NAD Metabolism in Cancer Therapeutics

Cancer cells have a unique energy metabolism for sustaining rapid proliferation. The preference for anaerobic glycolysis under normal oxygen conditions is a unique trait of cancer metabolism and is designated as the Warburg effect. Enhanced glycolysis also supports the generation of nucleotides, amino acids, lipids, and folic acid as the building blocks for cancer cell division. Nicotinamide adenine dinucleotide (NAD) is a co-enzyme that mediates redox reactions in a number of metabolic pathways, including glycolysis. Increased NAD levels enhance glycolysis and fuel cancer cells. In fact, nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis in mammalian cells, is frequently amplified in several cancer cells. In addition, Nampt-specific inhibitors significantly deplete NAD levels and subsequently suppress cancer cell proliferation through inhibition of energy production pathways, such as glycolysis, tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. NAD also serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD gylycohydrolase (CD38 and CD157); thus, NAD regulates DNA repair, gene expression, and stress response through these enzymes. Thus, NAD metabolism is implicated in cancer pathogenesis beyond energy metabolism and considered a promising therapeutic target for cancer treatment. In this review, we present recent findings with respect to NAD metabolism and cancer pathogenesis. We also discuss the current and future perspectives regarding the therapeutics that target NAD metabolic pathways

Leisure-time, occupational, and commuting physical activity and risk of type 2 diabetes in Japanese workers: a cohort study

Table S1. Association between moderate-intensity and vigorous-intensity exercise during leisure and risk of type 2 diabetes. Table S2. Risk of type 2 diabetes associated with specific type of leisure-time exercise. (DOCX 47 kb

Magnetocaloric and Magnetic Properties of Meta‐Magnetic Heusler Alloy Ni41Co9Mn31.5Ga18.5

Ni41Co9Mn31.5Ga18.5 is a magnetic Heusler alloy, which indicates metamagnetic transition at the reverse martensite transition. In this paper, caloric measurements were performed and discussed about magnetocaloric effect. We also performed magnetization measurements around Curie temperature TC in the martensite phase and analyzed by means of the spin fluctuation theory of itinerant electron magnetism. From the differential scanning calorimetry (DSC) measurements in zero fields, the value of the latent heat λ was obtained as 2.63 kJ/kg, and in magnetic fields the value was not changed. The entropy change ΔS was − 7.0 J/(kgK) in zero fields and gradually increases with increasing magnetic fields. The relative cooling power (RCP) was 104 J/kg at 2.0 T, which was comparable with In doped Ni41Co9Mn32Ga16In2 alloy

Image Quality of the Coronary Angiography with Noise Reduction Technology to Decrease the Radiation Dose

We examined the effects of a reduced exposure dose on the quality of images from an angiography device augmented with a noise reduction algorithm. Before its clinical application, we compared the diameter of the discrimination limit of the hole with that in the conventional method by a visual evaluation with a contrast-detail (C-D) phantom imaged using the target dose. Based on the results, a reducible dose was determined and applied clinically. The sample population consisted of patients being followed up after percutaneous coronary intervention (PCI) for coronary artery disease; we evaluated the effects of the exposure reduction on image quality. A significant dose reduction was observed by the noise-reduction method compared to the conventional method; the radiation dose to the flat panel detector (FPD) could be reduced to 70 nGy per frame. Clinically, a dose reduction of approx. 40% was obtained while maintaining image quality almost equal to that of the conventional method

Variational Quantum Algorithm for Non-equilibrium Steady States

We propose a quantum-classical hybrid algorithm to simulate the non-equilibrium steady state of an open quantum many-body system, named the dissipative-system Variational Quantum Eigensolver (dVQE). To employ the variational optimization technique for a unitary quantum circuit, we map a mixed state into a pure state with a doubled number of qubits and design the unitary quantum circuit to fulfill the requirements for a density matrix. This allows us to define a cost function that consists of the time evolution generator of the quantum master equation. Evaluation of physical observables is, in turn, carried out by a quantum circuit with the original number of qubits. We demonstrate our dVQE scheme by both numerical simulation on a classical computer and actual quantum simulation that makes use of the device provided in Rigetti Quantum Cloud Service.Comment: 13 pages, 9 figure

miRNAs regulate SIRT1 expression during mouse embryonic stem cell differentiation and in adult mouse tissues

SIRT1 is increasingly recognized as a critical regulator of stress responses, replicative senescence, inflammation, metabolism, and aging. SIRT1 expression is regulated transcriptionally and post-transcriptionally, and its enzymatic activity is controlled by NAD+ levels and interacting proteins. We found that SIRT1 protein levels were much higher in mouse embryonic stem cells (mESCs) than in differentiated tissues. miRNAs post-transcriptionally downregulated SIRT1 during mESC differentiation and maintained low levels of SIRT1 expression in differentiated tissues. Specifically, miR-181a and b, miR-9, miR-204, miR-199b, and miR-135a suppressed SIRT1 protein expression. Inhibition of mir-9, the SIRT1-targeting miRNA induced earliest during mESC differentiation, prevented SIRT1 downregulation. Conversely, SIRT1 protein levels were upregulated post-transcriptionally during the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. The regulation of SIRT1 protein levels by miRNAs might provide new opportunities for therapeutic tissue-specific modulation of SIRT1 expression and for reprogramming of somatic cells into iPS cells