[Show abstract][Hide abstract] ABSTRACT: Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt’s lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC.
The Journal of Microbiology 02/2015; 53(2). DOI:10.1007/s12275-015-4672-9 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A series of 1-aryl-3-(cyclicamino)-prop-2-en-1-one analogs was synthesized from commercial acetophenones in 2 or 3 steps. Compound 6, (E)-3-(piperidinyl)-1-(2'-hydroxyphenyl)-prop-2-en-1-one, exhibited the unique shape and intensity of the C-sp2-N-CH2 peaks in the H-1 and C-13 NMR spectra. Variable temperature (VT) nuclear magnetic resonance (NMR) and X-ray diffraction (XRD) studies of 6 revealed that the piperidine ring has a lower energy barrier to rotation than the 5-membered pyrrolidine 9 due to the less effective pi electron delocalization along the C-sp2-N bond.
[Show abstract][Hide abstract] ABSTRACT: Paraphilia is a psychiatric disease that has been difficult to cure. However, recently developed therapeutic methods hold promise. The patient was a 20-yr-old male with chief complaints of continuous masturbation, genital exposure, and aggressive behavior that started 2 yr ago. We administered leuprorelin 3.6 mg intramuscular injection per month, a depot gonadotrophin-releasing hormone analogue, to this patient who a severe mentally retardation with paraphilia. The clinical global impression (CGI)-severity, CGI-improvement and aberrant behavior checklist were performed. After one month, we observed significant improvement in symptoms, such as decreases of abnormal sexual behavior and sexual desire. The GnRH analogues are suggested to be used as an alternative or supplementary therapeutic method for sexual offenders after clinical studies.
Journal of Korean Medical Science 09/2014; 29(9):1320-4. DOI:10.3346/jkms.2014.29.9.1320 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estrogenic endocrine-disrupting chemicals (EDCs) are exogenous substances that act as competitive inhibitors of estrogen in the endocrine system. By disrupting the endocrine system, EDCs can cause severe disabilities and diseases, including cancers and altered sexual development. Although the influence of these molecules in the endocrine system is evident, the effects of EDCs on the immune system as well as their cytotoxicity have been poorly examined. Therefore, we selected 21 EDCs that are commonly found in Korean ecosystems, such as surface waters and effluents, and studied their immunologic effects by comparing nitric oxide (NO) production and cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (RAW cells), a macrophage cell line. Among the EDCs tested, fenitrothion (FTH) inhibited the messenger RNA (mRNA) expression of inducible NO synthase (iNOS), resulting in reduced NO production, while treatment with andostenedione (AD), diethyl phthalate, di-n-butyl phthalate (DBP), estriol, or molinate decreased production of NO in an iNOS-independent fashion. In contrast, benzo(a)pyrene (B(a)P) increased the production of NO in RAW cells. In addition, AD, DBP, or FTH inhibited the mRNA expression of tumor necrosis factor alpha or interleukin-1 beta. Treatment with 17-α-ethynylestradiol, 17-β-estradiol, 4-n-butyl phenol, or alachlor induced apoptosis of RAW cells, while dicyclohexyl phthalate and B(a)P caused cell death in an apoptosis-independent manner. These data suggest that EDCs can influence the immune response to pathogens by modulating the functions of macrophages.
[Show abstract][Hide abstract] ABSTRACT: The immune-modulatory as well as anti-influenza effects of Cordyceps extract were investigated using a DBA/2 mouse model. Three different concentrations of Cordyceps extract, red ginseng extract, or drinking water were orally administered to mice for seven days, and then the mice were intranasally infected with 2009 pandemic influenza H1N1 virus. Body weight changes and survival rate were measured daily post-infection. Plasma IL-12, TNF-α, and the frequency of natural killer (NK) cells were measured on day 4 post-infection. The DBA/2 strain was highly susceptible to H1N1 virus infection. We also found that Cordyceps extract had an antiinfluenza effect that was associated with stable body weight and reduced mortality. The anti-viral effect of Cordyceps extract on influenza infection was mediated presumably by increased IL-12 expression and greater number of NK cells. However, high TNF-α expression after infection of H1N1 virus in mice not receiving treatment with Cordyceps extract suggested a two-sided effect of the extract on host immune regulation.
The Journal of Microbiology 07/2014; 52(8). DOI:10.1007/s12275-014-4300-0 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we performed 2-dimensional electrophoresis with protein extracts from the lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins expression were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homologue of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation at least partly by increasing the expression of Klf4.
Journal of Microbiology and Biotechnology 03/2014; · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 μg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.
[Show abstract][Hide abstract] ABSTRACT: Nanomaterials have been developed for the target delivery of medicine because they show the characteristics of selective emission or controlled release. Although accumulated data suggest the efficacy of these materials for the target delivery, it still remains to be determined whether they modulate immune responses to pathogens or foreign materials. In this study, we examined whether Pluronic nanoparticles (NPs), a type of nanomaterial, alter immune responses mediated by macrophages. When RAW 264.7 cells (RAW cells) were treated with Pluronic NPs in the presence or absence of lipopolysaccharides (LPS), they produced normal levels of nitric oxide (NO). Furthermore, the treatment with Pluronic nanomaterials did not induce cytotoxicity with or without LPS. Further, LPS-stimulated RAW cells expressed comparable levels of proinflammatory cytokine genes, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, with or without treatment by Pluronic NPs. These data suggest that Pluronic NPs do not modulate immune responses mediated by macrophages.
Macromolecular Research 12/2013; 21(12). DOI:10.1007/s13233-013-1174-7 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Androgen-disrupting chemicals (ADCs) can alter male sexual development. Although the effects of ADCs on hormone disruption have been studied, their influence on the immune response is not fully understood. To investigate the effects of ADCs on innate immunity, we tested eight candidate ADCs for their influence on macrophages by measuring nitric oxide (NO) production and cell viability. Our results showed that treatment with a mixture of lipopolysaccharide and hexachlorobenzene increased NO production in RAW 264.7 cells, a murine macrophage cell line. In contrast, compared to exposure to a negative control, exposure to di-2-ethylhexyl adipate (DEHA), benzylbutyl phthalate (BBP), testosterone (TTT), or permethrin decreased NO production. DEHA, BBP, and TTT inhibited NO production in an inducible nitric oxide synthase-dependent manner. Treatment with bisphenol A (BPA), nonylphenol (NNP), or tributyltin chloride (TBTC) reduced NO production and induced cell death. While BPA induced RAW 264.7 cell death through apoptosis, NNP and TBTC caused cell death through necrosis. These results offer insights into the influences of ADCs on the innate immune system.
[Show abstract][Hide abstract] ABSTRACT: Objectives : It has been reported that higher percentage of B cells react with monoclonal D8/17 antibody in patients with rheumatic fever, childhood onset obsessive-compulsive disorder, Tourette's disorder, or prepubertal anorexia nervosa. The purpose of this study is to replicate the previous studies in a Korean young population with tic disorder and to identify any relationship between D8/17 and clinical symptoms. Methods : The binding of D8/17 to B cells was determined in patients with tic disorder (N=21) and healthy controls (N=9) by Fluorescence-Activated Cell Sorter analysis. Results : In the sample examined by this study, the average percentage of B cells expressing D8/17 in tic disorder was 2.05%; healthy controls was 3.15%. No statistically significant differences were found in the mean percentages of D8/17 between the two groups. Conclusion : The expression of D8/17 in B cells was very low in this study. No subjects with tic disorder or healthy controls was above 12% in D8/17 positive proportion. Further studies, including higher number of patients and control group members, should be performed.
[Show abstract][Hide abstract] ABSTRACT: Chronic inflammation can lead to several diseases, thus analysis of the inflammation state of live cells may have important clinical applications. However, there is not currently well-established method for specific detection of inflamed cells via live cell imaging. In this study, we developed an effective antibody (Ab)-based cell imaging method for the detection of inflamed cells using Ab-conjugated nano-beads. Several receptors were tested as potential biomarkers for cell inflammation, and corresponding fluorescence-labeled Abs and/or Ab-conjugated nano-beads were used to detect inflamed cells via fluorescence imaging. Interestingly, when we employed sequential use of TLR1 primary Ab and size-optimized nano-beads conjugated with secondary Ab, we were able to clearly discriminate inflamed cells from normal ones. The Ab-based cell-imaging method described herein provides an important basis for the development of high-throughput analysis of cell inflammation, potentially leading to the identification of factors involved in inflammation and anti-inflammatory drug candidates.
[Show abstract][Hide abstract] ABSTRACT: We investigated the mode of action underlying the anti-mycoplasma activity of cationic antimicrobial peptides (AMPs) using four known AMPs and Mycoplasma pulmonis as a model mycoplasma. Scanning electron microscopy revealed that the integrity of the M. pulmonis membrane was significantly damaged within 30min of AMPs exposure, which was confirmed by measuring the uptake of propidium iodine into the mycoplasma cells. The anti-mycoplasma activity of AMPs was found to depend on the binding affinity for phosphatidylcholine, which was incorporated into the mycoplasma membrane from the growth medium and preferentially distributed in the outer leaflet of the lipid bilayer.
[Show abstract][Hide abstract] ABSTRACT: Single-walled carbon nanotubes (SWCNTs) are potent nanomaterials that have diverse shapes and features. The utilization of these molecules for drug delivery is being investigated; thus, it is important to determine whether they alter immune responses against pathogens. In this study, we show that macrophages treated with a mixture of lipopolysaccharide and SWCNTs produced normal levels of nitric oxide and inducible nitric oxide synthase mRNA. However, these treatments induced cell death, presumably via necrosis. In addition, treating cells with SWCNTs induced the expression of tumor necrosis factor-α mRNA, a potent pro-inflammatory cytokine. These results suggest that SWCNTs may influence immune responses, which could result in unexpected effects following their administration for the purpose of drug delivery.
[Show abstract][Hide abstract] ABSTRACT: NPS-1034 is a drug candidate targeted for the regulation of c-MET/AXL receptor tyrosin kinase activity. NPS-1034 was developed to improve efficacy and reduce toxicity by targeting c-MET/AXL related signaling pathways. However, NPS-1034 is practically insoluble in almost all organic solvents as well as aqueous media (pH 1, 4.5, and 7.5). We attempted to improve the physicochemical properties of NPS-1034 by forming multicomponent systems with a wide variety of sulfonic acids including methanesulfonic acid, 1,2-ethanedisulfonic acid, p-toluenesulfonic acid, and camphorsulfonic acid. Solid state characterization of NPS-1034 salts and amorphous with sulfonic acids was conducted, and the crystal structures of four salts and NPS-1034 were compared and investigated. Sulfonic acid salts of NPS-1034 decreased the melting point of NPS-1034 as much as −155.43 °C. Solubilities of NPS-1034 and salts of NPS-1034 were measured to develop lipid-based formulation for the GLP toxicity study. Solvents studied include oleic acid, poly(ethylene glycol) 400, and ethanol. Solubility of amorphous of NPS-1034 with camphorsulfonic acid showed a significant increase in all three solvents. This work will give some insight into how various types of sulfonic acids interact with pharmaceutically important compounds containing the pyrrolepyridine moiety.
[Show abstract][Hide abstract] ABSTRACT: The clinical impact of polymicrobial infections has received increasing attention from the medical community. However, the potential effects of Pseudomonas aeruginosa infection on the development of host responses against Gram-positive bacteria, such as Staphylococcus aureus, are unknown. Here, P. aeruginosa infection was found to induce the expression of Toll-like receptor 2 (TLR2), which plays a dominant role in sensing pathogen-associated molecular patterns (PAMPs) expressed by Gram-positive bacteria. P. aeruginosa-dependent upregulation of TLR2 was not mediated by flagellin, or by the type III (T3SS) or type IV (T6SS) secretion systems, but was upregulated by lipopolysaccharide (LPS). Upregulation of TLR2 influenced the magnitude of proinflammatory responses to the secondary S. aureus infection, but there was no clear effect on phagocytosis of S. aureus by macrophages. Taken together, the results of this study demonstrate that P. aeruginosa infection results in the upregulation of TLR2 expression, subsequently enhancing innate immune responses against a secondary S. aureus infection. This article is protected by copyright. All rights reserved.
Pathogens and Disease 08/2013; 69(2). DOI:10.1111/2049-632X.12074 · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carthamus tinctorius L. (CT) is traditionally used to reduce ailments from diseases of the musculoskeletal system and connective tissue and diseases of blood circulation and the cardiovascular system. Flower extracts from CT are known to have antibacterial activity, anti-inflammatory activity, and to inhibit tumor promotion in mouse skin carcinogenesis. In order to discover new antiviral agents from CT extracts, we tested whether CT extracts contain antiviral activity against gammaherpesvirus infection. This study demonstrated that treatment with CT extracts disrupted KSHV latency in the viral-infected host cells, iSLK-BAC16. n-Hexane and EtOH fractions of CT extracts critically affected at least two stages of the KHSV life-cycle by abnormally inducing KSHV lytic reactivation and by severely preventing KSHV virion release from the viral host cells. In addition to the effects on KSHV itself, CT extract treatments induced cellular modifications by dysregulating cell-cycle and producing strong cytotoxicity. This study demonstrated for the first time that CT extracts have antiviral activities that could be applied to development of new anti-gammaherpesviral agents.
The Journal of Microbiology 08/2013; 51(4):490-8. DOI:10.1007/s12275-013-3282-7 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Purpose: Professional and public concern about the potential adverse effects of man-made electromagnetic fields (EMF) on the human body has dramatically expanded in recent years. Despite numerous attempts to investigate this issue, the long-standing challenge of reproducibility surrounding alternating EMF effects on human health remains unresolved. Our chief aim was to investigate a plausible mechanism for this phenomenon. Materials and methods: Growth of cultured human cancer cells, DU145 and Jurkat, exposed to power frequency magnetic field (MF) (60 Hz, 1 mT) for 3 days, was determined using a 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay and a trypan blue exclusion assay. This experiment was repeated at incubators long-term monitoring period up to 5.3 years. A periodogram analysis was performed to investigate periodic patterns in the MF and sham effects on cell growth. Results: Unlike conventional assumptions, the MF effect on growth in both cell types was promotive or suppressive in a period-dependent manner. The converse cell growth induced by the MF was consistent in incubators, with little variation. Conclusions: Spatiotemporal evidence suggests that the period-dependent converse cell growth by the MF may contribute to the poor reproducibility and explain the adverse effects observed in previous experimental and epidemiological investigations. Additionally, the novel approach of this study may be applied to design features required to experimentally determine the effects of EMF on living organisms in a convincing manner.
International Journal of Radiation Biology 07/2013; 89(12). DOI:10.3109/09553002.2013.825063 · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Closo-carborane has been considered as an efficient boron-carrier for boron neutron capture therapy (BNCT) and an attractive surrogate of lipophilic phenyl or cyclohexyl ring in drug design. Despite a great number of carborane-containing ligands have been synthesized and evaluated, molecular modeling studies of carborane ligands with macromolecules have been rarely reported. We herein describe a facile docking and scoring-function strategy of 16 carborane ligands with an estrogen receptor by using the commercial Gaussian, Chem3D Pro and Discovery Studio (DS) computational programs. Docked poses of the carborane ligands in silico exhibited similar binding modes to that of the crystal ligand in the active site of estrogen receptor. Score analysis of the best docked pose for each ligand indicated that the Ligscore1 and the Dockscore have a moderate correlation with in vitro biological activity. This is the first report on the scoring-correlation studies of carborane ligands with macromolecules. The integrated Gaussian-DS approach has a potential application for virtual screening, De novo design, and optimization of carborane ligands in medicinal chemistry.
Bulletin- Korean Chemical Society 04/2013; 34(4):1051-1054. DOI:10.5012/bkcs.2013.34.4.1051 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antimicrobial peptides act as important innate immune defense mediators against invading microbes such as Streptococcus pneumoniae. Among a number of antimicrobial peptides, β-defensin 2 (BD2) has strong antimicrobial activity against S. pneumoniae. However, little is known about the molecular signaling mechanisms leading to the BD2 expression. Here, we report that BD2 is strongly induced by S. pneumoniae in human airway cells including human middle-ear cells. Among diverse pneumococcal virulence factors, pneumolysin is required for inducing BD2 whose expression is under the control of p38 mitogen-activated protein kinase (MAPK). Pneumolysin also selectively regulates the expression of MAPK phosphatase 1 (MKP1), which inhibits the p38 signaling pathway, thereby leading to upregulation of BD2 to mount an effective defense against S. pneumoniae infection. These results provide novel insights into the molecular mechanisms underlying the coordinative regulation of BD2 expression via p38-MKP1 in the pathogenesis of airway infectious diseases.
The Journal of Microbiology 04/2013; 51(2):194-9. DOI:10.1007/s12275-013-2579-x · 1.53 Impact Factor