Molecular classification of medulloblastoma (MB) is well-established and reflects the cell origin and biological properties of tumor cells. However, limited data is available regarding the MB tumor microenvironment. Here, we present a mass spectrometry-based multi-omics pilot study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified characteristic tumor markers, including FSTL5, ART3, and FMOD, and revealed a strong prevalence of anti-inflammatory and tumor-promoting proteins characteristic for alternatively polarized myeloid cells in MB samples. The up-regulation of ADAMTS1, GAP43 and GPR37 indicated hypoxic conditions in the CSF of MB patients. This notion was independently supported by metabolomics, demonstrating the up-regulation of tryptophan, methionine, serine and lysine, which have all been described to be induced upon hypoxia in CSF. While cyclooxygenase products were hardly detectable, the epoxygenase product and beta-oxidation promoting lipid hormone 12,13-DiHOME was found to be strongly up-regulated. Taken together, the data suggest a vicious cycle driven by autophagy, the formation of 12,13-DiHOME and increased beta-oxidation, thus promoting a metabolic shift supporting the formation of drug resistance and stem cell properties of MB cells. In conclusion, the different omics-techniques clearly synergized and mutually supported a novel model for a specific pathomechanism.

Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc.

Systemic sclerosis (SSc) is an autoimmune disease with fibrosis of the skin and/or internal organs, causing a decrease in quality of life and survival. There is no causative therapy, and the pathophysiology of the SSc remains unclear. Studies showed that lipid metabolism was relevant for autoimmune diseases, but little is known about the role of lipids in SSc. In the present study, we sought to explore the phospholipid profile of SSc by using the lipidomics approach. We also aimed to analyze lipidomics results for different clinical manifestations of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry for the lipidomic profiling of plasma samples from patients with SSc. Our study showed, for the first time, significant changes in the level of phospholipids such as plasmalogens and sphingomyelins from the plasma of SSc patients as compared to controls. Phosphatidylcholine plasmalogens species and sphingomyelins were significantly increased in SSc patients as compared to controls. Our results also demonstrated a significant association of changes in the metabolism of phospholipids (phosphatidylcholine and phosphatidylethanolamine plasmalogens species and sphingomyelins) with different clinical manifestations of SSc. Further lipidomic studies might lead to the detection of lipids as new biomarkers or therapeutic targets of SSc.

We report on the manufacture of a state-of-the-art heterogeneous non-noble metal catalyst, which is based on a molecularly well-defined phosphine-tagged cobalt corrole complex. This precursor compound is readily synthesized from convenient starting materials while the active material is obtained through wet-impregnation of the pertinent metalliferous macrocycle onto carbon black followed by controlled pyrolysis of the loaded carrier material under an inert gas atmosphere. Thus, the obtained composite was then applied in the heterogeneous hydrogenation of various nitroarenes to yield a vast array of valuable aniline derivatives that were conveniently isolated as their hydrochloride salts. The introduced catalytic protocol is robust and user-friendly with the entire assembly of the reaction set-up enabling the conduction of the experiments on the laboratory bench without any protection from air.

We communicate the assembly of a solid, Ce-promoted Ni-based composite that was applied as catalyst for the hydrogenation of nitroarenes to afford the corresponding organic amines. The catalytically active material described herein was obtained through pyrolysis of a SiO₂-pellet-supported bimetallic Ni-Ce complex that was readily synthesized prior to use from a MeO-functionalized salen congener, Ni(OAc)₂·4 H₂O, and Ce(NO₃)₃·6 H₂O. Rewardingly, the requisite ligand for the pertinent solution phase precursor was accessible upon straightforward and time-saving imine condensation of ortho-vanillin with 1,3-diamino-2,2′-dimethylpropane. The introduced catalytic protocol is operationally simple in that the whole reaction set-up is quickly put together on the bench without the need of cumbersome handling in a glovebox or related containment systems. Moreover, the advantageous geometry and compact-sized nature of the used pellets renders the catalyst separation and recycling exceptionally easy.