ABSTRACT
Bladder cancer (BCa) is ninth amongst the most common types of cancer in the human population worldwide. The statistics of incidence and mortality of BCa are alarming and the currently applied diagnostic methods are still not sensitive enough. This leads to a large number of undiagnosed BCa cases, usually among patients in the early stages of the disease. Despite the fact that many risk factors of BCa have been recognized, the pathomechanism of development of bladder cancer has not been fully explained yet. Therefore, in the present study, multiplatform urinary metabolomics has been implemented in order to scrutinize potential diagnostic indicators of BCa that might help to explain its pathomechanism and be potentially useful in diagnosis and determination of stage of the disease. Urine samples collected from muscle-invasive high grade BCa patients (nâ¯=â¯24) and healthy volunteers (nâ¯=â¯24) were matched in terms of most common BCa risk factors i.e. gender, age, BMI and smoking status. They were analyzed by high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) using RP and HILIC chromatography, gas chromatography hyphenated with triple quadruple mass spectrometry detection (GC-QqQ/MS) in scan mode, and proton nuclear magnetic resonance (1H NMR). The six datasets obtained were submitted to univariate and multivariate statistical analyses. 17 metabolites significantly discriminated urinary profiles of BCa patients from urinary profiles of healthy volunteers. These metabolites are mainly involved in amino acid metabolism, pyrimidine and purine metabolism, as well as energy metabolism and might play a crucial role in the pathogenesis of BCa.
Subject(s)
Metabolomics , Urinary Bladder Neoplasms/urine , Aged , Chromatography, High Pressure Liquid , Female , Healthy Volunteers , Humans , Magnetic Resonance Spectroscopy , Male , Middle Aged , Tandem Mass Spectrometry , Urinary Bladder Neoplasms/metabolismABSTRACT
Accumulating evidence indicates that cerebral ischemia enhances neurogenesis in the adult brain. The mechanisms responsible for stem-cell development are poorly understood. Recent in vitro studies indicate the involvement of metalloproteinase (MMPs) in the regulation of proliferation and differentiation of neural progenitor cells. To elucidate if MMPs participate in neurogenesis-associated processes after ischemic insult, we aimed to establish spatial and temporal relationships between neural stem-cell development and the activity of MMPs in the adult brain hippocampus. Our results show that post ischemic acceleration in the proliferation of progenitors in the dentate gyrus is accompanied by increased activity of MMPs. On the contrary, in the damaged CA1 pyramidal layer the neurogenesis seems to be rather elusive. Simultaneously, the activity of MMPs fell below the control level. In conclusion, our results show that the activation of MMPs may, at least in part, contribute to ischemia-induced neurogenesis in the dentate gyrus of the adult brain.
Subject(s)
Brain Ischemia/pathology , Hippocampus/physiopathology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Neurogenesis/physiology , Animals , Bromodeoxyuridine/metabolism , Cell Count/methods , Cell Differentiation/physiology , Cell Proliferation , Disease Models, Animal , Gerbillinae , Glial Fibrillary Acidic Protein/metabolism , Male , Neurofilament Proteins/metabolism , Phosphopyruvate Hydratase/metabolism , Reperfusion , Time FactorsABSTRACT
Dinitrogen fixation activity was determined directly on experimental plots in mixtures of grass with red and white clover in the year of sowing as well as in the first year of full utilisation using the method of acetylene reduction (ARA). Furthermore, numbers of bacteria, actinomycetes, fungi and Azotobacter sp. were determined in soils under the experimental mixtures.
