There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer.

The use of illicit drugs causes unquestionable societal and economic damage. To implement actions aimed at combating drug abuse, it is necessary to assess illicit drug consumption patterns. The purpose of this paper was to develop, optimize, validate and apply a procedure for determining new psychoactive substances (NPSs) and classic drugs of abuse and their main metabolites in wastewater samples by using solid phase extraction (SPE) and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Moreover, detailed validation of the procedure was conducted. The developed SPE-HPLC-MS/MS procedure (within the sewage-based epidemiology strategy) allowed for the simultaneous, selective, very sensitive, accurate (recoveries ≥ 80.1%) and precise (CV ≤ 8.1%) determination of new and classic psychoactive substances in wastewater samples. This study is characterized by new scientific elements, especially in terms of the freeze-thaw and post-preparative stability of the selected psychoactive substances. This is the first time that NPSs (mephedrone and ketamine), the main metabolites of heroin (6-acetylmorphine, 6-AM) and marijuana (11-nor-9-carboxy-Δ9-tetrahydrocannabinol, THC-COOH) have been detected and monitored in Poland. This study is also the first to corroborate the data available from the EMCDDA and EUROPOL report and indicates that the retail market for cocaine is expanding in Eastern Europe. Drug abuse and illicit drug trafficking is a global phenomenon that causes a broad spectrum of social, health and economic problems 1-4. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the United Nations Office On Drugs and Crime (UNODC) reported that drug-related problems are becoming increasingly complex, especially with regard to the extremely dynamic nature of the new psychoactive substances market, stimulants, misused medicines and problematic cannabis use 3-7. Moreover, the verification of the presence of traditional illegal drugs (i.e., amphetamine, methamphetamine, ecstasy, etc.) in sewage samples is still needed because of environmental and forensic issues 8,9. The environmental impact of synthetic drug production has been highlighted in the last EMCDDA and EUROPOL report 7. Waste from drug production discharged into surface waters may harm aquatic life, can potentially contaminate the meat of cattle, which can affect the human food chain, and could further spread hazardous substances into the soil and waterways 7,10. In this context, it is crucial to pay greater attention to developing new methodologies as tools for monitoring illicit drug consumption and its trends and drug trafficking to combat drug abuse and improve quality of life 11-17. Illegal drug use is mostly an unofficial activity. Consequently, traditional survey methods, such as general population interviews and surveys, can be inaccurate and may also produce results based on conjectures 2,8,18,19. Conventional survey methods are not suitable for monitoring fast-changing drug markets over time 20. T...

Results demonstrated that metabolomics may be useful for elucidating biological mechanisms associated with the development and severity of PN symptoms, specifically pain and fatigue, in women with early-stage breast cancer.

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Sensitive and specific diagnostic and prognostic biomarkers for prostate cancer (PCa) are urgently needed. Urine samples are a non-invasive means to obtain abundant and readily accessible "liquid biopsies". Herein we used urine liquid biopsies to identify and characterize a novel group of urineenriched RNAs and metabolites in patients with PCa and normal individuals with or without benign prostatic disease. Differentially expressed RNAs were identified in urine samples by deep sequencing and metabolites in urine were measured by mass spectrometry. mRNA and metabolite profiles were distinct in patients with benign and malignant disease. Integrated analysis of urinary gene expression and metabolite signatures unveiled an aberrant glutamate metabolism and tricarboxylic acid (TCA) cycle node in prostate cancer-derived cells. Functional validation supported a role for glutamate metabolism and glutamate oxaloacetate transaminase 1 (GOT1)-dependent redox balance in PCa, which could be exploited for novel biomarkers and therapies. In this study, we discovered cancerspecific changes in urinary RNAs and metabolites, paving the way for the development of sensitive and specific urinary PCa diagnostic biomarkers either alone or in combination. Our methodology was based on single void urine samples (i.e., without prostatic massage). The integrated analysis of metabolomic and transcriptomic data from these liquid biopsies revealed a glutamate metabolism and tricarboxylic acid cycle node that was specific to prostate-derived cancer cells and cancer-specific metabolic changes in urine.More than 180,000 men are diagnosed with prostate cancer (PCa) in U.S. in the 2016, where 26,000 of these patients will die of the disease 1 . PCa is one of the second most frequently diagnosed cancer deaths among men worldwide 2 . The radiotherapy and surgery for localized PCa are known to be effective, however the prognosis for patients with the progressive disease is poor. A test to detect PCa with high sensitivity and specificity at an early stage is a clinical imperative. Moreover, there is a vital need for novel therapeutic tactics to manage this insidious and prevalent disease. open Scientific RepoRtS | (2020) 10:3716 | https://doi.org/10.1038/s41598-020-60616-z www.nature.com/scientificreports www.nature.com/scientificreports/ Serum prostate specific antigen (PSA) levels are been used for PCa diagnosis and screening for over thirty years, and digital rectal examination (DRE) for even longer 3 . However, PSA has modest sensitivity and specificity and does not discriminate indolent from aggressive cancers 3,4 . Prostate cancer antigen 3 (PCA3), a prostate-specific non-coding RNA, was approved by the FDA in 2012 as the first PCa molecular diagnostic test for a particular clinical indication (need for recurrence prostate biopsies in men aged >50 years with assumed PSA levels and/or DRE and/or one or more earlier negative biopsies) 5 . Nevertheless, the importance of the PCA3 test is limited by substantial individual variability, better performan...

The aim of this study was to assess the response to a honeybee venom by analyzing serum levels of 34 free amino acids. Another goal of this study was to apply complex analytic-bioinformatic-clinical strategy based on up-to-date achievements of mass spectrometry in metabolomic profiling. The amino acid profiles were determined using hybrid triple quadrupole/linear ion trap mass spectrometer coupled with a liquid chromatography instrument. Serum samples were collected from 27 beekeepers within 3 hours after they were stung and after a minimum of 6 weeks following the last sting. The differences in amino acid profiles were evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed statistically significant differences in the levels of L-glutamine (Gln), L-glutamic acid (Glu), L-methionine (Met) and 3-methyl-L-histidine (3MHis) between the two analyzed groups of serum samples. Gln and Glu appeared to be the most important metabolites for distinguishing the beekeepers tested shortly after a bee sting from those tested at least 6 weeks later. The role of some amino acids in the response of an organism to the honeybee sting was also discussed. This study indicated that proposed methodology may allow to identify the individuals just after the sting and those who were stung at least 6 weeks earlier. The results we obtained will contribute to better understanding of the human body response to the honeybee sting.

PurposeThe aim of the project was to apply ultra-high-performance liquid chromatography–quadrupole-Orbitrap-high-resolution mass spectrometry for serum metabolite profiling of non-small-cell lung cancer (NSCLC). This Orbitrap-based methodology has been applied for a study of NSCLC potential markers for the first time.MethodsAfter extraction using protein precipitation, sera were separated on the ACE Excel 2 C18-PFP (100 × 2.1 mm, 2.0 µm) column using gradient elution and analyzed within the range of 70–1000 m/z. Only patients with early stage disease (stages IA–IIB) were included in the study, providing opportunity to find biomarkers for early lung cancer detection. The resulting metabolite profiles were subjected to univariate and multivariate statistical tests.Results36 features were found significantly changed between NSCLC group and controls after FDR adjustment and 19 were identified using various metabolite databases (in-house library, HMDB, mzCloud). The study revealed a number of NSCLC biomarker candidates which belong to such compound classes as acylcarnitines, organic acids, and amino acids. Multivariate ROC curve built using 12 identified metabolites was characterized by AUC = 0.836 (0.722–0.946). There were no significant differences in the serum metabolite profiles between two most common histological types of lung cancer—adenocarcinoma and squamous cell carcinoma.ConclusionsThrough identification of novel potential tumor markers, Orbitrap-based global metabolic profiling is a useful strategy in cancer research. Our study can accelerate development of new diagnostic and therapeutic strategies in NSCLC. The metabolites involved in discrimination between NSCLC patients and the control subjects should be further explored using a targeted approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-017-2347-0) contains supplementary material, which is available to authorized users.