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1.
J Chromatogr A ; 1626: 461361, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32797840

RESUMO

The alkaloid enantiomers are well-known to have different physiological and pharmacological effects, and to play an important role in enantioselectivity metabolism with enzymes catalysis in tobacco plants. Here, we developed an improved method for simultaneous and high-precision determination of the individual enantiomers of nornicotine, anatabine and anabasine in four tobacco matrices, based on an achiral gas chromatography-nitrogen phosphorus detector (GCNPD) with commonly available Rtx-200 column using (1S)-(-)-camphanic chloride derivatization. The method development consists of the optimization of extraction and derivatization, screening of achiral column, analysis of the fragmentation mechanisms and evaluation of matrix effect (ME). Under the optimized experimental conditions, the current method exhibited excellent detection capability for the alkaloid enantiomers, with coefficients of determination (R2) > 0.9989 and normality test of residuals P > 0.05 in linear regression parameters. The ME can be neglected for the camphanic derivatives. The limit of detection (LOD) and limit of quantitation (LOQ) ranged from 0.087 to 0.24 µg g - 1 and 0.29 to 0.81 µg g - 1, respectively. The recoveries and within-laboratory relative standard deviations (RSDR) were 94.3%~104.2% and 0.51%~3.89%, respectively. The developed method was successfully applied to determine the enantiomeric profiling of cultivars and curing processes. Tobacco cultivars had a significant impact on the nornicotine, anatabine, anabasine concentration and enantiomeric fraction (EF) of (R)-nornicotine, whereas the only significant change induced by the curing processes was an increase in the EF of (R)-anabasine.


Assuntos
Alcaloides/análise , Anabasina/análise , Cromatografia Gasosa/métodos , Nicotina/análogos & derivados , Piridinas/análise , Tabaco/química , Alcaloides/química , Anabasina/química , Hidrocarbonetos Aromáticos com Pontes/química , Cloretos/química , Lactonas/química , Nicotina/análise , Nicotina/química , Piridinas/química , Estereoisomerismo
2.
Life Sci ; 257: 118111, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32682918

RESUMO

BACKGROUND AND AIMS: Bacterial translocation (BT) is strongly associated with disease progression and poor outcome in cirrhotic patients. The role of Pregnane X receptor (PXR) in regulating bacterial translocation in cirrhosis is unknown. We previously showed that Ginkgolide-A (GA), a natural PXR ligand, attenuated BT in cirrhotic mice by abrogating inflammation along the gut-liver-axis, and by protecting small intestinal tight junctions (TJ). Here, we aimed to investigate the effect of GA in activating PXR and associated antimicrobial peptides (AMPs) in regulating BT in experimental cirrhosis. METHODS: Male Swiss albino mice were administered CCl4 (0.5 mL/kg body-weight, i.p twice a week) for 12 consecutive weeks. After the 12th week, mice were randomized and administered with GA (100-mg/kg body-weight, oral) every-day for 2 weeks. At termination, blood, gut and liver tissues were collected for molecular studies. RESULTS: GA treatment to cirrhotic mice significantly increased the expression of small intestinal PXR and Regenerating family member 3 alpha (Reg3A), which were otherwise reduced in CCl4 cirrhotic mice. Moreover, compared to naive mice a significantly reduced Lactobacillus, and increased Bacteroides and Enterococcus 16s rRNA levels were observed in the small intestine and liver of cirrhotic mice. Treatment with GA to cirrhotic mice significantly reduced intestinal overgrowth and translocation of Enterococcus and Bacteroides to the liver. Furthermore, GA treatment significantly attenuated intestinal permeability and BT marker soluble-CD14 (sCD14), which were increased in CCl4 cirrhotic mice. CONCLUSION: The study showed for the first time that, GA treatment to cirrhotic rodents attenuates BT, by improving PXR and Reg3A expression.


Assuntos
Translocação Bacteriana/efeitos dos fármacos , Ginkgolídeos/farmacologia , Lactonas/farmacologia , Cirrose Hepática Experimental/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Receptor de Pregnano X/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Western Blotting , Células Hep G2 , Humanos , Cirrose Hepática Experimental/complicações , Masculino , Camundongos , Simulação de Acoplamento Molecular , Receptor de Pregnano X/efeitos dos fármacos
3.
Nat Commun ; 11(1): 3508, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32665554

RESUMO

Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.


Assuntos
Compostos Heterocíclicos com 3 Anéis/metabolismo , Ácidos Indolacéticos/metabolismo , Lactonas/metabolismo , Ervilhas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Ervilhas/genética , Reguladores de Crescimento de Planta/metabolismo
4.
J Biol Regul Homeost Agents ; 34(3): 785-794, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32723437

RESUMO

Previous reports indicated that specific cyclooxygenase-2 (COX-2) inhibitor suppresses osteoarthritis (OA). This study aimed to further explore the possible mechanism of Rofecoxib as a COX-2 inhibitor on the inhibition of chondrocyte (CH) hypertrophic development and tested the optimal treatment of Rofecoxib on CH. Basically, IL-1ß was used as a stimulus to establish a degenerated CH model. Immunofluorescence, Western blot, and RT-PCR were performed to determine the gene expression of Axin2, ß-catenin, GSK3ß, collagen X, collagen II, COX-2, PGE-2, SOX-9, Runx-2, and MMP- 13 expression. Cell Counting Kit (CCK-8) assay was used to analyze the viability of CHs. The data indicated that Rofecoxib significantly inhibited COX-2 expression and had less harmful effects on CH viability. Rofecoxib reversed the IL-1ß-induced upregulation of collagen X, COX-2, PGE-2, Runx-2, and MMP-13 expression, and promoted the viability of collagen II, SOX-9 expression of CHs. Furthermore, Rofecoxib suppressed Axin2, ß-catenin, and GSK3ß expression of the Wnt pathway, which was activated by IL-1ß or human recombinant Wnt-1 protein treatment. Therefore, Rofecoxib is an effective COX-2 inhibitor that protects CHs from hypertrophy by suppression of the Wnt/ß-catenin pathway.


Assuntos
Condrócitos/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Lactonas/farmacologia , Sulfonas/farmacologia , Via de Sinalização Wnt , Células Cultivadas , Condrócitos/citologia , Humanos , Hipertrofia , beta Catenina
5.
Gene ; 758: 144961, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32693148

RESUMO

Ginkgo biloba L. is regarded as the most ancient living tree, and its kernel has been used as a traditional Chinese medicine for more than 2,000 years. The leaf extracts of this tree have been among the bestselling herbal remedies in Western countries since the last century. To understand the biosynthesis of the pharmacologically active ingredients in G. biloba, flavonoids and terpenoid trilactones (TTLs), we sequenced the transcriptomes of G. biloba leaves, kernels and testae with Iso-Seq and RNA-Seq technologies and obtained 152,524 clean consensus reads. When these reads were used to improve the annotation of the G. biloba genome, 4,856 novel genes, 25,583 new isoforms of previously annotated genes and 4,363 lncRNAs were discovered. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that genes involved in growth, regulation and response to stress were more likely to be regulated by alternative splicing (AS) or alternative polyadenylation (APA), which represent the two most important posttranscriptional regulation mechanisms. It was found that some of the characterized genes involved in the biosynthesis of flavonoids and TTLs were also possibly regulated by AS and APA. Using phylogenetic and gene expression pattern analyses, some candidate genes for the biosynthesis of flavonoids and TTLs were screened. After qRT-PCR validation, the final candidate genes for flavonoid biosynthesis included three UDP-glycosyltransferases and one MYB transcription factor, while the candidate genes for TTL biosynthesis included two cytochrome P450 and one WRKY transcription factor. Our study suggested that Iso-Seq may play an important role in improving genome annotation, elucidating AS and APA mechanisms and discovering candidate genes involved in the biosynthesis of some secondary metabolites.


Assuntos
Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas/genética , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Lactonas/metabolismo , Terpenos/metabolismo , Processamento Alternativo/genética , Sistema Enzimático do Citocromo P-450/genética , Perfilação da Expressão Gênica , Genoma de Planta/genética , Extratos Vegetais , Transcriptoma , Sequenciamento Completo do Genoma
6.
J Chromatogr A ; 1624: 461155, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32540056

RESUMO

The topic in the present paper is to prepare molecularly imprinted polymer (MIP) using the template molecule with low purity. For the first time, a surrounding of macromolecular crowding was established to promote the formation of the complex of the template with functional monomer efficiently thus highly pure template molecule was unnecessary. In this study, the MIP monolith was synthesized using low purity lactucopicrin as template in place of highly pure one, and polystyrene was used as macromolecular crowding agent. 4-Vinylpyridine and ethyleneglycol dimethacrylate were used as functional monomer and crosslinker, respectively. Polymerization parameters, including the ratio of functional monomer/template, various template concentrations, and PS concentration on the affinity of the resulting MIP were systematically investigated. For the lactucopicrin MIP made with the purity of lactucopicrin of 92%, the imprinting factor can be up to 2.2. The resulting MIP was filled in solid phase extraction (SPE) cartridge to purify lactucopicrin from the crude extract of Cichorium glandulosum Boiss. et Huet. After two cycles of MIP SPE for the crude extract, the highest recovery and purity of lactucopicrin was 64.8% and 97.8%, respectively. The results indicated that the use of macromolecular crowding agent is an effective method for improving the performance of the MIP prepared with the template of low purity, particularly valuable to the cases in which the highly pure target molecule is hard to be obtained.


Assuntos
Impressão Molecular , Polímeros/química , Asteraceae/química , Reagentes para Ligações Cruzadas/química , Lactonas/química , Lactonas/isolamento & purificação , Metacrilatos/química , Polimerização , Poliestirenos/química , Piridinas/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Extração em Fase Sólida
7.
Phytochemistry ; 177: 112430, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32516579

RESUMO

Despite intensive research in recent years, the biosynthetic route to costunolide in sunflower so far remained obscured. Additional P450 sequences from public sunflower transcriptomic database were screened to search for candidate enzymes which are able to introduce the 6α-hydroxy-group required for the esterification with the carboxy group of germacarane A acid, the final step in costunolide formation. CYP71BL9, a new P450 enzyme from sunflower was shown to catalyze this hydroxylation, hence being identified as HaCOS. Phylogentically, HaCOS is closer related to HaG8H than to any other known costunolide synthase in Asteraceae.The enzyme was successfully employed to reconstruct the sunflower biosynthesis of costunolide in transformed tobacco. Contrary, in yeast, only minor amounts of sesquiterpene lactone was produced, while 5-hydroxyfarnesylic acid was formed instead. HaCOS in combination with HaG8H produced 8ß-hydroxycostunolide (eupatolide) in transformed plants, thus indicating that sunflower possesses two independent modes of eupatolide synthesis via HaCOS and via HaES. The lack of HaCOS expression and of costunolide in trichomes suggests that the enzyme triggers the costunolied synthesis of the inner tissues of sunflower and might be linked to growth regulation processes.


Assuntos
Helianthus , Sesquiterpenos , Lactonas , Tricomas
8.
Nature ; 583(7815): 277-281, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32528176

RESUMO

Plant hormones known as strigolactones control plant development and interactions between host plants and symbiotic fungi or parasitic weeds1-4. In Arabidopsis thaliana and rice, the proteins DWARF14 (D14), MORE AXILLARY GROWTH 2 (MAX2), SUPPRESSOR OF MAX2-LIKE 6, 7 and 8 (SMXL6, SMXL7 and SMXL8) and their orthologues form a complex upon strigolactone perception and play a central part in strigolactone signalling5-10. However, whether and how strigolactones activate downstream transcription remains largely unknown. Here we use a synthetic strigolactone to identify 401 strigolactone-responsive genes in Arabidopsis, and show that these plant hormones regulate shoot branching, leaf shape and anthocyanin accumulation mainly through transcriptional activation of the BRANCHED 1, TCP DOMAIN PROTEIN 1 and PRODUCTION OF ANTHOCYANIN PIGMENT 1 genes. We find that SMXL6 targets 729 genes in the Arabidopsis genome and represses the transcription of SMXL6, SMXL7 and SMXL8 by binding directly to their promoters, showing that SMXL6 serves as an autoregulated transcription factor to maintain the homeostasis of strigolactone signalling. These findings reveal an unanticipated mechanism through which a transcriptional repressor of hormone signalling can directly recognize DNA and regulate transcription in higher plants.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Compostos Heterocíclicos com 3 Anéis/metabolismo , Lactonas/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Transdução de Sinais/genética , Transcrição Genética , Antocianinas/biossíntese , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Genes de Plantas/genética , Reguladores de Crescimento de Planta/biossíntese , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1657-1663, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489046

RESUMO

To prepare ginkgolide B nanosuspension(GB-NS), and investigate its dissolution behaviors in vitro. The miniaturized media milling method was used to prepare nanosuspensions, with average particle size and polydispersity index as the evaluation indexes. The formulation and process of GB-NS were optimized by single factor experiment and Box-Behnken design-response surface method. The morphology was observed by scanning electron microscope(SEM), and thecrystallinity of GB-NS was investigated by X-rays diffraction(XRD). The paddle method was used to study the dissolution of GB-NS in vitro. The mean particle size of optimized GB-NS was(180±7) nm, with a polydispersity index of 0.196±0.036. SEM showed that GB-NS was rod-like or irregular granular. XRD showed that the crystallinity of GB-NS was significantly reduced compared with GB raw material. The cumulative dissolution rate of GB-NS reached 90% in 30 min, which was higher than that of GB raw material. The findings suggested that the miniaturized media milling method was simple, efficient and feasible to prepare GB-NS. And the dissolution rate of GB was significantly improved by nanosuspension technology.


Assuntos
Nanotecnologia , Ginkgolídeos , Lactonas , Nanopartículas , Tamanho da Partícula , Solubilidade , Suspensões
10.
Pediatrics ; 146(1)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32576595

RESUMO

Dyslexia is a common learning disorder that renders children susceptible to poor health outcomes and many elements of socioeconomic difficulty. It is commonly undiagnosed until a child has repeatedly failed to learn to read in elementary school; this late diagnosis not only places the child at an academic disadvantage but also can be a precursor to psychiatric comorbidities such as anxiety and depression. Genetic and neuroimaging research have revealed that dyslexia is heritable and that it is undergirded by brain differences that are present even before reading instruction begins. Cognitive-behavioral research has revealed that there are early literacy skill deficits that represent red flags for dyslexia risk and can be measured at a preschool age. Altogether, this evidence points to dyslexia as a disorder that can be flagged by a pediatrician before school entry, during a period of heightened brain plasticity when interventions are more likely to be effective. In this review, we discuss the clinical implications of the most recent advances in dyslexia research, which converge to indicate that early identification and screening are crucial to the prevention or mitigation of adverse secondary consequences of dyslexia. We further highlight evidence-based and practical strategies for the implementation of early risk identification in pediatric practice so that physicians can be empowered in their ability to treat, educate, and advocate for their patients and families with dyslexia.


Assuntos
Dislexia/diagnóstico , Aprendizagem/fisiologia , Neuroimagem/métodos , Leitura , Criança , Dislexia/psicologia , Diagnóstico Precoce , Humanos , Lactonas , Fatores de Risco
11.
Mol Pharmacol ; 98(2): 156-167, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32591477

RESUMO

The natural product (+)-discodermolide (DDM) is a microtubule stabilizing agent and potent inducer of senescence. We refined the structure of DDM and evaluated the activity of novel congeners in triple negative breast and ovarian cancers, malignancies that typically succumb to taxane resistance. Previous structure-activity analyses identified the lactone and diene as moieties conferring anticancer activity, thus identifying priorities for the structural refinement studies described herein. Congeners possessing the monodiene with a simplified lactone had superior anticancer efficacy relative to taxol, particularly in resistant models. Specifically, one of these congeners, B2, demonstrated 1) improved pharmacologic properties, specifically increased maximum response achievable and area under the curve, and decreased EC50; 2) a uniform dose-response profile across genetically heterogeneous cancer cell lines relative to taxol or DDM; 3) reduced propensity for senescence induction relative to DDM; 4) superior long-term activity in cancer cells versus taxol or DDM; and 5) attenuation of metastatic characteristics in treated cancer cells. To contrast the binding of B2 versus DDM in tubulin, X-ray crystallography studies revealed a shift in the position of the lactone ring associated with removal of the C2-methyl and C3-hydroxyl. Thus, B2 may be more adaptable to changes in the taxane site relative to DDM that could account for its favorable properties. In conclusion, we have identified a DDM congener with broad range anticancer efficacy that also has decreased risk of inducing chemotherapy-mediated senescence. SIGNIFICANCE STATEMENT: Here, we describe the anticancer activity of novel congeners of the tubulin-polymerizing molecule (+)-discodermolide. A lead molecule is identified that exhibits an improved dose-response profile in taxane-sensitive and taxane-resistant cancer cell models, diminished risk of chemotherapy-mediated senescence, and suppression of tumor cell invasion endpoints. X-ray crystallography studies identify subtle changes in the pose of binding to ß-tubulin that could account for the improved anticancer activity. These findings support continued preclinical development of discodermolide, particularly in the chemorefractory setting.


Assuntos
Alcanos/química , Carbamatos/química , Lactonas/síntese química , Neoplasias Ovarianas/metabolismo , Pironas/química , Neoplasias de Mama Triplo Negativas/metabolismo , Moduladores de Tubulina/síntese química , Células A549 , Área Sob a Curva , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico , Taxoides/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1717-1725, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489054

RESUMO

The effects of the growing periods, processing methods, nutritive organs and cut parts of the herbs on the quality of Andrographis Herba have been studied, which could provide scientific basis for producing high-quality crude materials of Andrographis Herba. A quantitative analysis of multi-components by single-marker(QAMS) method was used to simultaneously determine 4 diterpene lactones of andrographolide(AD), neoandrographolide(NAD), 14-deoxyandrographolide(14-DAD), and dehydroandrographolide(DHAD) in 78 batches of Andrographis Herba samples. Visual analysis, clustering analysis and partial least squares discrimination analysis(PLS-DA) were used for data processing and mining. The growing periods of Andrographis Herba were divide into the rapid growing stage(Ⅰ), the luxuriant foliage stage(Ⅱ), the bud stage(Ⅲ), the flower stage(Ⅳ), the fruiting stage(Ⅴ) and the later fruiting stage(Ⅵ), six ones in total. The results showed that the total contents of 4 diterpene lactones(TC) kept almost constant in growing periods of Ⅰ-Ⅲ, began to fall off in growing period Ⅳ, decreased rapidly in growing period Ⅴ and reduced to minimum in growing period Ⅵ. Therefore, the best harvesting period for Andrographis Herba was the bud stage. For the processing methods, none significant difference occurred for TC between drying by the sun and drying in the shade. However, in comparison of the samples dried by the sun, the samples dried in the shade exhibited lower content of AD, nonetheless, the higher contents of DHAD and NAD, indicating that the process of drying in the shade may lead to the decomposition and transformation of AD. Therefore, when the weather conditions permitted, the method drying by the sun should be used. The distributions of AD, DHAD and TC in the different cut parts and nutritive organs were determined as follows: upper cut parts > middle cut parts ≈ entire herbs > lower cut parts, leaves > entire herbs > stems. Furthermore, the contents of 4 diterpene lactones in leaves and herbs were much higher than those in stems. Therefore, it was suggested that the upper and middle cut parts of the herbs or the parts containing leaves should be preferred for harvesting to ensure the proportion of the leaves in Andrographis Herba.


Assuntos
Andrographis , Diterpenos , Lactonas , Folhas de Planta
13.
Clin Res Hepatol Gastroenterol ; 44(4): 403-406, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540142

RESUMO

2019 novel coronavirus pneumonia is a serious life-threatening disease and it has affected many people globally, especially the people who live in China. A high prevalence of hepatobiliary diseases has been observed in 2019-nCoV patients and some may require emergency surgery. In the context of the novel coronavirus pneumonia, new challenges have arisen for surgeons in terms of ways to effectively treat outpatients, safety of medical staffs in performing surgery treatment, and the lack of efficient postoperative management and follow-up procedure. It is hoped that through this article, surgeons will have a better system in hepatobiliary diseases classification, treatment selection, and protective measures to improve the clinical practice in accordance with the guidelines for the diagnosis and treatment of the novel coronavirus pneumonia.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/cirurgia , Pandemias , Pneumonia Viral/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Procedimentos Cirúrgicos Eletivos , Humanos , Lactonas , Pandemias/prevenção & controle , Seleção de Pacientes , Assistência Perioperatória , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Cuidados Pós-Operatórios , Sesquiterpenos , Telemedicina , Triagem
14.
Planta Med ; 86(11): 776-781, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32483775

RESUMO

Chemical investigation of the lichen Parmotrema tsavoense led to the isolation of 5 new depsidones, parmosidones F - J (1:  - 5: ). These compounds were structurally elucidated using spectroscopic methods including HRESIMS and 2D NMR data. Compounds 1, 3: , and 4: were evaluated for their inhibition of α-glucosidase. All exhibited potent α-glucosidase inhibitory activity with IC50 values ranging from 10.7 to 17.6 µM, which was much lower than that of the positive control acarbose (IC50 449 µM).


Assuntos
Líquens , alfa-Glucosidases , Depsídeos , Inibidores de Glicosídeo Hidrolases , Lactonas , Extratos Vegetais
15.
Chemosphere ; 255: 126945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32388260

RESUMO

This study investigated the effects of exogenous N-acyl-homoserine lactone (AHL) signal molecules, N-hexanoyl-l-homoserine lactone (C6-HSL) and N-octanoyl-l-homoserine lactone (C8-HSL), on treatment performance, sludge properties and microbial community structures in activated sludge systems. Results showed that the nitrification and denitrification efficiencies were enhanced with the addition of signal molecules. The particle size, irregularity, and internal mass transfer resistance of activated sludge flocs (ASFs) increased, primarily because dosing AHLs led to a content increase and chemical composition variation of extracellular polymeric substances (EPS) in sludge. Microbial analysis indicated an increase in both the bacterial richness and diversity of the systems. The relative abundances of the key functional groups, including bacteria related to C and N removal and EPS production, varied correspondingly. This study presents an insight into the comprehensive understanding of the effects of AHL-based quorum sensing on activated sludge treatment process.


Assuntos
Acil-Butirolactonas/química , Lactonas/química , 4-Butirolactona/análogos & derivados , Bactérias , Microbiota , Nitrificação , Nutrientes , Percepção de Quorum , Esgotos/química
16.
Nat Commun ; 11(1): 2114, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32355217

RESUMO

Most plants associate with beneficial arbuscular mycorrhizal (AM) fungi that facilitate soil nutrient acquisition. Prior to contact, partner recognition triggers reciprocal genetic remodelling to enable colonisation. The plant Dwarf14-Like (D14L) receptor conditions pre-symbiotic perception of AM fungi, and also detects the smoke constituent karrikin. D14L-dependent signalling mechanisms, underpinning AM symbiosis are unknown. Here, we present the identification of a negative regulator from rice, which operates downstream of the D14L receptor, corresponding to the homologue of the Arabidopsis thaliana Suppressor of MAX2-1 (AtSMAX1) that functions in karrikin signalling. We demonstrate that rice SMAX1 is a suppressor of AM symbiosis, negatively regulating fungal colonisation and transcription of crucial signalling components and conserved symbiosis genes. Similarly, rice SMAX1 negatively controls strigolactone biosynthesis, demonstrating an unexpected crosstalk between the strigolactone and karrikin signalling pathways. We conclude that removal of SMAX1, resulting from D14L signalling activation, de-represses essential symbiotic programmes and increases strigolactone hormone production.


Assuntos
Proteínas de Arabidopsis/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Micorrizas/fisiologia , Oryza/microbiologia , Proteínas de Plantas/fisiologia , Simbiose , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Furanos/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação , Compostos Heterocíclicos com 3 Anéis/metabolismo , Homozigoto , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lactonas/metabolismo , Família Multigênica , Oryza/genética , Filogenia , Proteínas de Plantas/genética , Raízes de Plantas/microbiologia , Piranos/metabolismo , RNA-Seq , Transdução de Sinais
17.
Phytochemistry ; 176: 112398, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32450381

RESUMO

This work presents the study of the roots of the Macaronesian paleoendemism Persea indica (L.) Spreng. The root biomass of this protected tree species has been produced by soil-less aeroponic culture under controlled environment. This system has important advantages over traditional plant production techniques because it provides opportunities to optimize the yield of metabolite production under well-controlled conditions, thereby facilitating commercial-scale production of bioactive compounds. Thus, for the first time a study of this type has permitted the isolation from the roots of seven undescribed dextrorotatory lactones: the alkane-γ-lactones (+)-majoranolide and (+)-dihydromajorenolide, the alkene-γ-lactones (+)-majorenolide and (+)-majorenolide acetate, and the alkyne-γ-lactones, (+)-majorynolide, (+)-majorynolide acetate and (+)-isomajorynolide. In addition, thirteen known compounds were also isolated including two possible avocadofurane precursors, avocadynone acetate and avocadenone acetate, the monoterpene esters cis- and trans-p-coumarate of (-)-borneol, and the ryanoid diterpenes cinnzeylanone, anhidrocinnzeylanine, cinnzeylanine, cinnzeylanol, epiryanodol, perseanol, cinncassiol E, perseaindicol and secoperseanol. The configuration at C-14 de two ryanodane diterpenes has also been revised in this work. Furthermore, (-)-borneol cis-p-coumarate has showed to be insecticidal to S. littoralis and cytotoxic to insect (Sf9) cells, (+)-majorenolide antifeedant to aphids and cytotoxic to Sf9, cinnceylanol antifeedant and insecticidal to S. littoralis, and (+)-majorynolide (2), insecticidal against S. littoralis, cytotoxic to Sf9 and nematicidal, suggesting a defensive role for these compounds.


Assuntos
Diterpenos , Persea , Alcanos , Alcenos , Alquinos , Animais , Lactonas , Raízes de Plantas
18.
Phytomedicine ; 71: 153239, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32447245

RESUMO

BACKGROUND AND PURPOSE: Multidrug resistance (MDR) remains the main obstacle in cancer treatment and overexpression of P-glycoprotein (P-gp) is one of the most common causes of chemoresistance. The development of novel P-gp inhibitors from natural products is a prospective strategy to combat MDR cancers. Among the natural sesquiterpene compounds, sesquiterpene pyridine alkaloids exhibit various biological properties. Therefore, in the present study, we evaluated the modulatory effects of wilforine on P-gp expression and function. The molecular mechanisms and kinetic models of wilforine-mediated P-gp inhibition were further investigated. METHODS: The human P-gp stable expression cells (ABCB1/Flp-InTM-293) and human cervical cancer cells (sensitive: HeLaS3; MDR: KBvin) were used. The cell viability was assessed by SRB assay. The inhibitory effect of wilforine on P-gp efflux and the underlying mechanism were evaluated by assays for calcein-AM uptake, rhodamine123 and doxorubicin efflux, ATPase activity, real-time quantitative RT-PCR, apoptosis, and cell cycle analysis. Molecular docking was performed by the docking software CDOCKER with BIOVIA Discovery Studio 4.5 (D.S. 4.5). RESULTS: We found that wilforine significantly inhibited the efflux activity of P-gp in a concentration-dependent manner. Further kinetic analysis demonstrated that wilforine significantly inhibited P-gp efflux function by competitive inhibition and stimulated the basal P-gp ATPase activity. In addition, wilforine re-sensitized MDR cancer cells to chemotherapeutic drugs. The docking model indicated that wilforine was bound to residues of P-gp such as LEU884, LYS887, THR176 and ASN172. CONCLUSION: These results suggest a novel future therapeutic strategy for MDR cancer using wilforine as an adjuvant treatment with chemotherapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lactonas/farmacologia , Piridinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos/fisiologia , Células HeLa , Humanos , Cinética , Lactonas/química , Simulação de Acoplamento Molecular , Estudos Prospectivos , Piridinas/química
19.
Proc Natl Acad Sci U S A ; 117(22): 12472-12480, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32409606

RESUMO

Momilactones are bioactive diterpenoids that contribute to plant defense against pathogens and allelopathic interactions between plants. Both cultivated and wild grass species of Oryza and Echinochloa crus-galli (barnyard grass) produce momilactones using a biosynthetic gene cluster (BGC) in their genomes. The bryophyte Calohypnum plumiforme (formerly Hypnum plumaeforme) also produces momilactones, and the bifunctional diterpene cyclase gene CpDTC1/HpDTC1, which is responsible for the production of the diterpene framework, has been characterized. To understand the molecular architecture of the momilactone biosynthetic genes in the moss genome and their evolutionary relationships with other momilactone-producing plants, we sequenced and annotated the C. plumiforme genome. The data revealed a 150-kb genomic region that contains two cytochrome P450 genes, the CpDTC1/HpDTC1 gene and the "dehydrogenase momilactone A synthase" gene tandemly arranged and inductively transcribed following stress exposure. The predicted enzymatic functions in yeast and recombinant assay and the successful pathway reconstitution in Nicotiana benthamiana suggest that it is a functional BGC responsible for momilactone production. Furthermore, in a survey of genomic sequences of a broad range of plant species, we found that momilactone BGC is limited to the two grasses (Oryza and Echinochloa) and C. plumiforme, with no synteny among these genomes. These results indicate that while the gene cluster in C. plumiforme is functionally similar to that in rice and barnyard grass, it is likely a product of convergent evolution. To the best of our knowledge, this report of a BGC for a specialized plant defense metabolite in bryophytes is unique.


Assuntos
Evolução Molecular , Genoma de Planta , Lactonas/metabolismo , Plantas/metabolismo , Vias Biossintéticas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/classificação , Plantas/genética
20.
PLoS Negl Trop Dis ; 14(5): e0008295, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379762

RESUMO

Genetic epidemiology can provide important insights into parasite transmission that can inform public health interventions. The current study compared long-term changes in the genetic diversity and structure of co-endemic Plasmodium falciparum and P. vivax populations. The study was conducted in Papua Indonesia, where high-grade chloroquine resistance in P. falciparum and P. vivax led to a universal policy of Artemisinin-based Combination Therapy (ACT) in 2006. Microsatellite typing and population genetic analyses were undertaken on available isolates collected between 2004 and 2017 from patients with uncomplicated malaria (n = 666 P. falciparum and n = 615 P. vivax). The proportion of polyclonal P. falciparum infections fell from 28% (38/135) before policy change (2004-2006) to 18% (22/125) at the end of the study (2015-2017); p<0.001. Over the same period, polyclonal P. vivax infections fell from 67% (80/119) to 35% (33/93); p<0.001. P. falciparum strains persisted for up to 9 years compared to 3 months for P. vivax, reflecting higher rates of outbreeding in the latter. Sub-structure was observed in the P. falciparum population, but not in P. vivax, confirming different patterns of outbreeding. The P. falciparum population exhibited 4 subpopulations that changed in frequency over time. Notably, a sharp rise was observed in the frequency of a minor subpopulation (K2) in the late post-ACT period, accounting for 100% of infections in late 2016-2017. The results confirm epidemiological evidence of reduced P. falciparum and P. vivax transmission over time. The smaller change in P. vivax population structure is consistent with greater outbreeding associated with relapsing infections and highlights the need for radical cure to reduce recurrent infections. The study emphasizes the challenge in disrupting P. vivax transmission and demonstrates the potential of molecular data to inform on the impact of public health interventions.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Monitoramento Epidemiológico , Lactonas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Vivax/tratamento farmacológico , Malária Vivax/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Feminino , Variação Genética , Técnicas de Genotipagem , Humanos , Indonésia , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Epidemiologia Molecular , Plasmodium falciparum/classificação , Plasmodium falciparum/genética , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/classificação , Plasmodium vivax/genética , Plasmodium vivax/isolamento & purificação , Adulto Jovem
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