Integrated transcriptomic and metabolomic analysis of rat serum to investigate potential target of puerarin in the treatment post-traumatic stress disorder.

BACKGROUND: Puerarin is a root extract of Pueraria lobate that can alleviate the behavioral disorders and could be therapy for post-traumatic stress disorder (PTSD). However, the underlying mechanism of puerarin in PTSD is unclear, so, we hypothesized that integration of its metabolomic and transcriptomic profiles in rat serum could help to identify the mechanisms of the protective action of puerarin. METHODS: We used the single prolonged stress procedure to establish a model of PTSD in rats and then subjected them to treatment with or without puerarin. Serum metabolomics and transcriptomics were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry and mRNA sequencing. The differential metabolites were evaluated by multivariate analysis, and Bayes discriminant analysis and receiver operator characteristic (ROC) analysis were used to discover potential diagnostic or therapeutic biomarkers. Transcriptomic data were obtained from mRNA sequencing, and we identified the key target genes of puerarin in the treatment of PTSD by integrated analysis of bioinformatics, real-time reverse transcription-polymerase chain reaction (RT-PCR) and data mining. Finally, an integrative analysis of the different metabolites and differentially expressed genes was performed using MetaboAnalysis to investigate the possible molecular mechanisms. RESULTS: The metabolomics analysis showed that 17 dysregulated metabolites in PTSD were reversed by puerarin treatment, and daidzein, 3-succinoylpyridine, 5-(2,5-dihydroxyhexyl) oxolan-2-one and elaidic acid were identified as potential biomarkers for the treatment and diagnosis of PTSD. Transcriptomics analysis showed that dysregulation of 99 genes in PTSD was reversed by puerarin treatment, and further revealed that CD36 molecule (CD36), HBS1-like translational GTPase (HBS1L), CD59 molecule (CD59) and dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) were not only key targets for puerarin's action in the treatment of PTSD but also potential biomarkers for the diagnosis and treatment of PTSD. Finally, integrated analysis of the metabolomic and transcriptomic data revealed that puerarin treatment for PTSD was mainly regulated by the metabolic pathways of one carbon pool by folate, synthesis and degradation of ketone bodies, and antigen processing and presentation. CONCLUSIONS: Our results are a new genetic insight into the mechanism of action of puerarin in PTSD treatment. We identified four metabolites and four genes that might be considered as novel biomarkers for the diagnosis and treatment of patients with PTSD.

The prognostic value of major facilitator superfamily domain-containing protein 2A in patients with hepatocellular carcinoma.

INTRODUCTION: We aimed to characterize the expression of major facilitator superfamily domain-containing protein 2A (MFSD2A) in hepatocellular carcinoma (HCC) patients and analyze its prognostic value. RESULTS: Immunohistochemistry revealed that low expression of MFSD2A was present in 37 of 79 cases (46.84%), which was significantly correlated with poor histological differentiation (P = 0.012). The plasma MFSD2A level in HCC patients was significantly lower than in healthy controls (P = 0.0079) and controls with chronic hepatitis B virus (HBV) infection (P = 0.0430). Moreover, patients with lower MFSD2A expression had shorter survival than higher expression (P = 0.021). Multivariate analysis revealed that MFSD2A was an independent prognostic predictor for HCC patients (P = 0.027). CONCLUSION: The current study indicate MFSD2A may be an optimal diagnostic and prognostic biomarker for HCC. METHODS: First, we examined MFSD2A expression in 24 paired HCC and nontumorous tissues by real-time quantitative PCR (RT-qPCR). Second, the protein levels of MFSD2A in 11 paired HCC and nontumorous tissues were investigated by western blotting (WB). Moreover, MFSD2A protein expression was evaluated by immunohistochemistry in 79 HCC patients. In addition, we detected the plasma level of MFSD2A in HCC patients and healthy individuals and investigated the relationship between MFSD2A expression and clinicopathological parameters or prognosis of HCC patients.

The anxiolytic-like effects of puerarin on an animal model of PTSD.

Post traumatic stress disorder (PTSD) is a mental illness that affected numerous people. The anti-PTSD-like effects of puerarin is unknown, although the antidepressant- and anxiolytic- like effects of puerarin have been reported. The PTSD behavioral deficits in rats were induced by single prolonged stress (SPS), mainly including the reduced time/entries in the open arms and the elevated time/entries in the closed arms in elevated plus maze test, increased freezing duration in contextual fear paradigm and lowered time/entries in the central zone in open field test. However, the behavioral deficits were attenuated by puerarin (50 and 100 mg/kg) without affecting the locomotor activity. For the evaluation of mechanism, the decreased levels of progesterone, allopregnanolone, and the increased levels of corticosterone, corticotropin releasing hormone, and adrenocorticotropic hormone in the brain or serum were induced by SPS, which is blocked by puerarin. In summary, the anti-PTSD-like effects of puerarin were associated with biosynthesis of neurosteroids and normalized levels of stress hormones in HPA axis.