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1.
J Agric Food Chem ; 72(11): 5926-5934, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38457471

RESUMO

Glycinin (11S) and ß-conglycinin (7S) from soybean (glycine max) cause diarrhea and intestinal barrier damage in young animals. Understanding the mechanisms underlying the damage caused by 7S and 11S, it is vital to develop strategies to eliminate allergenicity. Consequently, we investigated 7S/11S-mediated apoptosis in porcine intestinal epithelial (IPEC-J2) cells. IPEC-J2 cells suffered endoplasmic reticulum stress (ERS) in response to 7S and 11S, activating protein kinase RNA-like ER kinase, activating transcription factor 6, C/EBP homologous protein, and inositol-requiring enzyme 1 alpha. 4-Phenylbutyric acid (4-PBA) treatment alleviated ERS; reduced the NLR family pyrin domain containing 3, interleukin-1ß, and interleukin-18 levels; inhibited apoptosis; increased mitofusin 2 expression; and mitigated Ca2+ overload and mitochondria-associated ER membrane (MAM) dysfunction, thereby ameliorating IPEC-J2 injury. We demonstrated the pivotal role of ERS in MAM dysfunction and 7S- and 11S-mediated apoptosis, providing insights into 7S- and 11S-mediated intestinal barrier injury prevention and treatment.


Assuntos
Antígenos de Plantas , Apoptose , Globulinas , Soja , Fenilbutiratos , Proteínas de Armazenamento de Sementes , Proteínas de Soja , Animais , Suínos , Retículo Endoplasmático , Mitocôndrias , Estresse do Retículo Endoplasmático
2.
Res Vet Sci ; 169: 105177, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350170

RESUMO

Subclinical ketosis (SCK) in dairy cows is often misdiagnosed because it lacks clinical signs and detection indicators. However, it is highly prevalent and may transform into clinical ketosis if not treated promptly. Due to the negative energy balance, a large amount of fat is mobilized, producing NEFA that exceeds the upper limit of liver processing, which in turn leads to the disturbance of liver lipid metabolism. The silent information regulator 1 (SIRT1) is closely related to hepatic lipid metabolism disorders. Exosomes as signal transmitters, also play a role in the circulatory system. We hypothesize that the circulating exosome-mediated adenosine 5'-monophosphate (AMP)-activated protein kinase alpha (AMPKα)-SIRT1 pathway regulates lipid metabolism disorders in SCK cows. We extracted the exosomes required for the experiment from the peripheral circulating blood of non-ketotic (NK) and SCK cows. We investigated the effect of circulating exosomes on the expression levels of mRNA and protein of the AMPKα-SIRT1 pathway in non-esterified fatty acid (NEFA)-induced dairy cow primary hepatocytes using in vitro cell experiments. The results showed that circulating exosomes increased the expression levels of Lipolysis-related genes and proteins (AMPKα, SIRT1, and PGC-1α) in hepatocytes treated with 1.2 mM NEFA, and inhibited the expression of lipid synthesis-related genes and protein (SREBP-1C). The regulation of exosomes on lipid metabolism disorders caused by 1.2 mM NEFA treatment showed the same trend as for SIRT1-overexpressing adenovirus. The added exosomes could regulate NEFA-induced lipid metabolism in hepatocytes by mediating the AMPKα-SIRT1 pathway, consistent with the effect of transfected SIRT1 adenovirus.


Assuntos
Doenças dos Bovinos , Exossomos , Cetose , Transtornos do Metabolismo dos Lipídeos , Feminino , Animais , Bovinos , Metabolismo dos Lipídeos/fisiologia , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Ácidos Graxos não Esterificados , Exossomos/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/veterinária , Proteínas Quinases Ativadas por AMP/genética , Cetose/veterinária , Doenças dos Bovinos/metabolismo
3.
Biology (Basel) ; 12(9)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37759586

RESUMO

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

4.
Molecules ; 28(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37764275

RESUMO

Endoplasmic reticulum (ER) stress is a crucial factor in the pathogenesis of intestinal diseases. Soybean antigenic proteins (ß-conglycinin and soy glycinin) induce hypersensitivity reactions and intestinal barrier damage. However, whether this damage is associated with ER stress, autophagy, and the gut microbiome is largely unclear. Therefore, in this study, we aimed to investigate the effect of dietary supplementation with soy glycinin (11S glycinin) and ß-conglycinin (7S glycinin) on intestinal ER stress, autophagy, and flora in weaned piglets. Thirty healthy 21-day-old weaned "Duroc × Long White × Yorkshire" piglets were randomly divided into three groups and fed a basic, 7S-supplemented, or 11S-supplemented diet for one week. The results indicated that 7S/11S glycinin disrupted growth performance, damaged intestinal barrier integrity, and impaired goblet cell function in piglets (p < 0.05). Moreover, 7S/11S glycinin induced ER stress and blocked autophagic flux in the jejunum (p < 0.05) and increased the relative abundance of pathogenic flora (p < 0.01) and decreased that of beneficial flora (p < 0.05). In conclusion, 7S/11S glycinin induces intestinal ER stress, autophagic flux blockage, microbiota imbalance, and intestinal barrier damage in piglets.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Suínos , Intestinos , Estresse do Retículo Endoplasmático
5.
J Cardiovasc Transl Res ; 16(2): 341-357, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35984595

RESUMO

The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)-activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II-activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II-stimulated FBs. Collectively, Sal B can protect the Ang II-activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis.


Assuntos
Proteínas Quinases Ativadas por AMP , MicroRNAs , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Angiotensina II/farmacologia , Fibrose , MicroRNAs/metabolismo , Proteína Forkhead Box O1
6.
Front Vet Sci ; 9: 907299, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711805

RESUMO

Rutin, a common dietary flavonoid, exhibits remarkable pharmacological activities such as antioxidant and anti-inflammatory functions. Metabolic stress in mammals during the transition period affects mammary gland health. The aim of this experiment was to evaluate the protective effect of rutin supplementing against metabolic stress in the mammary glands of sheep during the transition period, particularly after parturition. Transition Hu sheep (2-3 years old with 62.90 ± 2.80 kg) were randomly divided into three groups, the control group was fed a diet without rutin, while rutin (50 and 100 mg/kg body weight/day) was administered to the two treatment groups (-28 day to +28 day relative to parturition). Serum and blood samples were collected from jugular vein on days -14, -7, +1, +2, +7, +14, +21, +28 relative to parturition. Mammary tissue biopsy samples of four sheep from the treatment group were harvested on day +28 postpartum. Compared to that in the control group, rutin supplementation resulted in lower ß-hydroxybutyrate (BHBA) while increasing the concentrations of non-esterified fatty acids (NEFA) and globulin after lactation. Furthermore, rutin treatment led to lower hydrogen peroxide (H2O2) and malonaldehyde (MDA) levels, resulting in increased catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant potential (T-AOC). Compared to that in the control group, rutin inhibits the mRNA expression of inflammatory markers such as tumor necrosis factor-α (TNF-α). In addition, rutin markedly downregulated the ratio of phosphorylated NF-κB p65 (p-p65) to total NF-κB p65 (p65). Meanwhile, rutin supplementation resulted in high mRNA abundance of the nuclear factor erythroid 2-like 2 (NFE2L2, formerly NRF2) and its target gene, heme oxygenase-1 (HO-1), which plays critical roles in maintaining the redox balance of the mammary gland. Furthermore, rutin treatment lowered the levels of various downstream apoptotic markers, including Bax, caspase3 and caspase9, while upregulating anti-apoptotic Bcl-2 protein. These data indicate the positive effect of rutin against inflammation, oxidative stress status, and anti-apoptotic activity in the mammary gland. The mechanism underlying these responses merits further study.

7.
Bioengineered ; 13(2): 4173-4184, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35114881

RESUMO

It aimed to investigate the mechanism of magnetic nanoparticles (MNPs) on atrial fibrillation and effect of n-isopropyl acrylamide coated MNPs (NIPA-co-MN) on the treatment of atrial fibrillation. Ten beagles weighing 20 - 25 kg were randomly divided into test group and control group. Dogs with atrial fibrillation were set as test group, and non-atrial fibrillation dogs as control group. The expression of long non-coding RNA (lncRNA) differentially expressed in the right anterior adipose pad in atrial fibrillation and non-atrial fibrillation dogs was detected by high-throughput sequencing. The relationship between lncRNA and cardiac autonomic nerve remodeling (CANR) was explored. In addition, 20 beagles weighing 20-25 kg were selected to study the therapeutic effect of n-isopropylacrylamide magnetic nanoparticles (NIPA-co-MN) on atrial fibrillation, and statistical analysis was performed. The volume and number of new neurons in the anterior right fat pad of atrium of test group were larger than the control group. The test group dogs produced 45 brand-new lncRNA, including 15 up-regulated transcripts and 30 down-regulated transcripts. MNPs injection can slow down the reduction of ventricular rate in right inferior ganglion plexus. The anterior right ganglion plexus resulted in a reduced amplitude of sinus tachyarrhythmia. This study provided references for the discovery of new diagnostic biomarkers or therapeutic targets and for the treatment of patients with atrial fibrillation.


Assuntos
Fibrilação Atrial/cirurgia , Vias Autônomas , Ablação por Cateter , Nanopartículas de Magnetita , RNA Longo não Codificante , Acrilamidas/química , Animais , Vias Autônomas/efeitos dos fármacos , Vias Autônomas/efeitos da radiação , Modelos Animais de Doenças , Cães , Átrios do Coração/inervação , Átrios do Coração/cirurgia , Sequenciamento de Nucleotídeos em Larga Escala , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Análise de Sequência de RNA , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Transcriptoma/efeitos da radiação
8.
Front Cardiovasc Med ; 9: 1069146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36588556

RESUMO

Background: Weight-adjusted waist circumference index (WWI) is a novel index positively associated with excessive fat accumulation. The current study aims to evaluate the association between WWI and the prevalent heart failure (HF), and to assess the value of WWI to improve the detection of HF in the general population. Methods: A total of 25,509 subjects from National Health and Nutrition Examination Survey 1999-2018 were included into our study. WWI was calculated as WC (cm) divided by the square root of weight (kg). HF was identified according to the subjects' reports. Results: The prevalence of reported HF was 2.96%. With adjustment of demographic, anthropometric, laboratory, and medical history data, one SD increment of WWI could cast an additional 19.5% risk for prevalent HF. After separating WWI into quartiles, the fourth quartile had a 1.670 times risk of prevalent HF compared to the first quartile. Furthermore, smooth curve fitting suggested that the association was linear in the entire range of WWI. Moreover, the association was robust to subgroups of age, sex, race, obesity, hypertension, and diabetes. Additionally, ROC analysis revealed a significant improvement for the detection of prevalent HF from WWI (0.890 vs. 0.894, P < 0.001); And continuous net reclassification index (0.225, P < 0.001) and integrated discrimination index (0.004, P < 0.001) also supported the improvement from WWI. Conclusion: Our data demonstrated a significant, linear, and robust association between WWI, a simple surrogate for fat mass accumulation, and the risk for prevalent HF in a representative population. Moreover, our results also suggested the potential value of WWI to refine the detection of prevalent HF in the general population.

9.
Bioengineered ; 13(1): 863-875, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969364

RESUMO

The purpose is to reveal the role and mechanism of long non-coding ribonucleic acid (lncRNA) in atrial fibrillation (AF) and atrial energy metabolism remodeling. The healthy adult New Zealand rabbit was chosen as the experimental animal, and the AF rabbit models were built. Besides, the lncRNA sequencing method based on nano sensor technology was employed to detect the differentially expressed lncRNAs, and the target lncRNA and its target genes were determined through bioinformatics analysis. Subsequently, TCONS_00016478 dysfunction experiment was performed. The gene level and protein level of TCONS_00016478, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and its downstream genes were detected. The results show that after sequencing, 99,755 new lncRNAs transcripts are found in total, of which 1,215 are significantly differentially expressed, 974 are down-regulated, and 241 are up-regulated. A new transcript TCONS_00016478 associated with the remodeling of atrial energy metabolism is further screened. Silencing TCONS_00016478 can significantly reduce PGC1-α, PPARγ, GLUT4, and CPT1 expression levels (P < 0.05). Thereby, TCONS_00016478 can affect the atrial energy metabolism remodeling and atrial fibrillation in experimental rabbits by regulating the PGC1-α/PPARγ signaling pathway.


Assuntos
Fibrilação Atrial/genética , Remodelamento Atrial/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Animais , Técnicas Biossensoriais , Biologia Computacional , Modelos Animais de Doenças , Metabolismo Energético , Feminino , Regulação da Expressão Gênica , Masculino , Nanotecnologia , Coelhos
10.
Front Cardiovasc Med ; 8: 630090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33778023

RESUMO

Objectives: To evaluate the clinical safety and efficacy of radiofrequency catheter ablation for atrial fibrillation patients with a history of stroke. Methods and Results: A total of 116 symptomatic, drug-refractory AF patients with a history of stroke, and 1:2 matched patients without a history of stroke were enrolled. Of these, 28 cases occurred stroke within 3 months (Group 1), 88 cases with stroke history longer than 3 months (Group 2), and 232 cases without stroke (Group 3). PVI was performed in all patients, extended to ablation of linear lesions ablation. The periprocedural stroke rates and other procedure-related in-hospital complications did not differ significantly among the three groups. The maintenance rate of SR after the procedure showed no significant difference (p = 0.333), 52.7, 66.4, and 70.7% in Group 1, 2, and 3, respectively. Furthermore, the comparison between a history of stroke and those without it were also shown no significant difference (p = 0.351). Conclusions: Radiofrequency ablation for AF patients occurred stroke, even within 3 months is safe and effective, without higher periprocedural complication rate and recurrence rate.

11.
Europace ; 23(5): 701-709, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33554255

RESUMO

AIMS: The aim of this study was to determine whether driver ablation effectively treats persistent atrial fibrillation (AF) in obese patients. METHODS AND RESULTS: We randomly assigned 124 persistent AF obese patients to two groups, one undergoing conventional ablation (n = 62) and the other undergoing driver ablation (n = 62). Sixty-two non-obese patients with persistent AF undergoing driver ablation served as matched controls. Bipolar electrogram dispersion was analysed for driver mapping. Epicardial adipose tissue (EAT) volume was measured using cardiac computed tomography. Obese patients had a higher proportion of driver regions in the posterior wall (56.5% vs. 32.3%, P = 0.007). Driver complexity, measured as the average number and area of driver regions, was higher in the obese group than in the non-obese group (3.5 ± 1.0 vs. 2.9 ± 0.9, P < 0.001; 15.5% ± 4.2% vs. 9.8 ± 2.6%, P < 0.001, respectively). Left atrial EAT volume correlated better with the proportion of area of driver regions than did body mass index (BMI) and total EAT (BMI: r2 = 0.250, P < 0.001; total EAT: r2 = 0.379, P < 0.001; and left atrial EAT: r2 = 0.439, P < 0.001). The rate of AF termination was significantly higher in the driver ablation group than in the conventional ablation group (82.9% vs. 22.8%, P < 0.001). During the follow-up period of 16.9 ± 6.5 months, patients in the driver ablation group had significantly better AF-free survival (91.91% vs. 79.0%, log rank test, P = 0.026) and AF/atrial tachycardia-free survival (83.9% vs. 64.5%, log rank test, P = 0.011) than did patients in the conventional ablation group. CONCLUSION: Obesity is associated with increased driver complexity. Driver ablation improves long-term outcomes in obese patients with persistent AF.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Humanos , Obesidade/complicações , Obesidade/diagnóstico , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Recidiva , Resultado do Tratamento
12.
Case Rep Cardiol ; 2020: 9691584, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32637178

RESUMO

Extrapulmonary vein focal sources have been recognized as the source of atrial fibrillation in some cases, and empiric electric isolation of the left atrial appendage has been proposed for long-standing persistent atrial fibrillation by some. Here, we present a case of redo ablation of long-standing persistent atrial fibrillation in which the left atrial appendage played a key role in maintaining AF during ablation, and atrial fibrillation was terminated by electrical isolation of the LAA. During the ablation, a rare phenomenon of half of the atria in atrial fibrillation while the other half of the atria in atrial flutter was seen.

13.
J Am Heart Assoc ; 7(16): e008842, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30369314

RESUMO

Background Activin receptor-like kinase 4 ( ALK 4) is highly expressed in mammal heart. Atrial fibrillation ( AF ) is closely related to ventricular pressure overload. Because pressure overload increases atrial pressure and leads to atrial remodeling, it would be informative to know whether ALK 4 exerts potential effects on atrial remodeling and AF vulnerability in a pressure-overload model. Methods and Results Wild-type littermates and ALK 4+/- mice were subjected to abdominal aortic constriction or a sham operation. After 4 or 8 weeks, echocardiographic and hemodynamic measurements were performed, and inducibility of AF was tested. The hearts were divided into atria and ventricles and then were fixed in formalin for staining, or they were weighted and snap-frozen for quantitative real-time polymerase chain reaction and Western blot analysis. Compared with wild-type littermates, ALK 4+/- mice demonstrated a similar extent of atrial hypertrophy but significantly suppressed atrial fibrosis at 8 weeks post-abdominal aortic constriction. ALK 4 haplodeficiency partially blocked abdominal aortic constriction-induced upregulation of monocyte chemotactic protein 1 and interleukin-6, and the increased chemotaxin of macrophages. ALK 4 haplodeficiency also blunted a reduction of connexin 40 and redistribution of connexin 43 from the intercalated disk to the lateral membranes, thereby improving localized conduction abnormalities. Meanwhile, ALK 4 haplodeficiency inhibited abdominal aortic constriction-induced decreased INa, ICa-L and IK1 densities as well as the accompanying action potential duration shortening. Mechanistically, ALK 4 haploinsufficiency resulted in the suppression of Smad2/3 activity in this model. Conclusions Our results demonstrate that ALK 4 haplodeficiency ameliorates atrial remodeling and vulnerability to AF in a pressure-overload model through inactivation of the Smad2/3 pathway, suggesting that ALK 4 might be a potential therapeutic target in combating pressure overload-induced AF .


Assuntos
Receptores de Ativinas Tipo I/genética , Receptores de Ativinas Tipo I/metabolismo , Fibrilação Atrial/genética , Remodelamento Atrial/genética , Cardiomegalia , Miócitos Cardíacos/metabolismo , Idoso , Animais , Aorta Abdominal/cirurgia , Quimiocina CCL2/metabolismo , Fatores Quimiotáticos/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Feminino , Fibrose , Predisposição Genética para Doença , Haploinsuficiência , Sistema de Condução Cardíaco , Humanos , Hipertensão , Interleucina-6/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Técnicas de Patch-Clamp , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo
14.
Int J Biol Sci ; 14(8): 849-857, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29989079

RESUMO

Microorganisms resided in human body play a vital role in metabolism, immune defense, nutrition absorption, cancer control and protection against pathogen colonization. The changes of microbial communities can cause human diseases. Based on the known microbe-disease association, we presented a novel computational model employing Random Walking with Restart optimized by Particle Swarm Optimization (PSO) on the heterogeneous interlinked network of Human Microbe-Disease Associations (PRWHMDA) (see Figure 1). Based on the known human microbe-disease associations, we constructed the heterogeneous interlinked network with Cosine similarity. The extended random walk with restart (RWR) method was derived to get the potential microbe-disease associations. PSO was utilized to get the optimal parameters of RWR. To evaluate the prediction effectiveness, we performed leave one out cross validation (LOOCV) and 5-fold cross validation (CV), which got the AUC (The area under ROC curve) of 0.915 (LOOCV) and the average AUCs of 0.8875 ± 0.0046 (5-fold CV). Moreover, we carried out three case studies of asthma, inflammatory bowel disease (IBD) and type 1 diabetes (T1D) for the further evaluation. The result showed that 10, 10 and 9 of top-10 predicted microbes were verified by previously published experimental results, respectively. It is anticipated that PRWHMDA can be effective to identify the disease-related microbes and maybe helpful to disclose the relationship between microorganisms and their human host.


Assuntos
Biologia Computacional/métodos , Microbiota/fisiologia , Algoritmos , Humanos
15.
Pacing Clin Electrophysiol ; 41(2): 172-178, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29023875

RESUMO

BACKGROUND: In longstanding persistent atrial fibrillation (LPeAF), the ideal endpoint of ablation remains to be determined. This study was to explore the value of pursuing AF termination or no with the same strategy during ablation on the long-term outcomes in patients with LPeAF. METHODS: Utilized "CCL" strategy is a fixed ablation approach consisting of circumferential pulmonary vein antrum isolation, ablation of complex fractionated atrial electrogram, and linear ablation between two anatomical structures (the mitral isthmus, left atrial roof). Note that 400 patients were randomized to group A (technical endpoint) and group B (pursuing AF termination). RESULTS: A group with technical endpoint had lower rate of acute AF termination (AF→sinus rhythm, 3.5% vs 18.1%; AF→atrial tachycardia, 23.7% vs 44.7%; P < 0.01) and shorter duration of ablation (164.9 ± 20.8 vs 223.4 ± 24.9, P < 0.01), radiofrequency delivery time (69.8 ± 18.1 vs 102.2 ± 26.3, P < 0.01), and x-ray exposure time (18.2 ± 8.8 vs 27.9 ± 12.4, P < 0.01) than those in B group (pursuing AF termination). During follow-up, freedom from atrial arrhythmias did not differ between the two groups after a single ablation procedure (46.5% vs 54.3%, P=0.12) and the final ablation procedure (60.1% vs 65.8%, P  =  0.24). CONCLUSION: In patients of LPeAF, pursuing AF termination during ablation was associated with similar long-term clinical outcome compared to that with technical endpoint. Ablation to termination is not the best strategy during ablation.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Eletrocardiografia , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do Tratamento
16.
Cardiology ; 138(1): 55-62, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28571007

RESUMO

OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies. TGF-ß1-stimulated atrial fibroblasts were treated with EPL or vehicle for the in vitro studies including Western blotting and qRT-PCR studies. In addition, Smad7 siRNA was used to knock down Smad7. RESULTS: EPL inhibited atrial fibrosis in the Tx mice. In addition, EPL suppressed the expression of fibrosis-related molecules induced by TGF-ß1 in vivo and in vitro. This occurred in concert with a downregulation of Smad7 protein expression and an upregulation of p-Smad2/3 protein expression. In addition, knockdown of Smad7 by siRNA abolished the protective roles of EPL. CONCLUSIONS: EPL inhibited atrial fibrosis in Tx mice. The underlying mechanism may involve increased protein expression of Smad7, which enhances the inhibitory feedback regulation of TGF-ß1/Smad signaling.


Assuntos
Fibrilação Atrial/patologia , Átrios do Coração/patologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Proteína Smad7/genética , Espironolactona/análogos & derivados , Animais , Fibrilação Atrial/tratamento farmacológico , Células Cultivadas , Eplerenona , Fibroblastos/efeitos dos fármacos , Fibrose , Átrios do Coração/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Espironolactona/farmacologia , Fator de Crescimento Transformador beta1/farmacologia
17.
PLoS One ; 12(3): e0173759, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28323847

RESUMO

OBJECTIVES: To explore the relationship between the MAPKs/TGF-ß1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-ß1/TRAF6 signaling pathway in atrial fibrosis. METHODS: A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-ß1, TRAF6, and connective tissue growth factor (CTGF), respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-ß-activated kinase 1 (TAK1). Serum angiotensin II (Ang II) levels were assayed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR). The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-ß1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR. CONCLUSION: The MAPKs/TGF-ß1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.


Assuntos
Fibrilação Atrial/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Complicações Pós-Operatórias/metabolismo , Cardiopatia Reumática/cirurgia , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Angiotensina II/sangue , Apêndice Atrial/metabolismo , Apêndice Atrial/patologia , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/patologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Feminino , Fibrose/diagnóstico , Fibrose/metabolismo , Fibrose/patologia , Fibrose/cirurgia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/patologia , Prognóstico , RNA Mensageiro/metabolismo , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/patologia , Índice de Gravidade de Doença
18.
Int J Cardiol ; 228: 853-860, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27888765

RESUMO

BACKGROUND: The electrophysiological characteristics of patients without recurrence after ablation of persistent atrial fibrillation (AF) have not been systematically determined. This study compared the electrophysiological characteristics in patients with and without recurrence of AF after persistent AF ablation. METHODS: Forty-five patients without recurrence of AF after persistent AF ablation were enrolled to assess electrophysiological characteristics including pulmonary vein (PV) reconnection, the mitral isthmus (MI) line and the roof line reconduction. Ninety-five patients with recurrence of AF after ablation were used as the control group. RESULTS: Among patients without recurrence, recovery of PV conduction was observed in 37 of 45 (82.2%) patients: 3/45 (6.7%) reconnection in 4 veins, 7/45 (15.6%) in 3 veins, 11/45 (24.4%) in 2 veins, and 16/45 (35.6%) in 1 vein. No significant differences were seen in the proportion of patients with PV reconnection compared to patients with recurrence (p>0.05). Among patients without recurrence, the MI line reconduction was observed in 3/45 (6.7%) patients; the roof line conduction was observed in 5/45 (11.1%) patients. In comparison, patients with clinical recurrence of AF had recovery of the MI line conduction in 27/95 (28.4%) and recovery of the roof line conduction in 26/95 (27.4%). Significant differences were seen between these two groups (6.7% vs 28.4%, p=0.004; 11.1% vs 27.4%, p=0.031). CONCLUSION: Although a high incidence of PV reconnection was similarly observed in patients with and without recurrence of AF, a lower incidence of lines reconduction was observed in patients without recurrence of AF.


Assuntos
Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Ablação por Cateter , Idoso , Fibrilação Atrial/diagnóstico , Estudos de Casos e Controles , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares , Recidiva , Resultado do Tratamento
19.
Hell J Nucl Med ; 19(3): 196-199, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27999826

RESUMO

Silent myocardial ischemia is typically defined as objective evidence of myocardial ischemia in patients without subjective ischemia symptoms. Currently, coronary artery angiography is the gold standard for diagnosis of asymptomatic coronary artery disease (CAD). Computed tomography coronary angiography (CTCA) can visually demonstrate the morphology, trend and extent of coronary stenosis and is commonly used in clinical screening of CAD. Myocardial perfusion imaging can be used not only to identify whether anatomical stenosis causes myocardial dysfunction, but to also assess the risk stratification and prognosis of myocardial disease (MD). Myocardial perfusion imaging using morphing combined with CTCA can simultaneously show the relationship between CAD and myocardial ischemia from an anatomical and functional aspect. This allows earlier diagnosis of asymptomatic CAD myocardial ischemia, accurate identification of the culprit vessels, and could prevent unnecessary interventional therapy. The 1-day dobutamine stress/resting met-hod is also one of the methods used. The combination of CTCA and the morphing technique can provide anatomical and functional information on coronary arteries at the same time, significantly improving the diagnostic sensitivity, specificity, and accuracy of MD.


Assuntos
Artefatos , Técnicas de Imagem de Sincronização Cardíaca/métodos , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Isquemia Miocárdica/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Doenças Assintomáticas , Humanos , Movimento (Física) , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Int J Cardiol ; 225: 82-86, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27716555

RESUMO

OBJECTIVE: The long-term outcomes of catheter ablation of atrial fibrillation (AF) developing post-cardiac valve replacement (VR) remain undefined. METHODS AND RESULTS: Eighty-nine post-VR patients with AF (44% longstanding persistent AF, LSP-AF) were enrolled. Cumulative success rate of circumferential pulmonary vein ablation (CPVA for paroxysmal AF) and bidirectional block of lines and disappearance of complex fractionated atrial electrograms (CFAEs for persistent and LSP-AF) as index and repeat procedural endpoints reached 57% (mean, 1.3 procedures) during the first year, and dropped to 42% at median follow-up of 40months (range, 24-70months) for multiple procedures (mean, 1.6±0.9 [1-5]); incidence of procedural complications was similar to that of conventional procedures. In multivariate analysis, larger right atrium (RA, 9.40 [2.64-33.36]; P=0.001) and rheumatic valvular disease etiology (OR, 5.49 [95% CI, 1.26-23.96]; P=0.023) were significant independent predictors of recurrent atrial tachyarrhythmia (ATa); in contrast, long-term freedom from ATa was comparable between single and double valve replacement groups (42.1% vs. 43.7%, P=0.880), or mechanical and bioprosthetic valves groups (41.7% vs. 50.0%, P=0.620). CONCLUSION: In this single-center prospective study, treatment of post-VR AF with commonly used ablation strategies including CPVA and linear and CFAE ablation had limited long-term success, with ATa recurrence risk appearing higher in the setting of RA enlargement and rheumatic valvular disease and unrelated to valves characteristics.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/tendências , Implante de Prótese de Valva Cardíaca/tendências , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Eletrocardiografia Ambulatorial/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
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