Novel personalized pathway-based metabolomics models reveal key metabolic pathways for breast cancer diagnosis

Comparison of logistic regression, SVM and random forest performance in the plasma training data set. Table S2. Pathway significance and relative log fold changes in our metabolomics data and TCGA breast cancer RNA-Seq data. Table S3. Detected metabolites and their differential test results among the two models. a All-stage diagnosis model. b Early-stage diagnosis model. Table S4. Single-variate logistic analysis of metabolites or pathways selected as features in the metabolite-based or pathway-based early-stage diagnosis model. Table S5. Comparison of pathway features in the full-size (101 input pathways) and half-size (51 input pathways) pathway-based early-stage diagnosis models. (DOCX 34 kb

A Metabolomics-Based Strategy for the Quality Control of Traditional Chinese Medicine: Shengmai Injection as a Case Study

Quality control of traditional Chinese medicines (TCMs) used clinically is becoming a challenge and has limited the development of TCM due to the high variability in concentration levels of active ingredients and markers as well as the lack of well-established criteria. Using Shengmai injection, which is a well-established TCM, as an example, we developed an integrated profiling approach that simultaneously captures the entire spectrum of ingredients and quantitatively determines the levels of seven key ingredients in the TCM product. A multivariate statistical model was constructed to establish a “seven-marker-” based quality standard that qualified the majority of samples in this study. This newly developed strategy showed that a panel of key ingredients or markers in the TCM product were relatively consistent within a statistically acceptable range. Therefore, this metabolomics-based approach will complement the current quality control standard using the concentration of several key ingredients or their total content and help improve the consistency and clinic efficacy of TCM products

Management of Hepatic Encephalopathy by Traditional Chinese Medicine

In spite of the impressive progress in the investigation of hepatic encephalopathy (HE), the complex mechanisms underlying the onset and deterioration of HE are still not fully understood. Currently, none of the existing theories provide conclusive explanations on the symptoms that link liver dysfunction to nervous system disorders and clinical manifestations. This paper summarized the diagnostic and therapeutic approaches used for HE in modern medicine and traditional Chinese medicine and provided future perspective in HE therapies from the viewpoint of holistic and personalized Chinese medicine

Genome-wide analyses of abiotic stress-related microRNAs and their targets in Arabidopsis thaliana

Abstract MicroRNAs (miRNAs) are known to regulate plant growth and development via regulating gene expression at both transcriptional and post-transcriptional levels. Although several miRNAs have been reported to be associated with abiotic stress responses in plant, systematic investigation of stress-related miRNAs and their targets in plants is limited. In this study, we systematically investigated stress-related miRNAs and their targets in Arabidopsis thaliana. We identified 94 putative stress-related miRNA genes, in which 8 miRNAs were new identified with stress-related response function based on targets prediction. Sequence analysis of these miRNA genes showed that most stress-related miRNAs possess TATA boxes in their promoters, and more than half contain at least two promoters. We also demonstrated that most stress-related miRNA genes contain stress-related elements in their promoters. Furthermore, conservation analysis showed that many stress-related miRNAs are species/family-specific and a subset of stress-related miRNAs may be derived from repeat sequences. Finally, we found that the stress-related miRNAs target 374 genes with 1,153 predicted target sites, of which 87.2% are targeted for gene cleavage and 12.8% affect protein translation. In conclusion, our findings provide an insight into both the function and evolution of stress-related miRNAs

Urine Metabolite Profiling Offers Potential Early Diagnosis of Oral Cancer

Oral cancer is the sixth most common human cancer, with a high morbidity rate and an overall 5-year survival rate of less than 50%. It is often not diagnosed until it has reached an advanced stage. Therefore, an early diagnostic and stratification strategy is of great importance for oral cancer. In the current study, urine samples of patients with oral squamous cell carcinoma (OSCC, n = 37), oral leukoplakia (OLK, n = 32) and healthy subjects (n = 34) were analyzed by gas chromatography-mass spectrometry (GC–MS). Using multivariate statistical analysis, the urinary metabolite profiles of OSCC, OLK and healthy control samples can be clearly discriminated and a panel of differentially expressed metabolites was obtained. Metabolites, valine and 6-hydroxynicotic acid, in combination yielded an accuracy of 98.9%, sensitivity of 94.4%, specificity of 91.4%, and positive predictive value of 91.9% in distinguishing OSCC from the controls. The combination of three differential metabolites, 6-hydroxynicotic acid, cysteine, and tyrosine, was able to discriminate between OSCC and OLK with an accuracy of 92.7%, sensitivity of 85.0%, specificity of 89.7%, and positive predictive value of 91.9%. This study demonstrated that the metabolite markers derived from this urinary metabolite profiling approach may hold promise as a diagnostic tool for early stage OSCC and its differentiation from other oral conditions

Design, fabrication, and cold test of a high frequency system for an H-band sheet beam travelling wave tube

The design, fabrication and cold test of a high frequency system (HFS) for an H-band (220-325GHz) sheet beam travelling wave tube is presented in this article. The HFS was composed of a 90-period double-staggered grating waveguide and a pair of identical L-shaped couplers with Bragg reflectors and matching steps. The HFS was manufactured by nano-computer numerical control machining and its electromagnetic properties were measured by using a vector network analyzer. The measured S-parameters were in good agreement with the simulated ones, which predicted a 3 dB bandwidth of ∼47.0 GHz. The maximum value of the measured transmission coefficient S 21 was -4.9 dB and the in-band port reflection S 11 was around -15.0 dB. Based on the cold testing-based HFS, simulations of the beam wave interaction predicted a stable output power of over 55.1 W in the frequency range of 230-280 GHz. In addition, the instabilities of the beam wave interaction were investigated in the simulation

Management of Hepatic Encephalopathy by Traditional Chinese Medicine

In spite of the impressive progress in the investigation of hepatic encephalopathy (HE), the complex mechanisms underlying the onset and deterioration of HE are still not fully understood. Currently, none of the existing theories provide conclusive explanations on the symptoms that link liver dysfunction to nervous system disorders and clinical manifestations. This paper summarized the diagnostic and therapeutic approaches used for HE in modern medicine and traditional Chinese medicine and provided future perspective in HE therapies from the viewpoint of holistic and personalized Chinese medicine

A Lipoprotein Lipase–Promoting Agent, NO-1886, Improves Glucose and Lipid Metabolism in High Fat, High Sucrose–Fed New Zealand White Rabbits

The synthetic compound NO-1886 is a lipoprotein lipase activator that lowers plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C). Recently, the authors found that NO-1886 also had an action of reducing plasma glucose in high-fat/high-sucrose diet–induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on insulin resistance and β-cell function in rabbits. Our results showed that high-fat/high-sucrose feeding increased plasma triglyceride, free fatty acid (FFA), and glucose levels and decreased HDL-C level. This diet also induced insulin resistance and impairment of acute insulin response to glucose loading. Supplementing 1% NO-1886 into the high-fat/high-sucrose diet resulted in decreased plasma triglyceride, FFA, and glucose levels and increased HDL-C level. The authors also found a clear increased glucose clearance and a protected acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 suppresses the elevation of blood glucose in rabbits induced by feeding a high-fat/high-sucrose diet, probably through controlling lipid metabolism and improving insulin resistance

Waterborne Manganese Exposure Alters Plasma, Brain, and Liver Metabolites Accompanied by Changes in Stereotypic Behaviors

Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography–time of flight–mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague–Dawley rats had access to deionized drinking water either Mn-free or containing 1 g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24 h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, - 14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats