Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There is no study about RCC integrating NMR-based metabolomics with transcriptomics. In this work, 1H-NMR spectroscopy combined with multivariate statistics was applied on urine samples, collected from 40 patients with clear cell RCC (ccRCC) before nephrectomy and 29 healthy controls; nine out of 40 patients also provided samples one-month after nephrectomy. We observed increases of creatine, alanine, lactate and pyruvate, and decreases of hippurate, citrate, and betaine in all ccRCC patients. A network analysis connected most of these metabolites with glomerular injury, renal inflammation and renal necrosis/cell death. Interestingly, intersecting metabolites with transcriptomic data from CD133+/CD24+ tumoral renal stem cells isolated from ccRCC patients, we found that both genes and metabolites differentially regulated in ccRCC patients belonged to HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis. Moreover, when comparing urinary metabolome of ccRCC patients after nephrectomy, some processes, such as the glomerular injury, renal hypertrophy, renal necrosis/cell death and renal proliferation, were no more represented.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia associated with alterations in carbohydrate, lipid, and protein metabolism. The prognosis of T2DM patients is highly dependent on the development of complications, and therefore the identification of biomarkers of T2DM progression, with minimally invasive techniques, is a huge need. In the present study, we applied a 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomic approach coupled with multivariate data analysis to identify serum metabolite profiles associated with T2DM development and progression. To perform this, we compared the serum metabolome of non-diabetic subjects, treatment-naïve non-complicated T2DM patients, and T2DM patients with complications in insulin monotherapy. Our analysis revealed a significant reduction of alanine, glutamine, glutamate, leucine, lysine, methionine, tyrosine, and phenylalanine in T2DM patients with respect to non-diabetic subjects. Moreover, isoleucine, leucine, lysine, tyrosine, and valine levels distinguished complicated patients from patients without complications. Overall, the metabolic pathway analysis suggested that branched-chain amino acid (BCAA) metabolism is significantly compromised in T2DM patients with complications, while perturbation in the metabolism of gluconeogenic amino acids other than BCAAs characterizes both early and advanced T2DM stages. In conclusion, we identified a metabolic serum signature associated with T2DM stages. These data could be integrated with clinical characteristics to build a composite T2DM/complications risk score to be validated in a prospective cohort.

cis‐PtCl2(PHCy2)2 (1) reacts at 0 °C in toluene with sodium metal to give the dinuclear PtI complexes cis‐[(PHCy2)(H)Pt(μ‐PCy2)]2 (2) and [(PHCy2)(Cl)Pt(μ‐PCy2)Pt(PHCy2)2](Pt−Pt) (3). On standing in solution, complex 3 isomerizes to trans‐[(PHCy2)(Cl)Pt(μ‐PCy2)2Pt(PHCy2)(H)] (4). When treated with sodium at room temperature, complex 3 transforms into [Pt(μ‐PCy2)(PHCy2)]2(Pt−Pt) (5). The sodium reduction of 1 carried out at room temperature leads to the direct formation of the phosphido bridged dinuclear complex [Pt(μ‐PCy2)(PHCy2)]2(Pt−Pt) (5) along with the mononuclear platinum(II) complex [trans‐Pt(PCy2H)2(PCy2)Cl] (6). Complex 6, which has also been obtained by reaction of 1 with LiPCy2, unambiguously shows by single‐crystal X‐ray diffraction the presence of a pyramidal terminal phosphido ligand. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Four novel hybrid drugs [Pt(acy)2(Me2phen)]I2 (1), [Pt(pen)2(Me2phen)](NO3)2 (2), [Pt(acy)2(phen)](NO3)2 (3), and [Pt(pen)2(phen)](NO3)2 (4) have been prepared by reaction of the antiviral guanine derivatives acyclovir (acy) and penciclovir (pen) with platinum complexes having 2,9‐Me2‐1,10‐phenanthroline (Me2phen) and 1,10‐phenanthroline (phen) as carrier ligands. Both the Me2phen and phen carrier ligands are able to hinder rotation of the guanine bases about the Pt−N(7) bonds rendering the interconversion among rotamers very slow on the NMR time scale. A favourable dipole−dipole interaction between the cis‐coordinated purine bases stabilises the HT rotamers, which are the only species detected in solution. The stability in a physiological medium and the anti‐HIV properties in vitro of the complexes have been evaluated. In a 0.1 M solution of NaCl, the compounds with Me2phen (1 and 2) were found to be very stable while the compounds with phen (3 and 4) underwent displacement of one purine base by a chloride ion. This rather unexpected result may have some relevance in connection with the stability of major DNA adducts of cisplatin in which two guanines are cross‐linked by a Pt(NH3)2 moiety. Although none of the complexes showed anti‐HIV activity, complexes 1 and 2, bearing methyl substituents in the ortho positions of the phenanthroline, were much more cytotoxic than 3 and 4. This is probably due to a greater stability of the former complexes in biological media caused by the presence of the two methyl groups wrapping the metal centre and inhibiting the nucleophilic attack of an incoming ligand at the platinum centre.

The lipid/protein stoichiometries of a naturally crystalline biological membrane, the purple membrane (PM) of Halobacterium salinarum , have been obtained by a combination of 31 P-and 1 H-NMR analyses of the lipid extract. In total, 10 lipid molecules per retinal were found to be present in the PM lipid extract: 2-3 molecules of phosphatidylglycerophosphate methyl ester (PGP-Me), 3 of glycolipid sulfate, 1 of phosphatidylglycerol, 1 of archaeal glycocardiolipin (GlyC), 2 of squalene plus minor amounts of phosphatidylglycerosulfate (PGS) and bisphosphatidylglycerol (archaeal cardiolipin) (BPG) and a negligible amount of vitamin MK8. The novel data of the present study are necessary to identify the lipids in the electron density map, and to shed light on the structural relationships of the lipid and protein components of the PM. -Corcelli, A., V. M. T. Lattanzio, G. Mascolo, P. Papadia, and F. Fanizzi. Lipidprotein stoichiometries in a crystalline biological membrane: NMR quantitative analysis of the lipid extract of the purple membrane.