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1.
Cardiovasc Toxicol ; 24(5): 499-512, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38589550

RESUMO

Calcific aortic valve stenosis (CAVS) is characterized by increasing inflammation and progressive calcification in the aortic valve leaflets and is a major cause of death in the aging population. This study aimed to identify the inflammatory proteins involved in CAVS and provide potential therapeutic targets. We investigated the observational and causal associations of 92 inflammatory proteins, which were measured using affinity-based proteomic assays. Firstly, the case-control cohort identified differential proteins associated with the occurrence and progression of CAVS. Subsequently, we delved into exploring the causal impacts of these associated proteins through Mendelian randomization. This involved utilizing genetic instruments derived from cis-protein quantitative loci identified in genome-wide association studies, encompassing a cohort of over 400,000 individuals. Finally, we investigated the gene transcription and protein expression levels of inflammatory proteins by single-cell and immunohistochemistry analysis. Multivariate logistic regression and spearman's correlation analysis showed that five proteins showed a significant positive correlation with disease severity. Mendelian randomization showed that elevated levels of two proteins, namely, matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2), were associated with an increased risk of CAVS. Immunohistochemistry and single-cell transcriptomes showed that expression levels of MMP1 and SIRT2 at the tissue and cell levels were significantly higher in calcified valves than in non-calcified control valves. These findings indicate that MMP1 and SIRT2 are causally related to CAVS and open up the possibility for identifying novel therapeutic targets.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Valva Aórtica/patologia , Biomarcadores , Calcinose , Mediadores da Inflamação , Metaloproteinase 1 da Matriz , Análise da Randomização Mendeliana , Proteômica , Humanos , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/patologia , Estenose da Valva Aórtica/genética , Calcinose/genética , Calcinose/metabolismo , Calcinose/sangue , Calcinose/patologia , Valva Aórtica/metabolismo , Masculino , Feminino , Idoso , Estudos de Casos e Controles , Biomarcadores/sangue , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/sangue , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Predisposição Genética para Doença , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/análise , Fenótipo
2.
PLoS One ; 15(8): e0238149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833991

RESUMO

As a characteristic edible fungus with a high nutritional value and medicinal effect, the Bachu mushroom has a broad market. To distinguish among Bachu mushrooms with high value and other fungi effectively and accurately, as well as to explore a universal identification method, this study proposed a method to identify Bachu mushrooms by Fourier Transform Infrared Spectroscopy (FT-IR) combined with machine learning. In this experiment, two kinds of common edible mushrooms, Lentinus edodes and club fungi, were selected and classified with Bachu mushrooms. Due to the different distribution of nutrients in the caps and stalks, the caps and stalks were studied in this experiment. By comparing the average normalized infrared spectra of the caps and stalks of the three types of fungi, we found differences in their infrared spectra, indicating that the latter can be used to classify and identify the three types of fungi. We also used machine learning to process the spectral data. The overall steps of data processing are as follows: use partial least squares (PLS) to extract spectral features, select the appropriate characteristic number, use different classification algorithms for classification, and finally determine the best algorithm according to the classification results. Among them, the basis of selecting the characteristic number was the cumulative variance interpretation rate. To improve the reliability of the experimental results, this study also used the classification results to verify the feasibility. The classification algorithms used in this study were the support vector machine (SVM), backpropagation neural network (BPNN) and k-nearest neighbors (KNN) algorithm. The results showed that the three algorithms achieved good results in the multivariate classification of the caps and stalks data. Moreover, the cumulative variance explanation rate could be used to select the characteristic number. Finally, by comparing the classification results of the three algorithms, the classification effect of KNN was found to be the best. Additionally, the classification results were as follows: according to the caps data classification, the accuracy was 99.06%; according to the stalks data classification, the accuracy was 99.82%. This study showed that infrared spectroscopy combined with a machine learning algorithm has the potential to be applied to identify Bachu mushrooms and the cumulative variance explanation rate can be used to select the characteristic number. This method can also be used to identify other types of edible fungi and has a broad application prospect.


Assuntos
Agaricales/classificação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Algoritmos , Confiabilidade dos Dados , Análise Discriminante , Fungos/classificação , Análise dos Mínimos Quadrados , Aprendizado de Máquina , Redes Neurais de Computação , Análise de Componente Principal/métodos , Reprodutibilidade dos Testes , Cogumelos Shiitake , Espectrofotometria Infravermelho/métodos , Máquina de Vetores de Suporte
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