Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model’s value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis.
To explore the effect of acupuncture on the endoplasmic reticulum stress IRE 1-CHOP signal pathway and the expression levels of related apoptosis genes in pancreatic tissue of rats with STZ-induced diabetes mellitus.
Methods
Eighty SD rats were selected, among which, 10 were fed with normal diet and taken as blank control group (“blank group” for short), the other 70 rats were fed with high fat and high glucose food and injected with small dosage of STZ intraperitoneally, and 30 models were established successfully. The models were randomly divided into acupuncture treatment group (“acupuncture group” for short), model control group (“model group” for short) and western medicine group (metformin) with 10 rats in each group. After treatment for 4 weeks, RBG, and the expression levels of CHOP, IRE 1, Bax, Bcl-2 protein and mRNA in pancreatic tissue of rats were determined.
Result
Compared with the conditions before treatment, RBG reduced obviously in the acupuncture group and western medicine group (P<0.05), and there was no statistical difference in RBG in the model group and blank group (P>0.05); the expression levels of CHOP, IRE 1 and Bax proteins in pancreatic tissue of rats in the model group were significantly higher than those in the blank group (P<0.05), the expression results in the acupuncture group and western medicine group were significantly lower than those in model group (P<0.05); the expression levels of CHOP, IRE 1 and Bax mRNAs in pancreatic tissue of rats in the model group were significantly higher than those in the blank group (P<0.01), the expression results in the acupuncture group and western medicine group were significantly lower than those in the model group (P<0.01); the expression level of Bcl-2 protein in the model group was significantly lower than that in the blank group (P<0.05), the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group (P<0.01); there was no statistical difference between the acupuncture group and western medicine group (P>0.05); the expression level of Bcl-2 mRNA in the model group was significantly lower than that in the blank group (P<0.01), the expression results in the acupuncture group and western medicine group were significantly higher than that in the model group (P<0.01); there was no statistical difference between the acupuncture group and western medicine group (P>0.05).
Conclusion
There was endoplasmic reticulum stress in the pancreatic tissue of rats with STZ-induced diabetes mellitus, and IRE 1-CHOP signal pathway was the main pathway for inhibiting the endoplasmic reticulum stress in the pancreatic tissue. Acupuncture can improve the endoplasmic reticulum stress in pancreatic tissue, inhibit apoptosis genes, and protect the pancreatic tissue through IRE 1-CHOP signal pathway. 相似文献