Potentiation of cadmium-induced cytotoxicity by sulfur amino acid deprivation through activation of extracellular signal-regulated kinase1/2 (ERK1/2) in conjunction with p38 kinase or c-jun N-terminal kinase (JNK). Complete inhibition of the potentiated toxicity by U0126 an ERK1/2 and p38 kinase inhibitor.

The mechanisms of cadmium-induced toxicity may include oxidative stress, altered redox homeostasis, and injuries to organelles. The current study was designed to study the effect of decreased cellular glutathione (GSH) content by sulfur amino acid deprivation on cadmium toxicity and to identify the signaling pathways responsible for the cytotoxicity. GSH content was increased by cadmium in H4IIE cells prior to cell death, which was prevented by excess GSH or cysteine. Cell viability, however, was not improved by GSH or cysteine complexation of cadmium. Cadmium-induced cytotoxicity was 40-fold potentiated in cells with decreased GSH by sulfur amino acid deprivation. Cadmium in combination with decreased GSH markedly increased apoptotic cell death. Mitogen-activated protein kinases including extracellular signal-regulated kinase 1/2, p38 kinase and c-Jun N-terminal kinase (JNK) were all activated 1-12 hr after sulfur amino acid deprivation. U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), which inhibited activation of extracellular signal-regulated kinase1/2 and p38 kinase in cells under sulfur amino acid deprivation, completely prevented potentiation in Cd-induced cytotoxicity and apoptosis. Potentiation of cadmium toxicity by sulfur amino acid deprivation was prevented in part by either PD98059 or SB203580, or in cells stably expressing dominant negative mutant of JNK1, and to greater extents by PD98059 in combination with either SB203580 or JNK1(-) transfection. These results demonstrated that decreased cellular GSH content potentiated cytotoxicity induced by cadmium at the level of human exposure, and that the potentiation of cytotoxicity resulted from activation of extracellular signal-regulated kinase1/2 in conjunction with p38 kinase or JNK.     

A new acylglycosyl sterol from quisqualis fructus

A new acylglycosyl sterol (4) was isolated from the MeOH extract of Quisqualis Fructus together with four known compounds. On the basis of spectroscopic data, their structures were elucidated as clerosterol (1), betulinic acid (2), methylursolate (3), 3-O-[6'-O-(8Z-octadecenoyl)-beta-D-glucopyranosyl]-clerosterol (4) and alpha-xylofuranosyluracil (5).     

South Korean alcohol free associations: negative expectancy not predicting drinks per occasion

Introduction and Aims. Cultural and biological particulars existing in East Asian countries are likely to mediate differences in the alcohol consumption experience. Despite this no research to date has directly explored the alcohol free association or expectancy of any East Asian nations. The current research aims to provide a set of South Korean alcohol expectancies. Design and Methods. Two hundred and thirty‐seven South Koreans participated in an alcohol free association test and completed a demographic survey. Results. The results both confirmed and contradicted areas of past alcohol expectancy research. There appears to be differences in associates with high probability of recall and alcohol expectancy, where negative, negative sedating and sedating expectancy categories were not found to be predictors of South Korean drinker level. Discussion and Conclusion. The results suggest that South Koreans have a more even level of negative expectancy across all drinker categories, possibly due to a combination of linguistic, cultural and biological difference found among this population. The results provide a list of South Korean alcohol free association norms for future alcohol research in the region, with the results also underlining the need for alcohol free association tests among East Asian nations.[Mahoney BJ, Graham D, Cottrell D, Kim K‐Y. South Korean alcohol free associations: Negative expectancy not predicting drinks per occasion. Drug Alcohol Rev 2012;31:469–476]     

Enhanced protection of Ins-1 β cells from apoptosis under hypoxia by delivery of DNA encoding secretion signal peptide-linked exendin-4

In this study, we developed an expression system of exendin-4, a glucagon-like peptide (GLP-1) analog, using a secretion signal peptide (SP) to facilitate exendin-4 secretion. For delivery of the exendin-4 expression system, high-molecular-weight polyethylenimine (25 kDa, PEI25k), low-molecular-weight polyethylenimine (2 kDa, PEI2k), and polyamidoamine (PAMAM) dendrimers were evaluated as gene carriers to Ins-1 β cells. As a result, PEI25k showed the highest transfection efficiency. For the construction of the exendin-4 expression vector, DNA coding the SP sequence was inserted upstream of the exendin-4 cDNA, resulting in the construction of pβ-SP-Ex-4. Transfection assay showed that the secretion level of exendin-4 increased in the pβ-SP-Ex-4 transfected cells, compared with the pβ-Ex-4 transfected cells. To identify the β-cell protection effect of pβ-SP-Ex-4 delivery, the Ins-1 β cells were transfected with pβ-SP-Ex-4 or pβ-Ex-4 and incubated under normoxia or hypoxia. An MTT assay showed that the pβ-SP-Ex-4 transfected cells had higher β-cell viability than the pβ-Ex-4 transfected cells under hypoxia. In addition, the pβ-SP-Ex-4 transfected cells exhibited lower caspase-3 activity than the pβ-Ex-4 transfected cells. Therefore, PEI25k/pβ-SP-Ex-4 complex may be useful to protect isolated β cells from apoptosis during transplantation.     

Hypoglycemic activity of medicinal plants

The hypoglycemic activity of water extracts of fifty six medicinal plants were evaluated in the streptozotocin-induced diabetic mice. Twelve medicinal plants have significantly antidiabetic activity; Mori Radicis Cortex, Kwang Fang Chi Radix, Paeoniae Radix, Eugeniae Flos, Atractylodis Rhizoma, Ophiopogonis Tuber, Rosae multiflorae Fructus, Glycyrrhizae Radix, Tetrapanacis Medulla, Bigno, Forsythiae Fructus and Sophorae Radix.     

Comparison of TGF-β, PDGF,and CTGF in hepatic fibrosis models using DMN,CCl4, and TAA

Three chemotoxins including dimethylnitrosamine (DMN), carbon tetrachloride (CCl₄), and thioacetamide (TAA) are commonly used in hepatofibrotic models. We aimed to draw characteristics of histopathology and pro-fibrogenic cytokines including TGF-β, PDGF and CTGF among three models. Rats were divided into six groups and intra-peritoneally injected with DMN (10?mg/kg, for three weeks, three consecutive days weekly), CCl₄ (1.6?g/kg, for 10 weeks, twice weekly), TAA (200?mg/kg, for 12 weeks, twice weekly) or their corresponded treatment for each control group. The liver weights were decreased in DMN model, but not other models. Ascites were occurred as 3-, 2-, and 7-rats in DMN, CCl₄, and TAA model, respectively. The lipid peroxidation was highest in CCl₄ model, serum levels of liver enzymes were increased as similar severity. The hepatofibrotic alterations were remarkable in DMN and TAA model, but not CCl₄ as evidenced by the Masson trichrome staining and hydroxyproline. The immunohistochemistry for α-SAM showed that the DMN model was most severely enhanced than other models. On the other hand, hepatic tissue levels of pro-fibrogenic cytokines including TGF-β, PDGF, and CTGF were generally increased in three models, but totally different among models or measurement resources. Especially, serum levels of three cytokines were remarkably increased by CCl₄ injection and CTGF levels in both hepatic tissue and serum were highest in CCl₄ group. Our results firstly demonstrated comparative study for features of morphological finding and pro-fibrogenic cytokines in serum and hepatic protein levels among three models. Above results would be a helpful reference for hepatofibrotic studies.     

Excavation of lead compounds that inhibit mast cell degranulation by combinatorial chemistry and activity-guided

An allergic reaction ensues after antigen binds to mast cell or basophil high affinity IgE receptor, Fc epsilonRI, resulting in degranulation of various inflammatory mediators that produce various allergic symptoms. In this study, i) we isolated the active component for the inhibition of mast cell degranulation from the extract of leaves of Castanea crenata and identified it as quercetin; ii) we established the total synthesis procedure of quercetin; iii) using quercetin as positive control, we excavated some lead compounds that possess inhibitory activities for mast cell degranulation by screening the chemical libraries of 1,3-oxazolidine derivatives prepared by solid phase combinatorial chemistry. Some of 1,3-oxazolidine compounds possessing acetyl and 3',4'-dichlorophenyl group displayed strong inhibitory activities on Fc epsilonRI-mediated mast cell degranulation, suggesting that they can be used as lead compounds for the development of anti-allergic agents.     

Hepatoprotective effect of lactic acid bacteria, inhibitors of β-glucuronidase production against intestinal microflora

The hepatoprotective activity of lactic acid bacteria (Lactobacillus brevis HY7401, Lactobacillus acidophilus CSG and Bifidobacterium longum HY8001), which inhibited beta-glucuronidase productivity of intestinal microflora, on t-BHP- or CCl4-induced hepatotoxicity of mice were evaluated. These oral administration of lactic acid bacteria lowered beta-glucuronidase production of intestinal microflora as well as Escherichia coli HGU-3. When lactic acid bacteria at a dose of 0.5 or 2 g (wet weight)/kg was orally administered on CCl4-induced liver injury in mice, these bacteria significantly inhibited the increase of plasma alanine transferase and aspartate transferase activities by 17-57% and 57-66% of the CCl4 control group, respectively. These lactic acid bacteria also showed the potent hepatoprotective effect against t-BHP-induced liver injury in mice. The inhibitory effects of these lactic acid bacteria were more potent than that of dimethyl diphenyl bicarboxylate (DDB), which have been used as a commercial hepatoprotective agent. Among these lactic acid bacteria, L. acidophilus CSG exhibited the most potent hepatoprotective effect. Based on these findings, we insist that an inhibitor of beta-glucuronidase production in intestine, such as lactic acid bacteria, may be hepatoprotective.