Objective To analyze the metabolic characteristics of myocardial infarction (MI) using metabolomics to better understand its pathogenesis and to explore new therapeutic directions for MI. Methods Serum metabolites in ten acute MI mice and five sham-control mice were analyzed by UHPLC-QqQ/MS, and SPSS was used for statistical analysis. MetaboAnalyst 5.0 was used to analyze the metabolic pathways of the differential metabolites and build a metabolic network. Results One hundred and twenty-nine metabolites were detected by UHPLC-QqQ/MS. Significant serum metabolite differences were found between MI mice and normal controls. Fifty out of 129 metabolites in serum were associated with MI. In addition, the most important metabolic pathways were D-glutamate metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate acid metabolism. ConclusionMetabolites in serine-related metabolic pathways reduce in serum in MI. We propose a new therapeutic direction for myocardial protection in MI.
ObjectiveTo explore the metabolic changes during the differentiation of 3T3-L1 adipocytes caused by the treatment of the transient receptor potential vanilloid 4 (TRPV4)-specific agonist GSK1016790A basing on ultra-performance liquid chromatography-mass spectrometry technology. MethodsMouse 3T3-L1 cells were treated with GSK1016790A at different concentrations (0.1, 1, and 10 μmol/L), and the effect of drugs on cell proliferation was detected by cell counting kit-8 method. A mature adipocyte model was constructed, and GSK1016790A was used to activate TRPV4 channel protein activity and verify the expression levels of TRPV4 and triglycerides. Cell metabolites were collected for metabolomic studies, differential metabolites were screened between groups, and related metabolic pathways were analyzed. Results After GSK1016790A intervened in mature adipocytes, the expression levels of TRPV4 mRNA and triglycerides in cells were significantly upregulated (P<0.05). Metabolomics detection found that GSK1016790A screened a total of 45 differential metabolites such as 2-amino-1,3,4-octadecanetriol, linoleic acid, sphingosine, sphinganine, sn-glycerol-3-phosphate and uridine, mainly involving 13 possible metabolic pathways such as sphingolipid metabolism and biosynthesis of unsaturated fatty acids. Conclusion GSK1016790A may promote adipogenesis in adipocytes by activating TRPV4 channel protein activity, and at the same time participate in regulating metabolic pathways such as the biosynthesis of unsaturated fatty acids pathway and sphingolipid metabolism pathway, affecting lipid metabolism in adipocytes.
Diabetic retinopathy (DR) is one of the microvascular complications of diabetes mellitus causing severe visual impairment, and it is the main cause of blindness in adults. Metabolic abnormalities play an important role in the occurrence and development of DR, including the abnormal levels of glucose metabolism, lipid metabolism, amino acid metabolism and purine metabolism, which indicate that there are disorders of phosphopentose pathway, arginine metabolism pathway, polyol pathway and ascorbic acid pathway in the progression of DR. Metabolomics has great advantages in exploring the pathogenesis and diagnosis of DR, helping to identify the characteristic metabolic changes of DR And discover potential biomarkers. However, the existing metabolomics studies on DR have some limitations, such as the potential biomarkers found in some studies are difficult to verify in other studies due to differences in race, age, gender and sample size. There are few studies on biomarkers at different stages of DR. Therefore, in the future, multi-center and large-scale clinical studies are needed to screen out biomarkers with practical clinical diagnostic value.
ObjectiveTandem mass spectrometry is used to observe the changes in amino acids level in peripheral blood of patients with chronic obstructive pulmonary disease (COPD) of different severity, and explore the related factors that affect the level of amino acids in COPD patients.MethodsA collection of 99 COPD patients from the First Affiliated Hospital of Jinzhou Medical University between May 2020 and August 2020 were divided into GOLD Ⅰ/Ⅱ group, GOLD Ⅲ group and GOLD Ⅳ group according to the results of their lung function. Thirty healthy physical examination subjects during the same period were enrolled as a healthy control group. Peripheral amino acids were detected by liquid chromatography-tandem mass spectrometry (LC-MS).ResultsThe metabolism of 11 amino acids was correlated with the onset of COPD and the disorder of amino acid metabolism became more significant with the aggravation of the disease, and branched-chain amino acids (leucine, valine) had statistically significant differences in the COPD patients with different GOLD grades (P<0.05 and VIP>1). The difference between glutamate and glutamine was statistically significant only in GOLD Ⅳ stage (P<0.05 and VIP>1). The content of tyrosine and phenylalanine gradually increased with the increase of disease severity, and had significant difference in GOLD stage Ⅳ (P<0.05).ConclusionsCOPD patients with different GOLD grades have obvious amino acid metabolism disorders, including insufficient intake of essential amino acids and increased amino acids related to muscle protein catabolism. Understanding the mechanism between amino acid metabolism and COPD may provide a new direction for the diagnosis and treatment of the disease.
With the development of life sciences and informatics, bioinformatics is developing as an interdisciplinary subject. Its main application is the relationship between genes and proteins and their expression. With the help of genomics, proteomics, transcriptomics, and metabolomics, researchers introduce bioinformatics research methods into fundus disease research. A series of gratifying research results have been achieved including the screening of genetic susceptibility genes, the screening of diagnostic markers, and the exploration of pathogenesis. Genomics has the characteristics of high efficiency and accuracy. It has been used to detect new mutation sites in retinoblastoma and retinal pigment degeneration research, which helps to further improve the pathogenesis of retinal genetic diseases. Transcriptomics, proteomics, and metabolomics have high throughput characteristics. They are used to analyze changes in the expression profiles of RNA, proteins, and metabolites in intraocular fluid or isolated cells in disease states, which help to screen biomarkers and further elucidate the pathogenesis. With the advancement of technology, bioinformatics will provide new ideas for the study of ocular fundus diseases.
ObjectiveTo summarize the research results of metabolites of breast cancer based on metabonomics technology, and systematically reviews them in order to provide a new direction for the research of metabolism of breast cancer.MethodBy searching the relevant literatures in recent years, the application of metabonomics in identifying high-risk breast cancer population, monitoring the progress of tumor and evaluating the response of radiotherapy and chemotherapy were analyzed and summarized.ResultsWith the development of high-resolution, high-sensitivity and high-throughput bioanalysis platform technology, metabolomics had been widely used in breast cancer research field by virtue of its unique perspective and technical advantages to more accurately, systematically and dynamically monitor the changes of host metabolites.ConclusionMetabolomics technology provides a new research direction for primary prevention, early screening and diagnosis of breast cancer and optimal treatment strategy selection.
Objective To explore the effect of corn oligopeptide (COP) on dexamethasone-induced muscle atrophy. Methods Forty-nine male Sprague-Dawley rats aged 8 weeks were divided into blank group (n=10) and model group (n=39). The rats in the model group were intraperitoneally injected with dexamethasone (1.0 mg/kg), and the rats in the blank group were injected with normal saline. After 19 days, one rat in the blank group and three rats in the model group were taken to observe whether the model was successfully constructed. After successful modeling, the rats in the model group were randomly divided into model control group, COP low-dose group (COP-L group, 0.5 g/kg), COP medium-dose group (COP-M group, 1.0 g/kg) and COP high-dose group (COP-H group, 2.0 g/kg), with 9 rats in each group. After 33 days, the grip strength of the rats was measured, and then the gastrocnemius, soleus, tibialis anterior and metatarsal muscles were separated and weighed, and muscle fiber diameter, relative expression of Atrogin-1 and MuRF-1 mRNA were measured. Non-targeted metabolomics of gastrocnemius muscle were measured. Results Compared with that in the blank group, the body weight of rats in the model group reduced (P<0.05), and myofibril rupture was observed, indicating that the model was successful. Compared with those in the model control group, the grip strength increased in the COP-L and COP-M groups (P<0.05); the muscle coefficients of gastrocnemius and soleus in the COP-L and COP-H groups increased (P<0.05), and the muscle coefficients of plantaris in the COP-L and COP-M groups increased (P<0.05); the muscle fiber diameter of the tibial anterior muscle increased in the three doses of COP groups (P<0.05), and the muscle fiber diameter of the plantaris muscle increased in the COP-M and COP-H groups (P<0.05); the relative expression of Atrogin-1 mRNA decreased in the three doses of COP groups (P<0.05), while the relative expression of MurF-1 mRNA in the COP-L and COP-H groups decreased (P<0.05). The amino acid synthesis pathway, glycolysis pathway, and acid metabolism pathway were activated in gastrocnemius muscle. Conclusions COP can significantly improve the muscle atrophy induced by dexamethasone. The mechanism may be related to the decrease of Atrogin-1 and MuRF-1 expression in ubiquitin-proteasome pathway and the increase of amino acid biosynthesis.
Diabetic kidney disease, as a common complication of diabetes, is one of the main causes of end-stage renal disease. Because of the rapid progress of its course and the limited means of treatment, it is of great clinical significance to seek biomarkers from early diagnosis for the treatment of diabetic kidney disease. At present, there are limited methods for early diagnosis of diabetic kidney disease. As a widely used research method, metabonomics can detect metabolites in diseases and provide biomarkers for disease diagnosis and prognosis. This article summarizes the changes of amino acids, lipids, organic acids and other metabolites in blood or urine of patients with diabetic kidney disease.