Structural Mutations in the Organellar Genomes of Valeriana sambucifolia f. dageletiana (Nakai. ex Maekawa) Hara Show Dynamic Gene Transfer.

Valeriana sambucifolia f. dageletiana (Nakai. ex Maekawa) Hara is a broad-leaved valerian endemic to Ulleung Island, a noted hot spot of endemism in Korea. However, despite its widespread pharmacological use, this plant remains comparatively understudied. Plant cells generally contain two types of organellar genomes (the plastome and the mitogenome) that have undergone independent evolution, which accordingly can provide valuable information for elucidating the phylogenetic relationships and evolutionary histories of terrestrial plants. Moreover, the extensive mega-data available for plant genomes, particularly those of plastomes, can enable researchers to gain an in-depth understanding of the transfer of genes between different types of genomes. In this study, we analyzed two organellar genomes (the 155,179 bp plastome and the 1,187,459 bp mitogenome) of V. sambucifolia f. dageletiana and detected extensive changes throughout the plastome sequence, including rapid structural mutations associated with inverted repeat (IR) contraction and genetic variation. We also described features characterizing the first reported mitogenome sequence obtained for a plant in the order Dipsacales and confirmed frequent gene transfer in this mitogenome. We identified eight non-plastome-originated regions (NPRs) distributed within the plastome of this endemic plant, for six of which there were no corresponding sequences in the current nucleotide sequence databases. Indeed, one of these unidentified NPRs unexpectedly showed certain similarities to sequences from bony fish. Although this is ostensibly difficult to explain, we suggest that this surprising association may conceivably reflect the occurrence of gene transfer from a bony fish to the plastome of an ancestor of V. sambucifolia f. dageletiana mediated by either fungi or bacteria.

In vivo and in vitro anti­allergic and anti­inflammatory effects of Dryopteris crassirhizoma through the modulation of the NF­Ä¸B signaling pathway in an ovalbumin­induced allergic asthma mouse model.

Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, anti­influenza virus, anti­tumor, anti­reverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)­induced allergic asthma mouse model and phorbol myristate acetate (PMA)­ and A23187­stimulated HMC­1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL­10 and interferon (IFN)­Î³) and decreased the levels Th2 cytokines (IL­4, IL­5 and IL­13) and proinflammatory cytokines (IL­6 and TNF­α). Furthermore, DC treatment inhibited the activation of NF­κB signaling (NF­κB, p­NF­κB, IκB and p­IκB), both in BALF and lung homogenates. Serum levels of total IgE and OVA­specific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the anti­inflammatory effect of OVA­specific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL­6 and TNF­α, and the activation of NF­κB signaling (NF­κB and p­NF­κB), in PMA and calcium ionophore A23187­stimulated HMC­1 cells. In summary, the current study demonstrated that DC acts a potent anti­allergic and anti­inflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187­stimulated HMC­1 cells via NF­κB signaling in an OVA­induced allergic asthma model.

The complete chloroplast genome sequence of Thymus quinquecostatus var. japonicus (Lamiaceae), an endemic to Ullenung Island of Korea.

The complete chloroplast (cp) genome sequence of Thymus quinquecostatus var. japonicus, an endemic species to Ulleung Island of Korea and used as plant material for folk remedies, was firstly analyzed in this study. It showed a typical circular structure composed of 151,782 bp in length and comprised of a large single-copy region (82,903bp) and a small single-copy region (17,667 bp) which were separated by two inverted repeat regions (25,606 bp). From the phylogenetic analyses of related taxa using the complete chloroplast genome sequences, it was proved that T. quinquecostatus var. japonicus is sister to the member of genus Mentha within the subfamily Nepetoideae.

Organellar genome analysis reveals endosymbiotic gene transfers in tomato.

We assembled three complete mitochondrial genomes (mitogenomes), two of Solanum lycopersicum and one of Solanum pennellii, and analyzed their intra- and interspecific variations. The mitogenomes were 423,596-446,257 bp in length. Despite numerous rearrangements between the S. lycopersicum and S. pennellii mitogenomes, over 97% of the mitogenomes were similar to each other. These mitogenomes were compared with plastid and nuclear genomes to investigate genetic material transfers among DNA-containing organelles in tomato. In all mitogenomes, 9,598 bp of plastome sequences were found. Numerous nuclear copies of mitochondrial DNA (NUMTs) and plastid DNA (NUPTs) were observed in the S. lycopersicum and S. pennellii nuclear genomes. Several long organellar DNA fragments were tightly clustered in the nuclear genome; however, the NUMT and NUPT locations differed between the two species. Our results demonstrate the recent occurrence of frequent endosymbiotic gene transfers in tomato genomes.

Successful Treatment of Combined Aspergillus and Cytomegalovirus Abscess in Brain and Lung After Liver Transplant for Toxic Fulminant Hepatitis.

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.

Rosae Multiflorae Fructus Hot Water Extract Inhibits a Murine Allergic Asthma Via the Suppression of Th2 Cytokine Production and Histamine Release from Mast Cells.

Mast cell-mediated anaphylactic reactions are involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, Rosae Multiflorae fructus (RMF) is known to have potent antioxidative, analgesic, and anti-inflammatory activities and to have no obvious acute toxicity. However, its specific effect on asthma is still unknown. In this study, we evaluated whether or not RMF hot water extracts (RMFW) could inhibit ovalbumin (OVA)-induced allergic asthma and evaluated compound 48/80-induced mast cell activation to elucidate the mechanisms of asthma inhibition by RMFW. Oral administration of RMFW decreased the number of eosinophils and lymphocytes in the lungs of mice challenged by OVA and downregulated histological changes such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. In addition, RMFW significantly reduced T helper 2 cytokines, TNF-α, IL-4, and IL-6 levels in the BAL fluid of mice challenged by OVA. Moreover, RMFW suppressed compound 48/80-induced rat peritoneal mast cell degranulation and inhibited histamine release from mast cells induced by compound 48/80 in a dose-dependent manner. These results suggest that RMFW may act as an antiallergic agent by inhibitingTh2 cytokine production from Th2 cells and histamine release from mast cells, and could be used as a therapy for patients with Th2-mediated or mast cell-mediated allergic diseases.

Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons.

α-Synuclein (α-syn) is a small lipid-binding protein implicated in several neurodegenerative diseases, including Parkinson's disease, whose pathobiology is conserved from yeast to man. There are no therapies targeting these underlying cellular pathologies, or indeed those of any major neurodegenerative disease. Using unbiased phenotypic screens as an alternative to target-based approaches, we discovered an N-aryl benzimidazole (NAB) that strongly and selectively protected diverse cell types from α-syn toxicity. Three chemical genetic screens in wild-type yeast cells established that NAB promoted endosomal transport events dependent on the E3 ubiquitin ligase Rsp5/Nedd4. These same steps were perturbed by α-syn itself. Thus, NAB identifies a druggable node in the biology of α-syn that can correct multiple aspects of its underlying pathology, including dysfunctional endosomal and endoplasmic reticulum-to-Golgi vesicle trafficking.

Effects of Anemarrhena asphodeloides on IgE-mediated passive cutaneous anaphylaxis, compound 48/80-induced systemic anaphylaxis and mast cell activation.

BACKGROUND: We investigated the effect of Anemarrhena asphodeloides Bunge (Liliaceae) water extract (AAWE) on mast cell-mediated anaphylactic reactions. Mast cell-mediated anaphylactic reaction is involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, AAWE is known to have antioxidant and anticancer activity. However, its specific effect on mast cell-mediated anaphylactic reactions is still unknown. METHODS: We examined whether or not AAWE could inhibit IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and mast cell activation. RESULTS: Oral administration of AAWE inhibited compound 48/80-induced systemic anaphylaxis in mice. AAWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl IgE antibody in rats. AAWE reduced compound 48/80-induced degranulation of rat peritoneal mast cells (RPMCs). Moreover, AAWE inhibited histamine release and calcium uptake of RPMCs induced by compound 48/80 in a dose-dependent manner. AAWE also significantly inhibited secretion of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in phorbol 12-myristate 13-acetate plus calcium ionophores A23187-stimulated RPMCs. CONCLUSIONS: These results suggest that AAWE suppresses compound 48/80-induced mast cell activation by inhibition of cellular mechanisms in signaling pathways, and would be beneficial for treatment of mast cell-mediated anaphylactic response.

Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions.

Agaricus blazei is a medicinal mushroom native to Brazil. It used to be a source of anti-tumor and immunmoactive compounds and considered a health food in many countries. However, its specific effect against mast cell-mediated anaphylactic reactions is still unknown. In the present study, we investigated the effect of Agaricus blazei water extract (ABWE) on mast cell-mediated anaphylaxis-like reactions. We examined whether ABWE could inhibit systemic anaphylaxis-like reaction, ear swelling response, passive cutaneous anaphylaxis, and mast cell activation. ABWE inhibited compound 48/80-induced systemic anaphylaxis-like reaction, ear swelling response, and passive cutaneous anaphylaxis-like reaction in mice. ABWE also inhibited anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. ABWE dose-dependently inhibited compound 48/80-induced or anti-DNP IgE-mediated histamine release from rat peritoneal mast cells (RPMC). Moreover, pretreatment with ABWE reduced compound 48/80-induced calcium uptake into RPMC. When ABWE was added, the level of intracellular cAMP in RPMC showed a significant increase compared with that of control cells. In addition, ABWE significantly inhibited compound 48/80-induced cAMP reduction in RPMC. These results propose that ABWE may be beneficial in the treatment of mast cell-mediated anaphylactic reactions.

Inhibitory effects of Houttuynia cordata water extracts on anaphylactic reaction and mast cell activation.

The present study was investigated the effect of Houttuynia cordata THUNB water extract (HCWE) on mast cell-mediated anaphylactic reactions. The mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. HCWE has been used as a traditional medicine in Korea and is known to have an antioxidant and anti-cancer activities. However, its specific effect of mast cell-mediated anaphylactic reactions is still unknown. We examined whether HCWE could inhibit compound 48/80-induced systemic anaphylaxis, IgE-mediated passive cutaneous anaphylaxis (PCA), and mast cell activation. The oral administration of HCWE inhibited compound 48/80-induced systemic anaphylaxis in mice. HCWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl (DNP) IgE antibody in rats. HCWE reduced the compound 48/80-induced mast cell degranulation and colchicine-induced deformation of rat peritoneal mast cells (RPMC). Moreover, HCWE dose-dependently inhibited histamine release and calcium uptake of RPMC induced by compound 48/80 or anti-DNP IgE. HCWE increased the level of intracellular cAMP and inhibited significantly the compound 48/80-induced cAMP reduction in RPMC. These results suggest that HCWE may be beneficial in the treatment of mast cell-mediated anaphylactic responses.