Mesoscopic heterogeneity in a nanocellulose-containing cell storage medium.

A nanocellulose (NC)-containing medium is a promising candidate for cell storage that allows cell floating without any stirring. We here found that the NC medium was spatially heterogeneous in terms of its rheological properties. The characteristic length of the heterogeneity was a few tens of micrometers and it decreased upon sonication treatment.

Mesoscopic Heterogeneity in Pore Size of Supramolecular Networks.

There has been a considerable interest in developing new types of gels based on a network of fibrous aggregate composed of low molecular weight gelators, also known as supramolecular gels (SMGs). Unlike conventional polymer gels with chemical cross-linking, the network formation in SMGs does not involve any covalent bonds. Thus, the network in SMGs has been often regarded as homogenous or less heterogeneous in comparison with that in chemically cross-linked polymer gels.

Evolution of heterogeneity accompanying sol-gel transitions in a supramolecular hydrogel.

When a peptide amphiphile is dispersed in water, it self-assembles into a fibrous network, leading to a supramolecular hydrogel. When the gel is physically disrupted by shaking, it transforms into a sol state. After aging at room temperature for a while, it spontaneously returns to the gel state, called sol-gel transition.

Sol-gel transition accelerated by the co-assembly of two components in supramolecular hydrogels.

N-Palmitoyl-Gly-His (PalGH) and glycerol 1-monopalmitate (GMP) in water co-assembled into fibrils with twisted ribbon structures and formed a homogeneous network, resulting in gel formation. Shaking the gel easily broke the fibril network leading to a sol in which high and low fibril density regions exist. After a period at room temperature, the higher density regions became interconnected.

NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase 3 inhibitor, suppress the asthmatic response in guinea pigs, with both bronchodilating and anti-inflammatory effects.

We evaluated the effects of NT-702 (parogrelil hydrochloride, NM-702, 4-bromo-6-[3-(4-chlorophenyl) propoxy]-5-[(pyridine-3-ylmethyl) amino] pyridazin-3(2H)-one hydrochloride), a selective phosphodiesterase 3 inhibitor, on the asthmatic response in guinea pigs. NT-702 at a concentration of 1 x 10(-7)M elevated the cyclic adenosine monophosphate content in prostaglandin E(2)-treated guinea pig tracheal smooth muscle cells. Leukotriene (LT) D(4)- and histamine-induced contraction of isolated guinea pig tracheal strips was inhibited by NT-702, with EC(50) values of 3.

Characterization of in vivo and in vitro electrophysiological and antiarrhythmic effects of a novel IKACh blocker, NIP-151: a comparison with an IKr-blocker dofetilide.

We investigated the electrophysiological and antiarrhythmic effects of a novel antiarrhythmic agent, NIP-151, and compared these effects with those of an IKr-blocker dofetilide. NIP-151 potently inhibited acetylcholine-activated K current (IKACh) with an IC50, with 1.6 nM in HEK293 cells expressing the GIRK1/4 channel, but it had little effect on IKr (IC50 = 57.

NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase inhibitor, improves reduced walking distance and lowered hindlimb plantar surface temperature in a rat experimental intermittent claudication model.

NT-702 (parogrelil hydrochloride, NM-702), 4-bromo-6-[3-(4-chlorophenyl)propoxy]-5-[(pyridin-3-ylmethyl)amino]pyridazin-3(2H)-one hydrochloride, a novel phosphodiesterase (PDE) inhibitor synthesized as a potent vasodilatory and antiplatelet agent, is being developed for the treatment of intermittent claudication (IC) in patients with peripheral arterial disease. We assessed the efficacy of NT-702 in an experimental IC model as compared with cilostazol and additionally investigated the pharmacological property in vitro and ex vivo. NT-702 selectively inhibited PDE3 (IC(50)=0.

NIP-141, a multiple ion channel blocker, terminates aconitine-induced atrial fibrillation and prevents the rapid pacing-induced atrial effective refractory period shortening in dogs.

Aims: NIP-141 is a novel multiple ion channel blocker with atrial selective effects. In this study, we examined the effects of NIP-141 on aconitine-induced atrial fibrillation (AF) and rapid atrial pacing-induced atrial effective refractory period (ERP) shortening in dogs.

Methods And Results: Aconitine AF was induced by the application of aconitine on the right appendage.

Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel.

Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031.

Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation.

It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IKACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IKACh to AF remains unknown. We investigated the role of the IKACh channel in canine AF models using tertiapin, a selective IKACh blocker.

A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis.

NIP-004 is a novel synthetic compound developed to display human thrombopoietin (TPO) receptor (c-Mpl) agonist activity. NIP-004 displays species specificity, stimulating proliferation or differentiation of human c-Mpl-expressing cells such as UT-7/TPO and human CD34(+) cells but not murine c-Mpl-expressing cells or cynomolgus monkey cells. To test the mechanism of its action, we constructed mutant forms of c-Mpl; murine c-Mpl(L490H) dis-played a response to NIP-004, whereas human c-Mpl(H499L) lost this response, indicating that histidine in the transmembrane domain of c-Mpl is essential for its activity.

Xanthocillins as thrombopoietin mimetic small molecules.

Four xanthocillins (1-4), including a new compound 4, were isolated from cultured marine fungus Basipetospora sp. as thrombopoietin (TPO) mimics. Compounds 1-4 promoted the proliferation of a TPO-sensitive human leukemia cell line, UT-7/TPO, and UT-7/EPO-mpl, genetically engineered to express c-Mpl, a receptor for TPO in dose-dependent manners.

Atria selective prolongation by NIP-142, an antiarrhythmic agent, of refractory period and action potential duration in guinea pig myocardium.

NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; I(KACh)) expressed in Xenopus oocytes. NIP-142 (10 and 100 microM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle.

A retinoid X receptor antagonist, HX531, improves leptin resistance without increasing plasma leptin level in KK-Ay mice under normal dietary conditions.

4-(5 H -2,3-(2,5-Dimethyl-2,5-hexano)-5-methyl-8-nitrodibenzo[b,e][1,4]diazepin-11-yl)benzoic acid (HX531) is a novel retinoid X receptor antagonist. This study provides evidence that HX531 improves leptin resistance without increasing plasma leptin levels in KK-A y mice, an animal model with high plasma leptin levels and leptin resistance. Under normal dietary conditions, 3 weeks of treatment with HX531 (0.

A novel peroxisome proliferator-activated receptor (PPAR)gamma agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARgamma activation.

NIP-222 is a novel peroxisome proliferator-activated receptor (PPAR)gamma agonist. This study provides evidence that NIP-222 decreases urinary albumin excretion (UAE) in diabetic mice independent of its PPARgamma activation. We compared the effect of NIP-222 and another PPARgamma agonist, troglitazone, on UAE, plasma glucose level, blood pressure, and creatinine clearance (C(cr)) in streptozotocin (STZ)-induced diabetic mice.

Temporal gene expression changes during adipogenesis in human mesenchymal stem cells.

Human bone marrow mesenchymal stem cells (hMSCs) give rise to adipocytes in response to adipogenic hormones. An in-house cDNA microarray representing 3400 genes was employed to characterize the modulation of genes involved in this process. A total of 197 genes showed temporal gene expression changes during adipogenesis, including genes encoding transcriptional regulators and signaling molecules.