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Different types of NiMoS/Al2O3 catalysts were prepared by a combination of sonochemical synthesis and chemical vapor deposition (CVD) methods. The performance of the prepared catalysts in the hydrodesulfurization (HDS) of dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT) was compared with that of catalysts prepared using the impregnation method. Ni that was selectively added to the MoS2 surface by CVD promoted the HDS activity to a greater extent than Ni added by impregnation, particularly for the direct-desulfurization (DDS) route of the reaction. This was attributed to the former method allowing an intimate interaction between the added Ni and the MoS2 surface, as confirmed by the XPS analysis of the catalysts. NiMoS/Al2O3 prepared by a combination of two methods, sonochemical and CVD, showed improvement in activity over the catalyst prepared by impregnation. Moreover, the hydrogenation (HYD) activity of the former catalyst was significantly higher than that of the latter due to the dominant effect of sonochemical synthesis on the activity. The improvement in activity was greater for the HDS of 4,6-DMDBT than for the HDS of DBT. [ABSTRACT FROM AUTHOR]

Presents a study that examined the overexpression of syntenin protein in metastatic human breast and gastric cancer cell lines. List of human breast cancer cell lines; Causes of human cancer deaths; Methods for comparing patterns of gene expression; Components of syntenin.

Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor-β superfamily, which is overexpressed in a variety of human cancers, including breast and gastric cancer. The function of MIC-1 in cancer remains controversial and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of ErbB2 in SK-BR-3 breast and SNU-216 gastric cancer cells. MIC-1 induced a significant phosphorylation of Akt and ERK-1/2, and also effected an increase in the levels of tyrosine phosphorylation of ErbB1, ErbB2 and ErbB3 in SK-BR-3 and SNU-216 cells. The treatment of these cells with AG825 and AG1478, inhibitors specific for ErbB2 tyrosine kinase, resulted in the complete abolition of MIC-1-induced Akt and ERK-1/2 phosphorylation. Furthermore, the small-interfering RNA-mediated downregulation of ErbB2 significantly reduced not only the phosphorylation of Akt and ERK-1/2 but also the invasiveness of the cells induced by MIC-1. Our results show that ErbB2 activation performs a crucial function in MIC-1-induced signaling pathways. Further investigations revealed that MIC-1 induced the expression of the hypoxia inducible factor-1α protein and the expression of its target genes, including vascular endothelial growth factor, via the activation of the mammalian target of rapamycin (mTOR) signaling pathway. Stimulation of SK-BR-3 with MIC-1 profoundly induces the phosphorylation of mTOR and its downstream substrates, including p70S6K and 4E-BP1. Collectively, these results show that MIC-1 may participate in the malignant progression of certain human cancer cells that overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. [ABSTRACT FROM AUTHOR]

Rubradirin, an ansamycin antibiotic has been purified from Streptomyces achromogenes var. rubradiris NRRL3061. It consists of four distinct structural moieties, rubransarol, 3- amino-4-hydroxy-coumarin, dihydroxydipicolinic acid, and 2,6-dideoxynitrosugar (DNS). Polymerase chain reaction (peR) primers were designed based on consensus sequences of dTDP-D-glucose 4,6-dehydratase, one of enzymes involved in the biosynthesis of 2,6-dideoxysugar. A peR product was obtained from S. achromogenes var. rubradiris. Hybridization of the peR product to a cosmid library constructed from S. achromogenes genomic DNA has led to the identification of three unlinked regions of DNA. One of three kinds of cosmid clones contains homologues of dTDP-D-glucose 4,6-dehydratase, 3-amino- 5-hydroxybenzoic acid (AHBA) synthase, and eryA genes. The size of the gene homologous to eryA is 30 kb, and the AHBA synthase gene homologue resides between the eryA homologous genes. A gene cluster of rubransarol and 2,6-dideoxynitrosugar is around 50 kb. Sequencing of the peR product from the AHBA synthase gene homologue isolated from S. achromogenes revealed 85 % amino acid sequence homology (73/86) with the AHBA synthase from a rifamycin-producer. dTDP-D-glucose 4,6-dehydratase gene homologue was sub cloned from one of the isolated cosmid clones and sequenced. It showed 65 % homology (43/66) with dTDP-D-glucose 4,6-dehydratase from a streptomycin-producer. [ABSTRACT FROM AUTHOR]

This study was undertaken to suggest an effective fisheries resources management system by using stock assessment and potential yield analyses of crucian carp population in the mid-upper system of the Seomjin River. Fieldwork was conducted seasonally from 2008 to 2009 in the mid-upper system of the Seomjin River. The stock assessment was carried out by the swept area method and the potential yield was estimated by improved fisheries resource potential estimation system based on the Allowable Biological Catch. Also, the yield-per-recruit analysis was used to review the efficient management implication of the resource, Carassius auratus. As a result, the age at first capture (tc) was estimated as 1.468 year, converted body length (BL) was 10.8 cm. Meaning the current fishing intensities, the instantaneous coefficient of fishing mortality (F) was 0.067 year-1, and the yield-per-recruit analysis showed that the current yield per recruit was estimated to be 15.999 g with F and tc. The instantaneous rate of fishing mortality that provides for Allowable Biological Catch (FABC) based on the current tc and F was estimated as 0.618 year-1. Therefore, the optimum fishing intensities could be achieved at the higher fishing intensity for Carassius auratus. The calculated annual stock of C. auratus was estimated as 7,608 kg, and the potential yield was estimated as 343 kg with tc and F at the fixed current level. Using yield-per-recruit analysis, if F and tc were set at 0.618 year-1 and 2 year, the yield per recruit and total allowable catch would be predicted to increase to 62 g and 2,531 kg by about 3.9 times and 7.3 times, respectively. [ABSTRACT FROM AUTHOR]

Background: Cryptopleurine, a phenanthroquinolizidine alkaloid, was known to exhibit anticancer activity; however, the underlying mechanism is poorly understood. Because the nuclear factor- κB (NF- κB) transcription factors control many physiological processes including inflammation, immunity, and development and progression of cancer, we investigated the effects of cryptopleurine on tumor necrosis factor alpha (TNF- α)-induced NF- κB activation pathway and on the expression of NF- κB-regulated gene products associated with many pathophysiological processes. Methodology and Principal Finding: MDA-MB231, MDA-MB435, MCF-7, HEK293, RAW264.7 and Hep3B cells were used to examine cryptopleurine's effect on the NF- κB activation pathway. Major assays were promoter-reporter gene assay, electrophoretic mobility shift assay (EMSA), in vitro immune complex kinase assay, real-time PCR, Western blot analysis, and Matrigel invasion assay. Experiments documenting cell proliferation and apoptosis were analyzed by MTT method and flow cytometry, respectively. The results indicated that cryptopleurine suppressed the NF- κB activation through the inhibition of I κB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF- κB alpha (I κB α) and the nuclear translocation and DNA-binding activity of p65. The suppression of NF- κB by cryptopleurine led to the downregulation of gene products involved in inflammation, cell survival, proliferation, invasion, and angiogenesis. Conclusions and Significance: Our results show that cryptopleurine inhibited NF- κB activation pathway, which leads to inhibition of inflammation, proliferation, and invasion, as well as potentiation of apoptosis. Our findings provide a new insight into the molecular mechanisms and a potential application of cryptopleurine for inflammatory diseases as well as certain cancers associated with abnormal NF- κB activation. [ABSTRACT FROM AUTHOR]

The four overlapping cosmids from the rubradirin producer , Streptomyces achromogenes var rubradiris NRRL 3061, have 58 ORFs within a 105.6 kb fragment. These ORFs harbored essential genes responsible for the formation and attachment of four distinct moieties, along with the genes associated with regulatory, resistance, and transport functions. The PKS ( rubA) and glycosyltransferase ( rubG2) genes were disrupted in order to demonstrate a complete elimination of rubradirin production. The rubradirin biosynthetic pathway was proposed based on the putative functions of the gene products, the functional identification of sugar genes, and the mutant strains. [ABSTRACT FROM AUTHOR]

A new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines, was produced by hybrid biosynthetic approach. We investigated ID6105-induced apoptosis and in vivo efficacy on experimental tumors, and also defined its optimal dosing schedule. From PARP cleavage assay and caspase-3 activation assay, we found that ID6105 can induce apoptosis in tumor cells and its ability was superior to doxorubicin. In human tumor xenograft models, ID6105 showed greater antitumor effects on SW620 and NCI-H23 than doxorubicin. The 1 mg/kg of ID6105 treatment reduced size of tumor by 93% in NCI-H23 model whereas doxorubicin (2 mg/kg) showed only 39% inhibition rate. In SW620 model, 0.3 mg/kg of ID6105 proved to be comparable to 2 mg/kg of doxorubicin. Testing with several dosing schedule such as qd10, qd5, and q4d3, we decided intravenous qd5 treatment was an optimal schedule as a dose regimen of ID6105. In conclusion, ID6105 is a potent apoptosis-inducing anthracycline and effective in treatment of tumors with qd5 dosing schedule. [ABSTRACT FROM AUTHOR]

Structural modification of a compound discovered during screening using an HRE-dependent reporter assay has revealed a novel class of HIF-1 inhibitors, which potently inhibit the HIF-1 protein accumulation and its target gene expression under hypoxic conditions in human hepatocellular carcinoma Hep3B cells. [ABSTRACT FROM AUTHOR]

Hybrid biosynthetic approach produced a new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines. Like other anthracyclines, ID6105 has the inhibitory effects on DNA synthesis as well as topoisomerase II. As preclinical studies of ID6105, we investigated ID6105’s efficacy on human tumors, and cardiotoxicity. In human tumor xenografts, the ID6105’s antitumor effects were greater than other anticancer drugs. ID6105 induced tumor regression in Hep G2 human hepatoma model, and slowed down the tumor growth rates in several tumor models. Doxorubicin-refractory tumors such as PC-3, DU-145, and CX-1 were sensitive to ID6105, and the growth of EKVX, lung cancer, which did not respond to paclitaxel, was also inhibited by ID6105, but tumor mass in CFPA, MCF7, and HCT-15 was not reduced by ID6105. The cardiotoxicity of ID6105 has also been assessed in rats. ID6105 did not induce any remarkable histopathological changes in hearts, and its lipid peroxidation in rat cardiac muscles did not occur as much as doxorubicin, indicating that the cardiotoxicity of ID6105 is remarkably lower than that of doxorubicin. Taking all into account, our results suggest that ID6105 would be a promising candidate for a novel anthracycline chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

Mannasantin B, a dilignan structurally related to manssantin A, is an inhibitor of NF-κB transactivation. In the present study, we found that it inhibited PMAinduced expression of IL-1β, IL-1β mRNA, and IL-1β promoter activity in U937 cells with IC50 values of about 50 nM. It also inhibited NF-IL6- and NF-κBinduced activation of IL-1β, with IC50 values of 78 nM and 1.6 μM, respectively, revealing a potent inhibitory effect on NF-IL6. Electrophoretic mobility shift assays showed that manassantin B had an inhibitory effect on DNA binding by NF-IL6, but not by NF-κB. Further analysis revealed that transactivation by NF-IL6 was also inhibited. Our results indicate that manassantin B suppresses expression of IL-1β in promonocytic cells by inhibiting not only NF-κB but also NF-IL6 activity. Furthermore, our observations suggest that manassantin B may be clinically useful as a potent inhibitor of NF-IL6 activity. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether Eleutherococcus senticosus stems could attenuate D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice. E. senticosus, known as Siberian ginseng, is a popular folk medicine used as a tonic in Asia. Preparations of E. senticosus used in this study were as follows; (i) 70% ethanol extract (ii) water extract (iii) ethanol-soluble part of the water extract (iv) polysaccharide obtained as an 80% ethanol insoluble of the water extract. Preparations were given by intraperitoneal (300 mg/kg and 50 mg/kg) or oral (300 mg/kg) injection at 12 hr and 1 hr before a D-galactosamine/lipopolysaccharide injection. The intraperitoneal injection of water extract and polysaccharide significantly lowered serum levels of tumour necrosis factor-α, aspartate transaminase and alanine transaminase, improved the histologic changes in liver, inhibited hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA fragmentation assay, and suppressed the lethality induced by D-galactosamine/lipopolysaccharide. The oral administration of water extract and polysaccharide also reduced serum aspartate transaminase, alanine transaminase and tumour necrosis factor-α levels. In contrast 70% ethanol extract and ethanol-soluble part of the water extract had no protective effect when treated intraperitoneally or orally. These results indicate E. senticosus stems attenuate fulminant hepatic failure induced by D-galactosamine/lipopolysaccharide in mice and the protective effect is due to water-soluble polysaccharides in E. senticosus stems. [ABSTRACT FROM AUTHOR]

Examines the synthesis of 4-acetylisocoumarin. Transformation of homophthalate into vinylogous amide ester; Ratio of acetyliocoumarin and formylisocoumarin after treatment of compound 13; Enantioselective reduction of AGI-7 by borane.

This article presents a study on the inactivation of the carbamoyltransferase gene which refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent, geldanarnycin. Geldanamycin and its closely related analogues, herbimycin B and macbecin, are naturally occurring antitumor antibiotics. Geldanamycin binds to the N-terminal ATP binding site of heat-shock protein (Hsp) 90, inhibiting its chaperone activity. Because Hsp90 client proteins are important in signal transduction and transcription, geldanamycin and its derivatives have the potential of serving as chemotherapeutic agents in a number of diseases.