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A new amide, named dehydropropylpantothenamide (1), was obtained by a co-culture of Nocardia tenerifensis IFM 10554T in the presence of the mouse macrophage-like cell line J774.1 in modified Czapek-Dox (mCD) medium. Compound 1 was synthesized from D-pantothenic acid calcium salt in 6 steps. The absolute configuration of natural compound 1 was determined by comparisons of the optical rotation and CD spectra of synthetic 1. In the present study, a new method for producing secondary metabolites was demonstrated using a "co-culture" in which the genus Nocardia was cultured in the presence of an animal cell line.

B-Cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) is a core component of the polycomb repressive complex 1 (PRC1). Abnormal expression of BMI1 is associated with a number of human malignances and cancer stem cells (CSCs), which cause chemotherapy resistance. Therefore, small molecules that inhibit BMI1 expression are potential candidates for cancer therapy. In this study, a cell-based reporter gene assay was developed that allowed BMI1 promoter activity to be measured in 293T human embryonic kidney cells based on luciferase expression levels. Using this screening assay, the methanol-soluble extracts of Beaumontia murtonii and Eugenia operculata were selected as leads. Bioassay-guided fractionation of the extracts led to the isolation of three known cardenolides (1–3) and one new compound (4) from B. murtonii and two known triterpenoids (5 and 6) and one new compound (7) from E. operculata. These seven compounds inhibited BMI1 promoter activity (IC50 range 0.093–23.0 μM), and the most...

Two new aminocyclitol amide derivatives, nabscessins A (1) and B (2), were isolated from the culture broth of a pathogenic actinomycete species, Nocardia abscessus IFM 10029T. The structures of nabscessins A and B were elucidated by spectral studies, and the compounds showed antifungal activity against Cryptococcus neoformans, with IC50 values of 32 and 16 μg/mL, respectively.

Two new phenazine derivatives, aotaphenazine (1) and 5,10-dihydrophencomycin (2), were isolated from the ethyl acetate extract of Streptomyces sp. IFM 11694. In addition, the known 1-phenazinecarboxylic acid (3), phencomycin (4) and 1,6-phenazinedicarboxylic acid (5) were identified. The structures of the isolated compounds (1-5) were characterized by spectroscopic methods including NMR and mass spectrometry data. Compound 1 showed the ability to overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance at concentration of 12.5 μM. Aotaphenazine (1) enhanced the levels of apoptosis inducing proteins DR4, DR5, p53 and also decreased the levels of cell survival protein Bcl-2 in TRAIL-resistant human gastric adenocarcinoma (AGS) cells in a dose-dependent manner.

The Wnt signal pathway modulates numerous biological processes, and its aberrant activation is related to various diseases. Therefore, inhibition of the Wnt signal may provide an effective (or efficient) strategy for these diseases. Cell-based luciferase assay targeting the Wnt signal (TOP assay) revealed that Hibiscus ficulneus extract inhibited the Wnt signal. The activity-guided isolation of the MeOH extract of H. ficulneus stems yielded four known (1-4) lignans along with myriceric acid (5). Compounds 1-4 potently inhibited the Wnt signal with TOPflash IC50 values of 1.0, 4.5, 6.3, and 1.9 μM, respectively. Compound 1 exhibited cytotoxicity against both Wnt-dependent (HCT116) and Wnt-independent (RKO) cells. Western blot analysis showed that 1 decreased the expression of full, cytosolic and nuclear β-catenin along with c-myc in STF/293 cells. Our results suggested that 1 may have inhibited the Wnt signal by decreasing β-catenin levels.

Purpose : To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line. Methods : M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified by thin layer chromatography (TLC), proton nuclear magnetic resonance (1H NMR) and mass spectrometry (MS). The growth inhibitory activity and mechanism of action of the extracts in HCT116 colon cancer cells were investigated by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blotting. Results : Successive fractions from M. oleifera leaf crude extracts by column chromatography were combined into four pooled batches (MOL1 - MOL4) according to their absorbance at 260 nm and TLC pattern. MOL2 and MOL3 contain astragalin and isoquercetin, respectively. The results from MTT assay indicated that cell proliferation was significantly (p < 0.05) inhibited in a concentration-dependent fashion, especially by MOL2, MOL3 and MOL4. MOL2 and MOL3 exhibited a stronger cell growth inhibition than their major ingredients. The anti-proliferative activity of MOL2 - MOL4 in HCT116 colon cancer cells was mediated by downregulation of ERK1/2 phosphorylation. Conclusion : M. oleifera leaf extract has a strong anti-proliferative activity which is exerted by decreasing ERK1/2 phosphorylation. Thus, the extract has a potential for use in cancer chemoprevention. Keywords : Moringa oleifera , Anti-proliferation, Colon cancer, AKT, ERK1/2 phosphorylation, Chemoprevention

Neurons in the cerebral cortex are not homogeneous. However, neuronal types have been ignored in most previous work studying neuronal processes in behaving monkeys. We propose a new method to identify neuronal types in extracellular recording studies of behaving monkeys. We classified neurons as either bursting or non-bursting, and then classified the bursting neurons into three types: (i) neurons displaying a burst of many spikes (maximum number of spikes within a burst; NSB maxor = 8) at a high discharge rate (maximum interspike interval; ISI max5 ms); (ii) neurons displaying a burst of fewer spikes (NSB maxor = 5) at a high discharge rate (ISI max5 ms); and (iii) neurons displaying a burst of a few spikes (NSB maxor = 7) at relatively long ISIs (ISI max5 ms). We found that the discharge patterns of the four groups corresponded to those of regular spiking (RS), fast spiking (FS), fast rhythmic bursting (FRB) and intrinsic bursting (IB) neurons demonstrated in intracellular recording studies using in vitro slice preparations, respectively. In addition, we examined correlations with the task events for neurons recorded in the frontal eye field and neuronal interactions for pairs of neurons recorded simultaneously from a single electrode. We found that they were substantially different between RS and FS types. These results suggest that neurons in the frontal cortex of behaving monkeys can be classified into four types based on their discharge patterns, and that these four types contribute differentially to cortical operations.

Previous studies have suggested that aging is associated with progressive arterial stiffness and widening of the pulse pressure, and pulse pressure has been found to be a risk factor of cardiovascular diseases. However, the effects of age, blood pressure (including pulse pressure) or atherogenic factors on thoracic aortic wall stiffness in patients with mild atherosis are unclear, so the present study used transesophageal echocardiography to examine 103 consecutive patients with various cardiovascular diseases. The extent of atherosis was evaluated in terms of intima-medial thickness (IMT), and 2 indices of wall stiffness in the aorta were calculated: elastic modulus and stiffness parameter (beta). In subjects with mild atherosis (IMT

We report a case of extraadrenal pheochromocytoma of Zuckerkandl imaged by dynamic magnetic resonance imaging (dynamic MRI) with a 0.5 tesla (T) machine. The dynamic MRI proved useful in disclosing the tumor clearly because of strong enhancement in its early phase. This case has the advantages of dynamic computed tomography (dyanmic CT) as well as of T2-weighted spin-echo (SE) MR images.

Biosynthesis of rabbit red cell carbonic anhydrase isozyme B and C was demonstrated in reticulocyte cell-free lysates by the specific immunoprecipitin reaction. Using this homologous protein synthesis system, it was found that 10−5 to 10−7 M thyroxine preferentially inhibited the synthesis of carbonic anhydrase B isozyme without affecting that of C isozyme. These results suggested that this inhibitory action of the protein synthesis by thyroxine may be responsible for the decreased level of the B type isozymes in human hyperthyroidism or experimental hyperthyroidism of rabbits.

Zinc deficiency states were produced in rabbit erythrocytes by experimentally induced bleeding anemia and hemolytic anemia. Parallel decreases in total zinc levels and the contents for major zinc protein, carbonic anhydrase I and II isozymes were observed in the erythrocytes. During the process of the anemias the zinc status in the erythrocytes varied remarkably and the relative increase of zinc ions other than that derived from carbonic anhydrase was observed, suggesting that the former zinc ions play an important role in forming a zinc pool in the erythrocytes under the anemic conditions.

A patient with a brain infarct was found to have chronic pulmonary embolism associated with perfusion defects on blood flow imaging with N-isopropyl-p-[I-123]iodoamphetamine (I-123 IMP). However, gradually increasing uptake of I-123 IMP was seen in later images, in areas distal to the embolus. The increased uptake to the embolized lung seemed to be through the systemic collateral circulation.

Levels of rabbit erythrocyte carbonic anhydrase B and C isozymes were determined in experimental hyperthyroidism using a quantitative immunologic technique. Levels of erythrocyte 2,3-diphosphoglycerate and protein binding iodine were simultaneously determined. Thyroxine and 3,5,3'-triiodothyronine were administered to rabbits orally for 30 days. A significant decrease in carbonic anhydrase B type was observed after 30 days, although no significant change was observed in carbonic anhydrase C type. These findings suggest that the steady state level of carbonic anhydrase B type in red cells is affected by thyroid hormone more readily than that of carbonic anhydrase C type. The level of red cell 2,3-diphosphoglycerate increased markedly after 10 days of treatment, corresponding to the increase of protein binding iodine. The clinical or pathologic significances were discussed in relation to the changes in the levels of these isozymes and 2,3-diphosphglycerate in red cells.