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1.
Opt Express ; 32(9): 16523-16532, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859277

RESUMO

The direction variation of the fundamental wave in the same nonlinear photonic crystal would cause different pattern of harmonics generation. In a 2D/3D crystal with dense reciprocal lattice vectors, there will be large numbers of conical harmonic beams evolving with direction change of the fundamental wave. By rearranging the Ewald sphere and superposing it into the Ewald shell, we have a hybrid Ewald construction. It becomes a simple but useful geometric method to comprehensively depict the distribution of these quasi-phase-matching second harmonics and their conical form evolution. It presents conical second harmonic beams by their related reciprocal lattice vectors and simplifies the beams' distribution according to spatial arrangement of those reciprocal lattice vectors. It finds that the conical beams will create, annihilate, or get enhanced in specific order when fundamental waves change incident directions. We applied the method on a periodically poled 2D LiTaO3 crystal and all observed phenomena, meet the method's predictions. In our experiment, we observed that the conical beams distorted along the optic axis of the sample due to anisotropy, which was generally overlooked by earlier researches. The eccentricities of their ring projections suggest a potential auxiliary approach for crystal dispersion measurement.

2.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753520

RESUMO

Protein stability affects the physiological functions of proteins and is also a desirable trait in many protein engineering tasks, yet improving protein stability is challenging because of limitations in methods for directly monitoring protein stability in cells. Here, we report an in vivo stability biosensor wherein a protein of interest (POI) is inserted into a microbial enzyme (CysGA) that catalyzes the formation of endogenous fluorescent compounds, thereby coupling POI stability to simple fluorescence readouts. We demonstrate the utility of the biosensor in directed evolution to obtain stabilized, less aggregation-prone variants of two POIs (including nonamyloidogenic variants of human islet amyloid polypeptide). Beyond engineering applications, we exploited our biosensor in deep mutational scanning for experimental delineation of the stability-related contributions of all residues throughout the catalytic domain of a histone H3K4 methyltransferase, thereby revealing its scientifically informative stability landscape. Thus, our highly accessible method for in vivo monitoring of the stability of diverse proteins will facilitate both basic research and applied protein engineering efforts.


Assuntos
Técnicas Biossensoriais , Evolução Molecular Direcionada/métodos , Metiltransferases/química , Engenharia de Proteínas , Estabilidade Proteica , Hidrolases Anidrido Ácido/química , Hidrolases Anidrido Ácido/genética , Domínio Catalítico , Escherichia coli , Fluorescência , Ensaios de Triagem em Larga Escala , Humanos , Metiltransferases/genética , Mutação , Acilfosfatase
3.
J Chem Inf Model ; 62(24): 6378-6385, 2022 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-35947427

RESUMO

Secondary metabolites from natural sources are promising starting points for discovering and developing drug prototypes and new drugs, as many current treatments for numerous diseases are directly or indirectly related to such compounds. Recent advances in bioinformatics tools and molecular networking methods have made it possible to identify novel bioactive compounds. In this study, a workflow combining network-based methods for identifying bioactive compounds found in natural products was streamlined by innovating an automated bioinformatics software. The workflow relies on Global Natural Product Social Molecular Networking (GNPS), a web-based mass spectrometry ecosystem that aims to be an open-access knowledge base for community-wide organization and sharing of raw, processed, or annotated fragmentation mass spectrometry data. By combining computational tools including MZmine2, GNPS, and Cytoscape, the integrated dashboard quickly creates bioactive molecular networks with minimal user intervention and reduces the processing time of the original workflow by over 80%. This newly automated workflow quickens the process of discovering bioactive compounds from natural products. This study uses extracts from Psidium guajava leaves to demonstrate the application of our automated software.


Assuntos
Produtos Biológicos , Produtos Biológicos/química , Ecossistema , Software , Espectrometria de Massas , Automação
4.
Artigo em Inglês | MEDLINE | ID: mdl-36058783

RESUMO

BACKGROUND: Polydatin, a glucoside of resveratrol, has been shown to have protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. METHODS: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. RESULTS: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1ß, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. CONCLUSIONS: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

5.
Pharm Res ; 38(11): 1847-1862, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34773182

RESUMO

PURPOSE: Sulcardine sulfate (Sul) is a novel antiarrhythmic agent with promising pharmacological properties, which is currently being evaluated in several clinical trials as an oral formulation. To meet the medication needs of patients with acute conditions, the injection formulation of Sul has been developed. The objective of this study was to systemically investigate the pharmacokinetic profiles of Sul after intravenous infusion. METHODS: This research included the plasma protein binding and metabolic stability studies in vitro, plasma pharmacokinetics, biodistribution, excretion studies in animals, and the prediction of the clinical PK of Sul injection using a physiologically based pharmacokinetics (PBPK) model. RESULTS: The metabolic stability was similarly in dogs and humans but lower in rats. The plasma protein binding rates showed a concentration-dependent manner and species differences. The pharmacokinetic behavior after intravenous administration was linear in rats within the dose range of 30-90 mg/kg, but nonlinear in dogs within 30-60 mg/kg. Sul could be rapidly and widely distributed in multiple tissues after intravenous administration. About 12% of the parent compound were excreted via the urine and only a small fraction via bile and feces,and eight metabolites were found and identified in the rat excretion. The PBPK models were developed and simulated the observed PK date well in both rats and dogs. The PBPK model refined with human data predicted the PK characteristics of the first intravenous infusion of Sul in human. CONCLUSIONS: Our study systematically explored the pharmacokinetic characteristics of Sul and successfully developed the PBPK model to predict of its clinical PK.


Assuntos
Antiarrítmicos/farmacocinética , Modelos Biológicos , Ésteres do Ácido Sulfúrico/farmacocinética , Animais , Antiarrítmicos/administração & dosagem , Cães , Avaliação Pré-Clínica de Medicamentos , Feminino , Eliminação Hepatobiliar , Humanos , Infusões Intravenosas , Injeções Intravenosas , Eliminação Intestinal , Masculino , Microssomos Hepáticos , Ratos , Eliminação Renal , Ésteres do Ácido Sulfúrico/administração & dosagem , Distribuição Tecidual
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 381-389, 2021 Apr.
Artigo em Zh | MEDLINE | ID: mdl-33840411

RESUMO

OBJECTIVE: To study the value of fecal calprotectin (FC) in the diagnosis of neonatal necrotizing enterocolitis (NEC) through a Meta analysis. METHODS: Web of Science, Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure, Weipu Periodical Database, Wanfang Data, Chinese Biomedical Literature Database were searched for related studies published up to May 2020, with manual search as supplementation. The QUADAS criteria were used to evaluate the quality of the articles included. Meta-DiSc 1.4 and Stata 15.0 software were used to perform the Meta analysis, including the evaluation of specificity, sensitivity, likelihood ratio, and diagnostic odds ratio. The sensitivity analysis and heterogeneity testing were performed, and the summary receiver operating characteristic (SROC) curve and Fagan diagram were plotted. RESULTS: A total of 15 articles were enrolled, involving 1 719 neonates. Among these articles, 4 had low quality, 2 had high quality, and the rest had medium quality. There was high heterogeneity between studies, and there was no threshold effect or publication bias. The random effects model analysis showed that FC had a pooled specificity of 0.80 (95%CI:0.78-0.82) and a sensitivity of 0.86 (95%CI:0.83-0.89) in the diagnosis of NEC, with a negative likelihood ratio of 0.19 (95%CI:0.14-0.26), a positive likelihood ratio of 4.71 (95%CI:3.57-6.23), and a diagnostic odds ratio of 29.56 (95%CI:17.98-48.61). The area under the SROC curve was 0.9131 and the Q* index was 0.8456. The Fagan diagram showed that the post-test probability of NEC indicated by negative FC was 13%, while that indicated by positive FC was 86%. The Meta regression analysis showed that the heterogeneity came from other non-threshold factors. CONCLUSIONS: FC has high potential and efficiency in the early diagnosis of NEC. FC measurement can be used for the diagnosis of NEC, but it should be combined with clinical manifestations and other related laboratory examinations.


Assuntos
Enterocolite Necrosante , Complexo Antígeno L1 Leucocitário , China , Enterocolite Necrosante/diagnóstico , Fezes , Humanos , Recém-Nascido , Curva ROC , Sensibilidade e Especificidade
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 964-969, 2020 Sep.
Artigo em Zh | MEDLINE | ID: mdl-32933627

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). METHODS: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. RESULTS: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). CONCLUSIONS: Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.


Assuntos
Miastenia Gravis , Tacrolimo/uso terapêutico , Atividades Cotidianas , Criança , Humanos , Imunossupressores , Miastenia Gravis/tratamento farmacológico , Recidiva Local de Neoplasia
8.
Phys Rev Lett ; 123(19): 190401, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31765183

RESUMO

Nonclassical correlations can be regarded as resources for quantum information processing. However, the classification problem of nonclassical correlations for quantum states remains a challenge, even for finite-size systems. Although there exists a set of criteria for determining individual nonclassical correlations, a unified framework that is capable of simultaneously classifying multiple correlations is still missing. In this Letter, we experimentally explored the possibility of applying machine-learning methods for simultaneously identifying nonclassical correlations. Specifically, by using partial information, we applied an artificial neural network, support vector machine, and decision tree for learning entanglement, quantum steering, and nonlocality. Overall, we found that, for a family of quantum states, all three approaches can achieve high accuracy for the classification problem. Moreover, the run time of the machine-learning methods to output the state label is experimentally found to be significantly less than that of state tomography.

9.
Biomed Chromatogr ; 33(8): e4556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30990904

RESUMO

GL-V9, a derivative of wogonin, shows much more potent anticancer properties than wogonin. In this study, a selective, sensitive and rapid ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the determination of GL-V9 in rat plasma. Plasma samples were processed using methanol to precipitate protein. Chromatographic separation of analytes was achieved on a C18 column using gradient elution within 4.5 min. The mobile phase consisted of acetonitrile and water including 0.1% (v/v) formic acid and 5 mm ammonium acetate. GL-V9 and caffeine (internal standard) were monitored by positive electrospray triple quadrupole mass spectrometer and quantified using multiple reaction monitoring (MRM) mode with the transitions of m/z 410.20 → 126.10 (GL-V9) and 195.10 → 138.00 (IS: caffeine), respectively. Good linearity was obtained over the range of 2-1000 ng/mL (R2 > 0.99) and the extraction recovery was 101.91 ± 11.34%. The intra- and inter-day precision variations were small (RSD 1.35-6.96%) and the relative error (RE) of accuracy was -7.35-6.27%. The established and validated UPLC-MS/MS method was successfully applied to study the pharmacokinetic behavior of GL-V9 after administration through different delivery routes. The results demonstrated that pulmonary delivery exhibited a greater advantage in terms of improving bioavailability compared with oral administration.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Flavanonas/sangue , Flavanonas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Administração por Inalação , Administração Oral , Animais , Estabilidade de Medicamentos , Flavanonas/administração & dosagem , Flavanonas/química , Limite de Detecção , Modelos Lineares , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
10.
Biopharm Drug Dispos ; 40(3-4): 151-161, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30931529

RESUMO

GL-V9, a derivative of wogonin, has potent anti-cancer activity. The absorption and metabolism of this compound have not been investigated systematically. This study aims to illustrate the pharmacokinetic characters of GL-V9 by exploring its metabolic status under different administration routes. To further clarify the absorption mechanism of GL-V9, an in situ single-pass perfusion model and a Caco-2 cell monolayer model were used. Meanwhile, a microsomal incubation system was used to evaluate the enzyme kinetic parameters. In vivo, the obtained gastrointestinal availability (Fa × Fg ) was 21.28 ± 5.38%. The unmetabolized fraction in the gut wall (Fgut wall ) was 98.59 ± 9.74%, while the hepatic bioavailability (Fh ) was 29.11 ± 5.22%. These results indicated that poor absorption and extensive metabolism may contribute greatly to the low bioavailability of GL-V9. The effective permeability (Peff ) in the duodenum and jejunum was 1.34 ± 0.50 × 10-4 and 0.90 ± 0.27 × 10-4  cm/s, respectively. The high permeability of GL-V9 indicated that other unknown factors (such as metabolism) may account for its systemic exposure problem. Studies in rat liver microsomal (RLMs) confirmed this hypothesis, and the Clint, CYP450s and UGT of GL-V9 was 0.20 ml/min/mg protein. In conclusion, these results suggest that GL-V9 possesses higher permeability than wogonin and the metabolism of GL-V9 is related to its disposition in rat intestine and liver.


Assuntos
Antineoplásicos/farmacocinética , Flavonoides/farmacocinética , Animais , Antineoplásicos/sangue , Antineoplásicos/química , Disponibilidade Biológica , Células CACO-2 , Flavonoides/sangue , Flavonoides/química , Suco Gástrico/química , Humanos , Absorção Intestinal , Mucosa Intestinal/metabolismo , Secreções Intestinais/química , Fígado/metabolismo , Masculino , Microssomos/metabolismo , Ratos Sprague-Dawley
11.
Sensors (Basel) ; 19(3)2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30678066

RESUMO

The design of urban clusters has played an important role in urban planning, but realizing the construction of these urban plans is quite a long process. Hence, how the progress is evaluated is significant for urban managers in the process of urban construction. Traditional methods for detecting urban clusters are inaccurate since the raw data is generally collected from small sample questionnaires of resident trips rather than large-scale studies. Spatiotemporal big data provides a new lens for understanding urban clusters in a natural and fine-grained way. In this article, we propose a novel method for Detecting and Evaluating Urban Clusters (DEUC) with taxi trajectories and Sina Weibo check-in data. Firstly, DEUC applies an agglomerative hierarchical clustering method to detect urban clusters based on the similarities in the daily travel space of urban residents. Secondly, DEUC infers resident demands for land-use functions using a naïve Bayes' theorem, and three indicators are adopted to assess the rationality of land-use functions in the detected clusters-namely, cross-regional travel index, commuting direction index, and fulfilled demand index. Thirdly, DEUC evaluates the progress of urban cluster construction by calculating a proposed conformance indicator. In the case study, we applied our method to detect and analyze urban clusters in Wuhan, China in the years 2009, 2014, and 2015. The results suggest the effectiveness of the proposed method, which can provide a scientific basis for urban construction.

12.
Molecules ; 24(8)2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013570

RESUMO

GL-V9 is a prominent derivative of wogonin with a wide therapeutic spectrum and potent anti-tumor activity. The metabolism characteristics of GL-V9 remain unclear. This study aimed to clarify the metabolic pathway of GL-V9 and investigate the generation of its glucuronidation metabolites in vitro and in vivo. HPLC-UV-TripleTOF was used to identify metabolites. The main metabolite that we found was chemically synthesized and the synthetic metabolite was utilized as standard substance for the subsequent metabolism studies of GL-V9, including enzyme kinetics in liver microsomes of five different species and reaction phenotyping metabolism using 12 recombinant human UDP-glucuronosyltransferase (UGT) isoforms. Results indicated that the glucuronidation reaction occurred at C5-OH group, and 5-O-glucuronide GL-V9 is the only glucuronide metabolite and major phase II metabolite of GL-V9. Among 12 recombinant human UGTs, rUGT1A9 showed the strongest catalytic capacity for the glucuronidation reaction of GL-V9. rUGT1A7 and rUGT1A8 were also involved in the glucuronidation metabolism. Km of rUGT1A7-1A9 was 3.25 ± 0.29, 13.92 ± 1.05, and 4.72 ± 0.28 µM, respectively. In conclusion, 5-O-glucuronide GL-V9 is the dominant phase II metabolite of GL-V9 in vivo and in vitro, whose formation rate and efficiency are closely related to isoform-specific metabolism profiles and the distribution of UGTs in different tissues of different species.


Assuntos
Flavanonas , Glucuronídeos/química , Glucuronosiltransferase/química , Microssomos Hepáticos/enzimologia , Animais , Flavanonas/química , Flavanonas/farmacocinética , Glucuronídeos/farmacocinética , Glucuronosiltransferase/metabolismo , Humanos , Isoenzimas/química , Isoenzimas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie
14.
Zhongguo Zhong Yao Za Zhi ; 43(6): 1268-1275, 2018 Mar.
Artigo em Zh | MEDLINE | ID: mdl-29676139

RESUMO

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.


Assuntos
Angina Pectoris/tratamento farmacológico , Angina Estável/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Método Duplo-Cego , Teste de Esforço , Humanos , Nitroglicerina
15.
Proc Natl Acad Sci U S A ; 111(47): 16676-81, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25389310

RESUMO

MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic conductivity. Delamination of MXene produces single-layer nanosheets with thickness of about a nanometer and lateral size of the order of micrometers. The high aspect ratio of delaminated MXene renders it promising nanofiller in multifunctional polymer nanocomposites. Herein, Ti3C2T(x) MXene was mixed with either a charged polydiallyldimethylammonium chloride (PDDA) or an electrically neutral polyvinyl alcohol (PVA) to produce Ti3C2T(x)/polymer composites. The as-fabricated composites are flexible and have electrical conductivities as high as 2.2 × 10(4) S/m in the case of the Ti3C2T(x)/PVA composite film and 2.4 × 10(5) S/m for pure Ti3C2T(x) films. The tensile strength of the Ti3C2T(x)/PVA composites was significantly enhanced compared with pure Ti3C2T(x) or PVA films. The intercalation and confinement of the polymer between the MXene flakes not only increased flexibility but also enhanced cationic intercalation, offering an impressive volumetric capacitance of ∼530 F/cm(3) for MXene/PVA-KOH composite film at 2 mV/s. To our knowledge, this study is a first, but crucial, step in exploring the potential of using MXenes in polymer-based multifunctional nanocomposites for a host of applications, such as structural components, energy storage devices, wearable electronics, electrochemical actuators, and radiofrequency shielding, to name a few.

16.
Neural Plast ; 2017: 4174010, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29158920

RESUMO

Neuropathic pain increases the risk of cardiovascular diseases including hypertension with the characteristic of sympathetic overactivity. The enhanced tonically active glutamatergic input to the rostral ventrolateral medulla (RVLM) contributes to sympathetic overactivity and blood pressure (BP) in cardiovascular diseases. We hypothesize that neuropathic pain enhances tonically active glutamatergic inputs to the RVLM, which contributes to high level of BP and sympathetic outflow. Animal model with the trigeminal neuropathic pain was induced by the infraorbital nerve-chronic constriction injury (ION-CCI). A significant increase in BP and renal sympathetic nerve activity (RSNA) was found in rats with ION-CCI (BP, n = 5, RSNA, n = 7, p < 0.05). The concentration of glutamate in the RVLM was significantly increased in the ION-CCI group (n = 4, p < 0.05). Blockade of glutamate receptors by injection of kynurenic acid into the RVLM significantly decreased BP and RSNA in the ION-CCI group (n = 5, p < 0.05). In two major sources (the paraventricular nucleus and periaqueductal gray) for glutamatergic inputs to the RVLM, the ION-CCI group (n = 5, p < 0.05) showed an increase in glutamate content and expression of glutaminase 2, vesicular glutamate transporter 2 proteins, and c-fos. Our results suggest that enhancement in tonically active glutamatergic inputs to the RVLM contributes to neuropathic pain-induced high blood pressure.


Assuntos
Ácido Glutâmico/metabolismo , Hipertensão/metabolismo , Bulbo/metabolismo , Neuralgia/metabolismo , Animais , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Glutaminase/metabolismo , Hiperalgesia/metabolismo , Hipertensão/etiologia , Masculino , Neuralgia/etiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Ratos Sprague-Dawley , Receptores de Glutamato/metabolismo , Sistema Nervoso Simpático/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
17.
Nitric Oxide ; 52: 56-65, 2016 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-26686278

RESUMO

Angiotensin-1-7 [Ang-(1-7)], acting via the Mas receptor in the central nervous system, is involved in the regulation of cardiovascular activity. Nitric oxide (NO) is implicated as an important modulator in the nucleus tractus solitarii (NTS), a key region involved in control of cardiovascular activity. The aim of the present study was to determine the role of phosphatidylinositol 3-kinase (PI3K) signaling in mediating the effect of Ang-(1-7) on NO generation in the NTS. In Sprague-Dawley rats, acute injection of Ang-(1-7) into the NTS significantly increased NO generation and neuronal/endothelial NO synthase (n/eNOS) activity, which were abolished by the selective Mas receptor antagonist d-Alanine-[Ang-(1-7)] (A-779), the PI3K inhibitor LY294002, or the Akt inhibitor triciribine (TCN). Western blotting analysis further demonstrated that Ang-(1-7) significantly increased levels of Akt/NOS phosphorylation in the NTS, and Ang-(1-7)-induced e/nNOS phosphorylation was antagonized by LY294002 or TCN. Furthermore, gene knockdown of PI3K by lentivirus containing small hairpin RNA in the NTS prevented the Ang-(1-7)-induced increases in NOS/Akt phosphorylation and NO production. The physiological (in vivo) experiments showed that pretreatment with the NOS inhibitor l-NAME, LY294002, or TCN abolished the decreases in blood pressure, heart rate, and renal sympathetic nerve activity induced by Ang-(1-7) injected into the NTS. Our findings suggest that nitric oxide release meditated by the Mas-PI3K-NOS signaling pathway is involved in the cardiovascular effects of Ang-(1-7) in the NTS.


Assuntos
Angiotensina I/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fragmentos de Peptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Núcleo Solitário/efeitos dos fármacos , Angiotensina I/administração & dosagem , Animais , Sistema Cardiovascular/enzimologia , Sistema Cardiovascular/metabolismo , Masculino , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/enzimologia , Núcleo Solitário/metabolismo
18.
Appl Opt ; 55(4): 943-6, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26836104

RESUMO

The microwave magnetic-field tunable filtering properties in a multichannel filter based on use of a one-dimensional finite magnetized plasma photonic crystal (PPC) are theoretically investigated. The considered PPC has a structure of air/(AB)N/air, where A is a dielectric layer, B is a plasma layer, and N is the stack number. First, in the absence of an externally applied magnetic field, the structure can work as a multichannel filter whose channel number is equal to N-1 for N>1. Next, in the presence of an externally applied field, the filtering properties become tunable, i.e., the channel frequencies can be shifted as a function of the applied magnetic field. We find that the effect of the magnetic field will cause the channel frequencies to be blue-shifted or red-shifted depending on the orientation of the applied magnetic field.

19.
J Surg Res ; 195(1): 219-27, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25577143

RESUMO

BACKGROUND: Sepsis is associated with acute lung injury (ALI) and high mortality. The aim of this study was to investigate the effects of different doses of penehyclidine hydrochloride (PHC) postconditioning on ALI induced by sepsis in a rat model. METHODS: A rat model of ALI was induced by intravenous injection of lipopolysaccharide (LPS). The different doses of PHC were administrated intravenously at 30 min after LPS administration (low dose, 0.3 mg/kg; medium dose, 1.0 mg/kg, and high dose, 3.0 mg/kg). After 6 h, arterial blood samples were obtained for blood gas analyses. Meanwhile, lung tissue was harvested and lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining) and wet-to-dry lung weight ratio. The tumor necrosis factor-α and interleukin-6 levels in bronchoalveolar lavage fluid, as well as the nuclear factor-kappa B protein expressions, and the myeloperoxidase activities in lung tissues were measured by immunohistochemistry or enzyme-linked immunosorbent assay, respectively. RESULTS: LPS-induced severe lung injury evidenced by increased pathologic scores and lung wet-to-dry weight ratio, which was accompanied by increases in the expression of pulmonary nuclear factor-kappa B protein and the activity of pulmonary myeloperoxidase and the levels of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid. The arterial oxygen tension (PaO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) decreased significantly and the carbon dioxide tension (PaCO2) increased notedly after an LPS injection. All doses of PHC could significantly ameliorate lung injury and improve the previously mentioned variables (P < 0.05 or 0.01). Furthermore, the protection of medium dose (1.0 mg/kg) could be better than that of low or high dose. CONCLUSIONS: These findings indicated that different doses of PHC, especially to medium dose, could prevent LPS-induced ALI in rats, at least in part, by inhibiting inflammatory response. Moreover, the protection of pharmacologic postconditioning with PHC is limited by a "ceiling effect."


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Quinuclidinas/administração & dosagem , Sepse/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Interleucina-6/análise , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , NF-kappa B/metabolismo , Peroxidase/metabolismo , Troca Gasosa Pulmonar/efeitos dos fármacos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise
20.
Genome ; 57(5): 267-77, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-25188288

RESUMO

Two uncorrelated nucleotide sequences, chloroplast intergenic spacer psbA-trnH and acetyl CoA carboxylase gene (Acc1), were used to perform phylogenetic analyses in 75 accessions of the genus Avena, representing 13 diploids, seven tetraploid, and four hexaploids by maximum parsimony and Bayesian inference. Phylogenic analyses based on the chloroplast intergenic spacer psbA-trnH confirmed that the A genome diploid might be the maternal donor of species of the genus Avena. Two haplotypes of the Acc1 gene region were obtained from the AB genome tetraploids, indicating an allopolyploid origin for the tetraploid species. Among the AB genome species, both gene trees revealed differences between Avena agadiriana and the other species, suggesting that an AS genome diploid might be the A genome donor and the other genome diploid donor might be the Ac genome diploid Avena canariensis or the Ad genome diploid Avena damascena. Three haplotypes of the Acc1 gene have been detected among the ACD genome hexaploid species. The haplotype that seems to represent the D genome clustered with the tetraploid species Avena murphyi and Avena maroccana, which supported the CD genomic designation instead of AC for A. murphyi and A. maroccana.


Assuntos
Acetil-CoA Carboxilase/genética , Cloroplastos/genética , Genes de Cloroplastos , Poaceae/genética , Teorema de Bayes , Núcleo Celular/genética , Evolução Molecular , Filogenia , Poaceae/classificação , Poliploidia , Análise de Sequência de DNA
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