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1.
Arch Virol ; 165(1): 97-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734749

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has spread globally and emerged as an urgent public health threat. Bacteriophages are considered an effective weapon against multidrug-resistant pathogens. In this study, we report a novel lytic phage, kpssk3, which is able to lyse CRKP and degrade exopolysaccharide (EPS). The morphological characteristics of kpssk3 observed by transmission electron microscopy, including a polyhedral head and a short tail, indicate that it belongs to the family Podoviridae. A one-step growth curve revealed that kpssk3 has a latent period of 10 min and a burst size of 200 plaque-forming units (pfu) per cell. kpssk3 was able to lyse 25 out of 27 (92.59%) clinically isolated CRKP strains, and it also exhibited high stability to changes in temperature and pH. kpssk3 has a linear dsDNA genome of 40,539 bp with 52.80% G+C content and 42 putative open reading frames (ORFs). No antibiotic resistance genes, virulence factors, or integrases were identified in the genome. Based on bioinformatic analysis, the tail fiber protein of phage kpssk3 was speculated to possess depolymerase activity towards EPS. By comparative genomics and phylogenetic analysis, it was determined that kpssk3 is a new T7-like virus and belongs to the subfamily Autographivirinae. The characterization and genomic analysis of kpssk3 will promote our understanding of phage biology and diversity and provide a potential strategy for controlling CRKP infection.


Assuntos
Farmacorresistência Bacteriana , Klebsiella pneumoniae/virologia , Podoviridae/classificação , Sequenciamento Completo do Genoma/métodos , Composição de Bases , Carbapenêmicos , Genoma Viral , Concentração de Íons de Hidrogênio , Lisogenia , Microscopia Eletrônica de Transmissão , Filogenia , Podoviridae/genética , Podoviridae/fisiologia , Termodinâmica , Proteínas da Cauda Viral/genética
2.
J Thorac Dis ; 11(9): 3846-3852, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31656657

RESUMO

Background: Self-expandable metallic Y-shaped airway stents (SEMYS) are commonly used in the management of airway stenosis and fistulae caused by thoracic neoplasms. Methods: A new technique using a slightly modified regular endotracheal tube has been developed for the deployment of SEMYS with flexible bronchoscopy alone. The technique and devices are described. Results: To date, successful deployment of SEMYS with this method has been carried out successfully in 17 out of 20 patients without major complications while the other 3 required conversion to rigid bronchoscopy because of limited pharyngeal cavity space, massive hemorrhage and severe cicatrization of the airway, respectively. Conclusions: This simplified deployment technique with the modified endotracheal tube enables safe, simple and fast insertion of SEMYS in a regular bronchoscopy suite, which may benefit the vast less privileged institutions where SEMYS are necessary but rigid bronchoscopy and fluoroscopy are not available. The skill of the bronchoscopist, cautious selection of patients and effective coordination of the operating team are crucial for the procedure.

3.
Anal Chim Acta ; 1080: 75-83, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409477

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains the top fatal infection continuing to threat public health, and the present detection method for MTB is facing great challenges with the global TB burden. In response to this issue, a novel electrochemical DNA biosensor was developed for detecting the IS6110 fragment within MTB. For the first time, the nanohybrid of gold nanoparticles decorated fullerene nanoparticles/nitrogen-doped graphene nanosheet (Au-nano-C60/NGS) directly served as a new signal tag to generate signal response without additional redox molecules and subsequently labeled with signal probes (SPs) to form tracer label to achieve signal amplification. Additionally, a biotin-avidin system was introduced to immobilize abundant capture probes (CPs), further improving the sensitivity of the proposed biosensor. After a typical sandwich hybridization, the proposed electrochemical DNA biosensor was incubated with tetraoctylammonium bromide (TOAB), which was used as a booster to induce the intrinsic redox activity of the tracer label, resulting in a discriminating current response. The proposed electrochemical DNA biosensor shows a broad linear range for MTB determination from 10 fM to 10 nM with a low limit of detection (LOD) of 3 fM. In addition, this proposed biosensor not only distinguishes mismatched DNA sequence, but also differentiates MTB from other pathogenic agents. More importantly, it has been preliminarily applied in clinical detection and displayed excellent ability to identify the PCR products of clinical samples. There is great potential for this developed method to be used in early diagnosis and monitor of TB.


Assuntos
DNA Bacteriano/análise , Fulerenos/química , Grafite/química , Nanopartículas Metálicas/química , Mycobacterium tuberculosis/isolamento & purificação , Nitrogênio/química , Técnicas Biossensoriais/métodos , Candida albicans/genética , Sondas de DNA/genética , DNA Bacteriano/genética , Técnicas Eletroquímicas/métodos , Ouro/química , Limite de Detecção , Mycobacterium tuberculosis/genética , Nanocompostos/química , Hibridização de Ácido Nucleico , Reprodutibilidade dos Testes , Staphylococcus aureus/genética
4.
Med Sci Monit ; 25: 6462-6473, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31461437

RESUMO

BACKGROUND High-mobility group box1 (HMGB1) is a cytokine that has been demonstrated to have an important role in inducing migration and homing of endothelial progenitor cells (EPCs) in the process of neovascularization during wound healing, but its specific mechanism remains elusive. The aim of this study was to investigate the effects of the HMGB-RAGE axis in EPC migration, as well as the underlying molecular mechanism responsible for these effects. MATERIAL AND METHODS EPCs were isolated from the mice and identified using flow cytometry and fluorescence staining. The effect of HMGB1 on the activity of EPCs was detected using the Cell Counting Kit-8 (CCK-8). Then, the migration of EPCs was detected by scratch wound-healing and cell migration assay. NO levels were analyzed by ELISA. The expression of p-PI3K, p-Akt, and p-eNOS was determined by Western blot analysis. RAGE expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. F-actin was assessed by fluorescent staining. RESULTS The results showed that HMGB1 induced a concentration-dependent migration of EPCs, and the migration was RAGE-dependent. The migration could be almost completely blocked by PI3K inhibitors and eNOS inhibitor. HMGB1-RAGE upregulated the expression of p-Akt, p-eNOS, and p-ERK. We also demonstrated that the MEK/ERK signaling pathway is not involved in the EPC migration induced by HMGB1-RAGE. CONCLUSIONS These data demonstrate that HMGB1 activates RAGE and induces PI3K/Akt/eNOS signaling transduction pathway activation to promote EPC migration. Therefore, the HMGB1-RAGE axis plays an important role in the EPC migration process and may become a potential target in wound healing.


Assuntos
Movimento Celular , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Proteína HMGB1/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Células da Medula Óssea/citologia , Proliferação de Células , Sobrevivência Celular , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos BALB C , Transdução de Sinais , Regulação para Cima/genética
5.
Biomaterials ; 216: 119253, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202103

RESUMO

The present work described a novel sandwich-type electrochemical aptasensor for rapid and sensitive determination of Mycobacterium tuberculosis MPT64 antigen. Herein, a novel carbon nanocomposite composed of fullerene nanoparticles, nitrogen-doped carbon nanotubes and graphene oxide (C60NPs-N-CNTs/GO) was facilely synthesized for the first time, which not only possessed a large specific surface area and excellent conductivity, but also exhibited outstanding inherent electroactive property, and therefore served as nanocarrier and redox nanoprobe simultaneously. Gold nanoparticles (AuNPs) was then uniformly anchored onto the surface of such nanocomposite via Au-N bonds to bind with MPT64 antigen aptamer Ⅱ (MAA Ⅱ), forming the tracer label to realize generation and amplification of electrochemical signal. Additionally, conductive polyethyleneimine (PEI)-functionalized Fe-based metal-organic framework (P-MOF) was used as a sensing platform to absorb bimetallic core-shell Au-Pt nanoparticles (Au@Pt), which could accelerate electron transfer and increase the immobilization of MPT64 antigen aptamer Ⅰ (MAA Ⅰ). After the typical sandwich-type protein-aptamer recognition, the inherent electroactivity of the tracer label was provoked by tetraoctylammonium bromide (TOAB), leading to a well-defined current response. Under the optimum condition, the proposed aptasensor showed a wide linear range for MPT64 detection from 1 fg/mL to 1 ng/mL with a limit of detection (LOD) as low as 0.33 fg/mL. More importantly, it was successfully used for MPT64 antigen detection in human serum, exhibiting a promising prospect for TB diagnosis in clinical practice.

6.
Arch Virol ; 164(6): 1527-1533, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30900072

RESUMO

A novel virulent bacteriophage, φAbp2, infecting multidrug-resistant (MDR) Acinetobacter baumannii was isolated from the wastewater of a sewage management centre at Southwest Hospital, China. Transmission electron microscopy and phylogenetic analysis revealed that φAbp2 belongs to the subfamily Peduovirinae. A one-step growth curve demonstrated that φAbp2 had a latent period of 15 min, a lysis period of 35 min, and a burst size of 222 particles per infected host cell. Moreover, φAbp2 showed a relatively broad host range in local A. baumannii, and it also exhibited tolerance over a wider range of thermal and pH conditions. Genomic sequencing revealed that φAbp2 has a circular double-stranded DNA genome with no sequence similarity to our previously isolated φAbp1. Eighty-eight putative open reading frames (ORFs) encoding 41 proteins of known function and 47 of unknown function were identified, and the G/C content was 37.84%. φAbp2 is a new member of the subfamily Peduovirinae of the family Myoviridae. Its genome sequence is very similar to that of the A. baumannii phage LZ35.


Assuntos
Acinetobacter baumannii/virologia , Genoma Viral , Myoviridae/classificação , Myoviridae/genética , Análise de Sequência de DNA/métodos , Bacteriófagos/classificação , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Composição de Bases , Farmacorresistência Bacteriana Múltipla , Microscopia Eletrônica de Transmissão , Anotação de Sequência Molecular , Myoviridae/isolamento & purificação , Fases de Leitura Aberta , Filogenia , Águas Residuárias/virologia
7.
EBioMedicine ; 37: 294-306, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30344125

RESUMO

BACKGROUND: Hepatic encephalopathy (HE), a severe neuropsychiatric complication, is associated with increased blood levels of ammonia and bile acids (BAs). We sought to determine (1) whether abnormally increased blood BAs in liver cirrhotic patients with HE is caused by elevation of apical sodium-dependent BA transporter (ASBT)-mediated BA reabsorption; and (2) whether increased BA reabsorption would exacerbate ammonia-induced brain injuries. METHODS: We quantitatively measured blood BA and ammonia levels in liver cirrhosis patients with or without HE and healthy controls. We characterized ASBT expression, BA profiles, and ammonia concentrations in a chronic liver disease (CLD) mouse model induced by streptozotocin-high fat diet (STZ-HFD) and an azoxymethane (AOM) - induced acute liver failure (ALF) mouse model. These two mouse models were treated with SC-435 (ASBT inhibitor) and budesonide (ASBT activator), respectively. FINDINGS: Blood concentrations of ammonia and conjugated BAs were substantially increased in cirrhotic patients with HE (n = 75) compared to cirrhotic patients without HE (n = 126). Pharmacological inhibition of the enterohepatic BA circulation using a luminal- restricted ASBT inhibitor, SC-435, in mice with AOM-induced ALF and STZ-HFD -induced CLD effectively reduced BA and ammonia concentrations in the blood and brain, and alleviated liver and brain damages. Budesonide treatment induced liver and brain damages in normal mice, and exacerbated these damages in AOM-treated mice. INTERPRETATION: ASBT mediated BA reabsorption increases intestinal luminal pH and facilitates conversion of intestinal ammonium to ammonia, leading to abnormally high levels of neurotoxic ammonia and cytotoxic BAs in the blood and brain. Inhibition of intestinal ASBT with SC-435 can effectively remove neurotoxic BAs and ammonia from the bloodstream and thus, mitigate liver and brain injuries resulting from liver failure.


Assuntos
Amônia/sangue , Ácidos e Sais Biliares/sangue , Doença Hepática Terminal/sangue , Encefalopatia Hepática/sangue , Falência Hepática Aguda/sangue , Animais , Linhagem Celular , Modelos Animais de Doenças , Doença Hepática Terminal/induzido quimicamente , Doença Hepática Terminal/patologia , Feminino , Encefalopatia Hepática/induzido quimicamente , Encefalopatia Hepática/patologia , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , Camundongos , Pessoa de Meia-Idade
8.
J Biol Chem ; 293(36): 14001-14011, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30006349

RESUMO

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 (RLN1), in neonatal rat ventricular cardiomyocytes (NRVMs). Furthermore, we found that the ß-adrenergic agonist isoproterenol (ISO) markedly stimulated RLN3 expression, and this stimulation was significantly attenuated in Nur77 knockdown cardiomyocytes and Nur77 knockout hearts. We showed that Nur77 significantly increased RLN3 promoter activity via specific binding to the RLN3 promoter, as demonstrated by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Furthermore, we found that Nur77 overexpression potently inhibited ISO-induced cardiomyocyte apoptosis, whereas this protective effect was significantly attenuated in RLN3 knockdown cardiomyocytes, suggesting that Nur77-induced RLN3 expression is an important mediator for the suppression of cardiomyocyte apoptosis. These findings show that Nur77 regulates RLN3 expression, therefore suppressing apoptosis in the heart, and suggest that activation of Nur77 may represent a useful therapeutic strategy for inhibition of cardiac fibrosis and heart failure.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Apoptose/efeitos dos fármacos , Miócitos Cardíacos/citologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/fisiologia , Relaxina/metabolismo , Animais , Isoproterenol/farmacologia , Proteínas do Tecido Nervoso/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Ratos , Relaxina/genética , Transcrição Genética , Regulação para Cima
9.
Neurol Sci ; 39(6): 1065-1072, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29582177

RESUMO

Sodium channel blocking antiepileptic drugs (SCB-AEDs) are common effective medications available for epilepsy. However, not all patients respond to this regimen and drug resistance is frequently encountered. Rs2298771(c.3184A > G/p.Thr1067Ala) and rs3812718(IVS5N +5G > A) polymorphisms are two of the most common polymorphisms in the SCN1A gene, which is closely related to resistance to SCB-AEDs. Therefore, we have conducted a meta-analysis to investigate the contribution of the two polymorphisms to resistance of SCB-AEDs. The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched up to September 2017, for studies on the association of SCN1A polymorphisms with resistance to SCB-AEDs. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A total of eight studies were eligible for the pooled analysis, of which eight studies included SCN1A rs3812718 polymorphism and four studies included SCN1A rs2298771 polymorphism. The results showed that SCN1A rs2298771 polymorphism was significantly associated with resistance to SCB-AEDs. (A vs. G: OR = 0.76, 95% CI 0.61-0.95, P = 0.02; AA vs. AG + GG: OR = 0.71, 95% CI 0.54-0.94, P = 0.022). However, no association was observed between SCN1A rs3812718 polymorphism and resistance to SCB-AEDs. Our results indicate that the A-allele of SCN1A rs2298771 polymorphism, especially AA genotype, may play an important role in responsiveness to SCB-AEDs, while SCN1A rs3812718 polymorphism is not associated with SCB-AEDs.


Assuntos
Anticonvulsivantes/uso terapêutico , Resistência a Medicamentos/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Bloqueadores dos Canais de Sódio/uso terapêutico , Estudos de Associação Genética , Humanos
10.
Sci Rep ; 5: 12657, 2015 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-26227784

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is a promising antitumor target. Novel NAMPT inhibitors with diverse chemotypes are highly desirable for development of antitumor agents. Using high throughput screening system targeting NAMPT on a chemical library of 30000 small-molecules, we found a non-fluorescent compound F671-0003 and a fluorescent compound M049-0244 with excellent in vitro activity (IC50: 85 nM and 170 nM respectively) and anti-proliferative activity against HepG2 cells. These two compounds significantly depleted cellular NAD levels. Exogenous NMN rescued their anti-proliferative activity against HepG2 cells. Structure-activity relationship study proposed a binding mode for NAMPT inhibitor F671-0003 and highlighted the importance of hydrogen bonding, hydrophobic and π-π interactions in inhibitor binding. Imaging study provided the evidence that fluorescent compound M049-0244 (3 µM) significantly stained living HepG2 cells. Cellular fluorescence was further verified to be NAMPT dependent by using RNA interference and NAMPT over expression transgenic mice. Our findings provide novel antitumor lead compounds and a "first-in-class" fluorescent probe for imaging NAMPT.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/química , Benzamidas/farmacologia , Citocinas/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Corantes Fluorescentes/química , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Quinoxalinas/química , Quinoxalinas/farmacologia , Animais , Citocinas/química , Descoberta de Drogas , Células Hep G2 , Humanos , Camundongos , Camundongos Transgênicos , Nicotinamida Fosforribosiltransferase/química , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade
11.
Sci Rep ; 5: 10043, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-26040985

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is a promising anticancer target. Using high throughput screening system targeting NAMPT, we obtained a potent NAMPT inhibitor MS0 (China Patent ZL201110447488.9) with excellent in vitro activity (IC50 = 9.87 ± 1.15 nM) and anti-proliferative activity against multiple human cancer cell lines including stem-like cancer cells. Structure-activity relationship studies yielded several highly effective analogues. These inhibitors specifically bound NAMPT, rather than downstream NMNAT. We provided the first chemical case using cellular thermal shift assay to explain the difference between in vitro and cellular activity; MS7 showed best in vitro activity (IC50 = 0.93 ± 0.29 nM) but worst cellular activity due to poor target engagement in living cells. Site-directed mutagenesis studies identified important residues for NAMPT catalytic activity and inhibitor binding. The present findings contribute to deep understanding the action mode of NAMPT inhibitors and future development of NAMPT inhibitors as anticancer agents.


Assuntos
Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/química , Ensaios de Triagem em Larga Escala , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Conformação Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Nicotinamida Fosforribosiltransferase/química , Ligação Proteica , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade
12.
Pharmacology ; 95(5-6): 279-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25997622

RESUMO

This study explored nephrotoxicity in elderly Chinese patients after exposure to vancomycin and other nephrotoxic risk factors. This was a single-center retrospective study. The patient population included those who were ≥60 years of age, had normal baseline serum creatinine values, and received vancomycin for ≥48 h between January 1, 2013 and August 30, 2014. Nephrotoxicity occurred in 29% of 124 patients. A baseline creatinine clearance ≥63.5 ml/min was more common in the nephrotoxic group. Patients with high (≥15 mg/l) rather than low (<15 mg/l) average vancomycin troughs had elevated nephrotoxicity (47.2 vs. 27.3%, p = 0.0001). Of the comorbid conditions evaluated, there were more patients with shock (p = 0.001), hypertension (p = 0.020) and congestive heart failure (p = 0.04) in the nephrotoxic group. Drugs frequently given at the same time with vancomycin, such as angiotensin receptor blockers and furosemide, were also associated with increased nephrotoxic risk. In conclusion, nephrotoxicity was frequently observed in patients with concurrent vancomycin trough concentrations ≥15 µg/ml and hypertension, shock, congestive heart failure. In addition, drugs concurrently used with vancomycin may also increase its nephrotoxicity. Therefore, renal function and vancomycin serum troughs should be closely monitored, especially in patients with other renal injury risk factors.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/epidemiologia , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
CNS Neurosci Ther ; 20(6): 539-47, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24750959

RESUMO

AIM: Visfatin, a novel adipokine, is predominantly produced by visceral adipose tissue and exists in intracellular and extracellular compartments. The intracellular form of visfatin is proved to be nicotinamide phosphoribosyltransferase (NAMPT) and exhibits neuroprotection through maintaining intracellular NAD(+) pool. However, whether extracellular form of visfatin has NAMPT activity and the effect of extracellular visfatin in cerebral ischemia are unknown. METHODS AND RESULTS: Plasma concentrations of visfatin, NAD(+) , and ATP were increased in mice upon cerebral ischemia. Cultured glia, but not neuron, was able to secrete visfatin. Oxygen-glucose deprivation (OGD) stress increased the secretion of visfatin from glia. Extracellular recombinant mouse wild-type visfatin, but not mouse H247A-mutant enzymatic-dead visfatin, had NAMPT enzymatic function in vitro. Treatment of wild-type visfatin, but not H247A-mutant enzymatic-dead visfatin, significantly attenuated detrimental effect of OGD on the cell viability and apoptosis in both cultured mouse neuron and glia. Treatment of neutralizing antibody, abolished the protective effect of extracellular visfatin on cell viability, but failed to block the antiapoptotic effect of extracellular visfatin. At last, we observed that plasma visfatin concentrations decreased in 6-month-old but not 3-month-old SHR-SP compared with that in age-matched Wistar-Kyoto rats. Inhibition of NAMPT enzymatic function of visfatin (by FK866) accelerated the occurrence of stroke in SHR-SP. CONCLUSIONS: Extracellular visfatin has NAMPT enzymatic activity and maybe be neuroprotective just as intracellular visfatin in cerebral ischemic injury.


Assuntos
Isquemia Encefálica/enzimologia , Líquido Extracelular/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Nicotinamida Fosforribosiltransferase/uso terapêutico , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Animais , Animais Recém-Nascidos , Anticorpos/farmacologia , Anticorpos/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Líquido Extracelular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuroglia/efeitos dos fármacos , Neuroglia/enzimologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fármacos Neuroprotetores/sangue , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/imunologia , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética
14.
J Org Chem ; 76(19): 8022-6, 2011 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-21838268

RESUMO

tert-Butyl perbenzoate is a substitute for benzoquinone for mild (room-temperature) Fujiwara-Moritani reactions between acetanilides and butyl acrylate under homogeneous conditions. The system was enhanced further by including Cu(OAc)(2) as a cocatalyst. Methyl methacrylate can be activated toward coupling under these conditions.

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