ABSTRACT
Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.
ABSTRACT
Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that 'mitochondrial energy metabolism disorder' may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.
ABSTRACT
Objective The aim is to understand the underestimation of body weight status and its associated factors among overweight and obese adults in China. Methods Nationally representative data were collected in 2013 by the China Chronic Disease and Risk Factor Surveillance which used a multistage stratified cluster sampling method. A total of 87 552 overweight and obese adults aged ≥18 years old were included. Demographic characteristics, weight perception and disease status were obtained from in-person interviews. Height, weight and blood pressure were measured through physical examination. Venous blood samples were obtained and assayed for fasting plasma glucose, 2-hour oral glucose tolerance test, total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Complex sampling was weighted and multiple logistic regression models were used for analyzing. Results Among overweight and obese adults, 74.7% (95% CI: 73.3%-76.1%) underestimated their weight status. The mild underestimation rate was 60.7% (59.6%-61.7%) while the severe was 14.0% (13.1%-14.9%). The aged, low education level, low annual income, rural area and obesity were risk factors for both weight status underestimation and severe underestimation (all P<0.05). Awareness of having hypertension and dyslipidemia were protective factors (all P<0.05). Conclusions Most overweight and obese adults in China underestimated their own weight status, which was affected by age, education and income level, awareness of having chronic diseases and other factors. Targeted interventions should be carried out for different characteristic groups.
ABSTRACT
Objective To analyze the effect of Compound Chaigui Prescription on the changes of serum metabolites in rats with depression by 1H-NMR metabolomics. Methods Rats model established were modeled by chronic mild unpredictable stress (CUMS) procedure. Compound Chaigui Prescription and positive drugs (venlafaxine) were used as intervention drugs. Rat serum was analyzed by nuclear magnetic resonance (NMR) method. After data pretreatment, SIMCA-P 14.1 software was introduced for multivariate statistical analysis to verify the antidepressant efficacy of Compound Chaigui Prescription from the perspective of small molecule metabolites, and find potential disease biomarkers and drug efficacy markers. Results The CUMS depression rat model was successfully replicated. The metabolomics results showed that the levels of isoleucine, trimethylamine oxide, and creatine in the serum of CUMS-depressed rats were significantly higher than those of the model group. The levels of N-acetyl-glycoprotein, choline, and glucose were decreased with a significant difference (P < 0.05, 0.01). Conclusion The serum metabolite levels in CUMS model rats were significantly corrected after Compound Chaigui Prescription intervention. This study can provide reference for the study of antidepression mechanism of Compound Chaigui Prescription.
ABSTRACT
To investigate the anti-oxidative effect of celastrol on HO-induced oxidative stress in the cell model of amyotrophic lateral sclerosis (ALS) and its molecular mechanism, NSC34 motor neuron-like cells were transfected with EGFP-G93A-SOD1 plasmid and used as in vitro ALS cell model. SOD1transfected NSC34 cells were treated with different doses of HOand celastrol. The survival rate of the cells was detected by CCK-8 assay, and malondialdehyde (MDA) content was detected by corresponding kit. The mRNA expression of glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione S-transferases (GST) were detected by real-time PCR. The activation of intracellular MEK/ERK and PI3K/Akt signal pathways was detected by Western blot. The results showed that pre-incubation of celastrol (50 nmol/L) for 4 h prior to HO(10 μmol/L) co-treatment for another 24 h significantly attenuated HO-induced cell death and MDA level in SOD1transfected NSC34 cells. Real-time PCR showed that the mRNA expressions of GCLC and GST were enhanced with pre-incubation of celastrol. Celastrol quickly induced phosphorylation of ERK1/2 and Akt within 30 min and 1 h respectively in SOD1transfected NSC34 cells. Pharmacological inhibitors of MEK (PD98059, 10 μmol/L) or Akt (MK2206, 10 μmol/L) could reverse the phosphorylation of ERK1/2 and Akt, and abolish up-regulation of GCLC and GST induced by celastrol at mRNA levels. Taken together, we conclude that celastrol exerts a beneficial antioxidant effect in SOD1NSC34 cells, which might be dependent on MEK/ERK and PI3K/Akt signaling pathway activation.