BackgroundInflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers.MethodsBased on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis.ResultsHsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3’-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83).ConclusionsComprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0974-6) contains supplementary material, which is available to authorized users.

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In summary, the CAP application in oncological surgery leads to strong anti-proliferative effects and opens up novel opportunities for the OC treatment.

obesity is one of the major risk factor for cardiovascular and metabolic diseases. A disproportional accumulation of fat at visceral (VAt) compared to subcutaneous sites (SAt) has been suspected as a key detrimental event. We used non-targeted metabolomics profiling to reveal metabolic pathways associated with higher VAt or SAt amount among subjects free of metabolic diseases to identify possible contributing metabolic pathways. The study population comprised 491 subjects [mean (standard deviation): age 44.6 yrs (13.0), body mass index 25.4 kg/m² (3.6), 60.1% females] without diabetes, hypertension, dyslipidemia, the metabolic syndrome or impaired renal function. We associated MRi-derived fat amounts with mass spectrometry-derived metabolites in plasma and urine using linear regression models adjusting for major confounders. We tested for sex-specific effects using interactions terms and performed sensitivity analyses for the influence of insulin resistance on the results. VAT and SAT were significantly associated with 155 (101 urine) and 49 (29 urine) metabolites, respectively, of which 45 (27 urine) were common to both. Major metabolic pathways were branched-chain amino acid metabolism (partially independent of insulin resistance), surrogate markers of oxidative stress and gut microbial diversity, and cortisol metabolism. We observed a novel positive association between VAt and plasma levels of the potential pharmacological agent piperine. Sex-specific effects were only a few, e.g. the female-specific association between VAT and O-methylascorbate. In brief, higher VAT was associated with an unfavorable metabolite profile in a sample of healthy, mostly non-obese individuals from the general population and only few sex-specific associations became apparent. equal amount of unknown compounds showed significant associations with VAT, including those related to either cortisol or piperine in the derived metabolic network (Fig. 3).Plasma and urine metabolites associated with SAT. Almost all association between SAT and metabolites were already described for VAT. Within each fluid, only two significant observations were unique to SAT (Figs. 1 and 2). Cortisol (inversely) and N1-methyl-2-pyridone-5-carboxamide (positively) levels in plasma as well as 3′-sialyllactose and the unknown compound X-12840 (both positively) levels in urine associated with SAT.

Vitamin D has an important role in calcium homeostasis and is known to have various health-promoting effects. Moreover, potential interactions between vitamin D and physical activity have been suggested. This study aims to investigate the relationship between 25-hydroxyvitamin D (25(OH)D) and exercise capacity quantified by cardiopulmonary exercise testing (CPET). For this, 1377 participants from the Study of Health in Pomerania (SHIP-1) and 750 participants from the independent SHIP-TREND cohort were investigated. Standardised incremental exercise tests on a cycle ergometer were performed to assess exercise capacity by VO 2 at anaerobic threshold, peakVO 2 , O 2 pulse and peak power output. Serum 25(OH)D levels were measured by an automated chemiluminescence immunoassay. In SHIP-1, 25(OH)D levels were positively associated with all considered parameters of cardiopulmonary exercise capacity. Subjects with high 25(OH)D levels (4th quartile) showed an up to 25 % higher exercise capacity compared with subjects with low 25(OH)D levels (1st quartile). All associations were replicated in the independent SHIP-TREND cohort and were independent of age, sex, season and other interfering factors. In conclusion, significant positive associations between 25(OH)D and parameters of CPET were detected in two large cohorts of healthy adults. . Further, to a small extent food, for example, fish, eggs and milk, could be a source of vitamin D in the diet (2,3) . 25(OH)D, the precursor of the active hormone calcitriol, has an important role in bone health (4)(5)(6) . During the past decade, several studies drew attention to vitamin D and its broad range of effects on health status and suggested that, besides the known effects on calcium homeostasis, vitamin D also could have an important role in CVD, cancer and autoimmune diseases (7) . However, the previously shown positive effects of vitamin D supplementation on fractures, tendency to fall or mortality (8)(9)(10) are a matter of current controversies because recent studies partially repudiated these findings (11,12) . Thereby, given these inconsistencies, additional research with respect to vitamin D and its health effects is needed.Few studies regarding the relation of vitamin D with physical performance have been conducted. Small studies among healthy subjects (2)(3)(4)(13)(14)(15)(16)(17)(18)(19) , mainly within a limited age range (2,3,(13)(14)(15)(16)(17)(18)(19) , as well as studies among patients with congestive heart failure (20) , renal failure (21) or chronic obstructive pulmonary disease (COPD) (22,23) , revealed positive associations between vitamin D levels and measures of physical performance. In detail, vitamin D levels >30 ng/ml were correlated to higher peakVO 2 (2,13,14) , as shown by Mowry et al. (r 0·36; P < 0·01) (13) and Ardestani et al. (r 0·29; P < 0·05) (14) , as well as static balance, gait speed or grip strength (3,4,(15)(16)(17)(18)(19) , as assessed by Short Physical Performance Battery Tests (SPPBT).Previous studies suggest various mechanisms ...