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1.
Anal Chim Acta ; 1183: 338981, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627510

RESUMO

An electrochemical assistance solid-phase microextraction (EA-SPME) was developed based on amino functionalized multi-walled carbon nanotube/polypyrrole (MWCNTs-NH2/PPy) composite coating. It was applied for the extraction of eight phenols in food contact material, including 2-chlorophenol, o-cresol, m-cresol, 2,4-dichlorophenol, 4-tert-butylphenol, 4-chlorophenol, 4-tertoctylphenol and alpha-naphthol. MWCNTs-NH2/PPy coating was characterized by scanning electron microscopy, transmission electron microscope, X-ray energy spectrometer, X-ray diffraction, Fourier transform infrared and thermogravimetric analysis. The adsorption mechanism of phenols on the composite coatings was investigated. The coating modified steel-wire as an extraction fiber has good electroconductibility, reproducibility and long service life. A determination method for the eight phenols was established by EA-SPME coupled with gas chromatography-flame ionization detection. Under the optimal experimental conditions (extraction temperature: 40 °C; extraction time: 30 min; stirring rate: 600 rpm; NaCl concentration: 0.15 g mL-1; desorption temperature: 250 °C and desorption time: 4 min), the detection linear range was 0.005-50 µg L-1 (R2>0.99), and the detection limit was 0.001-0.1 µg L-1 (S/N = 3). For the quintuple analysis of 50 µg L-1 phenols, the single fiber RSDs were 2.2-12.4%, and the fiber-to-fiber RSDs were 1.9-10.5%. The method was used to detect the migration quantity of the eight phenols from five canned packaging materials, which showed satisfactory recovery 87.3-118.9%.


Assuntos
Nanotubos de Carbono , Microextração em Fase Sólida , Fenóis , Polímeros , Pirróis , Reprodutibilidade dos Testes
2.
Breast Cancer Res Treat ; 189(3): 725-736, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392453

RESUMO

PURPOSE: To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. METHODS: The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. RESULTS: GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. CONCLUSION: GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.

3.
Cancer Med ; 10(17): 6089-6098, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34346560

RESUMO

Bilateral breast cancer (BBC) is an uncommon subset of breast cancer (BC), and it may present as synchronous bilateral breast cancer (sBBC) or metachronous bilateral breast cancer (mBBC). Through this study, we aimed to evaluate the proportion of BBC in BC and compare the clinicopathological characteristics, treatment, and outcomes of sBBC and mBBC at an academic cancer center in China. Patients with BC consecutively treated between 2006 and 2016 were retrospectively reviewed. Patients with BBC were included. In total, 3924 patients with BC were analyzed and 127 patients with BBC (28 sBBC, 99 mBBC) with a median follow-up of 98 months were identified. The proportion of BBC was 3.2% (0.7%, sBBC; 2.5%, mBBC). The median age at the first diagnosis of mBBC was significantly younger than that at the first diagnosis of sBBC (p = 0.027). Patients diagnosed as having sBBC were more likely to have a positive family history (p = 0.047). The first tumors of mBBC were detected at a significantly earlier tumor stage compared with those of sBBC (p = 0.028). The concordance rates of histopathologic type in the first and second tumors were 60.7% and 58.0% in sBBC and mBBC, respectively. sBBC had a significantly poorer disease-free survival than mBBC did (p = 0.001). BBC is a rare disease affecting the Chinese population. sBBC is associated with a greater prevalence of a family history of breast cancer and poorer prognosis, compared with mBBC.

4.
Biomolecules ; 11(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34207942

RESUMO

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.


Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Ritmo Circadiano/fisiologia , Nefropatias/fisiopatologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/fisiopatologia , China , Humanos , Hipertensão/fisiopatologia , Rim/fisiopatologia , Nefropatias/metabolismo
5.
Hepatol Commun ; 5(5): 798-811, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34027270

RESUMO

Bile acids (BAs) play important functions in the development of alcohol-associated liver disease (ALD). In the current study, urine BA concentrations in 38 patients with well-described alcohol-associated hepatitis (AH) as characterized by Model for End-Stage Liver Disease (MELD), 8 patients with alcohol-use disorder (AUD), and 19 healthy controls (HCs) were analyzed using liquid chromatography-mass spectrometry. Forty-three BAs were identified, and 22 BAs had significant changes in their abundance levels in patients with AH. The potential associations of clinical data were compared to candidate BAs in this pilot proof-of-concept study. MELD score showed positive correlations with several conjugated BAs and negative correlations with certain unconjugated BAs; taurine-conjugated chenodeoxycholic acid (CDCA) and MELD score showed the highest association. Cholic acid, CDCA, and apocholic acid had nonsignificant abundance changes in patients with nonsevere ALD compared to HCs but were significantly increased in those with severe AH. Receiver operating characteristic analysis showed that the differences in these three compounds were sufficiently large to distinguish severe AH from nonsevere ALD. Notably, the abundance levels of primary BAs were significantly increased while most of the secondary BAs were markedly decreased in AH compared to AUD. Most importantly, the amount of total BAs and the ratio of primary to secondary BAs increased while the ratio of unconjugated to conjugated BAs decreased as disease severity increased. Conclusion: Abundance changes of specific BAs are closely correlated with the severity of AH in this pilot study. Urine BAs (individually or as a group) could be potential noninvasive laboratory biomarkers for detecting early stage ALD and may have prognostic value in AH morbidity.

6.
FASEB J ; 35(5): e21530, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33813752

RESUMO

Circadian clock is involved in regulating most renal physiological functions, including water and electrolyte balance and blood pressure homeostasis, however, the role of circadian clock in renal pathophysiology remains largely unknown. Here we aimed to investigate the role of Bmal1, a core clock component, in the development of renal fibrosis, the hallmark of pathological features in many renal diseases. The inducible Bmal1 knockout mice (iKO) whose gene deletion occurred in adulthood were used in the study. Analysis of the urinary water, sodium and potassium excretion showed that the iKO mice exhibit abolished diurnal variations. In the model of renal fibrosis induced by unilateral ureteral obstruction, the iKO mice displayed significantly decreased tubulointerstitial fibrosis reflected by attenuated collagen deposition and mitigated expression of fibrotic markers α-SMA and fibronectin. The hedgehog pathway transcriptional effectors Gli1 and Gli2, which have been reported to be involved in the pathogenesis of renal fibrosis, were significantly decreased in the iKO mice. Mechanistically, ChIP assay and luciferase reporter assay revealed that BMAL1 bound to the promoter of and activate the transcription of Gli2, but not Gli1, suggesting that the involvement of Bmal1 in renal fibrosis was possibly mediated via Gli2-dependent mechanisms. Furthermore, treatment with TGF-ß increased Bmal1 in cultured murine proximal tubular cells. Knockdown of Bmal1 abolished, while overexpression of Bmal1 increased, Gli2 and the expression of fibrosis-related genes. Collectively, these results revealed a prominent role of the core clock gene Bmal1 in tubulointerstitial fibrosis. Moreover, we identified Gli2 as a novel target of Bmal1, which may mediate the adverse effect of Bmal1 in obstructive nephropathy.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Fibrose/prevenção & controle , Regulação da Expressão Gênica , Nefropatias/prevenção & controle , Proteínas Circadianas Period/fisiologia , Proteína Gli2 com Dedos de Zinco/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo
7.
J Chromatogr A ; 1633: 461627, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33128970

RESUMO

A Poly (3,4-ethylenedioxothiophene) (PEDOT)/UiO-66 composite was electrodeposited on an etched stainless-steel wire as head-space solid-phase microextraction (HS-SPME) coating. A robust, well controlled thickness, and uniform coating of metal organic framework composites can be realized by the electrodeposited strategy. The incorporated UiO-66 not only enhanced the uniformity and stability of the composite coating, but also effectively decreased the stacking phenomenon of PEDOT and improved its extraction efficiency, which was over 100 times higher than that of the PEDOT coating without UiO-66. The composite coating was used to enrich seven types of volatile organic compounds (VOCs) in ion-exchange resins, including methyl cyclohexane, benzene, toluene, ortho-xylene, styrene, para-xylene and divinyl-benzene. The results of adsorption isotherm analysis showed that π stacking effect played dominant role between the composite coating and VOCs in the extraction process. The composite coating was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform infrared and thermogravimetric analysis, respectively. A determination method for seven kinds of VOCs was established by HS-SPME coupled with gas chromatography-flame ionization detection (GC-FID). Under the optimal experimental conditions, the detection linear range (LRs) was 0.09-100 ng mL-1, and the detection limit (LODs) was 0.03-0.06 ng mL-1 (S/N = 3). The method was applied for the migration detection of VOCs in four types of ion-exchange resin, which showed satisfactory recovery (84.5-117.2%).


Assuntos
Técnicas de Química Analítica/métodos , Estruturas Metalorgânicas/química , Compostos Organometálicos/química , Ácidos Ftálicos/química , Polímeros/química , Tiofenos/química , Compostos Orgânicos Voláteis/isolamento & purificação , Adsorção , Benzeno/análise , Benzeno/isolamento & purificação , Cromatografia Gasosa , Ionização de Chama , Resinas de Troca Iônica/química , Limite de Detecção , Microextração em Fase Sólida , Aço Inoxidável/química , Tolueno/análise , Tolueno/isolamento & purificação , Compostos Orgânicos Voláteis/análise , Xilenos/análise , Xilenos/isolamento & purificação
9.
J Pharmacol Exp Ther ; 375(1): 40-48, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32759273

RESUMO

Deletion of microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibits inflammation and protects against atherosclerotic vascular diseases but displayed variable influence on pathologic cardiac remodeling. Overactivation of ß-adrenergic receptors (ß-ARs) causes heart dysfunction and cardiac remodeling, whereas the role of mPGES-1 in ß-AR-induced cardiac remodeling is unknown. Here we addressed this question using mPGES-1 knockout mice, subjecting them to isoproterenol, a synthetic nonselective agonist for ß-ARs, at 5 or 15 mg/kg per day to induce different degrees of cardiac remodeling in vivo. Cardiac structure and function were assessed by echocardiography 24 hours after the last of seven consecutive daily injections of isoproterenol, and cardiac fibrosis was examined by Masson trichrome stain in morphology and by real-time polymerase chain reaction for the expression of fibrosis-related genes. The results showed that deletion of mPGES-1 had no significant effect on isoproterenol-induced cardiac dysfunction or hypertrophy. However, the cardiac fibrosis was dramatically attenuated in the mPGES-1 knockout mice after either low-dose or high-dose isoproterenol exposure. Furthermore, in vitro study revealed that overexpression of mPGES-1 in cultured cardiac fibroblasts increased isoproterenol-induced fibrosis, whereas knocking down mPGES-1 in cardiac myocytes decreased the fibrogenesis of fibroblasts. In conclusion, mPGES-1 deletion protects against isoproterenol-induced cardiac fibrosis in mice, and targeting mPGES-1 may represent a novel strategy to attenuate pathologic cardiac fibrosis, induced by ß-AR agonists. SIGNIFICANCE STATEMENT: Inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) are being developed as alternative analgesics that are less likely to elicit cardiovascular hazards than cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs. We have demonstrated that deletion of mPGES-1 protects inflammatory vascular diseases and promotes post-myocardial infarction survival. The role of mPGES-1 in ß-adrenergic receptor-induced cardiomyopathy is unknown. Here we illustrated that deletion of mPGES-1 alleviated isoproterenol-induced cardiac fibrosis without deteriorating cardiac dysfunction. These results illustrated that targeting mPGES-1 may represent an efficacious approach to the treatment of inflammatory cardiovascular diseases.


Assuntos
Cardiomiopatias/genética , Microssomos/metabolismo , Miocárdio/patologia , Prostaglandina-E Sintases/genética , Receptores Adrenérgicos beta/metabolismo , Remodelação Ventricular/genética , Agonistas Adrenérgicos beta/farmacologia , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Células Cultivadas , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose , Isoproterenol/farmacologia , Masculino , Camundongos Knockout , Microssomos/efeitos dos fármacos , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Ventricular/efeitos dos fármacos
10.
Opt Lett ; 45(7): 1966-1969, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236043

RESUMO

The phase evolution of terahertz (THz) radiation from single-color femotsecond laser-induced air plasma controlled by a DC-bias is investigated experimentally. When the DC-bias is moved from the end to the beginning of the laser plasma filament, the produced THz waveform is advanced temporally, and its carrier-envelope phase is changed. Our phase spectrum analysis suggests that the slope and the intercept of the phase spectrum, respectively, determine the temporal shift and the carrier-envelope phase of the THz waveform. Therefore, the observed THz waveform evolution is mainly due to the THz propagation effect in plasma filament and the Gouy phase shift associated with the detection scheme. This Letter also illustrates explicitly the temporal order of THz radiation from different parts of a filament.

11.
Opt Lett ; 45(7): 2090, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236075

RESUMO

This publisher's note contains corrections to Opt. Lett.45, 1966 (2020).OPLEDP0146-959210.1364/OL.385292.

12.
Arterioscler Thromb Vasc Biol ; 40(6): 1523-1532, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32321308

RESUMO

OBJECTIVE: Although the molecular components of circadian rhythms oscillate in discrete cellular components of the vasculature and many aspects of vascular function display diurnal variation, the cellular connections between the molecular clock and inflammatory cardiovascular diseases remain to be elucidated. Previously we have shown that pre- versus postnatal deletion of Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1), the nonredundant core clock gene has contrasting effects on atherogenesis. Here we investigated the effect of myeloid cell Bmal1 deletion on atherogenesis and abdominal aortic aneurysm formation in mice. Approach and Results: Mice lacking Bmal1 in myeloid cells were generated by crossing Bmal1 flox/flox mice with lysozyme 2 promoter-driven Cre recombinase mice on a hyperlipidemic low-density lipoprotein receptor-deficient background and were fed on a high-fat diet to induce atherosclerosis. Atherogenesis was restrained, concomitant with a reduction of aortic proinflammatory gene expression in myeloid cell Bmal1 knockout mice. Body weight, blood pressure, blood glucose, triglycerides, and cholesterol were unaltered. Similarly, myeloid cell depletion of Bmal1 also restrained Ang II (angiotensin II) induced formation of abdominal aortic aneurysm in hyperlipidemic mice. In vitro, RNA-Seq analysis demonstrated a proinflammatory response in cultured macrophages in which there was overexpression of Bmal1. CONCLUSIONS: Myeloid cell Bmal1 deletion retards atherogenesis and restrains the formation of abdominal aortic aneurysm and may represent a potential therapeutic target for inflammatory cardiovascular diseases.


Assuntos
Fatores de Transcrição ARNTL/deficiência , Fatores de Transcrição ARNTL/fisiologia , Aneurisma da Aorta Abdominal/prevenção & controle , Aterosclerose/prevenção & controle , Hiperlipidemias/complicações , Células Mieloides/química , Fatores de Transcrição ARNTL/genética , Angiotensina II/farmacologia , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aterosclerose/etiologia , Aterosclerose/patologia , Células Cultivadas , Cruzamentos Genéticos , Dieta Hiperlipídica , Deleção de Genes , Expressão Gênica , Hiperlipidemias/etiologia , Inflamação , Integrases/genética , Macrófagos Peritoneais/química , Macrófagos Peritoneais/fisiologia , Camundongos , Camundongos Knockout , Muramidase/genética , Regiões Promotoras Genéticas/genética , Receptores de LDL/deficiência , Receptores de LDL/genética
13.
Exp Cell Res ; 390(1): 111949, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32145254

RESUMO

Farnesoid X receptor (FXR) is a metabolic nuclear receptor, which protects liver from many endogenous and exogenous injuries. Metallothioneins (MTs) belong to a low-molecular-weight protein family involved in metal homeostasis and the regulation of hepatic oxidative stress. In the present study, we aimed to investigate the effect of FXR on hepatic MT1 expression and the underlying mechanism. C57BL/6 mice or primary cultured mouse hepatocytes were treated with the synthetic FXR ligand GW4064 or natural ligand CDCA. RNA-Sequencing (RNA-seq) analysis was performed to identify gene expression profile in the livers of mice treated with GW4064. Real-time PCR and Western blot were applied to determine the expression of MT1 and other FXR target genes in the livers of mice and primary hepatocytes treated with GW4064 and CDCA. Cellular and subcellular locations of MT1 in the livers of mice treated with GW4064 were examined using immunohistochemistry assay. FXR small interfering RNAs (siRNA) was transfected to silence FXR. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were utilized to confirm the regulation of MT1 gene promoter activity by FXR. RNA-seq analysis revealed that GW4064 treatment significantly induced MT1 expression in mouse liver. Consistently, MT1 expression in the hepatocytes of mouse livers and cultured hepatocytes was upregulated by GW4064 as well as CDCA. In addition, adenovirus-mediated overexpression of FXR markedly increased, while siRNA-mediated FXR silencing significantly suppressed MT1 expression in cultured hepatocytes. Luciferase reporter and ChIP assays further confirmed that the MT1 gene was under the direct control of FXR. Collectively, our findings demonstrate that MT1 is a novel target gene of FXR and may contribute to antioxidative capacity of FXR in liver diseases.


Assuntos
Fígado/metabolismo , Metalotioneína/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Células Cultivadas , Hepatócitos/metabolismo , Humanos , Masculino , Metalotioneína/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores Citoplasmáticos e Nucleares/genética
14.
Angew Chem Int Ed Engl ; 59(7): 2860-2866, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-31743549

RESUMO

A novel palladium-catalyzed Heck-type reaction of thiocarbamates has been designed to construct bridged seven-membered-ring systems that are otherwise challenging to prepare. Taking advantage of this newly developed method, enantioselective syntheses of lyconadins A-E (1-5), lycopecurine (6), and dehydrolycopecurine (7) have been realized in a divergent fashion. Our synthetic strategy also features an intramolecular cyclization of a N-chloroamine to forge the C6-N bond, a transannular Mannich-type reaction of a cyclic nitrone to stitch the C4 and C13 together, and a cyclocondensation to deliver the (dihydro-)pyridone motif.

15.
JCI Insight ; 52019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30973828

RESUMO

Recently, by utilizing conventional and tamoxifen inducible Bmal1 (Brain and muscle Arnt-like protein 1) knockout mice, we found that delaying the loss of circadian rhythms to adulthood attenuates the impact on general integrity and survival at least under 12h light/12h dark conditions (LD). To understand further the contribution of Bmal1 in post-natal life under conditions of circadian disruption, we subjected inducible knockout mice (KO) and their littermate controls (Ctrl) to forced desynchrony protocols including cycles with non-24h periods, randomized light/dark cycles, and jet lag, and monitored their locomotor activity using radiotelemetry. Under these conditions, control mice cannot be entrained, as reflected by their maintenance of circadian behavior irrespective of schedules. By contrast, KO mice displayed higher activity levels in the dark phases of most cycles. Under a 3h light/3h dark regime, Ctrls displayed higher activity levels in the dark phases of all cycles although there were still obvious circadian rhythms, suggesting that an ultradian mechanism is also involved. Insulin sensitivity was markedly reduced by disrupted light schedules as expected in Ctrls, but not in the KOs. Thus, Bmal1 deletion in adult mice facilitates adaptation to new light/dark schedules and protects from insulin resistance induced by circadian disruption.


Assuntos
Fatores de Transcrição ARNTL/metabolismo , Adaptação Fisiológica , Transtornos Cronobiológicos/fisiopatologia , Ritmo Circadiano/fisiologia , Locomoção/fisiologia , Fatores de Transcrição ARNTL/genética , Animais , Transtornos Cronobiológicos/etiologia , Modelos Animais de Doenças , Humanos , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Knockout , Fotoperíodo , Tolerância ao Trabalho Programado/fisiologia
16.
Arterioscler Thromb Vasc Biol ; 38(12): 2819-2826, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30571171

RESUMO

Objective- Evening but not morning administration of low-dose aspirin has been reported to lower blood pressure in hypertensive patients. The present study was designed to determine whether this phenomenon could be replicated in mice, and if so, whether a time-dependent effect of aspirin on blood pressure was because of alteration of circadian clock function. Approach and Results- We recapitulated the protective effect of aspirin (50 µg/d for 7 days) at zeitgeber time 0 (active-to-rest transit), but not at zeitgeber time 12, on a high-salt diet-induced increase of blood pressure. However, the time of aspirin administration did not influence expression of canonical clock genes or their acetylation. We used mouse Bmal1 and Per2-luciferase reporters expressed in U2OS cells to determine the real-time effect of aspirin on circadian function but found that the oscillation of bioluminescence was unaltered. Timing of aspirin administration also failed to alter urinary prostaglandin metabolites or catecholamines, or the acetylation of its COX-1 (cyclooxygenase-1) target in platelets. Conclusions- The time-dependent hypotensive effect of aspirin in humans has been recapitulated in hypertensive mice. However, this does not seem to reflect a direct impact of aspirin on circadian clocks or on acetylation of platelet COX-1.


Assuntos
Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano , Hipertensão/prevenção & controle , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Linhagem Celular Tumoral , Relógios Circadianos/efeitos dos fármacos , Relógios Circadianos/genética , Ritmo Circadiano/efeitos dos fármacos , Ciclo-Oxigenase 1/sangue , Modelos Animais de Doenças , Cronoterapia Farmacológica , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Proteínas de Membrana/sangue , Camundongos Endogâmicos C57BL , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Cloreto de Sódio na Dieta , Fatores de Tempo
17.
Sci Rep ; 7(1): 7795, 2017 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-28798326

RESUMO

A growing number of algorithms have been proposed to map a scalar time series into ordinal partition transition networks. However, most observable phenomena in the empirical sciences are of a multivariate nature. We construct ordinal partition transition networks for multivariate time series. This approach yields weighted directed networks representing the pattern transition properties of time series in velocity space, which hence provides dynamic insights of the underling system. Furthermore, we propose a measure of entropy to characterize ordinal partition transition dynamics, which is sensitive to capturing the possible local geometric changes of phase space trajectories. We demonstrate the applicability of pattern transition networks to capture phase coherence to non-coherence transitions, and to characterize paths to phase synchronizations. Therefore, we conclude that the ordinal partition transition network approach provides complementary insight to the traditional symbolic analysis of nonlinear multivariate time series.

18.
J Infect Dev Ctries ; 10(1): 68-73, 2016 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-26829539

RESUMO

INTRODUCTION: Escherichia coli is a commensal bacterium in humans, animals, and the environment that is one of the microorganisms commonly resistant to antimicrobials. Cooked meat products, which are popular in China, are easily contaminated by E. coli during processing and storage. METHODOLOGY: In this study, a total of 75 E. coli isolates from cooked meat products in Henan province, China, were assayed for the presence of and horizontal transfer of class 1 integrons. RESULTS: Class 1 integrons were detected in 11 (14.7%) of these isolates, and contained four groups of resistance gene cassettes, including dfrA17-aadA5, dfrA1-aadA1, dfrA12-orfF-aadA2, and an uncommon array of aacA4-catB8-aadA1. The transfer frequency of selected integron-positve donors ranged from 10(-6) to 10(-4) transconjugants per recipient cell, and the integron-containing DNA from the donors could be transferred to E. coli J53Azr with the transformation frequency of 10(-7) to 10(-5). CONCLUSIONS: Class 1 integrons could be transferred to recipient E. coli J53 by conjugation and natural transformation. These findings suggest the role of commensal E. coli isolates from cooked meats as an important reservoir for integrons and the possible transfer of antimicrobial resistance genes to humans via the food chain.


Assuntos
Escherichia coli/genética , Escherichia coli/isolamento & purificação , Transferência Genética Horizontal , Integrons , Produtos da Carne/microbiologia , China , Conjugação Genética , Humanos , Transformação Bacteriana
19.
J Nutr ; 145(12): 2690-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26468492

RESUMO

BACKGROUND: Zinc deficiency has been well documented in alcoholic liver disease. OBJECTIVE: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia. METHODS: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00-5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis. RESULTS: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group. CONCLUSIONS: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats.


Assuntos
Suplementos Nutricionais , Endotoxemia/prevenção & controle , Fígado Gorduroso Alcoólico/prevenção & controle , Enteropatias/prevenção & controle , Zinco/administração & dosagem , Aldeído Desidrogenase/metabolismo , Animais , Claudina-1/análise , Citocinas/biossíntese , Endotoxinas/análise , Etanol/efeitos adversos , Fígado Gorduroso Alcoólico/fisiopatologia , Enteropatias/induzido quimicamente , Mucosa Intestinal/metabolismo , Intestinos/química , Intestinos/enzimologia , Fígado/patologia , Fígado/fisiopatologia , Ativação de Macrófagos , Masculino , Ocludina/análise , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas de Junções Íntimas/análise , Zinco/deficiência , Proteína da Zônula de Oclusão-1/análise
20.
Cell Cycle ; 13(17): 2707-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25486358

RESUMO

Tetraspanin CD151 interacts with laminin-binding integrins (i.e., α3ß1, α6ß1 and α6ß4) and other cell surface molecules to control diverse cellular and physiological processes, ranging from cell adhesion, migration and survival to tissue architecture and homeostasis. Here, we report a novel role of CD151 in maintaining the branching morphogenesis and activity of progenitor cells during the pubertal development of mammary glands. In contrast to the disruption of laminin-binding integrins, CD151 removal in mice enhanced the tertiary branching in mammary glands by 2.4-fold and the number of terminal end buds (TEBs) by 30%, while having minimal influence on either primary or secondary ductal branching. Consistent with these morphological changes are the skewed distribution of basal/myoepithelial cells and a 3.2-fold increase in proliferating Ki67-positive cells. These novel observations suggest that CD151 impacts the branching morphogenesis of mammary glands by upregulating the activities of bipotent progenitor cells. Indeed, our subsequent analyses indicate that upon CD151 removal the proportion of CD24(Hi)CD49f(Low) progenitor cells in the mammary gland increased by 34%, and their proliferating and differentiating activities were significantly upregulated. Importantly, fibronectin, a pro-branching extracellular matrix (ECM) protein deposited underlying mammary epithelial or progenitor cells, increased by >7.2-fold. Moreover, there was a concomitant increase in the expression and nuclear distribution of Slug, a transcription factor implicated in the maintenance of mammary progenitor cell activities. Taken together, our studies demonstrate that integrin-associated CD151 represses mammary branching morphogenesis by controlling progenitor cell activities, ECM integrity and transcription program.


Assuntos
Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Nicho de Células-Tronco , Células-Tronco/citologia , Células-Tronco/metabolismo , Tetraspanina 24/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Células Epiteliais/citologia , Matriz Extracelular/metabolismo , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Integrinas/metabolismo , Glândulas Mamárias Animais/enzimologia , Camundongos , Morfogênese , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo
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