the standard deviation of 30 regions of interest reduced to 4.17%. In consequence, the areal mass distribution of the fragments is well quantified. It should be noted that the uncertainty in the areal mass conversion mainly comes from the non-uniformity of the x-ray intensity distribution with about 5% and the measurement uncertainty of the step thicknesses with less than 10%.

3.
BMC Neurol ; 21(1): 33, 2021 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482768

RESUMEN

BACKGROUND: This review aims to evaluate the performance and clinical applicability of the A2DS2 scale via systematic review and meta-analysis. METHODS: The Medline, Embase, Cochrane Library, CBM, CNKI, and Wanfang databases were searched. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Funnel plots and Egger's test were used to evaluate publication bias. The bivariate random-effect model was used for calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC). A Fagan nomogram was applied to evaluate the clinical applicability of the A2DS2 scale. RESULTS: A total of 29 full-text articles met the inclusion criteria, including 19,056 patients. Bivariate mixed-effects regression models yielded a mean sensitivity of 0.78 (95 % CI: 0.73-0.83), a specificity of 0.79 (95 % CI: 0.73-0.84), a positive likelihood ratio of 3.7 (95 % CI: 2.9-4.6), and a negative likelihood ratio of 0.27 (95 % CI: 0.23-0.33). The area under the receiver operating characteristic curve was 0.85 (95 % CI: 0.82-0.88). If given a pre-test probability of 50 %, the Fagan nomogram showed that when A2DS2 was positive, the post-test probability improved to 79 %. In contrast, when A2DS2 was negative, it decreased to 22 %. The results of the subgroup analysis showed no effect on the diagnostic accuracy of the A2DS2 scale in predicting stroke-associated pneumonia, except for the optimal cut-off value. CONCLUSIONS: The A2DS2 scale demonstrates high clinical applicability and could be a valid scale for the early prediction of stroke-associated pneumonia in stroke patients.


Asunto(s)
Neumonía/etiología , Accidente Cerebrovascular/complicaciones , Humanos , Morbilidad , Valor Predictivo de las Pruebas , Factores de Riesgo
4.
BMC Cancer ; 20(1): 416, 2020 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-32404198

RESUMEN

BACKGROUND: KRAS mutations have been characterized as the major predictive biomarkers for resistance to cetuximab treatment. However, studies indicate that not all KRAS mutations are associated with equivalent treatment outcomes. KRAS G13D mutations were observed to account for approximately 16% of all KRAS mutations in advanced colorectal cancer patients, and whether these patients can benefit from cetuximab has not been determined. METHODS: An established KRAS G13D mutant colorectal cancer (CRC) patient-derived xenograft (PDX) model was treated with cetuximab. After repeated use of cetuximab, treatment-resistant PDX models were established. Tissue samples were collected before and during treatment, and multiomics data were subsequently sequenced and processed, including whole-exome, mRNA and miRNA data, to explore potential dynamic changes. RESULTS: Cetuximab treatment initially slowed tumor growth, but resistance developed not long after treatment. WES (whole-exome sequencing) and RNA sequencing found that 145 genes had low P values (< 0.01) when analyzed between the locus genotype and its related gene expression level. Among these genes, SWAP70 was believed to be a probable cause of acquired resistance. JAK2, PRKAA1, FGFR2 and RALBP1, as well as 10 filtered immune-related genes, also exhibited dynamic changes during the treatment. CONCLUSIONS: Cetuximab may be effective in KRAS G13D mutation patients. Dynamic changes in transcription, as determined by WES and RNA sequencing, occurred after repeated drug exposure, and these changes were believed to be the most likely cause of drug resistance.


Asunto(s)
Cetuximab/farmacología , Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos , Genoma Humano , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Transcriptoma/efectos de los fármacos , Animales , Antineoplásicos Inmunológicos/farmacología , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Femenino , Humanos , Ratones , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Zhonghua Yi Xue Za Zhi ; 95(39): 3196-200, 2015 Oct 20.
Artículo en Zh | MEDLINE | ID: mdl-26814117

RESUMEN

OBJECTIVE: To compare the interictal spontaneous brain activity between migraine without aura (MwoA) patients, Migraine with visual aura (MA) patients and healthy control subjects in order to provide further insights into the complex migraine pathophysiology. METHODS: Twenty-three eligible MwoA patients, twelve MA patients who were treated in the neurology clinics in the Second Hospital of Hebei Medical University from March to October 2014 and twenty-five gender-, age- and education- matched healthy volunteers participated in this study.After demographic and clinical characteristics were acquired, a 3.0-T MRI system was used to obtain rfMRI.ReHo method was applied to analyze the synchronization of the BOLD signal in the same time series among neighboring voxels of the brain. RESULTS: Compared with healthy controls, MwoA patients showed significant decreases in ReHo values in the right thalamus, right putamen, right prefrontal lobe and right hippocampus (P<0.05); while MA patients showed significant decreases in ReHo values in the right thalamus, right putamen, right cerebellum and brainstem, whereas a significant increase in ReHo values in the right occipital lobe (P<0.05). Furthermore, compared with MA patients, increased ReHo values in the right cerebellum and brainstem were shown in the MwoA group (P<0.05). CONCLUSIONS: The results suggest that the resting-state abnormalities of these regions may be associated with functional impairments in pain processing in migraine.Specifically, the results of brain regions may reflect both the similarities and differences of pathophysiological mechanisms relative to the major subtypes of migraine.


Asunto(s)
Migraña con Aura , Migraña sin Aura , Encéfalo , Humanos , Imagen por Resonancia Magnética
6.
J Int Med Res ; 52(3): 3000605241234585, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38443765

RESUMEN

Myasthenia gravis (MG) is often complicated by respiratory failure, an exacerbation known as myasthenic crisis. However, most patients with MG develop respiratory symptoms during the late course of the disease. Respiratory failure as an exclusive initial and primary complaint in patients with MG is rare and seldom reported. We herein describe a woman in her late 50s who presented with respiratory failure and was diagnosed with obesity hypoventilation syndrome at a local hospital. Her condition gradually worsened during the next 4 months and became accompanied by dysphagia. After 1 year of medical investigation, she was diagnosed in our hospital. A high level of anti-muscle-specific receptor tyrosine kinase antibody was found in her serum, and stimulation and electromyography results suggested MG. The patient's symptoms were improved by intravenous immunoglobulin and hormone therapy. This case reminds physicians to consider MG when encountering a patient who initially presents with respiratory failure.


Asunto(s)
Trastornos de Deglución , Miastenia Gravis , Insuficiencia Respiratoria , Femenino , Humanos , Electromiografía , Hospitales , Miastenia Gravis/complicaciones , Miastenia Gravis/diagnóstico , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/etiología , Persona de Mediana Edad
7.
F1000Res ; 12: 684, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37994351

RESUMEN

Background: Single-cell RNA sequencing (scRNA-seq) technologies have rapidly developed in recent years. The droplet-based single cell platforms enable the profiling of gene expression in tens of thousands of cells per sample. The goal of a typical scRNA-seq analysis is to identify different cell subpopulations and their respective marker genes. Additionally, trajectory analysis can be used to infer the developmental or differentiation trajectories of cells. Methods: This article demonstrates a comprehensive workflow for performing trajectory inference and time course analysis on a multi-sample single-cell RNA-seq experiment of the mouse mammary gland. The workflow uses open-source R software packages and covers all steps of the analysis pipeline, including quality control, doublet prediction, normalization, integration, dimension reduction, cell clustering, trajectory inference, and pseudo-bulk time course analysis. Sample integration and cell clustering follows the Seurat pipeline while the trajectory inference is conducted using the monocle3 package. The pseudo-bulk time course analysis uses the quasi-likelihood framework of edgeR. Results: Cells are ordered and positioned along a pseudotime trajectory that represented a biological process of cell differentiation and development. The study successfully identified genes that were significantly associated with pseudotime in the mouse mammary gland. Conclusions: The demonstrated workflow provides a valuable resource for researchers conducting scRNA-seq analysis using open-source software packages. The study successfully demonstrated the usefulness of trajectory analysis for understanding the developmental or differentiation trajectories of cells. This analysis can be applied to various biological processes such as cell development or disease progression, and can help identify potential biomarkers or therapeutic targets.


Asunto(s)
Perfilación de la Expresión Génica , Análisis de la Célula Individual , Animales , Ratones , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Programas Informáticos , Expresión Génica
8.
Comb Chem High Throughput Screen ; 26(6): 1233-1241, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35927816

RESUMEN

BACKGROUND: Experimental studies have shown that curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of curcumin in MCAO are not fully understood. OBJECTIVE: This study aims to investigate the key neurogenesis targets of curcumin action in mouse brain with MCAO. METHODS: The MCAO models were established in mice. High-throughput sequencing was used to identify differentially expressed mRNA, lncRNA, and circRNA. The reverse expressed mRNAs, lncRNA, and circRNA in sham vs. MCAO and MCAO vs. curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis-related genes was constructed. Next, neurogenesis-related lncRNA/ circRNA-miRNA-mRNA ceRNA networks were constructed. RESULTS: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment analysis of 1215 reverse expressed mRNAs found that they were involved in neurogenesis, neuron generation, neurogenesis regulation, and others. The PPI network of neurogenesis-related genes consisted of 115 nodes, including 27 down-regulated genes and 36 up-regulated genes. Furthermore, the neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNAs networks were constructed, and 5 lncRNA ceRNA networks and 3 circRNA ceRNA networks were explored. CONCLUSION: Our study revealed that curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNA networks are potential therapeutic targets of curcumin in MCAO. This study provided a theoretical basis for curcumin exerting neuroprotective effects in MCAO.


Asunto(s)
Curcumina , MicroARNs , Fármacos Neuroprotectores , ARN Largo no Codificante , Ratones , Animales , ARN Circular/genética , Curcumina/farmacología , ARN Largo no Codificante/genética , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/genética , Fármacos Neuroprotectores/farmacología , Redes Reguladoras de Genes , MicroARNs/genética , ARN Mensajero/genética , Biología Computacional , Secuenciación de Nucleótidos de Alto Rendimiento , Encéfalo
9.
Clin J Pain ; 39(4): 175-179, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36943161

RESUMEN

OBJECTIVES: The periaqueductal gray (PAG) is a key region in the descending pain modulatory system. We applied a Granger causality analysis-based approach to examine resting-state effective connectivity of the bilateral PAG regions in migraine patients without aura (MwoA). MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging data were obtained from 28 MwoA patients and 17 healthy controls. The effective connectivity of the bilateral PAG was characterized using a voxel-wised Granger causality analysis method. The resulting effective connectivity measurements were assessed for correlations with other clinical features. RESULTS: Compared with the healthy controls, MwoA patients showed increased effective connectivity from the left PAG to the left anterior cingulate gyrus and right postcentral gyrus. Meanwhile, MwoA patients also showed increased effective connectivity from the right PAG to the left precentral gyrus and increased effective connectivity from the left caudate and right middle occipital gyrus to the right PAG. DISCUSSION: Abnormally increased effective connectivity between PAG and limbic system, primary sensorimotor cortex, and visual cortex may play a key role in neuropathological features, perception, and affection of MwoA. The current study provides further insights into the complex scenario of MwoA mechanisms.


Asunto(s)
Epilepsia , Migraña sin Aura , Humanos , Sustancia Gris Periacueductal/diagnóstico por imagen , Migraña sin Aura/diagnóstico por imagen , Dolor , Giro del Cíngulo , Imagen por Resonancia Magnética/métodos , Encéfalo
10.
Brain Res Bull ; 190: 244-255, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36244580

RESUMEN

BACKGROUND: Ligustrazine is a traditional Chinese herbal medicine that has long been used to treat cerebral ischemic disorders. However, the molecular mechanisms of ligustrazine in cerebral ischemia/reperfusion (I/R) damage have not been clear elucidated. The aim of this study was to examine the neuroprotective mechanisms of ligustrazine in cerebral I/R. METHODS: 9 C57BL/6 mice were randomly divided to three groups: Sham group (n = 3), Middle cerebral artery occlusion (MCAO) group (n = 3), and MCAO + Ligustrazine group (n = 3). The neurological deficit score was evaluated, the cerebral infarct volume was measured by triphenylterazolium chloride (TTC) staining. Differentially expressed (DE) messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) were analyzed using the R package DEseq2 based on P-value < 0.05 and Log2 |fold change (FC)| ≥ 2 in sham group vs MCAO group and MCAO group vs ligustrazine group by high-throughput sequencing. Function enrichment analysis, the protein-protein interaction (PPI) of neurogenesis related genes were performed. The neurogenesis related competitive endogenous RNA (ceRNA) network was constructed. RESULTS: The expression of circ_0008146 was considerably higher in the MCAO group than the Sham group, and ligustrazine treatment markedly decreased the expression of circ_0008146 in MCAO. Next, the circ_0008146 ceRNA network was established, including circ_0008146-miR-709-Cx3cr1 ceRNA network. Besides, real time quantitative polymerase chain reaction (RT-qPCR) assay identified that miR-709 expression was considerably lower and Cx3cr1 expression was higher in the MCAO group than Sham group, and ligustrazine treatment markedly increased the miR-709 expression and reduced Cx3cr1 expression in MCAO. Further, silencing of circ_0008146 inhibited the concentration of Interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-α) and reduced neuron cell death and up-regulated miR-709 expression and down-regulated Cx3cr1 expression in Lipopolysaccharide (LPS) induced BV-2 cells. Dual-Luciferase reporter gene assay verified that circ_0008146 targeted miR-709. CONCLUSION: Ligustrazine targets circ_0008146/miR-709/Cx3cr1 axis to inhibit cell apoptosis and inflammation after cerebral ischemia/reperfusion injury.


Asunto(s)
Isquemia Encefálica , MicroARNs , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Ratones , Apoptosis/genética , Isquemia Encefálica/metabolismo , Receptor 1 de Quimiocinas CX3C , Infarto de la Arteria Cerebral Media/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/genética , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Fármacos Neuroprotectores/farmacología , Daño por Reperfusión/metabolismo , ARN Mensajero
11.
Neuromolecular Med ; 24(3): 299-310, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34705256

RESUMEN

Previous studies have demonstrated that increased O-linked N-acetylglucosamine (O-GlcNAc) level could promote cell survival following environmental stresses. This study aimed to explore the role of O-GlcNAc transferase (OGT) during cerebral ischemia/reperfusion (I/R) injury. The mouse model with cerebral I/R injury was induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The expression of ogt in brain tissues was detected by qRT-PCR, Western blot, and immunohistochemistry (IHC) staining assay. Neurological deficit was evaluated using a modified scoring system. The infarct volume was assessed by TTC staining assay. Neuronal apoptosis in brain tissues was evaluated by TUNEL staining assay. The level of cleaved caspase-3 in brain tissues was detected by Western blot and IHC staining assay. The expression of critical proteins involved in mitochondrial fission, including OPA1, Mfn1, and Mfn2, as well as Mff and Drp1 was detected by Western blot and IHC, respectively. The expression of ogt during cerebral I/R injury was significantly upregulated. Ogt knockdown significantly increased neurological score and infarct volume in I/R-induced mice. Meanwhile, ogt knockdown significantly enhanced neuronal apoptosis and cleaved caspase-3 level in brain tissues of I/R-induced mice. In addition, ogt knockdown markedly decreased serine 637 phosphorylation level of mitochondrial fission protein dynamin-related protein 1 (Drp1) and promoted Drp1 translocation from the cytosol to the mitochondria. Moreover, the specific Drp1 inhibitor mdivi-1 effectively attenuated ogt knockdown-induced brain injury of I/R-stimulated mice in vivo. Our study revealed that OGT protects against cerebral I/R injury by inhibiting the function of Drp1 in mice, suggesting that ogt may be a potential therapeutic target for cerebral I/R injury.


Asunto(s)
Isquemia Encefálica , N-Acetilglucosaminiltransferasas/metabolismo , Neuronas/metabolismo , Daño por Reperfusión , Animales , Apoptosis , Isquemia Encefálica/metabolismo , Caspasa 3/metabolismo , Dinaminas/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Ratones , Reperfusión , Daño por Reperfusión/metabolismo
12.
Mol Med Rep ; 22(2): 792-802, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32626985

RESUMEN

To provide insight into molecular diagnosis and individualized treatment of ischemic stroke (IS), several available datasets in IS were analyzed to identify the differentially expressed genes and microRNAs (miRNAs). Series matrix files from GSE22255 and GSE16561 (mRNA profiles), a well as GSE110993 (miRNA profile) were downloaded from the Gene Expression Omnibus database. System­level clustering was performed with GeneCluster 3.0 software, and gene annotation and pathway enrichment were performed with gene ontology analysis and Database for Annotation, Visualization and Integrated Discovery software. For a protein­protein interaction (PPI) network, Biological General Repository for Interaction Datasets and IntAct interaction information were integrated to determine the interaction of differentially expressed genes. The selected miRNA candidates were imported into the TargetScan, miRDB and miRecords databases for the prediction of target genes. The present study identified 128 upregulated and 231 downregulated genes in female stroke patients, and 604 upregulated and 337 downregulated genes in male stroke patients compared with sex­ and age­matched controls. The construction of a PPI network demonstrated that male stroke patients exhibited YWHAE, CUL3 and JUN as network center nodes, and in female patients CYLD, FOS and PIK3R1 interactions were the strongest. Notably, these interactions are mainly involved in immune inflammatory response, apoptosis and other biological pathways, such as blood coagulation. Female and male upregulated genes were cross­validated with another set of Illumina HumanRef­8 v3.0 expression beadchip (GSE16561). Functional item association networks, gene function networks and transcriptional regulatory networks were successfully constructed, and the relationships between miRNAs and target genes were successfully predicted. The present study identified a number of transcription factors, including DEFA1, PDK4, SDPR, TCN1 and MMP9, and miRNAs, including miRNA (miR)­21, miR­143/145, miR­125­5p and miR­122, which may serve important roles in the development of cerebral stroke and may be important molecular indicators for the treatment of IS.


Asunto(s)
Accidente Cerebrovascular Isquémico/genética , MicroARNs/metabolismo , ARN Circular/metabolismo , ARN Mensajero/metabolismo , Biología Computacional , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Humanos , Accidente Cerebrovascular Isquémico/sangre , Masculino , MicroARNs/genética , Anotación de Secuencia Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Mapas de Interacción de Proteínas/genética , ARN Circular/genética , ARN Mensajero/genética
13.
J Adv Res ; 24: 13-27, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32181013

RESUMEN

Strokes usually results in long-term disability and death, and they occur worldwide. Recently, increased research on both on the physiopathological mechanisms and the transcriptome during stroke progression, have highlighted the relationship between stroke progression and immunity, with a special focus on inflammation. Here, we applied proteome analysis to a middle carotid artery occlusion (MCAO) mouse model at 0 h, 6 h, 12 h and 24 h, in which proteome profiling was performed with 23 samples, and 41 differentially expressed proteins (DEPs) were identified. Bioinformatics studies on our data revealed the importance of the immune response and particularly identified the inflammatory response, cytokine- cytokine receptor interactions, the innate immune response and reactive oxygen species (ROS) during stroke progression. In addition, we compared our data with multiple gene expression omnibus (GEO) datasets with and without a time series, in which similar pathways were identified, and three proteins, C3, Apoa4 and S100a9, were highlighted as markers or drug targets for stroke; these three proteins were significantly upregulated in the MCAO model, both in our proteomic data and in the GEO database.

14.
Biomed Res Int ; 2020: 4501393, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32724801

RESUMEN

OBJECTIVE: With the growing incidence of ischemic stroke worldwide, there is an urgent need to identify blood biomarkers for ischemic stroke patients. Thus, our aim was to identify potential circulating microRNA (miRNA) as a potential biomarker and to explore its potential mechanism for ischemic stroke in rats. METHODS: The mRNA dataset GSE97537 and miRNA dataset GSE97532 were downloaded from the Gene Expression Omnibus (GEO) GSE97537 including 7 middle cerebral artery occlusion (MCAO) rat brain tissues and 5 sham-operated rat brain tissues GSE97532 including 6 MCAO rat blood samples and 3 sham-operated rat blood samples. Differentially expressed mRNAs and miRNAs with corrected p value ≤ 0.01 and fold change ≥2 or ≤0.05 were identified. To explore potential biological processes and pathways of differentially expressed mRNAs, functional enrichment analysis was performed. The target mRNAs of differentially expressed miRNAs were predicted using DNA Intelligent Analysis (DIANA)-microT tools. The target mRNAs and differentially expressed mRNAs were intersected. RESULTS: 1228 differentially expressed mRNAs in MCAO rat brain tissues were identified. Highly expressed mRNAs were mainly enriched in the inflammatory responses. Nine differentially expressed miRNAs were identified in MCAO rat blood samples. A total of 673 target mRNAs were predicted to significantly bind these differentially expressed miRNAs. Among them, 54 target mRNAs were differentially expressed in MCAO rat blood samples. Enrichment analysis results showed that these 54 target mRNAs were closely related to neurological diseases and immune responses. Among all miRNA-mRNA relationship, miR-3552-CASP3 interaction was identified, indicating that CASP3 might be mediated by miR-3552. Functional enrichment analysis revealed that CASP3 was involved in the apoptosis pathway, indicating that miR-3552 might participate in apoptosis by CASP3. CONCLUSION: Our findings reveal that circulating miR-3552 shows promise as a potential biomarker for ischemic stroke in rats.


Asunto(s)
Biomarcadores/sangre , Isquemia Encefálica/sangre , MicroARN Circulante/sangre , MicroARN Circulante/genética , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/genética , Animales , Apoptosis/genética , Isquemia Encefálica/genética , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes/genética , Inmunidad/genética , Infarto de la Arteria Cerebral Media/sangre , Infarto de la Arteria Cerebral Media/genética , Inflamación/sangre , Inflamación/genética , Ratas
15.
Aging (Albany NY) ; 12(23): 23849-23871, 2020 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-33221766

RESUMEN

Hepatocellular carcinoma (HCC) is a heterogeneous disease with various genetic and epigenetic abnormalities. Previous studies of HCC driver genes were primarily based on frequency of mutations and copy number alterations. Here, we performed an integrative analysis of genomic and epigenomic data from 377 HCC patients to identify driver genes that regulate gene expression in HCC. This integrative approach has significant advantages over single-platform analyses for identifying cancer drivers. Using this approach, HCC tissues were divided into four subgroups, based on expression of the transcription factor E2F and the mutation status of TP53. HCC tissues with E2F overexpression and TP53 mutation had the highest cell cycle activity, indicating a synergistic effect of E2F and TP53. We found that overexpression of the identified driver genes, stratifin (SFN) and SPP1, correlates with tumor grade and poor survival in HCC and promotes HCC cell proliferation. These findings indicate SFN and SPP1 function as oncogenes in HCC and highlight the important role of enhancers in the regulation of gene expression in HCC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Biología Computacional , Genómica , Neoplasias Hepáticas/genética , Integración de Sistemas , Proteínas 14-3-3/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Línea Celular Tumoral , Proliferación Celular , Variaciones en el Número de Copia de ADN , Metilación de ADN , Bases de Datos Genéticas , Factores de Transcripción E2F/genética , Epigénesis Genética , Exorribonucleasas/genética , Dosificación de Gen , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Mutación , Clasificación del Tumor , Osteopontina/genética , Fenotipo , Proteína p53 Supresora de Tumor/genética
16.
Genome Med ; 10(1): 42, 2018 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-29848370

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis and diagnosis. METHODS: Using the TCGA HCC dataset, we classified HCC patients into different methylation subtypes, identified differentially methylated and expressed genes, and analyzed cis- and trans-regulation of DNA methylation and gene expression. To find potential diagnostic biomarkers for HCC, we screened HCC-specific CpGs by comparing the methylation profiles of 375 samples from HCC patients, 50 normal liver samples, 184 normal blood samples, and 3780 samples from patients with other cancers. A logistic regression model was constructed to distinguish HCC patients from normal controls. Model performance was evaluated using three independent datasets (including 327 HCC samples and 122 normal samples) and ten newly collected biopsies. RESULTS: We identified a group of patients with a CpG island methylator phenotype (CIMP) and found that the overall survival of CIMP patients was poorer than that of non-CIMP patients. Our analyses showed that the cis-regulation of DNA methylation and gene expression was dominated by the negative correlation, while the trans-regulation was more complex. More importantly, we identified six HCC-specific hypermethylated sites as potential diagnostic biomarkers. The combination of six sites achieved ~ 92% sensitivity in predicting HCC, ~ 98% specificity in excluding normal livers, and ~ 98% specificity in excluding other cancers. Compared with previously published methylation markers, our markers are the only ones that can distinguish HCC from other cancers. CONCLUSIONS: Overall, our study systematically describes the DNA methylation characteristics of HCC and provides promising biomarkers for the diagnosis of HCC.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Metilación de ADN/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Islas de CpG/genética , Bases de Datos Genéticas , Genes Relacionados con las Neoplasias/genética , Humanos
17.
Rev Sci Instrum ; 82(9): 093504, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21974584

RESUMEN

Neutron penumbral imaging is a significant diagnostic technique in laser-driven inertial confinement fusion experiment. It is very important to develop a new reconstruction method to improve the resolution of neutron penumbral imaging. A new nonlinear reconstruction method based on total variation (TV) regularization is proposed in this paper. A TV-norm is used as regularized term to construct a smoothing functional for penumbral image reconstruction in the new method, in this way, the problem of penumbral image reconstruction is transformed to the problem of a functional minimization. In addition, a fixed point iteration scheme is introduced to solve the problem of functional minimization. The numerical experimental results show that, compared to linear reconstruction method based on Wiener filter, the TV regularized nonlinear reconstruction method is beneficial to improve the quality of reconstructed image with better performance of noise smoothing and edge preserving. Meanwhile, it can also obtain the spatial resolution with 5 µm which is higher than the Wiener method.

18.
JACC Cardiovasc Interv ; 3(6): 584-94, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20630451

RESUMEN

OBJECTIVES: We investigated the long-term clinical outcomes and independent predictors of major cardiac events in unprotected left main coronary artery disease (ULMCA) patients treated by percutaneous coronary intervention with drug-eluting stent (DES). BACKGROUND: There is limited information on long-term (>3 years) outcomes after DES implantation for ULMCA. Furthermore, bifurcation angle and SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score are emerging as parameters for patient risk stratification, and their prognostic implications have still to be elucidated. METHODS: One hundred forty-eight patients with ULMCA treated with DES were analyzed and compared with a historical cohort of 79 patients who received bare-metal stents for the treatment of ULMCA. Patient-oriented composite end point was defined as the occurrence of all-cause death, any myocardial infarction, or any revascularization. RESULTS: The 4-year cumulative incidence of all-cause death, any myocardial infarction, any revascularization, and patient-oriented composite were 35.6%, 3.8%, 25.2%, and 54.4%, respectively. These end points had relatively increased from 1 year to 4 years by Delta70%, Delta5%, Delta50%, and Delta68%, respectively. When compared with a historical cohort who received bare-metal stents for ULMCA treatment, landmark analysis performed after the first 2 years of follow-up demonstrated that the DES cohort had significantly higher patient-oriented composite end point over the last 2 years of follow-up (26% vs. 8%, p = 0.02). EuroSCORE (European System for Cardiac Operative Risk Evaluation), cardiogenic shock, and SYNTAX score were identified as independent predictors for the 4-year patient-oriented composite, whereas bifurcation angle was not. CONCLUSIONS: Late increase in patient-oriented composite end points after DES implantation for ULMCA warrants careful and long-term follow-up. SYNTAX score and EuroSCORE appear to have a significant prognostic value in long-term patient risk.


Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Fármacos Cardiovasculares/administración & dosificación , Estenosis Coronaria/terapia , Stents Liberadores de Fármacos , Metales , Paclitaxel/administración & dosificación , Sirolimus/administración & dosificación , Stents , Anciano , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/mortalidad , Estudios de Cohortes , Angiografía Coronaria , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio , Países Bajos , Selección de Paciente , Inhibidores de Agregación Plaquetaria/uso terapéutico , Modelos de Riesgos Proporcionales , Diseño de Prótesis , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
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