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1.
Artigo em Inglês | MEDLINE | ID: mdl-31974552

RESUMO

BACKGROUND: To investigate the current use status of official WeChat accounts for the Centers for Disease Control and Prevention in public health education and relevant factors that can impact the effectiveness of message delivery. METHODS: A retrospective survey was conducted to evaluate the effectiveness of official WeChat accounts. About 531 official WeChat accounts and 50 939 articles were analyzed using a cluster sampling survey design. The Kruskal-Wallis test and multivariate logistic regression were used to explore factors associated with the usefulness of the number of views and "Likes" of the articles. RESULTS: The study identified a total of 531 public WeChat accounts, including 19 province-level accounts, 179 municipal-level accounts and 333 county-level accounts. In the univariable analysis, the administrative level of the account, article order, time segment, article originality and thematic category were associated with the number of views and "Likes." Province-level accounts, first articles, the 5:00-6:00 time segment, original articles and theme 3 (emergencies) had higher numbers of views and "Likes" than the others (P < 0.05). CONCLUSIONS: Promoting health education through Official WeChat account is an effective, sustainable and feasible strategy. Potential indicators of the impact of public health education suggest that administrators should effectively use official WeChat accounts for public health education.

2.
J Chromatogr A ; 1609: 460496, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31519406

RESUMO

Velvet antlers (VA) have been used as medicines and nutraceuticals for over 2000 years. Meanwhile, deer antlers are the only mammalian organs that can fully regenerate after annual shedding. The antler formation and regeneration rely on the stem cells resident in antlerogenic periosteum (AP), transplantation of which can induce ectopic antler formation. Here, a comprehensive quantitative proteomic analysis of antlerogenic periosteal cells (AP cells), compared with the adjacent facial periosteal cells (FP cells), was carried out, from both extracellular and intracellular perspectives. In this study, the stable isotope labeling by amino acids in cell culture (SILAC) was applied to ensure the precision of quantification. Then, the protein equalization strategy and reverse-phase liquid chromatography (RPLC) separation in high pH were utilized to improve the depth of proteome profiling. Proteomics analysis of the conditioned media (CM) from AP and FP cells showed that significantly over-expressed extracellular proteins in AP cells were involved in cell proliferation, angiogenesis and neurogenesis. Combining the extracellular and intracellular proteomes, we found several potential secreted proteins might regulate antler formation and regeneration, such as SFRP4 and LUM. These results provide new insight into the underlying mechanism of antler formation and regeneration.

3.
J Proteomics ; 213: 103614, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31846764

RESUMO

Lysine methylation is a widespread protein post-translational modification showing essentialities in versatile cellular process. EZH2, a methyltransferase specifically trimethylates the lysine 27 of histone H3 and its aberrance in several cancers promotes the development of its inhibitors against hematological tumors. In this study, we presented a deep exploration of lysine mono-, di- and trimethylomes in EZH2 wild-type and Y641 mutant lymphoma cell lines. Our results showed that several substrates were modified in different methylation levels. Moreover, these methylated lysine residues could also undergo other types of PTMs. Combined with the differences proved in protein expression, lysine acetylation, lysine ubiquitylation and protein N-termianl acetylation level, our study underlined the substrate specificity of lysine methylation and its crosstalk with other types of PTMs. Totally, our study raised new insights into the global cellular methylation features in hematological cell lines, which provided further inspects into the distribution and function of lysine methylation. SIGNIFICANCE: Our study showed the global landscape of mono-, di- and trimethylomes in the EZH2-aberrant DLBCL cell lines, revealing the molecular characteristics of lysine methylation. Combined with the protein abundance and potential crosstalk among different types of PTMs, our study raised new insights into the global cellular methylation features in hematological tumors and provided further inspects into the distribution and function of lysine methylation.

4.
Anal Chem ; 92(1): 567-572, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31846294

RESUMO

Protein N-termini and their modifications not only represent different protein isoforms but also relate to the functional annotation and proteolytic activities. Currently, negative selection methods, such as terminal amine isotopic labeling of substrates (TAILS), are the most popular strategy to analyze the protein N-terminome, in which dimethylation or acetylation modification is commonly used to block the free amines of proteome samples. However, after tryptic digestion, the generated long peptides, caused by the missing cleavage of blocked lysine, could hardly be identified by MS, which hindered the deep-coverage analysis of N-terminome. Herein, to solve this problem, we developed an approach, named terminal amine guanidination of substrates (TAGS). 1H-Pyrazole-1-carboxamidine was used to effectively guanidinate lysine ε-amines and N-terminal α-amines, followed by tryptic digestion to generate N-terminal peptides without free amines and internal peptides with free amines. Then, the internal peptides with free amines were removed by hyperbranched polyglycerol-aldehyde polymers (HPG-ALDs) to achieve the negative enrichment of N-terminome. By TAGS, not only the cleavage rate of blocked lysine could be improved, but also the ionization efficiency of tryptic peptides was increased. In comparison, 1814 and 1620 protein N-termini were, respectively, identified by TAGS and TAILS in Saccharomyces cerevisiae (S. cerevisiae). Among them, 1012 N-termini were uniquely identified in TAGS. Furthermore, by the combination of TAGS and the stable isotope labeling with amino acids in cell culture (SILAC)/label-free quantitative method, we not only identified the known N-terminal cleavage fragment of gasdermin D but also identified some new cleavage sites during Val-boroPro-induced pyroptosis. All these results demonstrated that our developed approach, TAGS, might be of great promise for the comprehensive analysis of N-terminome and beneficial for promoting the identification of protein isoforms and studying in-depth the proteolytic activity of proteins.

5.
Biomed Res Int ; 2019: 3875418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662976

RESUMO

Background: Holmium laser enucleation of the prostate (HoLEP) is considered the standard endoscopic treatment of benign prostatic hyperplasia (BPH), but traditional HoLEP surgery will cause some postoperative complications. This study was attempted to evaluate the safety and efficacy of modified two-lobe technique versus traditional three-lobe technique of HoLEP focusing mainly on incidences of retrograde ejaculation (RE) and urinary incontinence (UI). Methods: From March 2014 to February 2017, 191 men with BPH were randomly assigned to two groups: 97 underwent modified two-lobe technique; 94 underwent traditional three-lobe technique. All patients were followed up for 12 months. Primary outcomes were incidences of RE and UI, and secondary outcomes were international prostate symptom score (IPSS), quality of life (QOL), maximal urine flowing rate (MFR), and residual urine among the studied patients. Results: Compared with the traditional technique, patients in the modified group had a statistically significant decrease in frequency of UI (1.03% vs 8.51%, p=0.036) and RE in the 6th month (33.33% vs 63.64%, p=0.030) and 12th month (13.33% vs 50%, p=0.034) and a significant increase in ejaculatory volume in the 6th month (p=0.050) and 12th month (p=0.003). Besides, the modified HoLEP was more beneficial to patients according to the change of QoL score at 1 month (p=0.002), 3 months (p=0.004), 6 months (p=0.026), and 12 months (p=0.015). Conclusions: The modified two-lobe technology of HoLEP reduced the incidence of RE and UI, which improved the quality of life of the patients after surgery compared to the traditional three-lobe technology. This trial is registered with ChiCTR1800018553.

6.
J Crit Care ; 54: 110-116, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31408805

RESUMO

PURPOSE: To compare twenty-two machine learning (ML) models against logistic regression on survival prediction in severe traumatic brain injury (STBI) patients in a single center study. MATERIALS AND METHODS: Data was collected from STBI patients admitted to the Sichuan Provincial People's Hospital between December 2009 and November 2011. Twenty-two machine learning (ML) models were tested, and their predictive performance compared with logistic regression (LR) model. Receiver operating characteristics (ROC), area under curve (AUC), accuracy, F-score, precision, recall and Decision Curve Analysis (DCA) were used as performance metrics. RESULTS: A total of 117 patients were enrolled. AUC of all ML models ranged from 86.3% to 94%. AUC of LR was 83%, and accuracy was 88%. The AUC of Cubic SVM, Quadratic SVM and Linear SVM were higher than that of LR. The precision ratio of LR was 95% and recall ratio was 91%, both were lower than most ML models. The F-Score of LR was 0.93, which was only slightly better than that of Linear Discriminant and Quadratic Discriminant. CONCLUSIONS: The twenty-two ML models selected have capabilities comparable to classical LR model for outcome prediction in STBI patients. Of these, Cubic SVM, Quadratic SVM, Linear SVM performed significantly better than LR.

7.
BMJ Open ; 9(7): e023841, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31272970

RESUMO

OBJECTIVES: Injection drug use is the most important risk factor for the spread of HIV in China over the past two decades. People who use drugs (PWUD) who were diagnosed at an early stage with HIV have gradually developed AIDS. This study investigated the factors associated with disease progression following HIV diagnosis in PWUD. DESIGN: This study used a retrospective cohort study. SETTING: This investigation was conducted in Dongguan city, Guangdong Province, China. PARTICIPANTS: A total of 2969 PWUD with HIV were recruited from 1 January 1995 to 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Kaplan-Meier method, Logistic regression and Cox proportional hazards regression model were applied to identify the related factors of progression to AIDS following HIV diagnosis. RESULTS: The study revealed that age at diagnosis, marital status, baseline CD4 T-cell counts and highly active antiretroviral therapy (HAART) were statistically significant (p<0.01), either in the patients with HIV or in patients with AIDS. Compared with HIV-infected individuals of 18 years, patients with AIDS who were at least 36 years of age possessed sharply increased HR for developing AIDS (HR=7.016, 95% CI 6.083 to 8.092, p=0.001). The single HIV-positive individuals (HR=0.691, 95% CI 0.588 to 0.811, p=0.001) were less likely to develop AIDS compared with married ones. Increasing baseline CD4 T-cell counts, HAART (HR=0.599, 95% CI 0.517 to 0.693, p=0.001) and condom usage (HR=0.825, 95% CI 0.710 to 0.959, p=0.012) were associated with delayed progression to AIDS. CONCLUSIONS: Our study found that increasing baseline CD4 T-cell counts, HAART and condom usage might be associated with delayed the progression of HIV to AIDS, while increasing age at diagnosis, marital status increased hazard for developing AIDS.

8.
Asia Pac J Clin Nutr ; 28(2): 411-418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192571

RESUMO

BACKGROUND AND OBJECTIVES: By combining the techniques of metabolomics and computational biology, this research aims to explore the mechanism of metabolic dynamics in critically injured patients and develop a new early warning method for mortality. METHODS AND STUDY DESIGN: A prospective cohort study was conducted, group plasma samples of critically injured patients were collected for 1H-NMR metabolomics analysis. The data was processed with partial least squares regression, to explore the role of enzyme-gene network regulatory mechanism in critically injured metabolic network regulation and to build a quantitative prediction model for early warning of fast death. RESULTS: In total, 60 patients were enrolled. There were significant differences in plasma metabolome between the surviving patients and the deceased ones. Compared to the surviving patients, 112 enzymes and genes regulating the 6 key metabolic marker disturbances of neopterin, corticosterone, 3-methylhistidine, homocysteine, Serine, tyrosine, prostaglandin E2, tryptophan, testosterone and estriol, were observed in the plasmas of deceased ones. Among patients of different injury stages, there were significant differences in plasma metabolome. Progressing from T0 to T50 stages of injury, increased levels of neopterin, corticosterone, prostaglandin E2, tryptophan and testosterone, together with decreased levels of homocysteine, and estriol, were observed. Eventually, the quantitative prediction model of death warning was established. Cross-validation results showed that the predictive effect was good (RMSE=0.18408, R2=0.87 p=0.036). CONCLUSIONS: Metabolomics approaches can be used to quantify the metabolic dynamics of patients with critically injuries and to predict death of critically injured patients by plasma 1H-NMR metabolomics.


Assuntos
Metaboloma/fisiologia , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade , Adulto , Biomarcadores/sangue , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
JMIR Mhealth Uhealth ; 7(6): e12245, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31250833

RESUMO

BACKGROUND: Social media is currently becoming a new channel for information acquisition and exchange. In China, with the growing popularity of WeChat and WeChat official accounts (WOAs), health promotion agencies have an opportunity to use them for successful information distribution and diffusion online. OBJECTIVE: We aimed to identify features of articles pushed by WOAs of Chinese provincial Centers for Disease Control and Prevention (CDC) that are associated with user engagement. METHODS: We searched and subscribed to 28 WOAs of provincial CDCs. Data for this study consisted of WeChat articles on these WOAs between January 1, 2017 and December 31, 2017. We developed a features frame containing title type, article content, article type, communication skills, number of marketing elements, and article length for each article and coded the data quantitatively using a coding scheme that assigned numeric values to article features. We examined the descriptive characteristics of articles for every WOA and generated descriptive statistics for six article features. The amount of reading and liking was converted into the level of reading and liking by the 75% position. Two-category univariate logistic regression and multivariable logistic regression were conducted to explore associations between the features of the articles and user engagement, operationalized as reading level and liking level. RESULTS: All provincial CDC WOAs provided a total of 5976 articles in 2017. Shanghai CDC articles attracted the most user engagement, and Ningxia CDC articles attracted the least. For all articles, the median reading was 551.5 and the median liking was 10. Multivariable logistic regression analysis revealed that article content, article type, communication skills, number of marketing elements, and article length were associated with reading level and liking level. However, title type was only associated with liking level. CONCLUSIONS: How social media can be used to best achieve health information dissemination and public health outcomes is a topic of much discussion and study in the public health community. Given the lack of related studies based on WeChat or official accounts, we conducted this study and found that article content, article type, communication skills, number of marketing elements, article length, and title type were associated with user engagement. Our study may provide public health and community leaders with insight into the diffusion of important health topics of concern.


Assuntos
Disseminação de Informação/métodos , Participação do Paciente/psicologia , Mensagem de Texto/normas , China , Programas Governamentais/métodos , Humanos , Participação do Paciente/métodos , Participação do Paciente/estatística & dados numéricos , Mensagem de Texto/instrumentação
10.
J Cell Mol Med ; 23(6): 4301-4312, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30993883

RESUMO

Aberrant activation of the signal transducer and activator of transcription 3 (STAT3) and the nuclear factor-κB (NF-κB) signalling pathways is associated with the development of cancer and inflammatory diseases. JAKs and IKKs are the key regulators in the STAT3 and NF-κB signalling respectively. Therefore, the two families of kinases have been the major targets for developing drugs to regulate the two signalling pathways. Here, we report a natural compound xanthatin from the traditional Chinese medicinal herb Xanthium L. as a potent inhibitor of both STAT3 and NF-κB signalling pathways. Our data demonstrated that xanthatin was a covalent inhibitor and its activities depended on its α-methylene-γ-butyrolactone group. It preferentially interacted with the Cys243 of JAK2 and the Cys412 and Cys464 of IKKß to inactivate their activities. In doing so, xanthatin preferentially inhibited the growth of cancer cell lines that have constitutively activated STAT3 and p65. These data suggest that xanthatin may be a promising anticancer and anti-inflammation drug candidate.

11.
J Thorac Dis ; 10(8): 4849-4857, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30233858

RESUMO

Background: Airway remodelling is a major contributor to hyper-responsiveness leading to chronic asthma; however, the underlying mechanisms remain unclear. This study aimed to investigate the effects of a neurokinin 1 receptor (NK1R) antagonist (WIN62577) on the migration of airway smooth muscle cells (ASMCs) and the expression of NK1R and alpha-tubulin in airway remodelling using young rats with asthma. Methods: Sprague-Dawley rats were randomly divided into a control group and airway remodelling group. Rats in the model group were stimulated with ovalbumin for 8 weeks. Primary ASMCs were cultured and purified from all rats, and then treated with different doses of WIN62577. The expression of NK1R and α-tubulin in ASMCs was assessed using immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting. Changes in ASMC migration were detected by a transwell chamber assay. Results: The transwell assay showed that the number of migrating ASMCs in the asthmatic airway remodelling group was significantly greater than that in the control group (P<0.01), which was inhibited by WIN62577 in a dose-dependent manner, with peak inhibition detected at 10-8 mol/L. The mRNA and protein expression levels of NK1R and α-tubulin were significantly higher in the asthmatic airway remodelling group than in the control group (P<0.05 and P<0.01, respectively), and were significantly decreased after treatment with WIN62577 (P<0.01 and P<0.05, respectively). Conclusions: NK1R antagonists may suppress ASMC migration in a rat model of airway remodelling by inhibiting tubulin expression, indicating a new potential target for the treatment and control of chronic asthma.

12.
Onco Targets Ther ; 11: 4913-4944, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30174436

RESUMO

Background: Beta-blockers are antihypertensive drugs and have shown potential in cancer prognosis. However, this benefit has not been well defined due to inconsistent results from the published studies. Methods: To investigate the association between administration of beta-blocker and cancer prognosis, we performed a meta-analysis. A literature search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to identify all relevant studies published up to September 1, 2017. Thirty-six studies involving 319,006 patients were included. Hazard ratios were pooled using a random-effects model. Subgroup analyses were conducted by stratifying ethnicity, duration of drug use, cancer stage, sample size, beta-blocker type, chronological order of drug use, and different types of cancers. Results: Overall, there was no evidence to suggest an association between beta-blocker use and overall survival (HR=0.94, 95% CI: 0.87-1.03), all-cause mortality (HR=0.99, 95% CI: 0.94-1.05), disease-free survival (HR=0.59, 95% CI: 0.30-1.17), progression-free survival (HR=0.90, 95% CI: 0.79-1.02), and recurrence-free survival (HR=0.99, 95% CI: 0.76-1.28), as well. In contrast, beta-blocker use was significantly associated with better cancer-specific survival (CSS) (HR=0.78, 95% CI: 0.65-0.95). Subgroup analysis generally supported main results. But there is still heterogeneity among cancer types that beta-blocker use is associated with improved survival among patients with ovarian cancer, pancreatic cancer, and melanoma. Conclusion: The present meta-analysis generally demonstrates no association between beta-blocker use and cancer prognosis except for CSS in all population groups examined. High-quality studies should be conducted to confirm this conclusion in future.

13.
Molecules ; 23(6)2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921758

RESUMO

Aberrant activations of the STAT3 (signal transducer and activator of transcription 3) signaling pathway are associated with cancer and inflammatory diseases. Three of the four Janus kinases, JAK1, JAK2, and Tyk2, are the major upstream kinases of STAT3 in responses to cytokine stimulations. Among them, JAK2 is the key kinase in the IL-6-induced STAT3 phosphorylation. Here we report the mechanisms of a natural compound parthenolide from the medicinal herb Feverfew in regulating the JAK/STAT3 signaling. We found that parthenolide was a potent inhibitor of JAKs. It covalently modified the Cys178, Cys243, Cys335, and Cys480 of JAK2 and suppressed its kinase activity. It also interacted with other JAKs in a similar fashion. The binding of parthenolide to JAKs was selective. It preferentially bound to the JAKs, but not to the abundant proteins, such as tubulin and actin. Parthenolide also induced reactive oxygen species (ROS), but the increased ROS did not seem to contribute to the inhibition of JAK/STAT3 signaling. Furthermore, parthenolide inhibited the IL-6-induced cancer cell migration and preferentially inhibited the growth of cancer cells that had constitutively activated STAT3. Our study suggests a novel strategy to inactivate JAKs and provides a promising anti-inflammation and anticancer drug candidate.


Assuntos
Janus Quinases/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
14.
Res Vet Sci ; 119: 205-208, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29958155

RESUMO

Up to now, no crystal structure of swine leukocyte antigen 2 (SLA-2) molecules was reported. In order to elucidate the structure of SLA-2 and to study the cytotoxic T lymphocyte (CTL) epitopes derived from foot-and-mouth disease virus (FMDV), a complex of swine major histocompatibility complex (MHC) class I molecule (SLA-2 haplotype, Hebao allele) with swine ß2-microglobulin and the CTL epitope FMDV-Hu64 (ALLRTATYY) derived from O serotype of FMDV VP1 protein (residues 64-72) was refolded and crystallized. The crystal, which belonged to space group P212121, diffracted to 2.5 Šresolution and had unit cell parameters a = 48.37, b = 97.75, c = 166.163 Å. These results will help to determine the first structure of a SLA-2 molecule in the context of an FMDV CTL epitope.


Assuntos
Epitopos de Linfócito T/química , Vírus da Febre Aftosa , Antígenos de Histocompatibilidade Classe I/química , Suínos , Animais , Cristalização , Raios X
15.
Appl Microbiol Biotechnol ; 102(14): 5965-5975, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29740674

RESUMO

Lung cancer is the second most common cause of cancer-related death in the world. Most cases of lung cancer are not curable, especially non-small cell lung cancer (NSCLC). Thus, novel treatment targets for this malignant disease are urgently needed. Here, we demonstrate the feasibility of Rac1 in treating p53-null human NSCLC H1299 as a novel drug target. Deacetylmycoepoxydiene (DA-MED), a cytotoxic natural polyketide, functions as a Rac1 agonist in p53-null NSCLC H1299 cells. DA-MED treatment drives Rac1 activation and promotes robust production of reactive oxygen species, activating mitochondrial permeability transition and the intrinsic apoptotic pathway. Knockdown of Rac1 decreases ROS production in DA-MED-treated cells, resulting in a concomitant decrease in DA-MED-induced apoptosis. DA-MED-activated Rac1 induces autophagy by inhibiting mammalian target of rapamycin, leading to anti-apoptotic and anti-metastatic effects. Therefore, this study provides novel insight into the complex cytotoxic and pro-survival mechanisms associated with a potent Rac1 agonist and suggests that further development of more potent Rac1 agonists could be an effective strategy for future non-small cell lung cancer treatments.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Pironas/farmacologia , Proteínas rac1 de Ligação ao GTP/agonistas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Concentração Inibidora 50 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
J Biol Rhythms ; 32(2): 109-120, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28347186

RESUMO

PAS domain-containing proteins can act as environmental sensors that capture external stimuli to allow coordination of organismal physiology with the outside world. These proteins permit diverse ligand binding and heterodimeric partnership, allowing for varied combinations of PAS-dependent protein-protein interactions and promoting crosstalk among signaling pathways. Previous studies report crosstalk between circadian clock proteins and the aryl hydrocarbon receptor (AhR). Activated AhR forms a heterodimer with the circadian clock protein Bmal1 and thereby functionally inhibits CLOCK/Bmal1 activity. If physiological activation of AhR through naturally occurring, endogenous ligands inhibits clock function, it seems plausible to hypothesize that decreased AhR expression releases AhR-induced inhibition of circadian rhythms. Because both AhR and the clock are important regulators of glucose metabolism, it follows that decreased AhR will also alter metabolic function. To test this hypothesis, rhythms of behavior, metabolic outputs, and circadian and metabolic gene expression were measured in AhR-deficient mice. Genetic depletion of AhR enhanced behavioral responses to changes in the light-dark cycle, increased rhythmic amplitude of circadian clock genes in the liver, and altered rhythms of glucose and insulin. This study provides evidence of AhR-induced inhibition that influences circadian rhythm amplitude.


Assuntos
Ritmo Circadiano , Periodicidade , Receptores de Hidrocarboneto Arílico/deficiência , Receptores de Hidrocarboneto Arílico/genética , Transdução de Sinais , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Relógios Circadianos , Expressão Gênica , Glucose/metabolismo , Camundongos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Fotoperíodo , Receptores de Hidrocarboneto Arílico/metabolismo
18.
Nat Prod Res ; 31(19): 2245-2249, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28281379

RESUMO

Five new α-pyrones namely nocapyrones O-S (2-6) and nocapyrone F (1) were isolated from a deep-sea sediment strain Nocardiopsis sp. YIM M13066. Their structures were elucidated by their NMR spectroscopic data, HR-ESI-MS and crystal X-ray diffraction. Their cytotoxic activities against H1299, HeLa, HL7702, MCF-7, PC3 and U251 cell lines were evaluated.


Assuntos
Actinomycetales/química , Pironas/isolamento & purificação , Pironas/farmacologia , Actinobacteria , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Pironas/química , Difração de Raios X
19.
Chronobiol Int ; 34(3): 318-336, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28102700

RESUMO

High fat diet (HFD) consumption alters the synchronized circadian timing system resulting in harmful loss, gain or shift of transcriptional oscillations. The aryl hydrocarbon receptor (AhR) shares structural homology to clock genes, containing both PAS domains and basic helix-loop helix structural motifs, allowing for interaction with components of the primary circadian feedback loop. Activation of AhR alters circadian rhythmicity, primarily through inhibition of Clock/Bmal1-mediated regulation of Per1. AhR-deficient mice are protected from diet-induced metabolic dysfunction, exhibiting enhanced insulin sensitivity and glucose tolerance. This study examined whether AhR haploinsufficiency can also protect against diet-induced alterations in rhythm. After feeding AhR+/+ and AhR+/- mice an HFD (60% fat) for 15 weeks, samples were collected every 4 hours over a 24-hour period. HFD altered the rhythm of serum glucose and the metabolic transcriptome, including hepatic nuclear receptors Rev-erbα and PPARγ in wild-type c57bl6/j mice. AhR reduction provided protection against diet-induced transcriptional oscillation changes; serum glucose and metabolic gene rhythms were protected from the disruption caused by HFD feeding. These data highlight the critical role of AhR signaling in the regulation of metabolism and provide a potential therapeutic target for diseases characterized by rhythmic desynchrony.


Assuntos
Ritmo Circadiano/fisiologia , Fígado/metabolismo , Receptores de Hidrocarboneto Arílico/deficiência , Fatores de Transcrição ARNTL/genética , Animais , Relógios Circadianos/fisiologia , Dieta Hiperlipídica , Masculino , Camundongos Transgênicos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo
20.
Nat Prod Res ; 31(1): 77-83, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27484832

RESUMO

Two new germacradiene-type sesquiterpenoids, including 1(10)E,5E-germacradiene-9ß,11-diol (or 9ß-hydroxyl germacradienol) (1) and 11-hydroxy-1(10)E,5E-germacradien-2-one (2-oxygermacradienol) (2), together with a known geosmin-type sesquiterpenoid (1ß,4ß,4aß,7α,8aα)-4,8a-dimethyloctahydronaphthalene-1,4a,7(2H)-triol (3), were elucidated by their NMR spectroscopic data, HR-ESI-MS and single-crystal X-ray diffraction from the halophilic strain Nocardiopsis chromatogenes YIM 90109. The antimicrobial activities were evaluated by paper diffusion method.


Assuntos
Actinomycetales/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Bactérias/efeitos dos fármacos , Fermentação , Fungos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrometria de Massas por Ionização por Electrospray , Difração de Raios X
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