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1.
Front Endocrinol (Lausanne) ; 14: 1172182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091853

RESUMO

Background: Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients. Methods: Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours. Results: COX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion. Conclusion: Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.


Assuntos
Glioma , Medicina de Precisão , Humanos , Prognóstico , Simulação de Acoplamento Molecular , DNA Mitocondrial , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Mitocôndrias/genética
2.
Ann Transl Med ; 10(19): 1057, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36330394

RESUMO

Background: Intracranial aneurysmal subarachnoid hemorrhage (aSAH) is a dangerous and highly fatal condition if ruptured. Significant advances have been made in the treatment of unruptured intracranial aneurysms (UIAs), but risk assessment methods for early diagnosis of intracranial aneurysm (IA) rupture remain limited. Methods: The datasets of IA GSE13353, GSE15629, and GSE54083 were downloaded through the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in unruptured and ruptured aneurysms were identified by R software using methods such as gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the DEGs, and logistic regression models were used to construct a prediction model to discriminate UIA from healthy samples. We then performed GSEA on the genes in the model, followed by model validation using the GSE54083 dataset. Finally, we used the single-sample (ss)GSEA method to investigate the relationship between the diagnostic model genes and immune cells and immune function. Results: A total of 79 DEGs were obtained in patients with IA rupture compared to unruptured controls. The results of KEGG and GO enrichment analysis showed that neutrophil activation is involved in immune response, neutrophil mediated immunity, and positive regulation of angiogenesis. Interestingly, the results of immunoassays demonstrated that the break in IA may be associated with immune T cells. We used DEGs and WGCNA to determine common genes. The logistic regression model was trained based on 24 intersecting genes, and eventually retained 2 genes, KIAA0226L and UPP1, which we found to be reliable using the validation set, and GSEA revealed that the diagnostic model was associated with the Hippo signaling pathway and vascular smooth muscle contraction, and viral protein interaction with cytokine and cytokine were also associated. Finally explored using the CMap database, Tivozanib could be a potential small molecule drug for the treatment of ruptured intracranial aneurysms (RIAs). Conclusions: We identified new diagnostic genes associated with IA rupture, which may provide a new way of aneurysm diagnosis.

3.
Front Genet ; 13: 940462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046228

RESUMO

Background: Glioblastoma multiforme (GBM) is the most aggressive primary nervous system brain tumor. There is still a lack of effective methods to control its progression and recurrence in clinical treatment. It is clinically found that Xiaoliu Decoction (XLD) has the effect of treating brain tumors and preventing tumor recurrence. However, its mechanism is still unclear. Methods: Search the Traditional Chinese Medicine System Pharmacology Database (TCSMP) for efficient substances for the treatment of XLD in the treatment of GBM, and target the targeted genes of the effective ingredients to construct a network. At the same time, download GBM-related gene expression data from the TCGA and GTEX databases, screen differential expression bases, and establish a drug target disease network. Through bioinformatics analysis, the target genes and shared genes of the selected Chinese medicines are analyzed. Finally, molecular docking was performed to further clarify the possibility of XLD in multiple GBMs. Results: We screened 894 differentially expressed genes in GBM, 230 XLD active ingredients and 169 predicted targets of its active compounds, of which 19 target genes are related to the differential expression of GBM. Bioinformatics analysis shows that these targets are closely related to cell proliferation, cell cycle regulation, and DNA synthesis. Finally, through molecular docking, it was further confirmed that Tanshinone IIA, the active ingredient of XLD, was tightly bound to key proteins. Conclusion: To sum up, the results of this study suggest that the mechanism of XLD in the treatment of GBM involves multiple targets and signal pathways related to tumorigenesis and development. This study not only provides a new theoretical basis for the treatment of glioblastoma multiforme with traditional Chinese medicine, but also provides a new idea for the research and development of targeted drugs for the treatment of glioblastoma multiforme.

4.
Ann Transl Med ; 10(10): 567, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35722393

RESUMO

Background: Intracerebral hemorrhage (ICH) is a type of stroke which results in a high disability and mortality rate and has a poor prognosis. Tongqiao Huoxue Decoction (TQHXD) is a classical Chinese prescription. Clinical practice has proven that TQHXD can promote blood circulation and can effectively treat ICH and its sequelae. However, the current mechanism is still unclear. Methods: The chemical components and target genes of TQHXD were collected from the Traditional Chinese medicine (TCM) Systems Pharmacology and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine analysis platforms, and the gene expression data of ICH tissues were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to obtain differentially co-expressed gene pairs and build a drug-target-disease network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the obtained target genes and shared genes. Finally, molecular docking was carried out to further clarify the utility of TQHXD for the treatment of ICH. Results: A total of 304 differentially expressed genes in ICH, 42 TQHXD active ingredients, and 279 predicted targets of its active compounds were obtained. Bioinformatics analysis showed that they were involved in angiogenesis, the regulation of wound healing, and other biological processes. Furthermore, their participation in fluid shear stress and the atherosclerosis signaling pathway indicated their close association with the pathological processes of ICH. Finally, molecular docking was carried out to further confirm the tightly binding structural sites of the effective components of TQHXD and key proteins. Conclusions: In summary, the results of this study suggest that the mechanism of action of TQHXD in the treatment of ICH involves multiple targets and signaling pathways related to its occurrence and development. This study not only provides a new theoretical basis for the treatment of ICH with traditional Chinese medicine, but also provides new ideas for the research and development of drugs for the treatment of ICH.

5.
Sensors (Basel) ; 18(6)2018 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-29899242

RESUMO

To reduce the difficulty of acquiring and transmitting data in mining hoist fault diagnosis systems and to mitigate the low efficiency and unreasonable reasoning process problems, a fault diagnosis method for mine hoisting equipment based on the Internet of Things (IoT) is proposed in this study. The IoT requires three basic architectural layers: a perception layer, network layer, and application layer. In the perception layer, we designed a collaborative acquisition system based on the ZigBee short distance wireless communication technology for key components of the mine hoisting equipment. Real-time data acquisition was achieved, and a network layer was created by using long-distance wireless General Packet Radio Service (GPRS) transmission. The transmission and reception platforms for remote data transmission were able to transmit data in real time. A fault diagnosis reasoning method is proposed based on the improved Dezert-Smarandache Theory (DSmT) evidence theory, and fault diagnosis reasoning is performed. Based on interactive technology, a humanized and visualized fault diagnosis platform is created in the application layer. The method is then verified. A fault diagnosis test of the mine hoisting mechanism shows that the proposed diagnosis method obtains complete diagnostic data, and the diagnosis results have high accuracy and reliability.

6.
Entropy (Basel) ; 20(7)2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33265610

RESUMO

Due to the weak entropy of the vibration signal in the strong noise environment, it is very difficult to extract compound fault features. EMD (Empirical Mode Decomposition), EEMD (Ensemble Empirical Mode Decomposition) and LMD (Local Mean Decomposition) are widely used in compound fault feature extraction. Although they can decompose different characteristic components into each IMF (Intrinsic Mode Function), there is still serious mode mixing because of the noise. VMD (Variational Mode Decomposition) is a rigorous mathematical theory that can alleviate the mode mixing. Each characteristic component of VMD contains a unique center frequency but it is a parametric decomposition method. An improper value of K will lead to over-decomposition or under-decomposition. So, the number of decomposition levels of VMD needs an adaptive determination. The commonly used adaptive methods are particle swarm optimization and ant colony algorithm but they consume a lot of computing time. This paper proposes a compound fault feature extraction method based on Multipoint Kurtosis (MKurt)-VMD. Firstly, MED (Minimum Entropy Deconvolution) denoises the vibration signal in the strong noise environment. Secondly, multipoint kurtosis extracts the periodic multiple faults and a multi-periodic vector is further constructed to determine the number of impulse periods which determine the K value of VMD. Thirdly, the noise-reduced signal is processed by VMD and the fault features are further determined by FFT. Finally, the proposed compound fault feature extraction method can alleviate the mode mixing in comparison with EEMD. The validity of this method is further confirmed by processing the measured signal and extracting the compound fault features such as the gear spalling and the roller fault, their fault periods are 22.4 and 111.2 respectively and the corresponding frequencies are 360 Hz and 72 Hz, respectively.

7.
Sensors (Basel) ; 17(7)2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28726754

RESUMO

Rotating machinery is often subjected to variable loads during operation. Thus, monitoring and identifying different load types is important. Here, five typical load types have been qualitatively studied for a rotor system. A novel load category identification method for rotor system based on vibration signals is proposed. This method is a combination of ensemble empirical mode decomposition (EEMD), energy feature extraction, and back propagation (BP) neural network. A dedicated load identification test bench for rotor system was developed. According to loads characteristics and test conditions, an experimental plan was formulated, and loading tests for five loads were conducted. Corresponding vibration signals of the rotor system were collected for each load condition via eddy current displacement sensor. Signals were reconstructed using EEMD, and then features were extracted followed by energy calculations. Finally, characteristics were input to the BP neural network, to identify different load types. Comparison and analysis of identifying data and test data revealed a general identification rate of 94.54%, achieving high identification accuracy and good robustness. This shows that the proposed method is feasible. Due to reliable and experimentally validated theoretical results, this method can be applied to load identification and fault diagnosis for rotor equipment used in engineering applications.

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