Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time‐ and concentration‐dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K‐Akt–mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin‐mediated pro‐apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K‐mTOR inhibitor NVP‐BEZ235. Taken together, these findings indicate that anti‐proliferation and pro‐apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K‐Akt–mTOR pathway, suggesting a potential therapeutic strategy against glioma.
Oxidative stress is defined as an injury resulting from a disturbance in the dynamic equilibrium of the redox environment due to the overproduction of active/radical oxygen exceeding the antioxidative ability of the body. This is a key step in the development of various diseases. Oxidative stress is modulated by different factors and events, including the modification of histones, which are the cores of nucleosomes. Histone modification includes acetylation and deacetylation of certain amino acid residues; this process is catalyzed by different enzymes. Histone deacetylase 6 (HDAC6) is a unique deacetylating protease that also catalyzes the deacetylation of different nonhistone substrates to regulate various physiologic processes. The intimate relationship between HDAC6 and oxidative stress has been demonstrated by different studies. The present paper aims to summarize the data obtained from a mechanistic study of HDAC6 and oxidative stress to guide further investigations on mechanistic characterization and drug development.
Oxidative stress is defined as injury resulting from the disturbance on dynamic equilibrium of redox environment due to over-production of active/ radical oxygen exceeding the anti-oxidative ability in the body. It is a key step of genesis and development of various diseases. Oxidative stress is modulated by different factors and events, including modification of histone, the core of nucleosome. Modification of histone includes acetylation and deacetylation on certain amino acid residues; the process is catalyzed by different enzymes. Histone deacetylase 6 (HDAC6) is a unique deaetylating protease; it also catalyzes deacetylation of different non-histone substrates so as to regulate various physiologic processes. The intimate relationship between HDAC6 and oxidative stress has been demonstrated by different lines of study. The present paper aims at summarizing the data obtained from mechanistic study between HDAC6 and oxidative stress, in order to provide guidance for further investigations in term of mechanistic characterization and drug development.
Oxidative stress is defined as injury resulting from the disturbance on dynamic equilibrium of redox environment due to over-production of active/ radical oxygen exceeding the anti-oxidative ability in the body. It is a key step of genesis and development of various diseases. Oxidative stress is modulated by different factors and events, including modification of histone, the core of nucleosome. Modification of histone includes acetylation and deacetylation on certain amino acid residues; the process is catalyzed by different enzymes. Histone deacetylase 6 (HDAC6) is a unique deaetylating protease; it also catalyzes deacetylation of different non-histone substrates so as to regulate various physiologic processes. The intimate relationship between HDAC6 and oxidative stress has been demonstrated by different lines of study. The present paper aims at summarizing the data obtained from mechanistic study between HDAC6 and oxidative stress, in order to provide guidance for further investigations in term of mechanistic characterization and drug development.
Electroencephalogram (EEG) signals are the gold standard tool for detecting epileptic seizures. Long-term EEG signal monitoring is a promising method to realize real-time and automatic epilepsy detection with the assistance of computer-aided techniques and the Internet of Medical Things (IoMT) devices. Machine learning (ML) algorithms combined with advanced feature extraction methods have been widely explored to precisely recognize EEG signals, while among which, little attention has been paid to high computing costs and severe information losses. The lack of model interpretability also impedes the wider application and deeper understanding of ML methods in epilepsy detection. In this research, a novel feature extraction method based on an autoencoder (AE) is proposed in the time domain. The architecture and mechanism are elaborated. In this method, specified features are defined and calculated on the basis of signal reconstruction quantification of the AE. The EEG recognition is performed to validate the effectiveness of the proposed detection method, and the prediction accuracy reached 97%. To further investigate the superiority of the proposed AE-based feature extraction method, a widely used feature extraction method, PCA, is allocated for comparison. In order to understand the underlying working mechanism, permutation importance and SHapley Additive exPlanations (SHAP) are conducted for model interpretability, and the results further confirm the reasonability and effectiveness of the extracted features by AE reconstruction. With high computing efficiency in the time domain and an extensively satisfactory accuracy, the proposed epilepsy detection method exhibits great superiority and potential in almost real-time and automatic epilepsy monitoring.
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