LET dependence of the formation of oxidative damage 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 2′-deoxyguanosine aqueous solution irradiated with heavy ions

To evaluate the contribution of indirect action mediated by OH radicals in biological effects of high LET radiations, we examined the production of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in 2′-deoxyguanosine aqueous solution using various ion species with an LET range from 20 to 300 keV/μm. The 8-OHdG yield decreased with increasing LET. In the hypoxic irradiation condition, the yield showed constant or rather increasing tendency above about 100 keV/μm, which is consistent with an oxygen-in-the-track hypothesis to explain the diminishment of oxygen effect.     

Enhanced radiation-induced cell killing by Herbimycin A pre-treatment

Herbimycin A (HA), as in Geldanamycin, binds to conserved pockets of heat shock protein 90 (Hsp90) and inhibits its chaperone functions. Hsp90 plays an integral role in cancer cell growth and survival, because it maintains the stability of several key proteins by its chaperone's activity. It is known that some of the proteins associated with radiation responses are functionally stabilized by Hsp90. In this study, we investigated the effect of HA on radiosensitivity in human cancer cells and the mechanism related to the sensitization. In order to gain a mechanistic insight of this sensitization, we examined repair of DNA double-strand breaks (DSBs) in irradiated human cancer cells pre-treated with HA, as unrepaired DSBs are thought to be the main cause of radiation-induced cell death. Cellular radiosensitivity was determined by clonogenic assay, and the DSB rejoining kinetics was examined by constant field gel electrophoresis. SQ-5, a lung squamous carcinoma cell line, showed synergistic increase in radiosensitivity when cells were pre-treated with HA. In addition, HA significantly inhibited repair of radiation-induced DSBs. These results suggest that the combination of HA and ionizing radiation may be a useful therapeutic strategy for treating certain cancer cells.     

Semidefinite complementarity reformulation for robust Nash equilibrium problems with Euclidean uncertainty sets

Consider the N-person non-cooperative game in which each player’s cost function and the opponents’ strategies are uncertain. For such an incomplete information game, the new solution concept called a robust Nash equilibrium has attracted much attention over the past several years. The robust Nash equilibrium results from each player’s decision-making based on the robust optimization policy. In this paper, we focus on the robust Nash equilibrium problem in which each player’s cost function is quadratic, and the uncertainty sets for the opponents’ strategies and the cost matrices are represented by means of Euclidean and Frobenius norms, respectively. Then, we show that the robust Nash equilibrium problem can be reformulated as a semidefinite complementarity problem (SDCP), by utilizing the semidefinite programming (SDP) reformulation technique in robust optimization. We also give some numerical example to illustrate the behavior of robust Nash equilibria.     

Therapeutic targets in the ASK1-dependent stress signaling pathways

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.     

Momentum transfer in nonequilibrium steady states

When a Brownian object interacts with noninteracting gas particles under nonequilibrium conditions, energy dissipation associated with Brownian motion causes an additional force on the object as a "momentum transfer deficit." This principle is demonstrated first by a new nonequilibrium steady state model and then applied to several known models such as an adiabatic piston for which a simple explanation has been lacking.     

Steric‐Factor‐Directed Alternating Supramolecular Copolymer Composed of Hydrogen‐Bonded Cyclohexanetricarboxamide Units

Hydrogen‐bonded supramolecular copolymers were easily prepared by mixing cyclohexanetricarboxamides with three ( 1 ) and six ( 2 ) alkylsilyl groups, and supramolecular fibers were fabricated. When the composition of 1 and 2 was at or close to equimolarity, the supramolecular copolymer chain was found to have an alternating sequence. This was attributed to the fact that the steric factor of the alkylsilyl side chains effectively controls the unit sequence of the supramolecular polymer chain.

     

d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats

Background: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. Objective: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic–euglycemic (HE)-clamp method and intramuscular signaling analysis. Methods: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. Results: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. Conclusions: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.     

Thermo- and pH-responsive gels for application in colon delivery systems

Swelling-controlled drug delivery copolymer gels were synthesized by introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) of pH-responsive methacrylic acid (MA-Ac) into thermo-responsive acryloyl- -proline ethyl ester (A-ProOEt). The threshold of swelling for copolymer gels consisting of A-ProOEt/MA-Gly and A-ProOEt/MA-Ac with a composition of 40/60 mol% was found to be pH 3.0 and pH 5.5, respectively, in buffer solutions at 37°C. The diffusion characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such copolymer gels were evaluated in buffer solutions at pHs more than 5.5, and it was found that A-ProOEt/MA-Gly gel possessed a Case II transport, while the A-ProOEt/MA-Ac gel exhibited a non-Fickian (or anomalous) diffusion behavior under the same conditions.