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Background: Renal cell carcinoma (RCC) is the most common and lethal malignancy of the kidney. Distinguishing RCC from benign renal tumors and healthy controls is still a clinical challenge. Urine metabolomics has been used to identify biomarkers of clinical diseases., Methods: In the present study, we explored the urine metabolomes of a cohort of 61 patients with renal tumors (39 RCC and 22 benign renal tumors) and 68 healthy controls using liquid chromatography coupled with high-resolution mass spectrometry (LC-MS)., Results: Metabolic profiling of urine could significantly differentiate RCC from healthy controls and benign renal tumors. Metabolic pathways, including lysine metabolism and phenylalanine metabolism, were found to be disturbed in the RCC group. Steroid hormone biosynthesis was significantly different between the benign tumor group and the RCC group. RCC biomarkers were further explored. A metabolite panel consisting of cortolone, testosterone and L-2-aminoadipate adenylate was discovered to have good ability of distinguishing RCC from benign tumors, with an AUC of 0.868 for tenfold cross-validation and 0.873 for the validation group. In addition, the panel of aminoadipic acid, 2-(formamido)-N1-(5-phospho-D-ribosyl) acetamidine and alpha-N-phenylacetyl-L-glutamine could distinguish the RCC group from the healthy control group, with an AUC of 0.841 for tenfold cross-validation and 0.894 for the validation group., Conclusions: This pilot study suggests that urine metabolomics may be useful in differentiating RCC from healthy controls and benign renal tumors.

Background: To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC., Methods: In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways., Results: The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria., Conclusions: UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC.

Dodder (Cuscuta spp.) species are obligate parasitic flowering plants that totally depend on host plants for growth and reproduction and severely suppress hosts' growth. As a rootless and leafless plant, excised dodder shoots exhibit rapid growth and elongation for several days to hunt for new host stems, and parasitization could be reestablished. This is one unique ability of the dodder to facilitate its success in nature. Clearly, excised dodder stems have to recycle stored nutrients to elongate as much as possible. However, the mechanism of stored nutrient recycling in the in vitro dodder shoots is still poorly understood. Here, we found that dodder is a carbohydrate-rich holoparasitic plant. During the in vitro dodder shoot development, starch was dramatically and thoroughly degraded in the dodder shoots. Sucrose derived from starch degradation in the basal stems was transported to the shoot tips, in which EMP and TCA pathways were activated to compensate for carbon demand for the following elongation according to the variations of sugar content related to the crucial gene expression, and the metabolomics analysis. Additionally, antioxidants were significantly accumulated in the shoot tips in contrast to those in the basal stems. The variations of phytohormones (jasmonic acid, indole-3-acetic acid, and abscisic acid) indicated that they played essential roles in this process. All these data suggested that starch and sucrose degradation, EMP and TCA activation, antioxidants, and phytohormones were crucial and associated with the in vitro dodder shoot elongation. [ABSTRACT FROM AUTHOR]

Plasma metabolomics and lipidomics have been commonly used for biomarker discovery. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the metabolomics characteristics in Chinese population has not been surveyed. In our study, we applied liquid chromatography-mass spectrometry-based approach to analyze Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults (aging from 15 to 79). Fatty-acid metabolism was found to be gender- and age-dependent in Chinese, similar with metabolomics characteristics in Japanese and white populations. Differently, lipids, such as TGs and DGs, were found to be gender-independent in Chinese population. Moreover, nicotinate and nicotinamide metabolism was found to be specifically age-related in Chinese. The application of plasma metabolome and lipidome for renal cell carcinoma diagnosis (143 RCC patients and 34 benign kidney tumor patients) showed good accuracy, with an area under the curve (AUC) of 0.971 for distinction from healthy control, and 0.839 for distinction from the benign. Bile acid metabolism was found to be related to RCC probably combination with intestinal microflora. Definition of the variation and characteristics of Chinese normal plasma metabolome and lipidome might provide a basis for disease biomarker analysis. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) and Renal cell carcinoma(RCC) are the two most frequent genitourinary cancers in China. In this study, a comprehensive liquid chromatography—mass spectrometry (LC-MS) based method, which utilizes both plasma metabolomics and lipidomics platform, has been carried out to discriminate the global plasma profiles of 64 patients with BC, 74 patients with RCC, and 141 healthy controls. Apparent separation was observed between cancer (BC and RCC) plasma samples and controls. The area under the receiving operator characteristic curve (AUC) was 0.985 and 0.993 by plasma metabolomics and lipidomics, respectively (external validation group: AUC was 0.944 and 0.976, respectively). Combined plasma metabolomics and lipidomics showed good predictive ability with an AUC of 1 (external validation group: AUC = 0.99). Then, separation was observed between the BC and RCC samples. The AUC was 0.862, 0.853 and 0.939, respectively, by plasma metabolomics, lipidomics and combined metabolomics and lipidomics (external validation group: AUC was 0.802, 0.898, and 0.942, respectively). Furthermore, we also found eight metabolites that showed good predictive ability for BC, RCC and control discrimination. This study indicated that plasma metabolomics and lipidomics may be effective for BC, RCC and control discrimination, and combined plasma metabolomics and lipidomics showed better predictive performance. This study would provide a reference for BC and RCC biomarker discovery, not only for early detection and screening, but also for differential diagnosis. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the second most lethal urinary cancer. RCC is frequently asymptomatic and it is already metastatic at diagnosis. There is an urgent necessity for RCC specific biomarkers selection for diagnostic and prognostic purposes. In present study, we applied liquid chromatography—mass spectrometry (LC-MS) based metabolomics to analyze urine samples of 100 RCC, 34 benign kidney tumors and 129 healthy controls. Differential metabolites were analyzed to investigate if urine metabolites could differentiate RCC from non-RCC. A panel consisting of 9 metabolites showed the best predictive ability for RCC from the health controls with an area under the curve (AUC) values of 0.905 for the training dataset and 0.885 for the validation dataset. Separation was observed between the RCC and benign samples with an AUC of 0.816. RCC clinical stages (T1 and T2 vs. T3 and T4) could be separated using a panel of urine metabolites with an AUC of 0.813. One metabolite, N-formylkynurenine, was discovered to have potential value for RCC diagnosis from non-RCC subjects with an AUC of 0.808. Pathway enrichment analysis indicated that tryptophan metabolism was an important pathway in RCC. Our data concluded that urine metabolomics could be used for RCC diagnosis and would provide candidates for further targeted metabolomics analysis of RCC. [ABSTRACT FROM AUTHOR]

Cholestasis is the main manifestation of cholestatic liver disease, which has a risk of progression to end-stage liver disease. Gardeniae Fructus is the dried fruit of Gardeniae jasminoides Ellis, a plant of the Rubiaceae family. Gardeniae Fructus has shown therapeutic potential in cholestasis-related liver diseases and it is generally believed that Gardeniae Fructus ameliorates cholestasis, which could be related to its influence on bile acids (BAs) metabolism. However, the specific targets of Gardeniae Fructus and its impact on enterohepatic circulation of BAs have not yet been fully elucidated. To systematically elucidate the mechanism by which Gardenia extract (GE, total iridoids in Gardeniae Fructus, which contains the predominant and characteristic phytoconstituents of Gardeniae Fructus) ameliorates alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Sprague-Dawley rats were orally administered water, obeticholic acid (OCA, 2 mg/kg), or GE (21 and 42 mg/kg) once daily for five days. On the third day, the model was established by administration of a single dose of ANIT (40 mg/kg) by oral gavage. Biochemical and pathological analyses, BA metabolomics, transcriptomics, and qRT-PCR were performed. The profile of BAs in serum and liver confirmed that GE attenuated ANIT-induced acute cholestasis by affecting BA metabolism in a dose-dependent manner. Liver transcriptomic analysis indicated that GE mainly influenced the primary bile acid (PBA) biosynthesis and bile secretion pathways. GE mainly affected PBA biosynthesis in liver by upregulating Cyp8b1 gene expression, thereby significantly reducing the level of total bile acids (TBA). GE mainly promoted PBA excretion from liver into duodenum by upregulating Fxr and Oatp1 gene expression, thereby increasing the excretion of PBA in feces, and inhibiting PBA in liver entering the blood by alternative routes to reduce TBA levels in serum and urine and improve the enterohepatic circulation of BAs. GE attenuated ANIT-induced hepatotoxicity and cholestasis in rats by upregulating Cyp8b1 expression to inhibit BA synthesis in the liver, while also promoting BA excretion via the intestinal-fecal route, and improving enterohepatic circulation of BAs. [Display omitted] • Gardenia extract (GE) attenuated ANIT-induced hepatotoxicity and cholestasis in rats. • GE inhibits the synthesis of BAs in the liver by upregulating the expression of Cyp8b1. • GE promoted BA excretion, and improved enterohepatic circulation of BAs. [ABSTRACT FROM AUTHOR]

Adverse reactions to traditional Chinese medicine injections involve pseudo-allergic reactions (PARs). However, in clinical practice, "immediate allergic reactions" and PARs in response to these injections are not often differentiated. This study aimed to clarify the type of reactions produced by Shengmai injections (SMI) and elucidate the possible mechanism. A mouse model was used to evaluate vascular permeability. Metabolomic and arachidonic acid metabolite (AAM) analyses were performed using UPLC-MS/MS, and the p38 MAPK/cPLA2 pathway was detected by western blotting. The first exposure to intravenous SMI rapidly and dose-dependently induced edema and exudative reactions in the ears and lungs. These reactions were not IgE-dependent and were likely to be PARs. Metabolomic analysis showed that endogenous substances were perturbed in SMI-treated mice, in which the arachidonic acid (AA) metabolic pathway was the most affected. SMI substantially increased the levels of AAMs in lung, including prostaglandins (PGs), leukotrienes (LTs), and hydroxy-eicosatetraenoic acids (HETEs). The p38 MAPK/cPLA2 signaling pathway was activated after a single SMI dose. Inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes reduced exudation and inflammation in the ears and lungs of mice. Production of inflammatory factors that increase vascular permeability may result in SMI-induced PARs, and p38 MAPK/cPLA2 signaling pathway and downstream AA metabolic pathway are involved in the reactions. [Display omitted] • SMI-induced PARs involve a direct inflammatory response without IgE. • AAMs were involved in SMI-induced PARs. • SMI can activate the p38MAPK/cPLA2 signaling pathway. • AA inhibitors Nimesulide and zileuton inhibit AAMs production. [ABSTRACT FROM AUTHOR]