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2.
J Agric Food Chem ; 66(34): 8976-8982, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30095908

RESUMO

Five new resorcylic acid lactones (RALs) hispidulactones A-E (1, 4, 5, 8, and 9), a new natural product (2), and four known ones (3, 6, 7, and 10) with different ring systems were isolated from the desert plant Chaetosphaeronema hispidulum. [corrected]. The new compounds were characterized by NMR data, CD spectra, and X-ray experiment. The new natural product (2) displayed strongly biological effects on the seedlings growth of Arabidopsis thaliana, Digitaria sanguinalis, and Echinochloa crusgalli with a dose-dependent relationship. Compounds 1, 2, and 6 were also tested cytotoxic activities against three cancer cell lines HCT116, Hela, and MCF7 and only did the new natural product (2) display biological activities with IC50 values at 54.86 ± 1.52, 4. 90 ± 0.02, and 20.04 ± 4.00 µM, respectively, whereas the IC50 values of the positive control cis-platinum were 11.36 ± 0.42, 3.54 ± 0.12, and 14.32 ± 1.01 µM, respectively.


Assuntos
Ascomicetos/química , Endófitos/química , Lactonas/química , Lactonas/farmacologia , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Digitaria/crescimento & desenvolvimento , Digitaria/microbiologia , Echinochloa/crescimento & desenvolvimento , Echinochloa/microbiologia , Células HCT116 , Células HeLa , Humanos , Lactonas/isolamento & purificação , Estrutura Molecular
3.
Org Lett ; 20(7): 1806-1809, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29537276

RESUMO

The highly photosensitive characteristic of poly-sulfide chetomins was first unveiled, and four new unstable analogues, chetomins A-D (1-4), with significant cytotoxicity were successfully purified in darkness. The visible-light-induced desulfurization and intermolecular disproportionation were revealed to initiate the interconversion of chetomin analogues, which explained the long-recognized puzzle of rarity and instability of chetomin analogues.


Assuntos
Dissulfetos/química , Alcaloides Indólicos/química , Chaetomium , Estrutura Molecular , Processos Fotoquímicos , Enxofre
4.
J Antibiot (Tokyo) ; 71(6): 613-617, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29540777

RESUMO

Endophytic fungi from desert, arid, and grassland areas are an ecologically important but unique group with poor chemical investigation. During our ongoing study to mine bioactive secondary metabolites from unique fungal environments, a new shunt product spiciferone F (1) including two new analogs spiciferones G (2) and H (3) together with four known ones spiciferone A (4), spiciferol A (5), 6, and 7 were isolated from endophytic fungus Phoma betae inhabiting in plant Kalidium foliatum (Pall.) Moq from Ningxia Province of West China. The planar, relative, and absolute configurations of these new compounds were elucidated by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism experiments. According to the shunt products, intermediates and analogs isolated from this endophytic fungus, the possible biosynthetic pathway of spiciferones was reconstructed. Compounds 1-7 were evaluated cytotoxic activities against three cancer cell lines HCT 116, HeLa, and MCF7, and only did 1 display strong biological effect against MCF7 with a half-maximal inhibitory concentration value at 7.73 ± 0.11 µM compared with the cis-platinum (14.32 ± 1.01 µM).


Assuntos
Ascomicetos/química , Endófitos/química , Compostos Heterocíclicos com 2 Anéis/farmacologia , Plantas/microbiologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , China , Dicroísmo Circular , Clima Desértico , Compostos Heterocíclicos com 2 Anéis/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
5.
Front Physiol ; 8: 801, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29089901

RESUMO

Background: High-altitude headache (HAH) is a notably common disorder affecting the daily life of travelers ascending to high altitude. Hematological parameters are important clinical examinations for various diseases. Today, hematological characteristics of HAH remain unrevealed. Above all, we aimed to ascertain hematological characteristics and independent risk factors/predictors associated with HAH before and after exposure at 3,700 m. Methods: Forty five healthy men were enrolled in present study. Demographic and clinical data, physiological and hematological parameters were collected 3 days before the ascent and after acute exposure at 3,700 m. Results: HAH patients featured significantly lower white blood cell count (WBC), neutrophil count (NEU#) and percentage (NEU%), and higher percentage of lymphocyte (LYM%) at 3,700 m and significantly lower NEU#, reticulocyte count (RET#) and percentage (RET%) at sea level (all P < 0.05). HAH severity was significantly and negatively associated with WBC, NEU#, and NEU% at 3,700 m and RET# at sea level, whereas was positively associated with LYM% at 3,700 m (all P < 0.05). Moreover, we have found that RET# at sea level and NEU% at 3,700 m was an independent predictor and risk factor for HAH, respectively. Conclusion: The present study is the first to examine the hematological characteristics of HAH. Furthermore, lower RET# at sea level and lower NEU% at 3,700 m is a novel independent predictor and risk factor for HAH, respectively.

6.
Mol Med Rep ; 16(6): 9441-9448, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039604

RESUMO

As a typical model of hypoxia­induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen­rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re­oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC­QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia­induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia­induced polycythemia.


Assuntos
Via de Pentose Fosfato , Policitemia/metabolismo , Policitemia/patologia , Doença da Altitude/sangue , Doença da Altitude/complicações , Doença da Altitude/metabolismo , Doença da Altitude/patologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Hipóxia Celular , Análise Discriminante , Hemoglobinas/metabolismo , Humanos , Análise dos Mínimos Quadrados , Metaboloma , Metabolômica , Oxigênio , Policitemia/sangue , Policitemia/complicações , Análise de Componente Principal , Reprodutibilidade dos Testes
7.
Mol Med Rep ; 16(5): 6828-6836, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901489

RESUMO

Hypoxic preconditioning (HPC) is well­known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra­performance liquid chromatography­quadrupole time­of­flight mass spectrometry (UPLC­QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.


Assuntos
Cromatografia Líquida de Alta Pressão , Hipóxia , Espectrometria de Massas por Ionização por Electrospray , Aminoácidos/sangue , Animais , Análise Discriminante , Modelos Animais de Doenças , Precondicionamento Isquêmico , Análise dos Mínimos Quadrados , Lisofosfatidilcolinas/sangue , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Palmitoilcarnitina/sangue , Análise de Componente Principal
8.
Front Physiol ; 8: 55, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28228730

RESUMO

Background: Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. Today, no established biomarkers are available for prediction the susceptibility of AMS. MicroRNAs emerge as promising sensitive and specific biomarkers for a variety of diseases. Thus, we sought to identify circulating microRNAs suitable for prediction the susceptible of AMS before exposure to high altitude. Methods: We enrolled 109 healthy man adults and collected blood samples before their exposure to high altitude. Then we took them to an elevation of 3648 m for 5 days. Circulating microRNAs expression was measured by microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). AMS was defined as Lake Louise score ≥3 and headache using Lake Louise Acute Mountain Sickness Scoring System. Results: A total of 31 microRNAs were differentially expressed between AMS and Non-AMS groups, 15 up-regulated and 16 down-regulated. Up-regulation of miR-369-3p, miR-449b-3p, miR-136-3p, and miR-4791 in patients with AMS compared with Non-AMS individuals were quantitatively confirmed using qRT-PCR (all, P < 0.001). With multiple logistic regression analysis, a unique signature encompassing miR-369-3p, miR-449b-3p, and miR-136-3p discriminate AMS from Non-AMS (area under the curve 0.986, 95%CI 0.970-1.000, P < 0.001, LR+: 14.21, LR-: 0.08). This signature yielded a 92.68% sensitivity and a 93.48% specificity for AMS vs. Non-AMS. Conclusion: The study here, for the first time, describes a signature of three circulating microRNAs as a robust biomarker to predict the susceptibility of AMS before exposure to high altitude.

9.
Front Physiol ; 7: 601, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994555

RESUMO

Background: Altitude acclimatization is a physiological process that restores oxygen delivery to the tissues and promotes oxygen use under high altitude hypoxia. High altitude sickness occurs in individuals without acclimatization. Unraveling the molecular underpinnings of altitude acclimatization could help understand the beneficial body responses to high altitude hypoxia as well as the altered biological events in un-acclimatized individuals. This study assessed physiological adjustments and circulating microRNA (cmiRNA) profiles in individuals exposed to high altitude, aiming to explore altitude acclimatization in humans. Methods: Ninety volunteers were enrolled in this study. Among them, 22 individuals provided samples for microRNA arrays; 68 additional individuals constituted the validation set. Un-acclimatized individuals were identified by the Lake Louise Scoring System. Thirty-three phenotypes were recorded pre- and post-exposure to high altitude, including stress hormones, lipid profiles, hematological indices, myocardial enzyme spectrum, and liver and kidney function related enzymes. CmiRNA expression profiles were assessed using miRCURYTM LNA Array (v.18.0) screening, with data validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Then, associations of plasma microRNA expression with physiological adjustments were evaluated. The biological relevance of the main differentially expressed cmiRNAs was explored by bioinformatics prediction. Results: Nineteen of the 33 phenotypes were significantly altered during early altitude acclimatization, including hematological indices, lipid profiles, and stress hormones; meanwhile, 86 cmiRNAs (79 up-regulated and 7 down-regulated) showed differential expression with statistical significance. Among them, 32 and 25 microRNAs were strongly correlated with low-density lipoprotein-cholesterol and total cholesterol elevations, respectively. In addition, 22 microRNAs were closely correlated with cortisol increase. In un-acclimatized individuals, 55 cmiRNAs were up-regulated and 36 down-regulated, compared with acclimatized individuals. The HIF signaling pathway was suppressed in un-acclimatized individuals. Conclusion: Physiological adjustments, including the hematological system, stress hormones, and lipid molecules contributed to early altitude acclimatization, and showed strong correlations with cmiRNA reprogramming. Moreover, acclimatized and un-acclimatized individuals showed different cmiRNA profile. Suppression of the HIF-1 signaling pathway by microRNA regulation may play a key role in the pathogenesis of un-acclimatization with high altitude hypoxia.

10.
Sci Rep ; 6: 22589, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26940428

RESUMO

The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia.


Assuntos
Adaptação Fisiológica , Doença da Altitude/diagnóstico , Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Hipóxia/diagnóstico , Doença Aguda , Suscetibilidade a Doenças , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Redes e Vias Metabólicas , Metabolômica , Prognóstico , Adulto Jovem
11.
PLoS One ; 8(10): e78285, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24205182

RESUMO

The presence of fungi on liquorice could contaminate the crop and result in elevated levels of mycotoxin. In this study, the mycobiota associated with fresh and dry liquorice was investigated in 3 producing regions of China. Potential toxigenic fungi were tested for ochratoxin A (OTA) and aflatoxin B1 (AFB1) production using liquid chromatography/mass spectrometry/mass spectrometry. Based on a polyphasic approach using morphological characters, ß-tubulin and RNA polymerase II second largest subunit gene phylogeny, a total of 9 genera consisting of 22 fungal species were identified, including two new Penicillium species (Penicillium glycyrrhizacola sp. nov. and Penicillium xingjiangense sp. nov.). The similarity of fungal communities associated with fresh and dry liquorice was low. Nineteen species belonging to 8 genera were detected from fresh liquorice with populations affiliated with P. glycyrrhizacola, P. chrysogenum and Aspergillus insuetus comprising the majority (78.74%, 33.33% and 47.06% of total) of the community from Gansu, Ningxia and Xinjiang samples, respectively. In contrast, ten species belonging to 4 genera were detected from dry liquorice with populations affiliated with P. chrysogenum, P. crustosum and Aspergillus terreus comprising the majority (64.00%, 52.38% and 90.91% of total) of the community from Gansu, Ningxia and Xinjiang samples, respectively. Subsequent LC/MS/MS analysis indicated that 5 fungal species were able to synthesize OTA in vitro including P. chrysogenum, P. glycyrrhizacola, P. polonicum, Aspergillus ochraceus and A. westerdijkiae, the OTA concentration varied from 12.99 to 39.03 µg/kg. AFB1 was absent in all tested strains. These results demonstrate the presence of OTA producing fungi on fresh liquorice and suggest that these fungi could survive on dry liquorice after traditional sun drying. Penicillium chrysogenum derived from surrounding environments is likely to be a stable contributor to high OTA level in liquorice. The harvesting and processing procedure needs to be monitored in order to keep liquorice free of toxigenic fungi.


Assuntos
Fungos/química , Glycyrrhiza/química , Glycyrrhiza/microbiologia , Micotoxinas/química , Ocratoxinas/química , Aflatoxina B1/química , China , Cromatografia Líquida/métodos , Contaminação de Alimentos/análise , Filogenia , RNA Polimerase II/química , Espectrometria de Massas em Tandem/métodos , Tubulina (Proteína)/química
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