Enhanced oxidative stress and the glycolytic switch in superficial urothelial carcinoma of urinary bladder

AbstractObjectiveTo examine whether oxidative stress and the glycolytic switch are correlated to tumor grading, tumor recurrence, and disease progression in urothelial carcinoma (UC) of the urinary bladder (UB).MethodsAll surgical specimens obtained from 27 patients (each containing their UC and normal tissues of UB) were subjected to a pathological examination by computerized tomography, and a portion of each specimen was used for the analysis of molecular biomarkers. The mRNA expression levels of pyruvate dehydrogenase kinase-1 (PDK1), hypoxia-inducible factor 1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase, and glucose transporter protein 1 (Glut-1) were measured using TaqMan-based real-time quantitative polymerase chain reaction. In addition, 8-hydroxy-2-deoxyguanosine (8-OHdG) and the mitochondrial DNA (mtDNA) copy number were also determined.ResultsThe 8-OHdG content and glycolytic genes expression were higher in UC of the UB than those in the normal tissues of UB, whereas the mtDNA copy number was depleted. According to the multivariate analysis, patients with Grade 3 tumors had higher expression levels of HIF-1α, LDHA, and Glut-1 than those with Grades 1 and 2 tumors. In addition, patients with locally recurrent tumors had a higher expression of HIF-1α and LDHA than those with nonrecurrent tumors. Furthermore, patients under disease progression had higher levels of HIF-1α and PDK1 than those not under disease progression.ConclusionsUC of the UB manifested that the glycolytic phenotype would reflect the Warburg effect. We suggest that the molecular mechanism in the regulation of glycolytic switch in UC of the UB might provide a specific biomarker for the future development of cancer diagnosis

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

The recent progress and future of oxygen reduction reaction catalysis: A review

© 2016 Elsevier Ltd Proton Exchange Membrane Fuel Cell (PEMFC) technology is an exciting alternative energy prospect, especially in the field of transportation. PEMFCs are three times as efficient as internal combustion (IC) engines and emit only water as a byproduct. The latter point is especially important in a day and age when climate change is upon us. However, platinum required to catalyze the sluggish oxygen reduction reaction (ORR) which takes place on the cathode of the PEMFC has rendered fuel cell automobiles economically unviable until now. Therefore, the pursuit of an inexpensive replacement for platinum has become an active research area. This review covers the promising progress made in this field since 2011. Some of the more promising catalysts reviewed include alloys such as Pt/Pd nanotubes which outperform their platinum counterpart by nine fold and a Pt/Ni alloy which improves upon Pt activity by 16 times. Platinum-free catalysts such as iron carbide and modified graphene which rival Pt activity are also reviewed

Six-membered ring systems: with O and/or S atoms

A large variety of publications involving O- and S-6-membered ring systems have appeared in 2017. The importance of these heterocyclic compounds is highlighted by the huge number of publications on the total synthesis of natural oxygen derivatives and of other communications dedicated to synthetic derivatives. Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared. Advances in the transition metal-catalyzed synthesis of pyran-2/4-ones (17TL263), N-heterocyclic carbene (NHC)-catalyzed achiral synthesis of pyran-2-one, coumarin and (thio)chromone derivatives (17OBC4731), on the synthesis and transformation of 2H-pyran-2-ones (17T2529) and 2-styrylchromones (17EJO3115) into other heterocyclic compounds, have been surveyed. The strategies to build up the tetrahydropyranyl core of brevisamide (17H(95)81) and the reactions of ketyl radicals, generated from carbonyl derivatives under transition-metal photoredox-catalyzed conditions, leading to isochromen- and chroman-type compounds (17CC13093) were disclosed. Developments in the synthesis of pentafluorosulfanyl(chromene and coumarin) derivatives (17TL4803), photoswitchable D9-tetrahydrocannabinol derivatives (17JA18206), and aminobenzopyranoxanthenes with nitrogen-containing rings (17JOC13626) have been studied.info:eu-repo/semantics/publishedVersio