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Background: The prevention and early screening of PCa is highly dependent on the identification of new biomarkers. In this study, we investigated whether plasma metabolic profiles from healthy males provide novel early biomarkers associated with future risk of PCa. Methods: Using the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, we identified plasma samples collected from 146 PCa cases up to 13 years prior to diagnosis and 272 matched controls. Plasma metabolic profiles were characterized using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Results: Orthogonal partial least squares discriminant analysis (OPLS-DA) discriminated PCa cases from controls, with a median area under the receiver operating characteristic curve (AU-ROC) of 0.92 using a 1000-time repeated random sub-sampling validation. Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) identified the top 10 most important metabolites (p &lt, 0.001) discriminating PCa cases from controls. Among them, phosphate, ethyl oleate, eicosadienoic acid were higher in individuals that developed PCa than in the controls during the follow-up. In contrast, 2-hydroxyadenine, sphinganine, L-glutamic acid, serotonin, 7-keto cholesterol, tiglyl carnitine, and sphingosine were lower. Conclusion: Our results support the dysregulation of amino acids and sphingolipid metabolism during the development of PCa. After validation in an independent cohort, these signatures may promote the development of new prevention and screening strategies to identify males at future risk of PCa.

Coronary heart disease (CHD) remains a major public health burden. Endothelial-dependent coronary artery vasoreactivity is a significant indicator of vascular function. Endothelial dysfunction is characterized by decreased nitric oxide (NO) bioavailability and predicts late cardiovascular events. Astragaloside IV (AGIV) is the main active component of the herb Astragalus membranaceus. Although it shows a significant protective effect against vascular endothelial dysfunction, the mechanisms of AGIV promoting the vascular dilation have not been elucidated. This study investigated the vasodilator effect of AGIV on rat aortic rings and the underlying effect of AGIV via the PI3K/Akt/eNOS signaling pathway. We measured the relaxation of isolated RARs after different concentrations of AGIV treatment. Rat aorta endothelial cells were cultured with different doses of AGIV, dimethylsulfoxide, and NG-nitro L-arginine methyl ester. The expression of phosphorylated (p)-Akt and -endothelial nitric oxide synthase (p-eNOS) were tested by Western blot analysis. The messenger (m)RNA expression of eNOS was quantified by real-time polymerase chain reaction. AGIV exerted a vasodilator effect on the aortic rings and increased the NO content in a concentration-dependent manner. The vasorelaxation was suppressed by an eNOS inhibitor. AGIV regulated the PI3K/Akt/eNOS signaling pathway via phosphorylation of Akt at Ser473 and dephosphorylation of eNOS at Thr495. The mRNA expression of eNOS was remarkably upregulated by AGIV. AGIV significantly induced the dilation of the aortic rings, leading to the vasodilator response by enhancing the eNOS release via the PI3K/Akt/eNOS signaling pathway.

Background Septic shock is the most severe phase of sepsis and is associated with high rates of mortality. However, early stage prediction of septic shock outcomes remains difficult. Metabolomic techniques have emerged as a promising tool for improving prognosis. Methods Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models separating the serum metabolomes of survivors from those of non-survivors were established with samples obtained at the intensive care unit (ICU) admission (H0) and 24 h later (H24). For 51 patients with available H0 and H24 samples, multi-level modeling was performed to provide insight into different metabolic evolutions that occurred between H0 and H24 in the surviving and non-surviving patients. Relative quantification and receiver operational characteristic curves (ROC) were applied to estimate the predictability of key discriminatory metabolites for septic shock mortality. Results Metabolites that were involved in energy supply and protein breakdown were primarily responsible for differentiating survivors from non-survivors. This was not only seen in the H0 and H24 discriminatory models, but also in the H0-H24 paired models. Reanalysis of extra H0-H24 paired samples in the established multi-level model demonstrated good performance of the model for the classification of samplings. According to the ROC results, nine discriminatory metabolites defined consistently from the unpaired model and the H0-H24 time-trend change (ΔH24-H0) show good prediction of mortality. These results suggest that NMR-based metabolomic analysis is useful for a better overall assessment of septic shock patients. Conclusions Dysregulation of the metabolites identified by this study is associated with poor outcomes for septic shock. Evaluation of these compounds during the first 24 h after ICU admission in the septic shock patient may be helpful for estimating the severity of cases and for predicting outcomes. Trial registration All human serum samples were collected and stored, provided by the “center of biologic resources for liver disease”, in Jean Verdier Hospital, Bondy, France (BB-0033-00027). Electronic supplementary material The online version of this article (10.1186/s13054-019-2456-z) contains supplementary material, which is available to authorized users.

Table S1. Assignment of spectra recorded with one exemplar serum sample from a septic shock patient. Figure S1. Assignment of spectra recorded with an example of a representative 1H-NMR spectrum. The assigned peaks corresponding with the key metabolite discriminants have been marked in the figure. Figure S2. A PCA calculated with H0 samples from 11 nonsurvivors who died during the first 24 h (red dots) and those from the other non-survivors who died from the second day to the seventh day after the first sampling (blue dots). Figure S3. PCA model separating survivors from non-survivors with H0 samples before the exclusion of outlier. One sample of a non-survivor was observed as an outlier for the PCA. This outlier has been removed before statistical analyses. Blue dots: survivors, yellow dots: non-survivors. Figure S4 (respectively S5). Cross-validation by 200 times permutation between X and Y for the OPLS-DA model with H0 samples (respectively H24). The green dots stand for the obtained R2 value and the blue dots stand for the obtained Q2 value within the 200 permutations. The Y-axis represents R2 and Q2 calculated for every model while the X-axis represents the correlation coefficient between original and permuted response data. Figure S6. Loading plots for paired OPLS-DA models showing important discriminatory metabolites that contribute to the separation between H0 and H24 samples. The paired models for the survivors and non-survivors are shown separately. The peaks are assigned to corresponding discriminatory metabolites. The correlations between the assigned metabolites and the model have been shown with the colors. a: loading plot for the separation between H0 and H24 for the survivors; b: loading plot for the separation between H0 and H24 for the non-survivors. (DOCX 829 kb)

Depression is a major mental disorder, and is currently recognized as the second-leading cause of disability worldwide. However, the therapeutic effect of antidepressants remains unsatisfactory. For centuries, Chinese herbal formulas (CHFs) have been widely used in the treatment of depression, achieving better therapeutic effects than placebo and having fewer side effects than conventional antidepressants. Here, we review the ethnopharmacology, phytochemistry, and pharmacology studies of nine common CHFs: "banxia houpo" decoction, "chaihu shugansan", "ganmaidazao" decoction, "kaixinsan", "shuganjieyu" capsules, "sinisan", "wuling" capsules, "xiaoyaosan", and "yueju". Eight clinical trials and seven meta-analyses have supported the theory that CHFs are effective treatments for depression, decreasing Hamilton Depression Scale scores and showing few adverse effects. Evidence from 75 preclinical studies has also elucidated the multitarget and multipathway mechanisms underlying the antidepressant effect of the nine CHFs. Decoctions, capsules, and pills all showed antidepressant effects, ranked in descending order of efficacy. According to traditional Chinese medicine theory, these CHFs have flexible compatibility and mainly act by soothing the liver and relieving depression. This review highlights the effective treatment choices and candidate compounds for patients, practitioners, and researchers in the field of traditional Chinese medicine. In summary, the current evidence supports the efficacy of CHFs in the treatment of depression, but additional large-scale randomized controlled clinical trials and sophisticated pharmacology studies should be performed.

Background. Rhubarb, a traditional Chinese medicine, promotes viscera and remove blood stasis. Rhubarb is skilled in smoothening meridians, improving blood circulation which exhibits better efficacy on cerebral ischemic stroke. In this study, we aimed to analyze the underlying mechanisms of rhubarb which treated rats of middle cerebral artery occlusion (MCAO) model according to an iTRAQ-based proteomics and bioinformatics analysis. 30 rats were randomly allocated into three groups including sham group (SG), model group (MG), and rhubarb group (RG). Rhubarb group was given a gavage of rhubarb decoction at dose of 3 g/kg and the remaining groups were prepared with normal saline by gavage. Rats from MG and RG were induced into MCAO model. The effects of rhubarb were estimated by Modified Neurological Severity Score (mNSS) and cerebral infarct volume. The brain tissues were measured via the quantitative proteomic approach of iTRAQ coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, the bioinformatics analysis of overlapping differentially expression proteins (DEPs) was conducted by DAVID, KEGG, and Cytoscape. Specific selective DEPs were validated by Western blotting. Rats treated with rhubarb after MCAO showed a significant reduction on mNSS and cerebral infarct volume compared with MG. In MG versus SG and RG versus MG, we identified a total of 4578 proteins, of which 287 were DEPs. There were 76 overlapping DEPs between MG versus SG and RG versus MG. Through bioinformatics analysis, 14 associated pathways were searched including cGMP-PKG signaling pathway, tuberculosis, synaptic vesicle cycle, amyotrophic lateral sclerosis, long-term potentiation, and so on. 76 overlapping DEPs mainly involved synaptic vesicle cycling biological processes based on GO annotation. Further, the selective overlapping DEPs were verified at the protein level by using Western blotting. Our present study reveals that rhubarb highlights promising neuroprotective effect. Rhubarb exerts novel therapeutic action via modulating multiple proteins, targets, and pathways.

Using (S)-(-)-2-chloropropionic acid ethyl ester and N-methylimidazole as raw materials, we designed and synthesized three N-methylimidazolium chiral ionic liquids by the nucleophilic substitution reaction or anion exchange reaction. These chiral ionic liquids structures were analyzed with structure optimization calculation, IR, and HNMR. Their reaction mechanism and physical chemistry properties were explored. As a result, these chiral ionic liquids possess optical activity, low melting point, high conductivity, and weak acidity, etc. They can serve as effective reaction media as well as chiral catalysts. They are presently being investigated as dispersion agent in molecular imprinting ployer in our laboratory.

In China, depression remains a disabling condition with high prevalence and a large clinical burden.