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Background. Urolithiasis is the process of stone formation in the urinary tract. Its etiology is only partly known, and efficient therapeutic approaches are currently lacking. Metabolomics is increasingly used in biomarkers discovery for its ability to identify mediators of relevant (patho)physiological processes. Amino acids may be involved in kidney stone formation. The aim of the present study was to investigate the presence of an amino acid signature in stone former urine through a targeted metabolomic approach. Methods. A panel of 35 amino acids and derivatives was assessed in urines from 15 stone former patients and 12 healthy subjects by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to define amino acid profiles of cases and controls. Results and Discussion. Our approach led to the definition of a specific amino acid fingerprint in people with kidney stones. A urinary amino acid profile of stone formers was characterized by lower levels of α-aminobutyric acid, asparagine, ethanolamine, isoleucine, methionine, phenylalanine, serine, tryptophan, and valine. Metabolomic analysis may lend insights into the pathophysiology of urolithiasis and allow tracking this prevalent condition over time. [ABSTRACT FROM AUTHOR]

Although histologically benign, adamantinomatous craniopharyngioma (AC) pediatric brain tumor is a locally aggressive disease that frequently determines symptoms and hormonal dysfunctions related to the mass effect on the surrounding structures. Another typical feature of this benign neoplasm is the presence of voluminous liquid cysts frequently associated with the solid component. Even if studies have been devoted to the proteomic characterization of the tumor intracystic fluid, poor explorations have been performed on its solid part, principally investigated by transcriptomics technologies. In the present study, seven specimens of AC whole tumor tissue have been analyzed by LC-MS for a preliminary assessment of the proteomic profile by a top-down/bottom-up integrated approach. Thymosin beta 4, ubiquitin, calmodulin, S100 proteins, prothymosin α isoform 2, alpha-defensins 1-4, and fragments largely belonging to vimentin, hemoglobin, and glial fibrillary acidic protein characterized the intact proteome. The identification of alpha-defensins, formerly characterized in AC intracystic fluid, reinforces the hypothesis of a role for inflammation in tumor pathogenesis. A total number of 1798 unique elements were identified by a bottom-up approach with a special focus on the 433 proteins commonly characterized in the 85.7% of the samples analyzed. Their gene ontology classification evidenced the involvement of the adherence system, intermediate filaments, and actin cytoskeleton in tumor pathogenesis and of elements part of the Wnt, FGF, and EGFR signaling pathways. In addition, proteins involved in calcium modulation, innate immunity, inflammation, CCKR and integrin signaling, and gonadotropin-releasing hormone receptor pathways were also outlined. Further than confirming proteomic data previously obtained on AC intracystic fluid, these results offer a preliminary overview of the AC whole tissue protein phenotype, adding new hints towards the comprehension of this still obscure pediatric brain tumor. [ABSTRACT FROM AUTHOR]

Daudon et al. have developed a complex morphoconstitutional classification of renal stone in six different morphological types and several subtypes. According to this classification, a precise correspondence exists between causes of renal stones and subtypes with a great clinical relevance and can be considering a sort of shortcut for the metabolic diagnosis in renal stone patients. Now the diagnosis of causes of renal stones generally requires repeated biochemical investigations on urine and blood samples and usually remains presumptive. We analyzed 150 urinary stones both by stereoscopic microscopy and Fourier transform infrared spectroscopy. The comparison of 150 stones did not reveal any disagreement. We have only 20 partial agreement, and clinicians agreed that the imprecise information obtained with morphological analysis alone would have missed an important clinical finding only in 3 cases. In conclusion, in our opinion, the analysis of urinary stone must combine two different analytical techniques: morphological analysis by stereomicroscope and biochemical analysis with the FT-IR. [ABSTRACT FROM AUTHOR]

Aim. Lactulose/mannitol ratio is used to assess intestinal barrier function. Aim of this work was to develop a robust and rapid method for the analysis of lactulose and mannitol in urine by liquid chromatography coupled to tandem mass spectrometry. Lactulose/mannitol ratio has been measured in pediatric patients suffering from irritable bowel syndrome. Methods. Calibration curves and raffinose, used as internal standard, were prepared in water : acetonitrile 20 : 80. Fifty μL of urine sample was added to 450 μL of internal standard solution. The chromatographic separation was performed using a Luna NH2 column operating at a flow rate of 200 μL/min and eluted with a linear gradient from 20% to 80% water in acetonitrile. Total run time is 9 minutes. The mass spectrometry operates in electrospray negative mode. Method was fully validated according to European Medicine Agency guidelines. Results and Conclusions. Linearity ranged from 10 to 1000 mg/L for mannitol and 2.5 to 1000 mg/L for lactulose. Imprecision in intra- and interassay was lower than 15% for both analytes. Accuracy was higher than 85%. Lactulose/mannitol ratio in pediatric patients is significantly higher than that measured in controls. The presented method, rapid and sensitive, is suitable in a clinical laboratory. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is the most common malignant brain tumor of pediatric age and is characterized by cells expressing stem, astroglial, and neuronal markers. Among them, stem-like cells (hMB-SLCs) represent a fraction of the tumor cell population with the potential of self-renewal and proliferation and have been associated with tumor poor prognosis. In this context, microRNAs have been described as playing a pivotal role in stem cells differentiation. In our paper, we analyze microRNAs profile and genes expression of hMB-SLCs before and after Retinoic Acid- (RA-) induced differentiation. We aimed to identify pivotal players of specific pathways sustaining stemness and/or tumor development and progression and integrate the results of our recent proteomic study. Our results uncovered 22 differentially expressed microRNAs that were used as input together with deregulated genes and proteins in the Genomatix Pathway System (GePS) analysis revealing 3 subnetworks that could be interestingly involved in the maintenance of hMB-SLCs proliferation. Taken together, our findings highlight microRNAs, genes, and proteins that are significantly modulated in hMB-SLCs with respect to their RA-differentiated counterparts and could open new perspectives for prognostic and therapeutic intervention on MB. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is the most common malignant brain tumor of pediatric age and is characterized by cells expressing stem, astroglial, and neuronal markers. Among them, stem-like cells (hMB-SLCs) represent a fraction of the tumor cell population with the potential of self-renewal and proliferation and have been associated with tumor poor prognosis. In this context, microRNAs have been described as playing a pivotal role in stem cells differentiation. In our paper, we analyze microRNAs profile and genes expression of hMB-SLCs before and after Retinoic Acid- (RA-) induced differentiation. We aimed to identify pivotal players of specific pathways sustaining stemness and/or tumor development and progression and integrate the results of our recent proteomic study. Our results uncovered 22 differentially expressed microRNAs that were used as input together with deregulated genes and proteins in the Genomatix Pathway System (GePS) analysis revealing 3 subnetworks that could be interestingly involved in the maintenance of hMB-SLCs proliferation. Taken together, our findings highlight microRNAs, genes, and proteins that are significantly modulated in hMB-SLCs with respect to their RA-differentiated counterparts and could open new perspectives for prognostic and therapeutic intervention on MB. [ABSTRACT FROM AUTHOR]