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In this study, we determined the complete mitochondrial genome (mt genome) of Semisulcospira gottschei for the first time and then compared it with the mt genome of species belonging to Cerithioidea. The mt genome consists of 13 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and non-coding region with a total length of 16,101 bp. The type of constitutive genes and the direction of the coding strand which appeared in the mt genome were the same as the ones observed in Cerithioidea except for the tRNA-Q and tRNA-R positions. The S. gottschei mt genome had a non-coding region with an AT-rich loop between tRNA-F and tRNA-C regions. In regard to molecular phylogeny, two types of analysis were performed to confirm the introgressive hybridization of S. gottschei and to identify the phylogenetic location among the species in Caenogastropoda. As a result, S. gottschei used in this study belonged to the same clade as other non-introgressed S. gottschei. As for the molecular phylogenic analysis of species belonging to Caenogastropoda, S. gottschei was found to be the closest to S. coreana taxonomically and to be included in Cerithioidea. [ABSTRACT FROM AUTHOR]

To understand the dietary ecology of the leopard cat (Prionailurus bengalensis), DNA analysis was performed to identify prey species using DNA isolated from teeth harvested from the faeces of this feline species. From 70 DNA samples, a total of 52 mitochondrial DNA (mtDNA)cytochrome b(cytb) gene sequences of mammals were identified. The results of a sequence identity test indicated that those sequences were derived from four rodent species (Apodemus agrarius,Apodemus peninsulae,Eothenomys regulusandTamias sibiricus) and two shrew species (Crocidura lasiuraandCrocidura shantungensis). The sequences contained nine uniquecytbsequences from site 1 and 13 from site 2. These results indicate that the leopard cat hunts rodents and shrews, and at least nine animals at site 1 and 13 animals at site 2 were eaten. These findings suggest that the animal molecular signatures that remain undigested in the faeces may provide useful ecological information about food items and may contribute to a better understanding of the leopard cat’s feeding ecology. [ABSTRACT FROM AUTHOR]

In our recent work, we demonstrated that the use of bio-derived rosin as a binder additive could improve the electrochemical performance of lithium titanium oxide (LTO) anodes. As a sequential study, four representative modified rosin-derivatives are used as additives for polyvinylidene difluoride (PVdF) binders in order to further improve the cell performance of LTO electrodes. The rosin derivative modified via simple hydrogenation retains carboxylic acids and is favorable to lithium ion transport when compared to the modified rosins, which loose these functional groups via esterification. The hydrogenated rosin additive increases cyclic capacities, initially by 10 mAh g − 1 and more so at high current charge/discharge rates. [ABSTRACT FROM AUTHOR]

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones ( 1- 7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine ( 1), xanthoangelol E ( 2), xanthokeismin A ( 4), and xanthoangelol B ( 5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory- κB α (I- κB α) and the translocation of nuclear factor κB (NF- κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones ( 1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I- κB α and nuclear translocation of NF- κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

The ethyl acetate-soluble fraction from the ethanolic extract of Angelica keiskei showed potent inhibitory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. We identified seven chalcones ( 1- 7) from EtOAc-soluble fractions through the activity-guided separation. Four active principles, identified as 4-hydroxyderrcine ( 1), xanthoangelol E ( 2), xanthokeismin A ( 4), and xanthoangelol B ( 5), inhibited the production of NO and the expression of proinflammatory cytokines, interleukin (IL)-1β and IL-6, in LPS-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these chalcones attenuated protein and mRNA levels of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, these active compounds suppressed the degradation of inhibitory- κB α (I- κB α) and the translocation of nuclear factor κB (NF- κB) into nuclei of LPS-activated macrophages. These data demonstrate that four chalcones ( 1, 2, 4, and 5) from A. keiskei can suppress the LPS-induced production of NO and the expression of iNOS/COX-2 genes by inhibiting the degradation of I- κB α and nuclear translocation of NF- κB. Taken together, four chalcones from A. keiskei may have efficacy as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Highlights: [•] Tussilagone (TSL) was purified from plant as an inhibitor of Wnt/β-catenin pathway. [•] TSL suppressed the β-catenin/T-cell factor transcriptional activity. [•] The proteasomal degradation of β-catenin was induced by TSL. [•] TSL suppressed the Wnt/β-catenin target genes, cyclin D1 and c-myc. [•] TSL inhibit the proliferation of colon cancer cells. [ABSTRACT FROM AUTHOR]

Microglial activation has been associated with neurodegenerative diseases by inducing the neuroinflammatory mediators such as nitric oxide (NO), TNF-α and IL-1β. (−)-Nyasol, a norlignan isolated from a medicinal plant Anemarrhena asphodeloides, showed anti-inflammatory potential in lipopolysaccharide (LPS)-activated BV-2 microglial cells. (−)-Nyasol inhibited the production of NO and prostaglandin E2 (PGE2) and also the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are responsible for the respective production of NO and PGE2. It also suppressed the mRNA levels of TNF-α and IL-1β in activated microglial cells. These effects of (−)-nyasol were correlated with the inactivation of p38 MAPK and the suppression of LPS-induced I-κBα degradation. Taken together, these results suggest that (−)-nyasol can be a modulator in neuroinflammatory conditions induced by microglial activation. [ABSTRACT FROM AUTHOR]

Abstract: Series of carbamate and thiocarbamate derivatives were designed and synthesized and their inhibitory activities of NO production in lipopolysaccharide-activated macrophages were evaluated. Several thoicarbamate derivatives revealed promising inhibitory activity. The structure–activity relationship study of these compounds is also reported. Among these compounds, compound 12b was the most potent with 6.5μM of IC50. They inhibited NO production through the suppression of iNOS protein and mRNA expression and nuclear translocation of p65. [Copyright &y& Elsevier]

A germacranolide sesquiterpene lactone, 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methylbutyloxy)-germacran-8α,12-olide (EDAG), isolated from Carpesium triste var. manshuricum, showed inhibitory activity in the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in LPS-activated macrophage cells. Molecular analysis reveals that these suppressive effects are correlated with the inhibition of NF-κB activation by EDAG. Immunoblotting showed that EDAG suppressed the LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Futhermore, EDAG showed reduced phosphorylation of ERK1/2 and p38 MAPK, whereas activation of JNK was not changed. These data suggest, at least in part, that EDAG utilizes the signal cascades of ERK1/2, p38 MAPK, and NF-κB for the suppression of iNOS gene expression. Un sesquiterpène lactone de type germacranolide, 2α,5-époxy-5,10-dihydroxy-6 α-angeloyloxy-9β-(3-méthylbutyloxy)-germacran-8α,12-olide (EDAG), isolé de Carpesium triste var. manshuricum, a montré une activité inhibitrice sur la production du monoxyde d'azote (NO) et l'expression de la protéine et de l'ARNm de la monoxyde d'azote synthase inductible (iNOS) dans les macrophages activés par des LPS. L'analyse moléculaire révèle que ces effets suppresseurs sont corrélés avec l'inhibition de l'activation du NF-κB par l'EDAG. L'immunobuvardage a montré que l'EDAG a supprimé la dégradation induite par les LPS de la protéine I-κBα et diminué la translocation nucléaire de la sous-unité p65. De plus, l'EDAG a diminué la phosphorylation de ERK1/2 et de la p38 MAPK, mais n'a pas modifié l'activation de la JNK. Ces résultats laissent à penser, du moins en partie, que l'EDAG utilise les cascades de signaux ERK1/2, p38 MAPK et NF-κB pour supprimer l'expression génique de iNOS. [ABSTRACT FROM AUTHOR]

Abstract: Carabrol, isolated from Carpesium macrocephalum, showed anti-inflammatory potential in LPS-induced RAW 264.7 murine macrophages. In present study, carabrol demonstrated the inhibitory activity on pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, mRNA and protein levels of iNOS and COX-2 were reduced by carabrol. Molecular analysis revealed that these suppressive effects were correlated with the inactivation of p38 and JNK via inhibition of NF-κB activation. Immunoblotting showed that carabrol suppressed LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Taken together, these results suggest that carabrol can be a modulator of pro-inflammatory signal transduction pathway in RAW 264.7 cells. [Copyright &y& Elsevier]

G-protein-coupled receptors (GPCR) are the largest family of receptors with over 500 members. Evaluation of GPCR gene expression in primary human tumors identified over-expression of GPCR in several tumor types. Analysis of cancer samples in different disease stages also suggests that some GPCR may be involved in early tumor progression and others may play a critical role in tumor invasion and metastasis. Currently, >50% of drug targets to various human diseases are based on GPCR. In this review, the relationships between several GPCR and melanoma development and/or progression will be discussed. Finally, the possibility of using one or more of these GPCR as therapeutic targets in melanoma will be summarized. [ABSTRACT FROM AUTHOR]

WecE gene, encoding a sugar aminotransferase (SAT), has been cloned from E. coli K12 and expressed in E. coli BL21 (DE3). The enzyme was purified and characterized. WecE used TDP-4-keto-6-deoxy-D-glucose (TDP-D-Glc4O) and L-glutamate as a good amino acceptor and donor, respectively, leading to the production of TDP-4-amino-4,6-dideoxy-D-galactose (TDP-Fuc4N), which was identified by NMR studies. WecE also showed a similar activity for TDP-4-keto 6-deoxy-D-mannose (TDP-D-Man4O), but no activity for GDP-4-keto-6-deoxy-D-mannose (GDP-D-Man4O), suggesting that the nucleotide moiety would become a key determinant to the substrate specificity of amine acceptor for the activity of the SAT. Multiple alignments showed that SATs have four highly conserved motifs located around the active site and could be divided into three subgroups (VIα, VIβ, and VIγ) that might be closely related with their substrate specificities. [Copyright &y& Elsevier]

Simple Summary: Biological invasion on islands poses ecological threats, and understanding invasion pathways can aid in preventing invasive species. Recently, brown rats (Rattus norvegicus) arrived on Dok-do, a remote, small island in the East Sea of Korea. Due to strict regulation on human disturbances, including trapping, we adopted 3-RADseq to compensate for our small sample size and determine the origin of the invading rats. Our genomic analysis will aid in controlling and managing invasive species on this protected island. Biological invasions are known to cause local extinctions on islands. Dok-do, a small, remote volcanic island in the East Sea of Korea in the western Pacific, has recently been invaded by rats, posing ecological problems. To infer their origin and invasion pathway, we collected rats from Dok-do and from the potential introduction source locations, Ulleung-do in the Pacific Ocean, and four east coastal ports. First, we identified that the brown rat (Rattus norvegicus) was the only rat species occurring at collecting sites based on the key morphological characteristics. To determine the population-level genetic diversity pattern, we applied the 3-RADseq approach. After a series of filtrations (minor allele frequency < 0.05, Hardy–Weinberg equilibrium p < 1 × 10−7), 4042 SNPs were retained for the final dataset from the 25,439 SNPs initially isolated. The spatial structure and genetic diversity pattern of brown rats suggested that the rat population on Dok-do was likely introduced from Ulleung-do. Our work provides practical information that will assist in the management of invasive brown rats in vulnerable island ecosystems. [ABSTRACT FROM AUTHOR]

• Transient receptor potential vanilloid 4 is known to activate the osmosensory cation channel by increasing the osmotic cell volume. • TRPV4 generates transcript variants of the intron-retention form through alternative splicing. • Two transcript structure were identified with several differences in amino acid structure due to frameshift. • TRPV4 x1 responded to salinity and temperature, whereas TRPV4 x2 responded mainly to temperature. Transient receptor potential vanilloid 4 (TRPV4) is an osmosensory cation channel that respond to an increase in cell volume and participates in various physiological functions. Among organisms in aquatic environments, euryhaline teleost is are suitable experimental models to study ion channel proteins related to physiological functions involving osmosensing. Among the studies of various regulatory molecules that mediate osmotic regulation in fish, however, information is lacking, particularly on the TRP family. This study investigated the structural characteristics of theTRPV4 gene of chum salmon (Oncorhynchus keta) and their responses to changes in salinity and temperature. Interestingly, TRPV4 generates transcript variants of the intron-retention form through alternative splicing, resulting in a frameshift leading to the generation of transcripts of different structures. In particular, TRPV4 x1 and TRPV x2 mRNAs were predominant in the gill and skin including at the lateral line. The expression levels of chum salmon TRPV4 x1 were significantly increased with increase in salinity and temperature, whereas TRPV4 x2 mainly responded to temperature decrease. Overall, these results demonstrate for the first time the effects of salinity and temperature on the expression of two salmonid TRPV4 transcript variants, suggesting their contribution to the regulation of hydromineral balance. [ABSTRACT FROM AUTHOR]

• PEBAX-5513/KBF 4 composite membranes for facilitated CO 2 transport. • Activated potassium ions as CO 2 carriers. • Enhanced performance for CO 2 /N 2 separation. This study showed that potassium tetrafluoroborate (KBF 4) could be used as a carrier to facilitate the transport of CO 2. A polymer electrolyte membrane was prepared by incorporating KBF 4 into poly (ether-block-amide) (PEBAX-5513) with a flexible PE group. The prepared PEBAX-5513/KBF 4 electrolyte membrane exhibited CO 2 separation performance that was improved by nine times compared to pure PEBAX-5513 and by about seven times compared to a PVP/KF electrolyte membrane. The membrane exhibited a selectivity of 27.9. This improved separation performance increased the transport of CO 2 owing to the reversible interaction of the dissociated potassium ions with CO 2 molecules. The dissociation of potassium ions upon thermal treatment of the material was confirmed by Fourier transform Raman spectroscopy, and the selective layer in which the separation mechanism was generated was confirmed by scanning electron microscopy. [ABSTRACT FROM AUTHOR]

Polymer composite membranes containing aniline were prepared for CO2/N2 separation. Aniline was selected for high separation performance as an additive containing both the benzene ring to interfere with gas transport and an amino group that could induce the accelerated transport of CO2 molecules. As a result, when aniline having both a benzene ring and an amino group was incorporated into polymer membranes, the selectivity was largely enhanced by the role of both gas barriers and CO2 carriers. Selective layers coated on the polysulfone were identified by scanning electron microscopy (SEM) images and the interaction with aniline in the polymer matrix was confirmed by FT-IR spectroscopy. The binding energy of oxygen in the polymer matrix was investigated by XPS, and the thermal stability of the composite membrane was confirmed by TGA. [ABSTRACT FROM AUTHOR]

Hovenia dulcis Thunb. fruit (HDF) is traditionally used for treating liver diseases and alcohol poisoning. The purpose of this study was to explore the effects of HDF on hyperproliferation, levels of inflammatory cytokines, and signaling mechanisms in human psoriatic keratinocyte HaCaT cells. HDF showed a preventive effect on tumor necrosis factor-α (TNF-α)-induced abnormal proliferation of psoriatic keratinocytes. Furthermore, real-time reverse transcription-PCR analysis showed that HDF suppressed the expressions of inflammatory cytokines; interleukin (IL)-1α and IL-1β and chemokines; CCL-20 and CXCL-8 in TNF-α-induced HaCaT cells. Western blotting revealed that HDF suppressed the levels of phosphorylated IκB and STAT3 together with a decline in the levels of phosphorylated mitogen-activated protein kinases (MAPKs). These outcomes indicate that HDF prevents the abnormal proliferation of keratinocytes and modulates inflammatory responses by suppressing nuclear factor-κB (NF-κB) and STAT3 activation through downregulation of the MAPK signaling pathway in TNF-α-induced psoriatic keratinocytes. Our study demonstrates that HDF is prospective and beneficial for psoriatic skin inflammation. [ABSTRACT FROM AUTHOR]

We have isolated four sesquiterpenoids fromTussilago farfara, a traditional herbal medicine in Korea and China, and investigated the protective effects on LPS-induced neuronal cell death. Four sesquiterpenoids inhibited the production of nitric oxide, prostaglandin E2and tumor necrosis factor-α in LPS-treated BV-2 cells through the inhibition of NF-κB pathway. These sesquiterpenoids also inhibited reactive oxygen species (ROS) generation in LPS-treated BV-2 cells. Furthermore, they inhibited LPS-induced neuronal cell death in co-culture system through the inhibition of NF-κB pathway and scavenging of ROS. These results indicated that sesquiterpenoids fromTussilago farfaramay have beneficial therapeutic potential for the treatment of neurodegenerative diseases through inhibition of microglial activation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tumor necrosis factor-alpha (TNF-α) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear. Objective: To explore the lipogenic effect by TNF-α and possible molecular mechanisms in sebocyte. Methods: Using SZ95 human sebocytes, lipid formation by TNF-α was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N-terminal kinase (JNK) and Akt in TNF-α-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors. Results: TNF-α treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-α-induced expression of FAS and SREBP-1. TNF-α could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA. Conclusions: TNF-α induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne. [Copyright &y& Elsevier]

Abstract: Two new and two known compounds were identified as estrogenic constituents from Broussonetia kazinoki. Their structures were elucidated as broussonin A (1), tupichinol C (2), kazinol U (3), and (+)-(2R) kazinol I (4). They showed estrogenic activity with ligand-binding activity of estrogen receptor, transcriptional activity of estrogen-responsive element-luciferase reporter genes. They also control the cellular gene expression levels of estrogen-responsive genes. Phytoestrogens from B. kazinoki may have beneficial effects in the treatment of menopausal symptoms. [Copyright &y& Elsevier]

Abstract: Three sesquiterpenoids, xanthatin (1), xanthinosin (2), and 4-oxo-bedfordia acid (3) were isolated from Xanthium strumarium as inhibitors of nitric oxide synthesis in activated microglia (IC50 values: 0.47, 11.2, 136.5μM, respectively). Compounds 1 and 2 suppressed the expression of iNOS and COX-2 and the activity of NF-κB through the inhibition of LPS-induced I-κB-α degradation in microglia. [Copyright &y& Elsevier]

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases. [ABSTRACT FROM AUTHOR]

Problem: The lymphatic vasculature controls leukocytes trafficking and limits the adaptive immune response. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophysiology. Especially, the dysfunction of regulatory T cells (Treg) at the maternal‐fetal interface may be one of the causes of severe PE. In particular, activation of Tregs to obtain immune tolerance requires adequate antigen presentation through the lymphatic system. We hypothesized that impaired lymphangiogenesis and imbalanced Tregs at the maternal‐fetal interface are associated with the pathophysiology of severe PE. However, the current research addressing this hypothesis is limited. Therefore, to compare differences in lymphangiogenesis in severe PE and normal conditions, we aimed to examine the location of lymphatics at the maternal‐fetal interface and to investigate the association between lymphangiogenesis and Tregs in severe PE. Method of Study: We obtained entire uterus from normal pregnant mice. Placental and fetal membranes, including decidua, were obtained from 10 pregnant women with severe PE and 10 gestational age‐matched controls. Immunohistochemistry for LYVE1 was used to localize the distribution of lymphatic vessels and CD4, CD25, and FOXP3 for Treg. Results: LYVE1‐positive vessels were present in the uterine wall of mice. LYVE1‐positive lymphatic vessels were localized on the human decidua. Tubular lymphatics were abundant in the control decidua, but significantly reduced in severe PE. Furthermore, lymphatic vessel density correlated with the number of decidual Tregs. Conclusion: Abnormal decidual lymphangiogenesis is associated with reduced numbers of decidual Tregs in severe PE. [ABSTRACT FROM AUTHOR]

The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) by microglia may cause neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. From the activity-guided purification of Cullen corylifolium (L.) Medik. (syn. Psoralea corylifolia L.), three prenylated chalcones were identified: isobavachalcone (1), bavachromene (2), and kanzonol B (3). These prenylated chalcones showed concentration-dependent inhibitory effects on NO and PGE2 production in lipopolysaccharide (LPS)-activated microglia. Western blotting and RT-PCR analysis demonstrated that these prenylchalcones reduced the expression of protein and mRNA of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-activated microglia. Furthermore, three prenylated chalcones blocked the inhibitory-κBα (I-κBα) degradation and down-regulated nuclear factor κB (NF-κB) level of nucleus in LPS-stimulated BV-2 microglia. Therefore, these prenylated chalcones from Psoralea corylifolia may be beneficial for the treatment of neuro-inflammatory diseases by modulating iNOS and COX-2 expressions in activated microglial cells. [ABSTRACT FROM AUTHOR]

Abstract: Ethonopharmacological relevance: Thuja orientalis (L) ENDL (Cupressaceae) is an evergreen arbor that is distributed throughout Northeast Asia. This plant has been used as a traditional medicine for the treatment of various inflammatory diseases such as dermatitis, gout and chronic tracheitis. Aim of the study: To isolate the active principles responsible for the anti-inflammatory activities of Thuja orientalis and to disclose their mechanism of action in lipopolysaccharide (LPS)-stimulated macrophages. Materials and methods: The methanolic leaves and stem extracts of the Thuja orientalis were successively fractionated into EtOAc, n-BuOH and the remaining aqueous fractions. The EtOAc soluble fraction, which exhibited significant inhibitory activity on LPS-induced nitric oxide (NO) production, was followed by successive activity-guided chromatography to yield seven diterpenoids. The anti-inflammatory properties of active constituents were evaluated by RT-PCR, Western blotting and reporter gene assay in cell culture system. Results: A new labdane diterpene, 15-nor-14-oxolabda-8(17),13(16)-dien-19-oic acid (1), and six known diterpenoids (2–7) were isolated from the EtOAc extracts of Thuja orientalis. The isolated compounds 1–7 were evaluated for the inhibitory activity of LPS-induced NO production in RAW264.7 macrophage cells. Compound 1 was the most potent among the isolated compounds for the inhibition of LPS-induced NO production (IC50 1: 3.56μM). Compound 1 reduced the production of pro-inflammatory mediators and suppressed the expression of the inflammatory enzymes of iNOS and COX-2. In addition, compound 1 attenuated the LPS-induced transcriptional activity of NF-κB by the inhibition of inhibitory-κBα degradation, and suppressed the activity of extracellular signal regulated kinase (ERK). Conclusions: This study demonstrates that a new labdane diterpene from Thuja orientalis inhibits the inflammatory responses by the suppression of NF-κB activity and ERK phosphorylation. This compound might be a valuable candidate for the development of anti-inflammatory drugs. [Copyright &y& Elsevier]

Abstract: The overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) causes neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Four lignans, (+)-eudesmin (1), (+)-magnolin (2), (+)-yangambin (3) and a new structure named as epimagnolin B (4) were isolated from Magnolia fargesii (Magnoliaceae) as the inhibitors of NO production in LPS-activated microglia. The most potent compound 4 inhibited the production of NO and PGE2 and the expression of respective enzyme iNOS and COX-2 through the suppression of I-κB-α degradation and nuclear translocation of p65 subunit of NF-κB. [Copyright &y& Elsevier]

Abstract: The N-glycans in human immunoglobulin G were engineered through the bacterial glycosyltransferase-catalyzed galactosylation and sialylation with in situ regeneration of sugar-nucleotides. For the galactosylation and sialylation, β1,4-galactosyltransferase from H. pylori and α2,3-sialyltransferase from N. gonorrhoeae were expressed in Escherichia coli. For the regeneration of UDP-galactose and CMP-NeuAc, the required enzymes were also expressed in E. coli and their extracts were employed as biocatalysts. Using the catalytic system, we carried out the galactosylation of terminal GlcNAc residues with UDP-Gal regeneration and sialylation of terminal Gal residues with CMP-NeuAc regeneration, respectively. When the oligosaccharides in human IgG were analyzed by HPLC (NP and WAX) and MALDI-TOF, the galactosylation reaction showed 86.1% increase in terminal galactosylation of N-linked oligosaccharide in IgG, and the sialylation reaction gave 69.6% increase in terminal sialylation. To achieve a maximum sialylation of IgG, simultaneous galactosylation and sialylation reaction was conducted by incubating all of the biocatalysts required for the galactosylation, sialylation and sugar-nucleotide regenerations in one reactor, resulting in 80.2% increase in terminal sialylation. [Copyright &y& Elsevier]

Abstract: A series of 2-aminodihydroquinoline analogs were synthesized and their in vitro cytotoxicities against metastatic breast adenocarcinoma cell line MDA-MB-231 were tested. Five out of 16 compounds exhibited promising activity and structure–activity relationship revealed major role of dialkylaminoethyl substituents on dihydroquinoline ring for the activity. Two compounds, 5f and 5h, presented cytotoxicity with IC50 values of about 2μM when the compounds were treated to the cells without serum. The cell proliferation was inhibited mildly when the cells cultured with serum. Flow cytometry analyses showed that those compounds arrested the cells at G2/M checkpoint when the cell cycle is active while they induce apoptosis when the cell growth is restricted due to the absence of growth factors. These results suggest the two novel compounds may have anticancer activity through cell cycle arrest and pro apoptosis mechanism. [Copyright &y& Elsevier]

Aberrant activation of a Wnt/β-catenin pathway results in nuclear accumulation of β-catenin in colon cancer. Inhibiting β-catenin is one strategy for treating colon cancer. Here, we identified Z-ajoene, a sulfur containing compound isolated from crushed garlic, as an inhibitor of colon cancer cell growth. Z-Ajoene repressed β-catenin response transcriptional activity, intracellular β-catenin levels, and its representative target protein levels (c-Myc and cyclin D1) in SW480 colon cancer cells. To clarify the regulatory mechanism of decreased β-catenin levels, we examined the effect of Z-ajoene on β-catenin phosphorylation, which is involved in β-catenin degradation. Z-Ajoene promoted the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner, which is an essential step in β-catenin degradation in the cytosol. These findings indicate that Z-ajoene from garlic may be a potential chemotherapeutic agent by modulating CK1α activity and the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]