Small heterodimer partner deficiency exacerbates binge drinking­induced liver injury via modulation of natural killer T cell and neutrophil infiltration.

Binge drinking among alcohol consumers is a common occurrence, and may result in the development of numerous diseases, including liver disorders. It has previously been reported that natural killer T (NKT) cells induce alcohol­associated liver injury by promoting neutrophil infiltration. In the present study, the role of the orphan nuclear receptor small heterodimer partner (SHP), which is encoded by the NR0B2 gene, in acute binge drinking­induced liver injury was investigated. SHP­knockout (KO) and wild­type (WT) control mice were intragastrically administered single doses of alcohol. The plasma concentrations of alanine aminotransferase and aspartate aminotransferase in SHP­KO mice following alcohol treatment were significantly increased compared with WT mice. However, results of oil red O staining and 2',7'­dichlorodihydrofluorescein diacetate staining indicated that levels of acute binge drinking­associated hepatic lipid accumulation and oxidative stress were not significantly different between WT and SHP­KO alcohol­treated mice. Notably, tumor necrosis factor­α mRNA expression in the liver of SHP­KO mice was significantly increased following alcohol administration, compared with WT mice. Furthermore, the mRNA expression levels of C­C motif chemokine ligand 2, C­X­C motif chemokine ligand 2 and interleukin­4, which are all potent chemoattractants of NKT cells, as well as neutrophil expression levels, were significantly increased in the livers of SHP­KO mice compared with WT mice following alcohol administration, as determined by reverse transcription­quantitative polymerase chain reaction and flow cytometry. Enhanced infiltration of NKT cells, determined by flow cytometry, was also demonstrated in the livers of SHP­KO mice following alcohol administration, compared with WT mice. The results of the present study indicate that SHP may be involved in liver­associated protective mechanisms, with regards to the attenuation of damage caused by acute binge drinking, via regulation of NKT cell and neutrophil migration to the liver. The modulation of SHP may be a novel therapeutic strategy for the treatment of acute binge drinking­induced liver injury.

An injectable collagen/poly(γ-glutamic acid) hydrogel as a scaffold of stem cells and α-lipoic acid for enhanced protection against renal dysfunction.

Mesenchymal stem cells (MSCs) can ameliorate renal injury and accelerate repair of acute kidney injury. Herein, we developed a collagen/poly(γ-glutamic acid) (γ-PGA) hydrogel as an injectable scaffold for the delivery of mouse MSCs (mMSCs) and anti-oxidant drugs into injured sites. By the introduction of γ-PGA into conventional collagen, the viscosity of collagen was reduced at ambient temperature for easy handling, while the elastic and viscous moduli of collagen were increased and a new porous structure was generated near body temperature. When in situ gel-forming collagen/γ-PGA hydrogels loaded with mMSCs and α-lipoic acid (LA) were administered to a mouse model of renal dysfunction, they significantly attenuated the level of blood urea nitrogen and creatinine, which resulted from the increased retention of therapeutic mMSCs and the controlled release of anti-oxidant drugs at the injured site. These findings suggested that this novel type of hydrogel could be applied as an injectable scaffold for use in regenerative medicine.

Anti-atherogenic effect of Humulus japonicus in apolipoprotein E-deficient mice.

Humulus japonicus (HJ) is used as a traditional medicine in Korea owing to its multiple properties including anti-mycobacterial, antioxidant and antihypertensive effects. The present study aimed to examine the anti­inflammatory and anti-atherogenic effects of a methanol extract of HJ. In lipopolysaccharide-stimulated RAW 264.7 cells, HJ significantly suppressed the mRNA expression and secretion of pro-inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1ß and IL-6)], and the release of inflammatory mediators such as nitrite and prostaglandin E2, together with a concomitant decrease in the mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. To examine whether HJ is capable of inhibiting experimental atherogenesis in an animal model, we randomly divided apolipoprotein E-deficient (apoE-/-) mice into three groups: mice fed an atherogenic diet plus vehicle (0.5% carboxymethyl cellulose) as the control vehicle group, and mice fed an atherogenic diet plus either 100 (HJ100) or 500 mg/kg (HJ500) of HJ as the experimental groups. After 12 weeks of HJ administration, lipid accumulation and the formation of atherosclerotic lesions in the aorta (en face) and the aortic sinus markedly decreased in the HJ500 group compared with the corresponding values in the vehicle control group. Moreover, monocyte and macrophage infiltration in the aortic sinus was markedly reduced in the HJ500 group. Reverse transcription-quantitative polymerase chain reaction analysis of the whole aorta showed that the mRNA levels of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, CD68 and IL-18 were significantly decreased in the HJ500 group. Collectively, these findings suggest that HJ may suppress atherosclerosis by inhibiting lipid accumulation and the expression of pro-atherogenic factors, and it may be effective at preventing the development of atherosclerosis.

New class of scorpionate: tris(tetrazolyl)-iron complex and its different coordination modes for alkali metal ions.

We report formation of a new metallascorpionate ligand, [FeL3](3-) (IPtz), containing a Fe core and three 5-(2-hydroxyphenyl)-1H-tetrazole (LH2) ligands. It features two different binding sites, oxygen and nitrogen triangles, which consist of three oxygen or nitrogen donors from tetrazole. The binding affinities of the complex for three alkali metal ions were studied using UV spectrophotometry titrations. All three alkali metal ions show high affinities and binding constants (>3 × 10(6) M(-1)), based on the 1:1 binding isotherms to IPtz. The coordination modes of the alkali metals and IPtz in the solid were studied using X-ray crystallography; two different electron-donor sites show different coordination numbers for Li(+), Na(+), and K(+) ions. The oxygen triangles have the κ(2) coordination mode with Li(+) and κ(3) coordination mode with Na(+) and K(+) ions, whereas the nitrogen triangles show κ(3) coordination with K(+) only. The different binding affinities of IPtz in the solid were manipulated using multiple metal precursors. A Fe-K-Zn trimetallic complex was constructed by assembly of an IPtz ligand, K, and Zn precursors and characterized using X-ray crystallography. Oxygen donors are coordinated with the K ion via the κ(3) coordination mode, and nitrogen donors are coordinated with Zn metal by κ(3) coordination. The solid-state structure was confirmed to be a honeycomb coordination polymer with a one-dimensional infinite metallic array, i.e., -(K-K-Fe-Zn-Fe-K)n-.

CO2/ethylene oxide copolymerization and ligand variation for a highly active salen-cobalt(III) complex tethering 4 quaternary ammonium salts.

A cobalt(III) complex (1) of a salcy-type ligand tethering 4 quaternary ammonium salts, which is thought to act as a highly active catalyst for CO2/propylene oxide (PO) copolymerization, also shows high activity (TOF, 25,900 h(-1); TON, 518,000; 2.72 kg polymer per g cat) and selectivity (>98%) for CO2/ethylene oxide (EO) copolymerization that results in high-molecular-weight polymers (M(n), 200,000-300,000) that have strictly alternating repeating units. The related cobalt(III) complexes 11-14 were prepared through variations of the ligand framework of 1 by replacing the trans-1,2-diaminocyclohexane unit with 2,2-dimethyl-1,3-propanediamine, trans-1,2-diaminocyclopentane, or 1,1'-binaphthyl-2,2'-diamine or by replacing the aldimine bond with ketimine. These ligand frameworks are thought to favour the formation of the cis-ß configuration in complexation, and the formation of the cis-ß configuration in 11-14 was confirmed through NMR studies or X-ray crystallographic studies of model complexes not bearing the quaternary ammonium salts. Complexes 11, 13, and 14, which adopt the cis-ß configuration even in DMSO did not show any activity for CO2/PO copolymerization. Complex 12, which was constructed with trans-1,2-diaminocyclopentane and fluctuated in DMSO between the coordination and de-coordination of the acetate ligand as observed for 1, showed fairly high activity (TOF, 12,400 h(-1)). This fluctuating behaviour may play a role in polymerization. However, complex 12 did not compete with 1 in terms of activity, selectivity, and the catalyst cost.