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1.
Biosens Bioelectron ; 154: 112067, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056962

RESUMO

The creatinine concentration of human urine is closely related to human kidney health and its rapid, quantitative, and low-cost detection has always been demanded. Herein, a surface-enhanced Raman spectroscopic (SERS) method for rapid and cost-effective quantification of creatinine concentrations in human urine was developed. A Au nanoparticle solution (Au sol) was used as a SERS substrate and the influence of different agglomerating salts on its sensitivity toward detecting creatinine concentrations was studied and optimized, as well as the effect of both the salt and Au sol concentrations. The variation in creatinine spectra over time on different substrates was also examined, demonstrating reproducible quantitative analysis of creatinine concentrations in solution. By adjusting the pH, a simple liquid-liquid solvent extraction procedure, which extracted creatinine from human urine, was used to increase the SERS detection selectivity toward creatinine in complex matrices. The quantitative results were compared to those obtained with a clinically validated enzymatic "creatinine kit (CK)." The limit of detection (LOD) for the SERS technique was 1.45 mg L-1, compared with 3.4 mg L-1 for the CK method. Furthermore, cross-comparing the results from the two methods, the average difference was 5.84% and the whole SERS detection process could be completed within 2 min compared with 11 min for the CK, indicating the practicality of the quantitative SERS technique. This novel quantitative technique shows promises as a high-throughput platform for relevant clinical and forensic analysis.

2.
Eur J Pharmacol ; 853: 74-83, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30880181

RESUMO

The inhibition of transient outward potassium current (Ito) is the major ionic mechanism for quinidine to treat Brugada syndrome; however, quinidine is inaccessible in many countries. The present study compared the inhibitory effect of the nonselective ß-adrenergic blocker carvedilol with quinidine on human Kv4.3 (hKv4.3, encoding for Ito) channel and action potential notch using a whole-cell patch technique in HEK 293 cell line expressing KCND3 as well as in ventricular epicardial myocytes of rabbit hearts. It was found that carvedilol and quinidine inhibited hKv4.3 current in a concentration-dependent manner. The IC50 of carvedilol was 1.2 µM for inhibiting hKv4.3 charge area, while the IC50 of quinidine was 2.9 µM (0.2 Hz). Both carvedilol and quinidine showed typical open channel blocking properties (i.e. decreasing the time to peak of activation and increasing the inactivation of hKv4.3), negatively shifted the V1/2 of activation and inactivation, and slowed the recovery from inactivation of the channel. Although carvedilol had weaker in use- and rate-dependent inhibition of hKv4.3 peak current than quinidine, its reduction of the charge area was more than quinidine at all frequencies (0.2-3.3 Hz). Moreover, the inhibitory effect of carvedilol on action potential notch was greater than quinidine. These results provide the novel information that carvedilol, like quinidine, significantly inhibits hKv4.3 and action potential notch, suggesting that carvedilol is likely an alternative drug for preventing malignant ventricular arrhythmias in patients with Brugada syndrome in countries where quinidine is unavailable.


Assuntos
Carvedilol/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Quinidina/farmacologia , Canais de Potássio Shal/antagonistas & inibidores , Canais de Potássio Shal/genética , Potenciais de Ação/efeitos dos fármacos , Animais , Expressão Gênica , Células HEK293 , Ventrículos do Coração/citologia , Humanos , Concentração Inibidora 50 , Ativação do Canal Iônico/efeitos dos fármacos , Cinética , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estabilidade Proteica/efeitos dos fármacos , Coelhos , Canais de Potássio Shal/metabolismo
3.
J Cell Mol Med ; 22(10): 4688-4699, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30117680

RESUMO

Our recent study showed that bradykinin increases cell cycling progression and migration of human cardiac c-Kit+ progenitor cells by activating pAkt and pERK1/2 signals. This study investigated whether bradykinin-mediated Ca2+ signalling participates in regulating cellular functions in cultured human cardiac c-Kit+ progenitor cells using laser scanning confocal microscopy and biochemical approaches. It was found that bradykinin increased cytosolic free Ca2+ ( Cai2+ ) by triggering a transient Ca2+ release from ER IP3Rs followed by sustained Ca2+ influx through store-operated Ca2+ entry (SOCE) channel. Blockade of B2 receptor with HOE140 or IP3Rs with araguspongin B or silencing IP3R3 with siRNA abolished both Ca2+ release and Ca2+ influx. It is interesting to note that the bradykinin-induced cell cycle progression and migration were not observed in cells with siRNA-silenced IP3R3 or the SOCE component TRPC1, Orai1 or STIM1. Also the bradykinin-induced increase in pAkt and pERK1/2 as well as cyclin D1 was reduced in these cells. These results demonstrate for the first time that bradykinin-mediated increase in free Cai2+ via ER-IP3R3 Ca2+ release followed by Ca2+ influx through SOCE channel plays a crucial role in regulating cell growth and migration via activating pAkt, pERK1/2 and cyclin D1 in human cardiac c-Kit+ progenitor cells.


Assuntos
Bradicinina/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Cálcio/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Células-Tronco/efeitos dos fármacos , Cátions Bivalentes , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Transporte de Íons/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína ORAI1/antagonistas & inibidores , Proteína ORAI1/genética , Proteína ORAI1/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-kit/metabolismo , Quinolizinas/farmacologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Molécula 1 de Interação Estromal/antagonistas & inibidores , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismo
4.
Biomark Med ; 12(8): 871-880, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29900754

RESUMO

AIM: To explore circulating miRNA-302 family members for acute heart failure (AHF) diagnosis. METHODS: Three groups of subjects, in other words, AHF patients, AHF free patients and healthy controls were recruited. Circulating levels of miR-302 family members were measured and analyzed for AHF diagnosis. RESULTS: Plasma miR-302s except miR-302f were significantly elevated in AHF patients. MiR-302b-3p had the highest area under curve value of 0.87. There were strong positive correlations between miR-302s and NT-proBNP levels. MiR-302b-3p levels were significantly higher in left ventricular ejection fraction ≤45% and New York Heart Association class IV patients compared with left ventricular ejection fraction >45% and New York Heart Association class II patients, respectively. CONCLUSION: Levels of circulating miR-302s, miR-302b-3p in particular, could be potentially applied for AHF diagnosis and the differentiation of disease severity.


Assuntos
Insuficiência Cardíaca , MicroRNAs/sangue , Volume Sistólico , Doença Aguda , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
5.
Front Pharmacol ; 9: 497, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867499

RESUMO

The present study investigates the potential signal pathway of acacetin in cardioprotection against ischemia/reperfusion injury using an in vitro hypoxia/reoxygenation model in primary cultured neonatal rat cardiomyocytes and H9C2 cardiomyoblasts. It was found that acacetin (0.3-3 µM) significantly decreased the apoptosis and reactive oxygen species production induced by hypoxia/reoxygenation injury in cardiomyocytes and H9C2 cardiomyoblasts via reducing the pro-apoptotic proteins Bax and cleaved-caspase-3 and increasing the anti-apoptotic protein Bcl-2. In addition, acacetin not only suppressed the release of pro-inflammatory cytokines TLR-4 and IL-6 induced by hypoxia/reoxygenation injury, but also increased the secretion of anti-inflammatory cytokine IL-10. Moreover, acacetin increased Nrf2 and HO-1 in a concentration-dependent manner, and rescued SOD1 and SOD2 reduction induced by hypoxia/reoxygenation insult. These beneficial effects of acacetin disappeared in cells with silenced Nrf2, suggesting that Nrf2 activation participates in the cardioprotective effect of acacetin against hypoxia/reoxygenation insult. However, acacetin-induced Nrf2 activation was not observed in cells with silenced AMPK and in ventricular tissues of rat hearts treated with the AMPK inhibitor Compound C and subjected to ischemia/reperfusion injury. Our results demonstrate for the first time that AMPK-mediated Nrf2 activation is involved in the cardiomyocytes protection of acacetin against hypoxia/reoxygenation injury by activating a series of intracellular signals involved in anti-oxidation, anti-inflammation, and anti-apoptosis.

6.
Br J Pharmacol ; 174(3): 254-266, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27886373

RESUMO

BACKGROUND AND PURPOSE: Clemizole, a histamine H1 receptor antagonist has a potential therapeutic effect on hepatitis C infection and also potently inhibits TRPC5 ion channels. The aim of the present study was to investigate whether clemizole blocks cardiac K+ currents and thus affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch techniques was used to examine the effects of clemizole on hERG channel current, IKs and Kv 1.5 channel current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts. Isolated hearts from guinea pigs were used to determine the effect on the ECG. KEY RESULTS: Clemizole decreased hERG current by blocking both open and closed states of the channel in a concentration-dependent manner (IC50 : 0.07 µM). The S631A, S636A, Y652A and F656V hERG mutant channels reduced the inhibitory effect of clemizole (IC50 : 0.82, 0.89, 1.49 and 2.98 µM, respectively), suggesting that clemizole is a pore blocker of hERG channels. Clemizole also moderately decreased IKs and human Kv 1.5 channel current. Moreover, clemizole increased the duration of the ventricular action potential in guinea pig hearts and the QTc interval in isolated perfused hearts from guinea pigs, in a concentration-dependent manner (0.1-1.0 µM). CONCLUSION AND IMPLICATIONS: Our results provide the first evidence that clemizole potently blocks hERG channels, moderately inhibits cardiac IKs , delays cardiac repolarization and thereby prolongs QT interval. Thus, caution should be taken when clemizole is used as a TRPC5 channel blocker or for treating hepatitis C infection.


Assuntos
Benzimidazóis/farmacologia , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Antagonistas dos Receptores Histamínicos H1/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Benzimidazóis/administração & dosagem , Relação Dose-Resposta a Droga , Eletrocardiografia , Feminino , Cobaias , Células HEK293 , Ventrículos do Coração/metabolismo , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Concentração Inibidora 50 , Síndrome do QT Longo/induzido quimicamente , Masculino , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/administração & dosagem
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