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1.
Drug Des Devel Ther ; 14: 669-676, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32109992

RESUMEN

Objective: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting. Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3-18 months after coronary stenting was assessed. Results: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day. Conclusion: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.

2.
Medicine (Baltimore) ; 98(50): e18213, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852078

RESUMEN

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.


Asunto(s)
Índice de Masa Corporal , Obesidad/complicaciones , Cáncer Papilar Tiroideo/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Tiroidectomía/métodos , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Estudios Retrospectivos , Cáncer Papilar Tiroideo/etiología , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/etiología , Neoplasias de la Tiroides/cirugía
3.
J Biomed Opt ; 24(5): 1-13, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30977334

RESUMEN

More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from "thick oligomer stacks" to "thin oligomer stacks" (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pump-probe microscopy for the detection and study of melanin-associated diseases.

4.
Diagn Cytopathol ; 47(3): 187-193, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30499203

RESUMEN

BACKGROUND: Thyroid nodules are very common. Ultrasound (US) and fine needle aspiration (FNA) are both integral in cancer screening. This study investigated the concordance between thyroid nodule sizes measured by US and gross pathologic examination and their relationship with malignancy. METHODS: A retrospective design was used to select consecutive patients with proven carcinoma of the thyroid. The number and maximum diameter of nodules, rates and types of malignancy, as well as predictors of malignancy were determined. RESULTS: The 10 944 patients examined had 15 283 thyroid nodules, 44.6% of which were malignant. Of the 4449 nodules sampled by FNA and the 8748 not sampled by FNA, 76.5% and 30.5% were malignant, respectively. The sensitivity, specificity, positive and negative predictive values (NPVs), and overall accuracy of FNA based on final pathology were 97.9%, 96.3%, 98.8%, 93.5%, and 97.5%, respectively. Nodule sizes determined by US were comparable with most nodules having either the same size range (n = 2959, 77.7%) or differing only by one size range (n = 770, 20.5%). CONCLUSIONS: Thyroid nodule size is inversely related to malignancy risk, as larger nodules have lower malignancy rates. Nodule size estimated by US shows relatively good correlation with final pathologic size. However, thyroid nodules should undergo FNA regardless of size. If the FNA is not benign, nodule size should influence therapeutic decision making.


Asunto(s)
Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Adulto , Anciano , Biopsia con Aguja Fina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía
5.
Biomed Pharmacother ; 109: 621-628, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30399599

RESUMEN

Aminophenols, which are widely used as components of hair dye and medicine, may function as environmental endocrine disruptors by regulating the proliferation of endocrine-related cancers. Estrogen receptor α (ERα) is a key regulator of breast cancer. Recently, it was found that ERα may also participate in the transformation and progression of thyroid tumors, but its interaction with aminophenols and its function in thyroid tumors is not clear. In this study, the transcription factor activity of ERα in BHP10-3 cells (a thyroid tumor cell line) was examined using luciferase assays. The promoter recruitment of ERα was examined using chromatin co-precipitation (ChIP). Additionally, in an in vivo study, BHP10-3 cells were transplanted into nude mice. Upon administration of aminophenols, the transcription factor activity of ERα was significantly increased in BHP10-3 cells, and the recruitment of ERα to the promoter of its target gene was increased. Aminophenols enhanced the in vitro and in vivo proliferation of BHP10-3 cells. By discovering that aminophenols induce the onco-promoting activity of ERα, our study extends the understanding of the function of aminophenols and suggests that ERα is a potential therapeutic target for the treatment of thyroid tumors.


Asunto(s)
Aminofenoles/toxicidad , Proliferación Celular/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Neoplasias de la Tiroides/metabolismo , Factores de Transcripción/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/fisiología , Femenino , Ratones , Ratones Desnudos , Neoplasias de la Tiroides/inducido químicamente , Neoplasias de la Tiroides/patología
6.
Nano Lett ; 18(10): 6181-6187, 2018 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-30204445

RESUMEN

Light switchable materials are essential to optoelectronic applications in photovoltaics, memories, sensors, and communications. Natural switchable materials suffer from weak absorption and slow response times, preventing their use in low-power, ultrafast applications. Integrating light switchable materials with metasurface perfect absorbers offers an innovative route to achieving desirable features for nanophotonic devices, such as directional emission, low-power and broadband operation, high radiative quantum efficiency, and large spontaneous emission rates. Here we show an enhanced two-photon photochromism based on a metasurface perfect absorber: film-coupled colloidal silver nanocubes. The photochromic molecules, spiropyrans, are sandwiched between the silver nanocubes and the gold substrate. With nearly 100% absorption and an accompanying large field enhancement in the molecular junction, the transformation of spiropyrans to merocyanines is observed under excitation with 792 nm laser light. Fluorescence lifetime measurements on the merocyanine form reveal that large Purcell enhancement in the film-coupled nanocubes leads to large enhancements of the spontaneous emission rate and a high quantum efficiency. An averaged incident power as low as 10 µW is enough to initiate the two-photon isomerization of spiropyran in the film-coupled nanocubes, and a power of 100nW is able to excite the merocyanines to emit fluorescence. The power consumption is orders of magnitude lower than bare spiropyran thin films on silicon and gold, which is highly desirable for the writing and reading processes relevant to optical data storage. By sweeping the plasmonic resonance of the film-coupled nanocubes, wavelength specificity is demonstrated, which opens up new possibilities for minimizing the cross talk between adjacent bits in nanophotonic devices.

7.
J Agric Food Chem ; 66(31): 8371-8381, 2018 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-30008205

RESUMEN

d-Lactate dehydrogenase (d-LDH) catalyzes the reversible reaction pyruvate + NADH + H+ ↔ lactate + NAD+, which is a principal step in the production of d-lactate in lactic acid bacteria. In this study, we identified and characterized the major d-LDH (d-LDH1) from three d-LDHs in Leuconostoc mesenteroides, which has been extensively used in food processing. A molecular simulation study of d-LDH1 showed that the conformation changes during substrate binding. During catalysis, Tyr101 and Arg235 bind the substrates by hydrogen bonds and His296 acts as a general acid/base for proton transfer. These residues are also highly conserved and have coevolved. Point mutations proved that the substrate binding sites and catalytic site are crucial for enzyme activity. Network and phylogenetic analyses indicated that d-LDH1 and the homologues are widely distributed but are most abundant in bacteria and fungi. This study expands the understanding of the functions, catalytic mechanism, and evolution of d-LDH.


Asunto(s)
Lactato Deshidrogenasas/metabolismo , Ácido Láctico/biosíntesis , Lactobacillales/enzimología , Sitios de Unión , Catálisis , Dominio Catalítico , Secuencia Conservada , Evolución Molecular , Manipulación de Alimentos/métodos , Enlaces de Hidrógeno , Lactato Deshidrogenasas/química , Leuconostoc mesenteroides/enzimología , Mutación Puntual , Unión Proteica , Conformación Proteica
8.
J Agric Food Chem ; 66(30): 8086-8093, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29998731

RESUMEN

One putative l-lactate dehydrogenase gene (l- ldh) and three putative d- ldh genes from Leuconostoc mesenteroides ATCC 8293 were overexpressed, and their enzymatic properties were investigated. Only one gene showed d-LDH activity, catalyzing pyruvate and d-lactate interconversion, whereas the other genes displayed l- and d-malate dehydrogenase (MDH) activity, catalyzing oxaloacetate and l- and d-malate interconversion, suggesting that strain ATCC 8293 may not harbor an l- ldh gene. Putative phosphoenolpyruvate carboxylase (PEPC)- and malolactic enzyme (MLE)-encoding genes were identified from strain ATCC 8293, and sequence analysis showed that they could exhibit PEPC and MLE activities, respectively. l-Lactate production and transcriptional expression of the mle gene in this strain were highly increased in the presence of l-malate. We propose that in strain ATCC 8293, which lacks an l- ldh gene, l-lactate is produced through sequential enzymatic conversions from phosphoenolpyruvate to oxaloacetate, then l-malate, and finally l-lactate by PEPC, l-MDH, and MLE, respectively.


Asunto(s)
Proteínas Bacterianas/metabolismo , Ácido Láctico/biosíntesis , Leuconostoc mesenteroides/enzimología , Malato Deshidrogenasa/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Vías Biosintéticas , Estabilidad de Enzimas , Cinética , Leuconostoc mesenteroides/química , Leuconostoc mesenteroides/genética , Leuconostoc mesenteroides/metabolismo , Malato Deshidrogenasa/química , Malato Deshidrogenasa/genética , Malatos/metabolismo , Ácido Pirúvico/metabolismo , Especificidad por Sustrato
9.
Opt Express ; 26(3): 3004-3012, 2018 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-29401833

RESUMEN

We study the angle-dependent optical reflectance spectrum of a metasurface consisting of a periodic array of film-coupled plasmonic nanopatch particles. The nanopatch metasurface exhibits a strong, angle-independent absorption resonance at a wavelength defined by the nanopatch geometry and relative density. When the nanopatches are arranged in a regular lattice, a second, sharp absorption dip is present that varies strongly as a function of the incidence angle. This second resonance is a collective effect involving the excitation of surface plasmon modes and relates to a Wood's anomaly. Using an analytical model, we compute the surface modes of the structure and confirm details about the various mechanisms that contribute to the reflection spectra. The measured reflectance spectra are in excellent agreement with both analytical calculations and full-wave numerical simulations.

10.
Sci Rep ; 7: 43489, 2017 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-28233868

RESUMEN

Salicylaldehyde (SAL) dehydrogenase (SALD) is responsible for the oxidation of SAL to salicylate using nicotinamide adenine dinucleotide (NAD+) as a cofactor in the naphthalene degradation pathway. We report the use of a protein sequence similarity network to make functional inferences about SALDs. Network and phylogenetic analyses indicated that SALDs and the homologues are present in bacteria and fungi. The key residues in SALDs were analyzed by evolutionary methods and a molecular simulation analysis. The results showed that the catalytic residue is most highly conserved, followed by the residues binding NAD+ and then the residues binding SAL. A molecular simulation analysis demonstrated the binding energies of the amino acids to NAD+ and/or SAL and showed that a conformational change is induced by binding. A SALD from Alteromonas naphthalenivorans (SALDan) that undergoes trimeric oligomerization was characterized enzymatically. The results showed that SALDan could catalyze the oxidation of a variety of aromatic aldehydes. Site-directed mutagenesis of selected residues binding NAD+ and/or SAL affected the enzyme's catalytic efficiency, but did not eliminate catalysis. Finally, the relationships among the evolution, catalytic mechanism, and functions of SALD are discussed. Taken together, this study provides an expanded understanding of the evolution, functions, and catalytic mechanism of SALD.


Asunto(s)
Aldehído Oxidorreductasas/metabolismo , Evolución Biológica , Biología Computacional , Redes y Vías Metabólicas , Naftalenos/metabolismo , Aldehído Oxidorreductasas/química , Aldehído Oxidorreductasas/genética , Secuencia de Aminoácidos , Bacterias/clasificación , Bacterias/genética , Bacterias/metabolismo , Biología Computacional/métodos , Bases de Datos Genéticas , Hongos/clasificación , Hongos/genética , Hongos/metabolismo , Conformación Molecular , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Naftalenos/química , Filogenia , Análisis de Secuencia de ADN , Especificidad por Sustrato
11.
Int J Syst Evol Microbiol ; 67(2): 346-351, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27902268

RESUMEN

A Gram-stain-negative and strictly aerobic bacterium, designated strain SAG6T, was isolated from estuary sediment in South Korea. Cells of strain SAG6T were found to be oxidase- and catalase-positive rods with gliding motility. Cell growth was observed at 15-40 °C (optimum 30 °C), at pH 6.5-10.0 (optimum pH 7.0) and in the presence of 0.5-13.0 % (w/v) NaCl (optimum 2.0 %). Ubiquinone-10 was the only detected respiratory quinone and summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and C12 : 0 were the major fatty acids identified (>5 % of the total fatty acids). The polar lipids of strain SAG6T consisted of phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminolipid and two unidentified lipids. The G+C content of the genomic DNA was 66.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SAG6T formed a tight phyletic lineage within the genus Roseovarius. Strain SAG6T was most closely related to Roseovarius indicus B108T with 97.6 % 16S rRNA gene sequence similarity. Based on phenotypic, chemotaxonomic and molecular features, strain SAG6T clearly represents a novel species of the genus Roseovarius, for which the name Roseovarius confluentis sp. nov. is proposed. The type strain is SAG6T (=KACC 18598T=JCM 31541T).


Asunto(s)
Estuarios , Sedimentos Geológicos/microbiología , Filogenia , Rhodobacteraceae/clasificación , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Rhodobacteraceae/genética , Rhodobacteraceae/aislamiento & purificación , Análisis de Secuencia de ADN , Ubiquinona/química
12.
Int J Syst Evol Microbiol ; 67(4): 914-919, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27926821

RESUMEN

A Gram-staining-negative and strictly aerobic bacterium, designated strain S2-A1T, was isolated from estuary sediment in South Korea. Cells of strain S2-A1T were oxidase- and catalase-positive rods without a gliding motility. Growth was observed at 15-40 °C (optimum, 37 °C), at pH 6.0-10.0 (optimum, pH 7.0-7.5) and in the presence of 0-4.0 % (w/v) NaCl (optimum, 0.5-1.0 %). The sole respiratory quinone was MK-7. iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c) and summed feature 9 (comprising iso-C17 : 1ω9c/C16 : 0 10-methyl) were found as the major fatty acids (>5 % of the total fatty acids). The polar lipids of strain S2-A1T consisted of phosphatidylethanolamine, an unidentified aminophospholipid, three unidentified aminolipids and five unidentified lipids. The G+C content of the genomic DNA was 45.6 mol%. Strain S2-A1T was most closely related to Algoriphagus taeanensisHMC4223T with a 97.7 % 16S rRNA gene sequence similarity. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S2-A1T formed a tight phyletic lineage with members of the genus Algoriphagus. On the basis of phenotypic, chemotaxonomic and molecular features, strain S2-A1T clearly represents a novel species of the genus Algoriphagus, for which the name Algoriphagus aestuariicola sp. nov. is proposed. The type strain is S2-A1T (=KACC 18987T=JCM 31546T).


Asunto(s)
Bacteroidetes/clasificación , Estuarios , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , República de Corea , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
13.
Biochim Biophys Acta Gen Subj ; 1861(2): 323-334, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27919802

RESUMEN

BACKGROUND: The 2-oxoglutarate/Fe(II)-dependent oxygenase (2OG oxygenase) superfamily is extremely diverse and includes enzymes responsible for protein modification, DNA and mRNA repair, and synthesis of secondary metabolites. METHODS: To investigate the evolutionary relationship and make functional inferences within this remarkably diverse superfamily in bacteria, we used a protein sequence similarity network and other bioinformatics tools to analyze the bacterial proteins in the superfamily. RESULTS: The network based on experimentally characterized 2OG oxygenases reflects functional clustering. Networks based on all of the bacterial 2OG oxygenases from the Interpro database indicate that only few proteins in this superfamily are functionally defined. The uneven distribution of the enzymes supports the hypothesis that horizontal gene transfer plays an important role in 2OG oxygenase evolution. A hydrophobic tyrosine residue binding the primary substrates at the N-termini is conserved. At the C-termini, the iron-binding, oxoglutarate-binding, and hydrophobic motifs are conserved and coevolved. Considering the proteins in the family are largely unexplored, we annotated them by the Pfam database and hundreds of novel and multi-domain proteins are discovered. Among them, a two-domain protein containing an N-terminal peroxiredoxin domain and a C-terminal 2OG oxygenase domain was characterized enzymatically. The results show that the enzyme could catalyze the reduction of peroxide using 2-oxoglutarate as an electron donor. CONCLUSIONS: Our observations suggest relatively low evolutionary pressure on the bacterial 2OG oxygenases and a straightforward electron transfer pathway catalyzed by the two-domain 2OG oxygenase. GENERAL SIGNIFICANCE: This work enables an expanded understanding of the diversity, evolution, and functions of bacterial 2OG oxygenases.


Asunto(s)
Bacterias/metabolismo , Compuestos Ferrosos/metabolismo , Ácidos Cetoglutáricos/metabolismo , Oxigenasas/metabolismo , Sitios de Unión/fisiología , Catálisis , Biología Computacional/métodos , Oxidación-Reducción , Peróxidos/metabolismo , Peroxirredoxinas/metabolismo , Dominios Proteicos , Homología de Secuencia de Aminoácido , Tirosina/metabolismo
14.
Front Microbiol ; 6: 1380, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26733945

RESUMEN

A putative zinc-dependent protease (TK0512) in Thermococcus kodakarensis KOD1 shares a conserved motif with archaemetzincins, which are metalloproteases found in archaea, bacteria, and eukarya. Phylogenetic and sequence analyses showed that TK0512 and its homologues in Thermococcaceae represent new members in the archaemetzincins family, which we named AMZ-tk. We further confirmed its proteolytic activity biochemically by overexpression of the recombinant AMZ-tk in Escherichia coli and characterization of the purified enzyme. In the presence of zinc, the purified enzyme degraded casein, while adding EDTA strongly inhibited the enzyme activity. AMZ-tk also exhibited self-cleavage activity that required Zn(2+). These results demonstrated that AMZ-tk is a zinc-dependent protease within the archaemetzincin family. The enzyme displayed activity at alkaline pHs ranging from 7.0 to 10.0, with the optimal pH being 8.0. The optimum temperature for the catalytic activity of AMZ-tk was 55°C. Quantitative reverse transcription-PCR revealed that transcription of AMZ-tk was also up-regulated after exposing the cells to 55 and 65°C. Mutant analysis suggested that Zn(2+) binding histidine and catalytic glutamate play key roles in proteolysis. AMZ-tk was thermostable on incubation for 4 h at 70°C in the presence of EDTA. AMZ-tk also retained >50% of its original activity in the presence of both laboratory surfactants and commercial laundry detergents. AMZ-tk further showed antibacterial activity against several bacteria. Therefore, AMZ-tk is of considerable interest for many purposes in view of its activity at alkaline pH, detergents, and thermostability.

15.
PLoS One ; 8(12): e85639, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24386485

RESUMEN

BACKGROUND: The potential mechanisms of microRNA-1 (miR-1) in the electrical remodeling of atrial fibrillation remain unclear. The purpose of this study was to evaluate the effects of miR-1 on the atrial effective refractory period (AERP) in a right atrial tachypacing model and to elucidate the potential mechanisms. METHODS AND RESULTS: QRT-PCR and western blot were used to detect the expression of the miR-1, KCNE1, and KCNB2 genes after 1-week of right atrial tachypacing in New Zealand white rabbits. The AERP was measured using a programmable multichannel stimulator, and atrial fibrillation was induced by burst stimulation in vivo. The slowly activating delayed rectifier potassium current (IKs) and AERP in atrial cells were measured by whole cell patch clamp in vitro. Right atrial tachypacing upregulated miR-1 expression and downregulated KCNE1 and KCNB2 in this study, while the AERP was decreased and the atrial IKs increased. The downregulation of KCNE1 and KCNB2 levels was greater when miR-1 was further upregulated through in vivo lentiviral infection. Electrophysiological tests indicated a shorter AERP, a great increase in the IKs and a higher atrial fibrillation inducibility. In addition, similar results were found when the levels of KCNE1 and KCNB2 were downregulated by small interfering RNA while keeping miR-1 level unaltered. Conversely, knockdown of miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs. KCNE1 and KCNB2 as the target genes for miR-1 were confirmed by luciferase activity assay. CONCLUSIONS: These results indicate that miR-1 accelerates right atrial tachypacing-induced AERP shortening by targeting potassium channel genes, which further suggests that miR-1 plays an important role in the electrical remodeling of atrial fibrillation and exhibits significant clinical relevance as a potential therapeutic target for atrial fibrillation.


Asunto(s)
Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , MicroARNs/metabolismo , Canales de Potasio Shab/biosíntesis , Regulación hacia Arriba , Animales , Fibrilación Atrial/genética , Modelos Animales de Enfermedad , MicroARNs/genética , Conejos , Canales de Potasio Shab/genética
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