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1.
J Arrhythm ; 40(4): 839-848, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39139906

RESUMO

Background: Laser balloon (LB) pulmonary vein isolation (PVI) is an established ablation technique for atrial fibrillation (AF). We report long-term follow-up and procedural data of LB-PVI and we compare the first and second LB generation. Methods: Patients undergoing LB ablation with first- (LB1) or second-generation LB (LB2) for AF were retrospectively enrolled and divided into two groups. Procedural endpoint was complete PVI. Clinical success was defined as no recurrence of AF/atrial tachycardia after a 90 days blanking period. Results: 538 patients were included (age 66 ± 10 years, 58% paroxysmal AF), 427 in LB1 and 111 in LB2. 2079 PVs were targeted and 2073 (99.7%) were successfully isolated; 2027 (97.5%) using solely the LB. Additional touch-up ablation was limited (46 PVs; 2.2%) with no difference between the groups. Procedural (LB1: 120 ± 33 minutes vs. LB2: 99 ± 22 min; p < .001) and fluoroscopy time (LB1: 11.2 ± 5 min vs. LB2: 8.5 ± 3 min; p < .001) were shorter with LB2. The complication rate was 8.9% (LB1: 10.1% vs. LB2: 4.5%; p = .067) with most complications resulting from the access site (21/48). Overall freedom from AF after 1-year was 73.7% (paroxysmal AF: 76.9%; persistent AF: 69.3%; p < .001) with no difference between the groups (LB1: 73.4% vs. LB2: 74.7%; p = .491). Conclusion: LB showed a high efficacy and acceptable safety, with numerically lower complication rates with the second-generation LB. Procedure and fluoroscopy times were shorter with LB2. Overall, 73.7% of patients were free from AF at 1-year, with comparable results among both generations.

4.
Int Immunopharmacol ; 138: 112517, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38924866

RESUMO

Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.


Assuntos
Apoptose , Movimento Celular , Melanoma , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Quercetina , Transdução de Sinais , Quercetina/análogos & derivados , Quercetina/farmacologia , Quercetina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Humanos , Apoptose/efeitos dos fármacos , Animais , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
5.
J Cardiovasc Electrophysiol ; 35(7): 1412-1421, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38750671

RESUMO

BACKGROUND: Management of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited. METHODS: Highly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body-weight-reduction underwent CBA. RESULTS: Data of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch-up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real-time-isolation (78.6% vs. 78.5%), single-shot-isolation (86.5% vs. 88.8%), but significantly longer time-to-sustained-isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture-site-complication (6.9% vs. 1.6%) in Group A. One-year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re-Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089). CONCLUSION: For very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.


Assuntos
Fibrilação Atrial , Índice de Massa Corporal , Criocirurgia , Estudos de Viabilidade , Obesidade , Veias Pulmonares , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/diagnóstico , Criocirurgia/efeitos adversos , Masculino , Feminino , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Fatores de Tempo , Obesidade/diagnóstico , Obesidade/complicações , Obesidade/fisiopatologia , Veias Pulmonares/cirurgia , Veias Pulmonares/fisiopatologia , Frequência Cardíaca , Índice de Gravidade de Doença , Potenciais de Ação , Estudos Retrospectivos , Recidiva
6.
Adv Mater ; 36(29): e2400115, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38752837

RESUMO

All-solid-state lithium metal batteries (ASSLMBs) are considered as the most promising candidates for the next-generation high-safety batteries. To achieve high energy density in ASSLMBs, it is essential that the solid-state electrolytes (SSEs) are lightweight, thin, and possess superior electrochemical stability. In this study, a feasible and scalable fabrication approach to construct 3D supporting skeleton using an electro-blown spinning technique is proposed. This skeleton not only enhances the mechanical strength but also hinders the migration of Li-salt anions, improving the lithium-ion transference number of the SSE. This provides a homogeneous distribution of Li-ion flux and local current density, promoting uniform Li deposition. As a result, based on the mechanically robust and thin SSEs, the Li symmetric cells show outstanding Li plating/stripping reversibility. Besides, a stable interface contact between SSE and Li anode has been established with the formation of an F-enriched solid electrolyte interface layer. The solid-state Li|sulfurized polyacrylonitrile (Li|SPAN) cell achieves a capacity retention ratio of 94.0% after 350 cycles at 0.5 C. Also, the high-voltage Li|LCO cell shows a capacity retention of 92.4% at 0.5 C after 500 cycles. This fabrication approach for SSEs is applicable for commercially large-scale production and application in high-energy-density and high-safety ASSLMBs.

7.
Int Immunopharmacol ; 134: 112261, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38761783

RESUMO

BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.


Assuntos
Anti-Inflamatórios , Citocinas , Modelos Animais de Doenças , Flavonoides , Glucosídeos , Células HaCaT , Imiquimode , Queratinócitos , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos BALB C , Psoríase , Animais , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/induzido quimicamente , Psoríase/patologia , Camundongos , Humanos , Células RAW 264.7 , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Citocinas/metabolismo , Queratinócitos/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Proliferação de Células/efeitos dos fármacos , Masculino , Espécies Reativas de Oxigênio/metabolismo , Dermatite/tratamento farmacológico , Dermatite/patologia , Dermatite/imunologia , Linhagem Celular
8.
J Interv Card Electrophysiol ; 67(5): 1247-1255, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38573537

RESUMO

BACKGROUND: Vascular complications are a common occurrence during atrial fibrillation ablation. Observational studies indicate that the utilization of ultrasound (US)-guided puncture may decrease the incidence of vascular complications; however, its routine use is not established in many centres. METHODS: Patients undergoing catheter ablation for atrial fibrillation were included sequentially. All patients receiving US-guided punctures were prospectively enrolled (US group), while patients who underwent the procedure with standard puncture technique served as control group (No-US group). Periprocedural vascular complications requiring intervention within 30 days of the procedure were defined as the primary endpoint. RESULTS: A total of 599 patients (average age: 69 ± 11 years, 62.9% male) were analysed. The incidence of vascular complications was lower with the US-guided puncture than with the anatomic landmark-guided puncture (14/299 [4.7%] vs. 27/300 [9%], p = 0.036). The US-guided vascular access significantly reduced the rate of false aneurysms (3/299 [1%] vs. 12/300 [4%], p = 0.019). In addition, the occurrence of arteriovenous fistula (2/299 [0.7%] vs. 4/300 [1.3%], p = 0.686) and haematoma requiring treatment (9/299 [3%] vs. 11/300 [3.7%], p = 0.655) were also lower in the US group. US-guided puncture did not prolong the procedure time (mean procedure time: 57.48 ± 24.47 min vs. 56.09 ± 23.36 min, p = 0.478). Multivariate regression analysis identified female gender (OR 2.079, CI 95% 1.096-3.945, p = 0.025) and conventional vascular access (OR 2.079, CI 95% 1.025-3.908, p = 0.042) as predictors of vascular complications. CONCLUSIONS: The implementation of US-guided vascular access for left atrial catheter ablation resulted in a significant decrease of the overall vascular complication rate.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Ultrassonografia de Intervenção , Humanos , Masculino , Feminino , Ablação por Cateter/métodos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Idoso , Ultrassonografia de Intervenção/métodos , Hospitais com Alto Volume de Atendimentos , Estudos Prospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Punções , Incidência , Pessoa de Meia-Idade
10.
Cancer Lett ; 590: 216840, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38604311

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, highlighting the urgent need to elucidate the underlying oncogenic mechanisms. VIRMA is a classic isoform of methyltransferases that participates in epigenetic transcriptomic modification in eukaryotic mRNAs. However, the exact roles of VIRMA in PDAC remain unclear. Here, we identified that VIRMA is highly expressed in PDAC, and histone modifications of the promoter may partly account for this dysregulation. Moreover, VIRMA is closely related to glycolysis and poor prognosis in PDAC. We further determined that STRA6 is a direct downstream target of VIRMA in PDAC by RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq). VIRMA is involved in gene expression regulation via 3' UTR targeting of STRA6 mRNA. Furthermore, the m6A reader IGF2BP2 was shown to critically contribute to the stability of STRA6 mRNA. We describe the role of VIRMA in promoting signaling via the STRA6/STAT3 axis, which results in increased levels of HIF-1α, a key activator of glycolysis. In vivo and in vitro experiments reveal that the VIRMA-STRA6-STAT3-HIF-1α axis plays an instrumental role in glycolysis and tumor progression in PDAC. In conclusion, we demonstrate that VIRMA can increase glycolysis in PDAC by upregulating STRA6, a cell surface membrane protein that stimulates the STAT3 pathway, thereby activating HIF-1α and leading to pancreatic cancer malignancy. Overall, our data strongly suggest that the VIRMA-STRA6-STAT3-HIF-1α axis is a viable therapeutic target in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Regulação Neoplásica da Expressão Gênica , Glicólise , Neoplasias Pancreáticas , Regulação para Cima , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Glicólise/genética , Linhagem Celular Tumoral , Animais , Progressão da Doença , Metiltransferases/genética , Metiltransferases/metabolismo , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Masculino , Camundongos Nus , Transdução de Sinais
12.
Nano Lett ; 24(17): 5292-5300, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648075

RESUMO

Understanding the structure-property relationship of lithium-ion conducting solid oxide electrolytes is essential to accelerate their development and commercialization. However, the structural complexity of nonideal materials increases the difficulty of study. Here, we develop an algorithmic framework to understand the effect of microstructure on the properties by linking the microscopic morphology images to their ionic conductivities. We adopt garnet and perovskite polycrystalline oxides as examples and quantify the microscopic morphologies via extracting determined physical parameters from the images. It directly visualizes the effect of physical parameters on their corresponding ionic conductivities. As a result, we can determine the microstructural features of a Li-ion conductor with high ionic conductivity, which can guide the synthesis of highly conductive solid electrolytes. Our work provides a novel approach to understanding the microstructure-property relationship for solid-state ionic materials, showing the potential to extend to other structural/functional ceramics with various physical properties in other fields.

13.
Sci Rep ; 14(1): 5816, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461337

RESUMO

The classroom video has a complex background and dense targets. This study utilizes small object detection technology to analyze and evaluate students' behavior in the classroom, aiming to objectively and accurately assess classroom quality. Firstly, noise is removed from the images using a median filter, and the contrast of the images is enhanced through histogram equalization. Label smoothing is applied to reduce the model's sensitivity to labels. Then, features are extracted from the preprocessed images, and multi-scale feature fusion is employed to enhance semantic expression across multiple scales. Finally, a combination loss function is utilized to improve the accuracy of multi-object recognition tasks. Real-time detection of students' behaviors in the classroom is performed based on the small object detection model. The average head-up rate in the classroom is calculated, and the quality of teaching is evaluated and analyzed. This study explores the methods and applications of small object detection technology based on actual teaching cases and analyzes and evaluates its effectiveness in evaluating the quality of higher education classroom teaching. The research findings demonstrate the significant importance of small object detection technology in effectively evaluating students' learning conditions in higher education classrooms, leading to improved teaching quality and personalized education.

14.
Cancer Lett ; 588: 216784, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38458594

RESUMO

Glycolytic metabolism is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and tumor-associated stromal cells play important roles in tumor metabolism. We previously reported that tumor-associated macrophages (TAMs) facilitate PDAC progression. However, little is known about whether TAMs are involved in regulating glycolysis in PDAC. Here, we found a positive correlation between CD68+ TAM infiltration and FDG maximal standardized uptake (FDG SUVmax) on PET-CT images of PDAC. We discovered that the glycolytic gene set was prominently enriched in the high TAM infiltration group through Gene Set Enrichment Analysis using The Cancer Genome Atlas database. Mechanistically, TAMs secreted IL-8 to promote GLUT3 expression in PDAC cells, enhancing tumor glycolysis both in vitro and in vivo, whereas this effect could be blocked by the IL-8 receptor inhibitor reparixin. Furthermore, IL-8 promoted the translocation of phosphorylated STAT3 into the nucleus to activate the GLUT3 promoter. Overall, we demonstrated that TAMs boosted PDAC cell glycolysis through the IL-8/STAT3/GLUT3 signaling pathway. Our cumulative findings suggest that the abrogation of TAM-induced tumor glycolysis by reparixin might exhibit an antitumor impact and offer a potential therapeutic target for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sulfonamidas , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Macrófagos Associados a Tumor/metabolismo , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Macrófagos/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Transdução de Sinais , Glicólise , Linhagem Celular Tumoral , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
15.
Aging (Albany NY) ; 16(5): 4759-4777, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38461449

RESUMO

Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of ß-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with ß-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of ß-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of ß-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas ß-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of ß-sitosterol in the treatment of liver fibrosis, suggesting that ß-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.


Assuntos
NF-kappa B , Ranunculus , Camundongos , Animais , NF-kappa B/metabolismo , Ranunculus/metabolismo , Farmacologia em Rede , Cirrose Hepática/metabolismo , Perfilação da Expressão Gênica , Fígado/metabolismo
16.
J Cancer Res Clin Oncol ; 150(3): 127, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483604

RESUMO

PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.


Assuntos
Neoplasias Pancreáticas , Humanos , Biomarcadores , Glicogênio Fosforilase Encefálica/genética , Glicogênio Fosforilase Encefálica/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Prognóstico , Transdução de Sinais/genética
17.
Cardiovasc Diabetol ; 23(1): 78, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402177

RESUMO

OBJECTIVE: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.


Assuntos
Fibrilação Atrial , Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Fibrilação Ventricular
18.
Heart Rhythm ; 21(7): 1001-1007, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38365127

RESUMO

BACKGROUND: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown. OBJECTIVE: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups. METHODS: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure. RESULTS: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003). CONCLUSION: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Átrios do Coração , Veias Pulmonares , Humanos , Feminino , Idoso , Fibrilação Atrial/cirurgia , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Masculino , Ablação por Cateter/métodos , Átrios do Coração/fisiopatologia , Prevalência , Veias Pulmonares/cirurgia , Fatores Sexuais , Idoso de 80 Anos ou mais , Cicatriz/etiologia , Cicatriz/epidemiologia , Recidiva , Resultado do Tratamento , Seguimentos
19.
Aging (Albany NY) ; 16(3): 2617-2637, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305809

RESUMO

Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Quercetina/análogos & derivados , Humanos , Detecção Precoce de Câncer , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Simulação de Acoplamento Molecular , Pâncreas , Perfilação da Expressão Gênica , Apoptose/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana , Receptores de Ácidos Lisofosfatídicos
20.
Water Res ; 251: 121103, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38183842

RESUMO

Recently, extensive attention has been paid to antibiotic resistance genes (ARGs) transmission. However, little available literature could be found about ARGs transmission in stormwater bioretention cells, especially the role of water matrix on ARGs transmission. Batch experiments were conducted to investigate target ARGs (blaTEM, tetR and aphA) transmission behaviors in substrate layer from stormwater bioretention cells under different water matrices, including nutrient elements (e.g., carbon, nitrogen and phosphorus), water environmental conditions (dissolved oxygen (DO), pH and salinity, etc.) and pollution factors (like heavy metals, antibiotics and disinfectants), showing that ARGs conjugation frequency increased sharply with the enhancement of water matrices (expect DO and pH), while there were obvious increasing tendencies for all ARGs transformation frequencies under only the pollution factor. The correlation between dominant bacteria and ARGs transmission implied that conjugation and transformation of ARGs were mainly determined by Firmicutes, Bacteroidota, Latescibacterota, Chloroflexi and Cyanobacteria at the phylum level, and by Sphingomonas, Ensifer, IMCC26256, Rubellimicrobium, Saccharimonadales, Vicinamibacteraceae, Nocardioides, JG30-KF-CM66 at the genus level. The mentioned dominant bacteria were responsible for intracellular reactive oxygen species (ROS) and cell membrane permeability (CMP) in the substrate layer, where the amplification of intracellular ROS variation were the largest with 144 and 147 % under the condition of TP and salinity, respectively, and the one of CMP variation were the highest more than 165 % under various pollution factors. Furthermore, both increasing DO and reducing salinity could be potential approaches for the inhibition of ARGs transmission in bioretention cells taking into account the simultaneous removal of conventional pollutants.


Assuntos
Antibacterianos , Bactérias , Espécies Reativas de Oxigênio , Poluição Ambiental , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos
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