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BACKGROUND: Juvenile hormone (JH) signaling inhibitors may be used as insect growth regulators because of their ability to control metamorphosis and reproduction in insects by regulating the action of JH. RESULTS: We identified ethyl (E)‐3‐(4‐{[7‐ (4‐methoxycarbonylbenzyloxy)‐1,4‐benzodioxan‐6‐yl]methyl}phenyl)prop‐2‐enoate (EMBP) and observed its strong precocious metamorphosis‐inducing activity against silkworm larvae. To further elucidate its mechanism of action, we investigated the effect of EMBP on the JH‐mediated signaling pathway in vitro and in vivo. In a reporter assay using a Bombyx mori cell line, EMBP strongly suppressed the induction of reporter gene expression by Juvenile hormone I (JH I) in a concentration‐dependent manner. A parallel rightward shift was observed in the dose–response curve of JH I after treatment with EMBP, indicating that EMBP competitively inhibited JH. Moreover, we monitored developmental changes in the JH‐responsive gene, Krüppel homolog 1 (Kr‐h1), and ecdysone‐responsive gene, Broad‐Complex (BRC), in EMBP‐treated silkworm larvae. EMBP suppressed only the expression of Kr‐h1 in third‐instar larvae. CONCLUSION: Our results demonstrated that EMBP specifically regulates the JH‐mediated Kr‐h1 signaling pathway. EMBP could be used as a lead compound in the development of new insect growth regulators. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Although C5a receptor (C5aR) interacting with its agonist C5a promotes acute inflammation during the initiation phase, the roles of the recycling C5aR during the resolution phase are still unclear. We found that C5aR interacted with its antagonist/agonist ribosomal protein S19 (RP S19) polymer or a RP S19 polymer functional analogue S‐tagged C5a/RP S19, which connects an RP S19 C‐terminus (IAGQVAAANKKH) to the S‐tagged C5a C‐terminus, promoted acute inflammation at the resolution phase via an activation of the apoptosis‐inducing transcription factor delta lactoferrin (δLf) in neutrophils and the membrane mobilizing factor full‐length annexin A3 (ANXA3) in macrophages. To confirm the antagonistic system of the recycling C5aR, S‐tagged δLf‐coupled BrCN‐activated Sepharose 4B beads were incubated with cytoplasmic proteins and identified a neutrophil‐specific δANXA3 via pull‐down experiments. The S‐tagged C5a/RP S19‐induced agonistic functions in macrophage‐like cells that were differentiated from human promyelocytic leukemia HL‐60 cells by phorbol‐12‐myristate‐13‐acetate were suppressed by δLf and δANXA3 co‐overexpression. δANXA3 seems to participate in the antagonistic system of the neutrophil C5aR involving IAGQVAAANKKH and δLf. Most likely, δANXA3 works as antagonist for the recycling C5aR on neutrophils during the resolution phase of acute inflammation. [ABSTRACT FROM AUTHOR]

With both qualitative and quantitative approaches, this study examined the success factors of cultural tourism development. It discussed reasons why some cities may find it challenging to sustain cultural tourism development. The findings suggested that the lack of advantageous factors may be because all factors were highly related and that one factor's defect in marketing could easily affect the performance of all other factors. The challenge for cultural tourism development in a less competitive destination may be more related to elementary problems such as governmental leadership and funding rather than the important factors emphasized in theoretical models. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: The expression of interleukin (IL)-12R β2 molecule is a crucial regulatory factor in the T-helper type (Th) 1 differentiation of T cells. To elucidate the role of the cell-mediated immune (CMI) response in the pathogenesis of periodontitis, Japanese periodontal patients were subjected to single nucleotide polymorphism (SNP) analyses of the 5′ flanking region of IL12RB2, whose variants are frequently detected in lepromatous leprosy patients, in which the very weak cellular immune response is caused by low expression of IL-12R β2. Material and Methods: The gene polymorphisms of the 5′ flanking region of IL12RB2 were examined in subjects with several types of periodontal disease and in healthy controls. Serum immunoglobulin (Ig) G antibody titres against periodontopathic bacteria were measured and compared in periodontal patients with and without variant alleles of IL12RB2. Results: The frequencies of variant alleles of IL12RB2 were significantly higher in aggressive periodontitis patients as compared with healthy controls or chronic periodontitis patients. Serum IgG titres against all periodontal bacteria examined in subjects carrying variant alleles were higher than those in subjects without variant alleles. Conclusion: IL-12R β2 SNPs could be useful as genetic markers to access the susceptibility of the general population to periodontal disease. Low CMI responses or high humoral responses are associated with the pathogenesis of inflammatory periodontal diseases. [ABSTRACT FROM AUTHOR]

α-Galactosylceramide (α-GalCer) shows antitumor effects by activating natural killer (NK) cells indirectly through stimulation of the secretion of cytokines by NKT cells, whereas interleukin (IL)-18 shows antitumor effects by activating NK cells directly. In the present study, we examined the antitumor effect of the combined administration of α-GalCer and IL-18. An injection of NK cell-sensitive mouse B16 melanoma cells into a mouse tail vein produced pulmonary metastasis. The daily administration of α-GalCer or IL-18 alone for 4 days starting 1 day after the injection of B16 melanoma cells markedly suppressed the number of pulmonary metastatic foci, and their combined administration enhanced the antitumor effect compared with single administration. The antitumor effect of their combined administration was completely abolished by treatment of mice with anti-asialo GM1 serum, which depletes NK cells but not NKT cells. Combined administration of α-GalCer and IL-18 enhanced the cytotoxicity of NK cells and increased the number of NK cells in the lung. Analysis of NKT cell-dependent and NK cell-independent secretion of cytokines, to which NK cells can respond, showed that the administration of α-GalCer increased the secretion of IL-2, IL-4, interferon-γ, IL-12, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and IL-10, and the combined administration of α-GalCer and IL-18 enhanced the secretion of IL-2, IL-4, interferon-γ, and granulocyte-macrophage colony-stimulating factor further but only slightly. These results show that IL-18 in combination with α-GalCer exerts an antitumor effect on NK cell-sensitive tumors primarily by the direct stimulation of NK cells by IL-18 and the indirect stimulation of NK cells by α-GalCer through its activation of NKT cells. ( Cancer Sci 2008; 99: 113–120) [ABSTRACT FROM AUTHOR]

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant. [ABSTRACT FROM AUTHOR]

Prunes contain large amounts of phenolics and show high antioxidant activity. The aim of this study is to clarify the contents of caffeoylquinic acid (CQA) isomers, and to estimate the contribution of these isomers to the antioxidant activity of prunes. Furthermore, structural elucidation and evaluation of antioxidant activity of prune components were also performed. CQA isomers in prunes were quantified by HPLC analysis, and it has become apparent that prunes contain relatively high amount of 4-O-caffeoylquinic acid. The contribution of CQA isomers to the antioxidant activity of prunes was revealed to be 28.4% on the basis of oxygen radical absorbance capacity (ORAC); hence, it was indicated that residual ORAC is dependent on unknown antioxidant components. Total 28 compounds were isolated and their structures were elucidated by NMR and MS analyses. Four abscisic acid related compounds, a chromanon, and a bipyrrole were novel. Each CQA isomer in prunes showed high antioxidant activities when measured by the oil stability index (OSI) method, O_2^- scavenging activity, and ORAC. Other isolated compounds such as hydroxycinnamic acids, benzoic acids, coumarins, lignans, and flavonoid showed high ORAC values. Furthermore, a novel chromanon indicated a remarkable synergistic effect on ORAC of CQA isomers. [ABSTRACT FROM AUTHOR]