SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma.

Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.

Accurate oxidation potentials of 40 benzene and biphenyl derivatives with heteroatom substituents.

The redox equilibrium method was used to determine accurate oxidation potentials in acetonitrile for 40 heteroatom-substituted compounds. These include methoxy-substituted benzenes and biphenyls, aromatic amines, and substituted acetanilides. The redox equilibrium method allowed oxidation potentials to be determined with high precision (≤ ±6 mV). Whereas most of the relative oxidation potentials follow well-established chemical trends, interestingly, the oxidation potentials of substituted N-methylacetanilides were found to be higher than those of the corresponding acetanilides. Density functional theory calculations provided insight into the origin of these surprising results in terms of the preferred conformations of the amides versus their cation radicals.

Accurate oxidation potentials of benzene and biphenyl derivatives via electron-transfer equilibria and transient kinetics.

Nanosecond transient absorption methods were used to determine accurate oxidation potentials (E(ox)) in acetonitrile for benzene and a number of its alkyl-substituted derivatives. E(ox) values were obtained from a combination of equilibrium electron-transfer measurements and electron-transfer kinetics of radical cations produced from pairs of benzene and biphenyl derivatives, with one member of the pair acting as a reference. Using a redox-ladder approach, thermodynamic oxidation potentials were determined for 21 benzene and biphenyl derivatives. Of particular interest, E(ox) values of 2.48 +/- 0.03 and 2.26 +/- 0.02 V vs SCE were obtained for benzene and toluene, respectively. Because of a significant increase in solvent stabilization of the radical cations with decreasing alkyl substitution, the difference between ionization and oxidation potentials of benzene is approximately 0.5 eV larger than that of hexamethylbenzene. Oxidation potentials of the biphenyl derivatives show an excellent correlation with substituent sigma+ values, which allows E(ox) predictions for other biphenyl derivatives. Significant dimer radical cation formation was observed in several cases and equilibrium constants for dimerization were determined. Methodologies are described for determining accurate electron-transfer equilibrium constants even when dimer radical cations are formed. Additional equilibrium measurements in trifluoroacetic acid, methylene chloride, and ethyl acetate demonstrated that solvation differences can substantially alter and even reverse relative E(ox) values.