Gender difference in the relationship between anemia and vitamin D in Korean adults: the fifth Korea National Health and Nutrition Examination Survey.

This study was conducted to assess the relationship between vitamin D deficiency and anemia, by gender, in Korean adults. The data of 16,060 adults were analyzed (men, 6,840; premenopausal women, 4,916; postmenopausal women, 4,340) from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V) (2010-2012). There were several key findings. First, after adjusting for related variables, the odds ratio (OR) of anemia [hemoglobin (Hb) <13 g/dl in men or Hb <12 g/dl in women] using the vitamin D normal group {25-hydroxyvitamin [25(OH)D] ≥15.0 ng/ml} as reference, was significant for the vitamin D deficient group [25(OH)D <15.0 ng/ml] in the overall population [OR, 1.310; 95% confidence interval (CI), 1.168-1.470]. Second, the OR of anemia, using the vitamin D normal group as reference, was significant for the vitamin D deficient group in premenopausal women (OR, 1.293; 95% CI, 1.105-1.513). However, vitamin D deficiency in the vitamin D normal group in men (OR, 1.093; 95% CI, 0.806-1.484) and postmenopausal women (OR, 1.130; 95% CI, 0.906-1.409) was not significant. In conclusion, Vitamin D deficiency is positively associated with anemia in premenopausal women, but not in men and postmenopausal women.

The effects of aroma massage and foot bath on psychophysiological response in stroke patients.

[Purpose] This research aimed to examine the effects of back massage and foot bath with blended essential oil on psychophysiological response in stroke patients. [Subjects and Methods] The subjects were 14 adult stroke patients randomly divided into the experimental group (7 patients) and the control group (7 patients). Physical and psychological stress, mood state and sleep satisfaction was measured using evaluation instruments and body temperature was measured with infrared thermography (T-1000). [Results] Measurements included physical and psychological stress, and mood state of the experiment group became significantly lower than that of the control group. The body temperature and sleeping satisfaction of the experimental group became significantly higher than that of the control group. [Conclusion] The present study suggested that aroma therapy and foot bath that can be used as alternative physical therapy that offers an overall beneficial effect on psychophysiological response such as reduced stress, mood state and increased body temperature, sleeping satisfaction of stroke patients.

Comprehensive chemical profiling of Pinellia species tuber and processed Pinellia tuber by gas chromatography-mass spectrometry and liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

A comprehensive profiling method was established for the determination of various chemicals in Pinellia (P.) ternata and pedatisecta species. The profiling method comprises a fast ultrasonic extraction with various solvents, followed by GC-MS and LC-APCI-MS analysis. A total of 73 polar components as trimethylsilyl (TMS) derivatives were detected in methanol extract by GC-MS. The main components of the P. species were profiled as several kinds of fatty acids, amino acids, nucleic acids, carbohydrates, and phenolic compounds. The hexane extract was analyzed by LC-APCI-MS for the lipid profiling. A total of 35 lipid constituents [fatty acids and their esters, mono-, di-, and tri-acylglycerols] and four phytosterols were observed and tentatively characterized by LC-APCI-MS/MS. Among the phytochemicals detected in the hexane extract, triacylglycerols (TAGs) as the major component were identified by LC-APCI-MS and MS/MS. Based on the identified components, a significant difference in the chemical compositions of P. species tuber and processed P. ternata was found that the complete disappearance of TAGs and a considerable decrement of sucrose were observed in processed P. ternata. Furthermore, the degradation mechanism for TAGs in the presence of alum solution is suggested to occur during the processing P. ternata. Malic acid was found to be a characteristic compound for the classification of P. ternata and pedatisecta with different geographic origins. Based on the validated GC/MS method, twenty-four P. ternata, processed P. ternata and P. pedatisecta samples were profiled to measure the overall abundance of specific groups of compound and to identify diagnostic compounds. In addition, principal component analysis (PCA) on the GC/MS profiling data revealed a clear classification of P. species samples. In this study, the full chemical complement was for the first time reported for quality evaluation of P. species. The method can be usefully applied for phytochemical analysis of related herbal medicines.

Crystal Structure of C-Terminal Coiled-Coil Domain of SYCP1 Reveals Non-Canonical Anti-Parallel Dimeric Structure of Transverse Filament at the Synaptonemal Complex.

The synaptonemal complex protein 1 (SYCP1) is the main structural element of transverse filaments (TFs) of the synaptonemal complex (SC), which is a meiosis-specific complex structure formed at the synapse of homologue chromosomes to hold them together. The N-terminal domain of SYCP1 is known to be located within the central elements (CEs), whereas the C-terminal domain is located toward lateral elements (LEs). SYCP1 is a well-known meiosis marker that is also known to be a prognostic marker in the early stage of several cancers including breast, gliomas, and ovarian cancers. The structure of SC, especially the TF structure formed mainly by SYCP1, remains unclear without any structural information. To elucidate a molecular basis of SC formation and function, we first solved the crystal structure of C-terminal coiled-coil domain of SYCP1. The coiled-coil domain of SYCP1 forms asymmetric, anti-parallel dimers in solution.

Nocarimidazoles A and B from a Marine-Derived Actinomycete of the Genus Nocardiopsis.

Chemical investigation of a marine-derived actinomycete isolated from marine sediments collected off the coast of southern California and identified as a Nocardiopsis sp. (strain CNQ115) led to the isolation of two new 4-aminoimidazole alkaloids, nocarimidazoles A (1) and B (2). The chemical structures of nocarimidazoles A and B were assigned by interpretation of NMR spectroscopic data and through methylation to yield monomethyl and dimethyl derivatives. Nocarimidazoles A and B possess a 4-aminoimidazole ring combined with a conjugated carbonyl side chain, which is rarely found in microbial secondary metabolites.

Development of Inhibitors of Salicylic Acid Signaling.

Salicylic acid (SA) plays important roles in the induction of systemic acquired resistance (SAR) in plants. Determining the mechanism of SAR will extend our understanding of plant defenses against pathogens. We recently reported that PAMD is an inhibitor of SA signaling, which suppresses the expression of the pathogenesis-related PR genes and is expected to facilitate the understanding of SA signaling. However, PAMD strongly inhibits plant growth. To minimize the side effects of PAMD, we synthesized a number of PAMD derivatives, and identified compound 4 that strongly suppresses the expression of the PR genes with fewer adverse effects on plant growth than PAMD. We further showed that the adverse effects on plant growth were partially caused the stabilization of DELLA, which is also related to the pathogen responses. These results indicate that compound 4 would facilitate our understanding of SA signaling and its cross talk with other plant hormones.

Crystal structure of human POP1 and its distinct structural feature for PYD domain.

Inflammatory caspases, such as caspase-1, which is critical for the innate immune response, are activated upon the formation of a molecular complex called the inflammasome. The inflammasome is composed of three proteins, the Nod-like receptor (NLRP, NLRC or AIM2), apoptosis associated speck-loke protein containing a caspase-recruitment domain (ASC), and caspase-1. ASC is an adaptor molecule that contains an N-terminal PYD domain and a C-terminal CARD domain for interaction with other proteins. Upon activation, the N-terminal PYD of ASC homotypically interacts with the PYD domain of the Nod-like receptor, while its C-terminal CARD homotypically interacts with the CARD domain of caspase-1. PYD only protein 1 (POP1) negatively regulates inflammatory response by blocking the formation of the inflammasome. POP1 directly binds to ASC via a PYD:PYD interaction, thereby preventing ASC recruitment to Nod-like receptor NLRPs. POP1-mediated regulation of inflammation is of great biological importance. Here, we report the crystal structure of human POP1 and speculate about the inhibitory mechanism of POP1-mediated inflammasome formation based on the current structure.

Smooth muscle relaxation activity of an aqueous extract of dried immature fruit of Poncirus trifoliata (PF-W) on an isolated strip of rat ileum.

We demonstrated that an aqueous extract of dried immature fruit of Poncirus trifoliate (PF-W) produces relaxation of intestinal smooth muscle using the ileac strips of a rat. Furthermore, the underlying mechanism of its relaxant activity was investigated. PF-W was prepared using the standard extraction protocol. A 1.5 - 2 cm long rat ileac strip was placed in an organ bath with Tyrode's solution and smooth muscle contractility was recorded by connecting it to a force transducer. Various compounds were added to the organ baths, and changes in muscular contractility were measured. PF-W concentration-dependently induced relaxation of rat ileac strips that were contracted both spontaneously and via acetylcholine treatment. Various potassium channel blockers did not inhibit the relaxation by PF-W. No difference in the effect of PF-W was observed between ileac strips treated with low (20 mM) and high concentrations (60 mM) of KCl. PF-W inhibited the contraction of rat ileac strips induced by extracellular calcium. PF-W acts as a potent smooth muscle relaxant, implicating its possible action as a rapid acting reliever for abdominal pains and a cure for intestinal convulsion. Considering that PF-W also exhibits prokinetic activity, its use in various gastrointestinal disorders seems promising.

Effects of flavone derivatives on antigen-stimulated degranulation in RBL-2H3 cells.

Mast cells are primarily responsible for IgE-mediated allergic responses. The activation level of mast cells is reflected in their degree of degranulation. This can in turn be determined by measuring the amount of ß-hexosaminidase release, a key parameter in degranulation. In this study, 40 flavone derivatives, including flavone, 14 methoxyflavones, 13 hydroxyflavones, and 12 hydroxymethoxyflavones, were evaluated for their inhibition of degranulation in rat basophilic leukemia RBL-2H3 cells. 3',7-Dihydroxyflavone inhibited degranulation (IC(50) = 13.56 µM), which was comparable to PP2 (3-(4-chlorophenyl)-1-(1,1-dimethylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine) used as a control. In addition, we report quantitative relationships between the structural properties of flavones and their inhibitory effects on degranulation.

Screening and characterization of a chemical regulator for plant disease resistance.

Plants activate systemic acquired resistance (SAR), a form of long-lasting induced defense, to confer protection against a broad spectrum of pathogens. SAR induction is associated with the salicylic acid (SA)-mediated defense signaling networks. For detailed understandings of the SA-mediated signaling of SAR induction, we screened chemical inhibitors that block SA-mediated signaling from a 9600-compound chemical library. As a result, we identified one candidate chemical, 4-phenyl-2-{[3-(tri-fluoromethyl)anilino]methylidene}cyclohexane-1,3-dione (PAMD), that suppresses the expression of pathogenesis-related (PR) gene. PAMD also down-regulates SA-induced gene expression and enhances susceptibility to pathogen.

Synthesis and cytotoxicity evaluation of substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzofluorene-5,6-diones.

The substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzo[a]fluorene-5,6-diones were synthesized from 6,7-dichlorophthalazine-5,8-dione and 6,7-dichloroquinoline-5,8-dione, respectively. The cytotoxic activities of the prepared compounds were evaluated by an SRB (Sulforhodamine B) assay against the following human cancer cell lines: A549 (lung), SK-OV-3 (ovarian), SK-MEL-2 (melanoma), XF 498 (CNS), and HCT 15 (colon). Almost all synthesized pyridazino[4,5-b]phenazine-5,12-diones (7a-j) presented higher cytotoxicity than that of doxorubicin (IC(50)=0.097-0.225 microM) against the cancer cell lines. In particular, the cytotoxicity of compounds 7f (R(1)=Et) and 7h (R(1), R(2)=Me) against all human cancer cell lines examined was about 10 times higher than that of doxorubicin. However, the cytotoxicities of several synthesized azabenzo[a]fluorene-5,6-diones (12a, 12c, 12d, 12e, and 12g) against the cancer cell lines in vitro were comparable to those of doxorubicin.

Inhibitory effects of a benz[f]indole-4,9-dione analog on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells.

In our previous study, a synthetic benz[f]indole-4,9-dione analog, 2-amino-3-ethoxycarbonyl-N-methylbenz[f]indole-4,9-dione (SME-6), exhibited a potential anti-tumor activity. We, in this study, further explored the anti-metastatic and anti-invasive effect of SME-6 by determining the regulation of matrix metalloproteinases (MMPs). MMPs, zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix as well as non-matrix substrates. On this line, we examined the influence of SME-6 on the expressions of MMP-2, -9, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-1, -2), and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent suppressions of MMPs and TIMP-2 mRNA levels were observed in SME-6-treated HT1080 human fibrosarcoma cells detected by reverse transcriptase-polymerase chain reaction. TIMP-1 mRNA level, however, was induced in a dose-dependent manner. Gelatin zymographic analysis also exhibited a significant down-regulation of MMP-2 and -9 expression in HT1080 cells treated with SME-6 compared to controls. Furthermore, SME-6 inhibited the invasion, motility, and migration of tumor cells. Taken together, these data provide a possible role of SME-6 as a potential antitumor agent with the markedly inhibition of the metastatic and invasive capacity of malignant cells.

Synthesis and cytotoxicity evaluation of 6,11-dihydro-pyridazo- and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-diones.

The 6,11-dihydro-pyridazo[2,3-b]phenazine-6,11-dione and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione derivatives were synthesized from 6,7-dichloro-5,8-phthalazinedione and 6,7-dichloro-5,8-quinolinedione, respectively, producing a series of new anticancer drugs. The cytotoxic activities of the prepared compounds were evaluated by a SRB (Sulforhodamine B) assay against the following tumor cell lines: A459 (human lung), SK-OV-3 (human ovarian), SK-MEL-2 (human melanoma), XF498 (human CNS), and HCT 15 (human colon). Almost all the derivatives of the 6,11-dihydro-pyridazo[2[,3-b]phenazine-6,11-dione and 6,11-dihydro-pyrido[2,3-b]phenazine-6,11-dione, tetracyclic heteroquinone analogues with four or three nitrogen atoms, exhibited excellent cytotoxicity on almost all the human tumor cell lines tested. Specifically, 6,11-dihydro-pyridazo[2,3-b]phenazine-6,11-dione (4a) exhibited potent activity against all the tumor cell lines, and in particular, its cytotoxic effect against HCT 15 (ED(50)=0.004 microg/mL) was 25 times greater than that of doxorubicin (ED(50)=0.093 microg/mL).

Cytotoxicity and DNA topoisomerase inhibitory activity of benz[f]indole-4,9-dione analogs.

A series of benz[f]indole-4,9-diones, based on the antitumor activity of 1,4-naphthoquinone, were synthesized and evaluated for their cytotoxic activity in cultured human cancer cell lines A549 (lung cancer), Col2 (colon cancer), and SNU-638 (stomach cancer), and also for the inhibition of human DNA topoisomerases I and II activity in vitro. Several compounds including 2-amino-3-ethoxycarbonyl-N-methyl-benz[f]indole-4,9-dione showed a potential cytotoxic activity judged by IC50<20.0 microg/ml in the panel of cancer cell lines. Especially, 2-hydroxy-3-ethoxycarbonyl-N-(3,4-dimethylphenyl)-benz[f]indole-4,9-dione had potential selective cytotoxicity against lung cancer cells (IC50=0.4 microg/ml)) compared to colon (IC50>20.0 microg/ml) and stomach (IC50>20.0 microg/ml) cancer cells. To further investigate the cytotoxic mechanism, the effects of test compounds on DNA topoisomerase I and II activities were used. In a topoisomerase I-mediated relaxation assay using human placenta DNA topoisomerase I and supercoiled pHOTI plasmid DNA, 2-amino-3-ethoxycarbonyl-N-(4-fluorophenyl)-benz[f]indole-4,9-dione had the most potent inhibitory activity among the compounds tested. However, most of the compounds showed only weak inhibition of the DNA topoisomerase II-mediated KDNA (Kinetoplast DNA) decatenation assay, except for 2-amino-3-ethoxycarbonyl-N-(4-methylphenyl)-benz[f]indole-4,9-dione and 2-amino-3-ethoxycarbonyl-N-(2-bromoehtyl)-benz[f]indole-4,9-dione with a moderate inhibitory activity. These results suggest that several active compounds had relatively selective inhibitory activity against toposiomearse I compared to toposiomerase II. No obvious correlation was observed between the cytotoxicity of the individual compound and the inhibitory activity of DNA relaxation and decatenation by topoisomerase I and II, respectively, in vitro.