RESUMEN
Researchers continue to explore drug targets to treat the characteristic pathologies of Alzheimer's disease (AD). Some drugs relieve the pathological processes of AD to some extent, but the failed clinical trials indicate that multifunctional agents seem more likely to achieve the therapy goals for this neurodegenerative disease. Herein, a novel compound named melatonin-trientine (TM) has been covalently synthesized with the natural antioxidant compounds melatonin and the metal ion chelator trientine. After toxicological and pharmacokinetic verification, we elucidated the effects of intraperitoneal administration of TM on AD-like pathology in 6-month-old mice that express both the ß-amyloid (Aß) precursor protein and presenilin-1 (APP/PS1). We found that TM significantly decreased Aß deposition and neuronal degeneration in the brains of the APP/PS1 double transgenic mice. This result may be due to the upregulation of iron regulatory protein-2 (IRP2), insulin degrading enzyme (IDE), and low density lipoprotein receptor related protein 1 (LRP1), which leads to decreases in APP and Aß levels. Additionally, TM may promote APP non-amyloidogenic processing by activating the melatonin receptor-2 (MT2)-dependent signaling pathways, but not MT1. In addition, TM plays an important role in blocking γ-secretase, tau hyperphosphorylation, neuroinflammation, oxidative stress, and metal ion dyshomeostasis. Our results suggest that TM may effectively maximize the therapeutic efficacy of targeting multiple mechanisms associated with AD pathology.
Asunto(s)
Enfermedad de Alzheimer , Melatonina , Enfermedades Neurodegenerativas , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Quelantes/farmacología , Modelos Animales de Enfermedad , Melatonina/farmacología , Melatonina/uso terapéutico , Ratones , Ratones Transgénicos , Trientina/uso terapéuticoRESUMEN
ABATRACTNine compounds, five phenolic glycosides (1, 2, 4-6), three phenylpropanoids (7-9), and a furanone glycoside (3), were isolated from aqueous soluble extract of the dried roots of Anemone chinensis Bunge. The structures of new compounds (1-4) were elucidated by comprehensive spectroscopic data analysis as well as chemical evidence. Pulsatillanin A (1) demonstrated significant antioxidant effects through scavenging free radical in DPPH assay, and relieved the oxidative stress in LPS-induced RAW 264.7 cells by reducing ROS production, enhancing antioxidant enzyme SOD activity, replenishing depleted GSH in a dose-dependent manner. Western blot analysis revealed that 1 showed antioxidant activity via activating Nrf2 signaling pathway.[Formula: see text].
Asunto(s)
Anemone , Antioxidantes , Antioxidantes/química , Glicósidos/química , Glicósidos/farmacología , Lipopolisacáridos , Factor 2 Relacionado con NF-E2 , Fenoles/análisis , Extractos Vegetales/química , Especies Reactivas de Oxígeno , Superóxido DismutasaRESUMEN
BACKGROUND: Neuroinflammation is thought to be a cause of Alzheimer's disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD. METHODS: BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD. Sophisticated molecular technologies including quantitative (q) RT-PCR, western blot, enzyme linked immunosorbent assay (ELISA), co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were employed to reveal the inherent mechanisms. RESULTS: As a consequence, key roles of OPTN in regulating neuroinflammation were identified by depressing the activity of absent in melanoma 2 (AIM2) inflammasomes and receptor interacting serine/threonine kinase 1 (RIPK1)-mediated NF-κB inflammatory mechanisms. In detail, we found that expression of OPTN was downregulated, which resulted in activation of AIM2 inflammasomes due to a deficiency in mitophagy in APP/PS1 Tg mice. By ectopic expression, OPTN blocks the effects of Aß oligomer (Aßo) on activating AIM2 inflammasomes by inhibiting mRNA expression of AIM2 and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), leading to a reduction in the active form of caspase-1 and interleukin (IL)-1ß in microglial cells. Moreover, RIPK1 was also found to be negatively regulated by OPTN via ubiquitin protease hydrolysis, resulting in the synthesis of IL-1ß by activating the transcriptional activity of NF-κB in BV2 cells. As an E3 ligase, the UBAN domain of OPTN binds to the death domain (DD) of RIPK1 to facilitate its ubiquitination. Based on these observations, ectopically expressed OPTN in APP/PS1 Tg mice deactivated microglial cells and astrocytes via the AIM2 inflammasome and RIPK-dependent NF-κB pathways, leading to reduce neuroinflammation. CONCLUSIONS: These results suggest that OPTN can alleviate neuroinflammation through AIM2 and RIPK1 pathways, suggesting that OPTN deficiency may be a potential factor leading to the occurrence of AD.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Inflamasomas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Animales , Apoptosis/fisiología , Encéfalo/metabolismo , Caspasa 1/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular , Proteínas de Unión al ADN/genética , Humanos , Interleucina-1beta/metabolismo , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Transgénicos , Enfermedades Neuroinflamatorias/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genéticaRESUMEN
A yellow, Gram-stain-negative, aerobic, non-gliding, non-spore-forming, rod-shaped strain, designated YIM 102600T, was isolated from the faeces of Macaca mulatta dwelling in the Yunnan Wild Animal Park, Yunnan Province, South-West PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 102600T was a member of the genus Flavobacterium, and closely related to Flavobacterium qiangtangense F3T (96.9â% similarity) and Flavobacterium noncentrifugens R-HLS-17T (96.0â% similarity). Phylogenetic trees showed that strain YIM 102600T formed a clade with F. qiangtangense F3T and F. noncentrifugens R-HLS-17T. Growth occurred at 4-30 °C (optimum, 28 °C), pH 7.0-8.0 (pH 7.5) and NaCl concentration 0-2â% (w/v; 0-1â%, w/v). The major fatty acids were iso-C15:0 and summed feature 3 (comprising C16:1 ω7c and/or C16:1 ω6c). The predominant polar lipid was phosphatidylethanolamine and the sole respiratory quinone was menaquinone-6. The DNA G+C content was 36.4 mol%. The calculated digital DNA-DNA hybridization values between strain YIM 102600T and other species of Flavobacterium ranged from 70.0 to 75.0 % and average nucleotide identity values were in a range between 13.7 to 23.5 %. Based above the consensus of phenotypic and phylogenetic analyses as well as whole genome comparisons, strain YIM 102600T (=KCTC 52099T=CCTCC AB 201632T) is proposed to represent type strain of a novel species, Flavobacterium macacae sp. nov.
Asunto(s)
Flavobacterium/clasificación , Macaca mulatta/microbiología , Filogenia , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Heces/microbiología , Flavobacterium/aislamiento & purificación , Hibridación de Ácido Nucleico , Fosfatidiletanolaminas/química , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
Three new phenazine metabolites, strepphenazine A-C (1-3), along with a known compound baraphenazine E 4 were isolated from the culture broth of a Streptomyces strain YIM PH20095. The structures were elucidated based on the spectral data. Compounds 1-4 showed different antifungal activity against Fusarium oxysporum, Plectosphaerella cucumerina, Alternaria panax, and Phoma herbarum, which caused root-rot disease of Panax notoginseng with minimal inhibitory concentrations (MICs) of 16-64 µg/mL; compared with compound 4, compounds 1-3 showed better antifungal activity against some of these pathogenic fungi with MICs of 16-32 µg/mL, while compound 4 showed antifungal activity against F. oxysporum, P. cucumerina, and A. panax with the same MICs of 64 µg/mL. Thus, strain YIM PH20095 provides new sources for the development of biological control agents to prevent the infection of pathogenic fungi of P. notoginseng.
Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Panax notoginseng/microbiología , Fenazinas/química , Fenazinas/farmacología , Streptomyces/química , Alternaria/efectos de los fármacos , Alternaria/crecimiento & desarrollo , Antifúngicos/aislamiento & purificación , Antifúngicos/metabolismo , Fusarium/efectos de los fármacos , Fusarium/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fenazinas/aislamiento & purificación , Fenazinas/metabolismo , Enfermedades de las Plantas/microbiologíaRESUMEN
BACKGROUND: Recent studies have revealed that vitamin D deficiency may increase the risk of Alzheimer's disease, and vitamin D supplementation may be effective strategy to ameliorate the neurodegenerative process in Alzheimer's disease patients. Paricalcitol (PAL), a low-calcemic vitamin D receptor agonist, is clinically used to treat secondary hyperparathyroidism. However, the potential application of PAL for treating neurodegenerative disorders remains unexplored. METHODS: The APP/PS1 mice were intraperitoneally injected with PAL or vehicle every other day for 15â¯weeks. The ß-amyloid (Aß) production was confirmed using immunostaining and enzyme linked immunosorbent assay. The underlying mechanism was verified by western blot and immunostaining in vivo and in vitro. FINDINGS: Long-term PAL treatment clearly reduced ß-amyloid (Aß) generation and neuronal loss in APP/PS1 transgenic mouse brains. PAL stimulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) possibly through inhibiting sterol regulatory element binding protein-2 (SREBP2); PAL also promoted LRP1-mediated ß-site APP cleavage enzyme 1 (BACE1) transport to late endosomes, thus increasing the lysosomal degradation of BACE1. Furthermore, PAL diminished 8-hydroxyguanosine (8-OHdG) generation in neuronal mitochondria via enhancing base excision repair (BER), resulting in the attenuation of calpain-1-mediated neuronal loss. INTERPRETATION: The present data demonstrate that PAL can reduce Aß generation through accelerating BACE1 lysosomal degradation and can inhibit neuronal loss through suppressing mitochondrial 8-OHdG generation. Hence, PAL might be a promising agent for treating Alzheimer's disease. FUND: This study was financially supported by the Natural Science Foundation of China (U1608282).
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide/genética , Ácido Aspártico Endopeptidasas/genética , Ergocalciferoles/farmacología , Neuronas/efectos de los fármacos , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/genética , Animales , Encéfalo/metabolismo , Encéfalo/patología , Calpaína/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Lisosomas/efectos de los fármacos , Lisosomas/genética , Ratones , Ratones Transgénicos , Mitocondrias/metabolismo , Neuronas/patología , Oligopéptidos/genética , Presenilina-1/genética , Proteolisis/efectos de los fármacosRESUMEN
Alzheimer's disease (AD) is reportedly associated with the accumulation of calcium ions (Ca2+), and this accumulation is responsible for the phosphorylation of tau. Although several lines of evidence demonstrate the above phenomenon, the inherent mechanisms remain unknown. Using APP/PS1 Tg mice and neuroblastoma (N)2a cells as in vivo and in vitro experimental models, we observed that Ca2+ stimulated the phosphorylation of tau by activating microsomal PGE synthase 1 (mPGES1) in a prostaglandin (PG) E2-dependent EP receptor-activating manner. Specifically, the highly accumulated Ca2+ stimulated the expression of mPGES1 and the synthesis of PGE2. Treatment with the inhibitor of Ca2+ transporter, NMDAR, attenuated the expression of mPGES1 and the production of PGE2 were attenuated in S(+)-ketamine-treated APP/PS1 Tg mice. Elevated levels of PGE2 were responsible for the hyperphosphorylation of tau in an EP-1-, EP-2-, and EP-3-dependent but not EP4-dependent cyclin-dependent kinase (Cdk) 5-activating manner. Reciprocally, the knockdown of the expression of mPGES1 ameliorated the expected cognitive decline by inhibiting the phosphorylation of tau in APP/PS1 Tg mice. Moreover, CDK5 was found to be located downstream of EP1-3 to regulate the phosphorylation of tau though the cleavage of p35 to p25. Finally, the phosphorylation of tau by Ca2+ contributed to the cognitive decline of APP/PS1 Tg mice.
RESUMEN
Alzheimer's disease (AD) is reported to be associated with the accumulation of calcium ions (Ca2+), which is responsible for the phosphorylation of tau. Although a series of evidence have demonstrated this phenomenon, the inherent mechanisms remain unknown. Using tauP301S and cyclooxygenase-2 (COX-2) transgenic mice and neuroblastoma (n)2a cells as in vivo and in vitro experimental models, we found that Ca2+ stimulates the phosphorylation of tau by activating COX-2 in a prostaglandin (PG) E2-dependent EP receptor-activating manner. Specifically, Ca2+ incubation stimulated COX-2 and PGE2 synthase activity, microsomal PGE synthase 1 and the synthesis of PGE2 by activating the transcriptional activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in n2a cells. Elevated levels of PGE2 were responsible for phosphorylating tau in an EP-1, -2, and -3 but not EP4-dependent glycogen synthase kinase 3-activating manner. These observations were corroborated by results that showed tau was phosphorylated when it colocalized with activated COX-2 in tauP301S and COX-2 transgenic mice or n2a cells. To further validate these observations, treatment of mice with the COX-2 inhibitor rofecoxib decreased the phosphorylation of tau via EP1-3 but not EP4. Collectively, our observations fill the gaps between Ca2+ and the phosphorylation of tau in a COX-2-dependent mechanism, which potentially provides therapeutic targets for combating AD.
Asunto(s)
Calcio/metabolismo , Ciclooxigenasa 2/metabolismo , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Animales , Western Blotting , Inhibidores de la Ciclooxigenasa 2/farmacología , Humanos , Lactonas/farmacología , Masculino , Aprendizaje por Laberinto , Ratones , Ratones Transgénicos , Fosforilación , Prostaglandina-E Sintasas/metabolismo , Quinazolinas/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa , Serina , Sulfonas/farmacologíaRESUMEN
Huge numbers of bacteria reside in the digestive tract of host and these microorganisms play a vital role in the host health, especially in the digestion of food and the development of immune system. Host phylogeny and diet, especially long-term diet, both have great influence on the gut bacterial community. Other aspects of host, such as gender, age, and the geography and weather they lived, are also correlated to their gut bacterial community. Feces are usually used for gut bacteria study and fecal bacteria can represent the distal gut bacteria. In order to determine the influence of the host phylogeny and diet on the composition of distal gut bacterial community and to interpret bacterial population and diversity in the intestinal of animals, the distal gut bacterial community of four kinds of primates and five kinds of carnivora (including herbivorous, omnivorous, and carnivorous) were investigated using high-throughput sequencing and the isolation of the Actinobacteria from fresh feces of several primates was processed. The results showed the host phylogeny had a greater influence on the distal gut bacterial community of the primates and carnivora than the host diet. A total of 44 bacteria phyla and two archaea phyla were detected, which indicated that the distal gut bacteria of these animals were abundant. The distal gut bacteria were relatively stable and wildly shared in primates and carnivora. The difference in distal gut bacteria of the two animal orders is mainly determined by relative abundance of most distal gut bacteria rather than by the taxa of these bacteria.
Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Carnívoros , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Primates , Actinobacteria , Animales , Archaea/genética , Bacterias/genética , Heces/microbiología , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Five new compounds including five iridoids (1-5) and six known compounds were isolated from the rhizomes of Scrophularia ningpoensis. Their structures were determined by extensive NMR and IR, MS spectroscopic data analyses. The anti-inflammatory, antibacterial, antifungal, and cytotoxic activities of the isolated compounds were evaluated. Compound 11 exhibited significant inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophage cells.
Asunto(s)
Antiinflamatorios/química , Iridoides/química , Scrophularia/química , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Iridoides/aislamiento & purificación , Lipopolisacáridos/toxicidad , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Conformación Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Rizoma/química , Rizoma/metabolismo , Scrophularia/metabolismo , Espectrofotometría InfrarrojaRESUMEN
Alzheimer's disease (AD) is characterized by the loss of neurogenesis and excessive induction of apoptosis. The induction of neurogenesis and inhibition of apoptosis may be a promising therapeutic approach to combating the disease. Celecoxib (CB), a cyclooxygenase-2 specific inhibitor, could offer neuroprotection. Specifically, the CB-encapsulated erythrocyte membranes (CB-RBCMs) sustained the release of CB over a period of 72 h in vitro and exhibited high brain biodistribution efficiency following intranasal administration, which resulted in the clearance of aggregated ß-amyloid proteins (Aß) in neurons. The high accumulation of the CB-RBCMs in neurons resulted in a decrease in the neurotoxicity of CB and an increase in the migratory activity of neurons, and alleviated cognitive decline in APP/PS1 transgenic (Tg) mice. Indeed, COX-2 metabolic products including prostaglandin E2 (PGE2) and PGD2, PGE2 induced neurogenesis by enhancing the expression of SOD2 and 14-3-3ζ, and PGD2 stimulated apoptosis by increasing the expression of BIK and decreasing the expression of ARRB1. To this end, the CB-RBCMs achieved better effects on concurrently increasing neurogenesis and decreasing apoptosis than the phospholipid membrane-encapsulated CB liposomes (CB-PSPD-LPs), which are critical for the development and progression of AD. Therefore, CB-RBCMs provide a rational design to treat AD by promoting the self-repairing capacity of the brain.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Apoptosis , Celecoxib/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Membrana Eritrocítica/metabolismo , Neurogénesis , Presenilina-1/metabolismo , Proteínas 14-3-3/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Animales , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Celecoxib/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/patología , Dinoprostona/farmacología , Membrana Eritrocítica/efectos de los fármacos , Células HEK293 , Humanos , Liposomas/ultraestructura , Ratones Transgénicos , Proteínas Mitocondriales/metabolismo , Modelos Biológicos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fosfolípidos/química , Prostaglandina D2/farmacología , Ratas Wistar , Superóxido Dismutasa/metabolismo , Distribución Tisular/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , beta-Arrestina 1/metabolismoRESUMEN
A novel actinobacterium, designated YIM 101593T, was isolated from the faeces of a primate (Rhinopithecus roxellanae) living in Yunnan Wild Animal Park in Yunnan province, south-west China. The isolate was Gram-stain-positive, facultatively anaerobic, coccus-shaped, oxidase-negative and motile. The cell wall contained meso-diaminopimelic acid as its diagnostic diamino acid, and mannose, ribose, glucose, galactose and arabinose were detected as the main whole-cell sugars. The predominant menaquinone was MK-8(H2). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two glycolipids, three unidentified phospholipids and two unidentified lipids. The major fatty acids were C17â:â1ω8c, C15â:â0 and summed feature 4 (anteiso-C17â:â1 B and/or iso-C17â:â1 I). The DNA G+C content was 69.8 mol%. The 16S rRNA gene sequence similarity between strain YIM 101593T and Mobilicoccus pelagius was 97.9â%, and the two strains formed a distinct lineage stably on the basis of phylogenetic analysis. In addition, DNA-DNA relatedness between the two strains was 49.0±5.1â%. On the basis of chemotaxonomical and physiological characteristics and the phylogenetic analysis, strain YIM 101593T should be considered to represent a novel species of the genus Mobilicoccus, for which we propose the name Mobilicoccus caccae sp. nov., with the type strain YIM 101593T (=DSM 27611T=CCTCC AB 2013229T).
Asunto(s)
Actinomycetales/clasificación , Heces/microbiología , Filogenia , Primates/microbiología , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , ADN Ribosómico/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel strain, YIM 100770T, was isolated from Rhinoceros unicornis faeces collected from Yunnan Wild Animal Park, China. The taxonomic status was determined based on the physiological, biochemical and phylogenetic characteristics. Strain YIM 100770T was observed to be rod-shaped, non-motile, Gram-stain negative and aerobic. The G+C content of the genomic DNA was determined to be 68.5 mol%. The cells of strain YIM 100770T contain ubiquinone Q-10 as the respiratory quinone. The major fatty acids (>1%) were identified as Summed feature 8 (C18:1 ω7c and/or C18:1 ω6c; 78.1%), Summed feature 4 (iso-C17:1-I and/or anteiso-C17:1-B; 12.9%), C19:0 cyclo ω8c (2.8%), C16:0 (2.2%) and C18:0 (2.2%). Comparison of 16S rRNA gene sequences revealed the strain show high similarities with the members of the genera Psychroglaciecola (94.5%), Methylobacterium (90.5-94.1%) and Microvirga (92.0-93.3%) in the family Methylobacteriaceae. In addition, the strain also showed high similarities with the members of the genera Chelatococcus (93.7-94.0%) and Pseudochelatococcus (93.1-93.7%) in the family Beijerinckiacea, and the genus Bosea (93.1-93.8%) in the family Bradyrhizobiaceae. The phylogenetic analysis, combined with the chemical characteristics, suggest that the strain represents a novel genus in the order Rhizobiales of the class Alphaproteobacteria, for which the name Enterovirga rhinocerotis gen. nov., sp. nov. is proposed. The type strain of E. rhinocerotis is YIM 100770T (=DSM 25903T = CCTCC AB 2012048T).
Asunto(s)
Alphaproteobacteria/clasificación , Alphaproteobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Perisodáctilos/microbiología , Alphaproteobacteria/genética , Animales , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/análisis , Heces/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
A novel, yellow, aerobic strain, YIM 101168T, isolated from the faeces of a dove (Columba livia), was studied to determine its taxonomic position. Cells were Gram-stain-positive, short rod-shaped, oxidase-negative, catalase-positive and non-motile. The strain could grow at 7-37 °C, at pH 6-10 and in the presence of 0-13 % (w/v) NaCl. The strain had a 16S rRNA gene sequence similarity and DNA-DNA hybridization relatedness value with Microbacteriumgubbeenense NCIMB 30129T of 97.8 % and 41.5±8.7 %, respectively. Ornithine was detected as the diagnostic amino acid in the hydrolysate of the cell wall. Whole-cell sugars were found to be galactose, glucose, rhamnose, mannose and ribose. Major fatty acids (>10 %) were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. Major menaquinones were identified as MK-10, MK-11 and MK-12. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipids and four unidentified lipids. The phylogenetic analyses as well as the chemotaxonomic and phenotypic characteristics indicate that strain YIM 101168T represents a novel species of the genus Microbacterium; the name Microbacterium faecale sp. nov. is proposed for the novel species and the type strain is YIM 101168T (=DSM 27232T=KCTC 39554T=CGMCC 1.15152T).
Asunto(s)
Actinomycetales/clasificación , Columbidae/microbiología , Filogenia , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Aminoácidos/química , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Heces/microbiología , Glucolípidos/química , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/químicaRESUMEN
A novel aerobic, non-motile, Gram-positive, rod-shaped actinobacterium, designated YIM 100951(T), was isolated from the faeces of civets (Viverra zibetha) living in the National Nature Protect Region in Selangor, Malaysia. Strain YIM 100951(T) shows high similarities with Microbacterium barkeri DSM 20145(T) (97.6 %), Microbacterium oryzae MB10(T) (97.3 %), Microbacterium lemovicicum ViU22(T) (97.1 %) and Microbacterium indicum BBH6(T) (97.0 %) based on their 16S rRNA genes. However, phylogenetic analysis showed that strain YIM 100951(T) formed a clade with Microbacterium halotolerans YIM 70130(T) (96.7 %), Microbacterium populi 10-107-8(T) (96.7 %) and Microbacterium sediminis YLB-01(T) (96.9 %). DNA-DNA hybridization was carried out between strains YIM 100951(T) and M. barkeri DSM 20145(T), the result showed a value of 23.2 ± 4.5 %. In addition, some of the physiological, biochemical and chemotaxonomic characteristics of strain YIM 100951(T) are different from the closely related strains. Thus, we suggest that strain YIM 100951(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium gilvum sp. nov. is proposed. The type strain is YIM 100951(T) (=DSM 26235(T) = CCTCC AB 2012971(T)).
Asunto(s)
Actinomycetales/clasificación , Actinomycetales/aislamiento & purificación , Heces/microbiología , Filogenia , Viverridae/microbiología , Actinomycetales/genética , Actinomycetales/metabolismo , Animales , Pared Celular/química , ADN Bacteriano/genética , ADN Ribosómico/genética , Ácidos Grasos/metabolismo , Malasia , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Especificidad de la Especie , Vitamina K 2/metabolismoRESUMEN
A Gram-stain-positive, facultatively anaerobic, short rod-shaped, oxidase-negative and non-motile novel strain, designated YIM 101505T, was isolated from the faeces of a primate, Assamese macaque, and was studied to determine its taxonomic position. The cell wall contained meso-diaminopimelic acid and short-chain mycolic acids. Whole cell sugars were mannose, galactose and arabinose as major components. The major fatty acids (>10 %) were C18 : 1ω9c, C16 : 0 and C17 : 1ω8c and the major menaquinone was MK-9(H2). The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, glycolipid and six unidentified lipids. The new isolate shared most of the typical chemotaxonomic characteristics of members of the genus Corynebacterium. The closest related species was Corynebacterium efficiens based on 16S rRNA gene (98.1 % similarity) and partial rpoB gene (91.4 % similarity) sequences. Similarities with other species of this genus were below 97 % based on the 16S rRNA gene. The DNA-DNA hybridization value between YIM 101505T and C. efficiens DSM 44549T was 47.7±3.6 %. Moreover, the physiological and biochemical characteristics of YIM 101505T and C. efficiens DSM 44549T were different. Thus, strain YIM 101505T is considered to represent a novel member of the genus Corynebacterium, for which the name Corynebacterium faecale sp. nov. is proposed. The type strain is YIM 101505T (=DSM 45971T=CCTCC AB 2013226T).
Asunto(s)
Corynebacterium/clasificación , Corynebacterium/aislamiento & purificación , Heces/microbiología , Macaca/microbiología , Animales , Técnicas de Tipificación Bacteriana , China , Corynebacterium/química , Corynebacterium/citología , ADN Bacteriano/genética , Fosfolípidos/análisis , Filogenia , Análisis de Secuencia de ADNRESUMEN
Two novel actinobacteria, designated strains YIM 101617(T) and YIM 101632(T), were isolated from Lama pacos (alpaca) and Viverra zibetha (civet) faeces in Yunnan Wild Animal Park in Yunnan province, southwestern China. Both strains should be placed in genus Enteractinococcus based on phylogenetic analysis. Based on 16S rRNA gene sequence analysis, strain YIM 101617(T) exhibits high similarity to Enteractinococcus fodinae DSM 22966(T) (97.70 %) and Enteractinococcus coprophilus YIM 100590(T) (97.45 %), whilst YIM 101632(T) exhibits high similarity to Enteractinococcus coprophilus YIM 100590(T) (97.25 %), and the similarity between YIM 101617(T) and YIM 101632(T) is 95.90 %. However, DNA-DNA hybridization values of the two strains with the type strains in the genus Enteractinococcus were low (<70 %). Most morphological and chemotaxonomic characteristics of the two strains were found to be similar to those of species in the genus Enteractinococcus but also some differences were observed. The DNA G+C contents of strains YIM 101617(T) and YIM 101632(T) were determined to be 55.9 and 56.4 mol%, respectively. Based on these data, the two strains are concluded to represent two different novel species in the genus Enteractinococcus. The names Enteractinococcus lamae sp. nov. (type strain YIM 101617(T)=DSM 27612(T)=CCTCC AB 2013230(T)) and Enteractinococcus viverrae sp. nov. (type strain YIM 101632(T)=KCTC 39552(T)=CCTCC AB 2013280(T)) are proposed, respectively.
Asunto(s)
Heces/microbiología , Micrococcaceae/clasificación , Micrococcaceae/aislamiento & purificación , Animales , Animales de Zoológico/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , Camélidos del Nuevo Mundo/microbiología , China , Análisis por Conglomerados , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Micrococcaceae/genética , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Viverridae/microbiologíaRESUMEN
Four new prenylindole derivatives, (R)-6-(2,3-dihydroxy-3-methylbutyl)indole (1), (R)-6-(2,3-dihydroxy-3-methylbutyl)indolin-2-one (2), and an unseparated mixture of (Z)-6-(4-hydroxy-3-methylbut-2-en-1-yl)indolin-2-one (3a) and (E)-6-(4-hydroxy-3-methylbut-2-en-1-yl)indolin-2-one (3b) with a ratio of 3 : 2, were isolated from the culture broth of a streptomycete isolated from Ailuropoda melanoleuca feces. Their structures were elucidated on the basis of 1D and 2D NMR spectroscopic techniques. The absolute configuration of 1 was determined by Mosher's method.
Asunto(s)
Heces/microbiología , Indoles/química , Streptomyces/química , Ursidae/microbiología , Animales , Indoles/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Prior work has shown that iron interacts with hyperphosphorylated tau, which contributes to the formation of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD), whereas iron chelator desferrioxamine (DFO) slows down the clinical progression of the cognitive decline associated with this disease. However, the effects of DFO on tau phosphorylation in the presence or absence of iron have yet to be determined. Using amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mouse brain as a model system, we investigated the effects and potential mechanisms of intranasal administration of DFO on iron induced abnormal tau phosphorylation. High-dose iron treatment markedly increased the levels of tau phosphorylation at the sites of Thr205, Thr231 and Ser396, whereas highly induced tau phosphorylation was abolished by intranasal administration of DFO in APP/PS1 transgenic mice. Moreover, DFO intranasal administration also decreases Fe-induced the activities of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase 3ß (GSK3ß), which in turn suppressing tau phosphorylation. Cumulatively, our data show that intranasal DFO treatment exerts its suppressive effects on iron induced tau phosphorylation via CDK5 and GSK3ß pathways. More importantly, elucidation of DFO mechanism in suppressing tau phosphorylation may provide insights for developing therapeutic strategies to combat AD.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Deferoxamina/farmacología , Hipocampo/efectos de los fármacos , Hierro/farmacología , Proteínas tau/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Western Blotting , Hipocampo/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Fosforilación , Presenilina-1/genéticaRESUMEN
A novel actinobacterium, designated strain YIM 100590(T), was isolated from Panthera tigris amoyensis faeces collected from Yunnan Wild Animal Park in Yunnan province, south-west China. Phylogenetic analysis based on 16S rRNA gene sequence data showed that strain YIM 100590(T) is a member of the family Micrococcaceae. Cells were coccoid to oval (0.7-1.5 µm in diameter) occurring singly or in clusters. Growth was observed at 10-37 °C (optimum 28 °C) and at pH 7.0-11.0 (optimum pH 8.0). The major fatty acids were iso-C(15:0) (32.22%), anteiso-C(15:0) (31.64%) and iso-C(16:0) (17.38%). The peptidoglycan was of A4α type (L-Lys-Gly-L-Glu). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides, dimannosyl diacylglycerol, an unknown glycolipid and two unknown phospholipids. The quinone system comprised menaquinones MK-7 (91.9%) and MK-8 (8.3%). The DNA G+C content of strain YIM 100590(T) was 56.2 mol%. Chemotaxonomic data indicated that the strain belongs to the family Micrococcaceae. On the basis of morphological and chemotaxonomic data and phylogenetic analysis, strain YIM 100590(T) is considered to represent a novel species of a new genus within the family Micrococcaceae, for which the name Enteractinococcus coprophilus gen. nov., sp. nov. is proposed. The type strain of Enteractinococcus coprophilus is YIM 100590(T) (=DSM 24083(T)=JCM 17352(T)). Yaniella fodinae DSM 22966(T) was transferred to the new genus as Enteractinococcus fodinae comb. nov. (type strain G5(T)=DSM 22966(T)=JCM 17931(T)=MTCC 9846(T)).