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1.
Mol Psychiatry ; 29(3): 793-808, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145987

RESUMO

Context-induced retrieval of drug withdrawal memory is one of the important reasons for drug relapses. Previous studies have shown that different projection neurons in different brain regions or in the same brain region such as the basolateral amygdala (BLA) participate in context-induced retrieval of drug withdrawal memory. However, whether these different projection neurons participate in the retrieval of drug withdrawal memory with same or different molecular pathways remains a topic for research. The present results showed that (1) BLA neurons projecting to the prelimbic cortex (BLA-PrL) and BLA neurons projecting to the nucleus accumbens (BLA-NAc) participated in context-induced retrieval of morphine withdrawal memory; (2) there was an increase in the expression of Arc and pERK in BLA-NAc neurons, but not in BLA-PrL neurons during context-induced retrieval of morphine withdrawal memory; (3) pERK was the upstream molecule of Arc, whereas D1 receptor was the upstream molecule of pERK in BLA-NAc neurons during context-induced retrieval of morphine withdrawal memory; (4) D1 receptors also strengthened AMPA receptors, but not NMDA receptors, -mediated glutamatergic input to BLA-NAc neurons via pERK during context-induced retrieval of morphine withdrawal memory. These results suggest that different projection neurons of the BLA participate in the retrieval of morphine withdrawal memory with diverse molecular pathways.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Morfina , Neurônios , Núcleo Accumbens , Síndrome de Abstinência a Substâncias , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Masculino , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/fisiopatologia , Morfina/farmacologia , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Memória/fisiologia , Receptores de AMPA/metabolismo , Ratos , Dependência de Morfina/metabolismo , Tonsila do Cerebelo/metabolismo , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Vias Neurais/metabolismo , Córtex Pré-Frontal/metabolismo
2.
Crit Rev Immunol ; 44(4): 23-39, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505919

RESUMO

Enhancer of zeste homolog 2 (EZH2)gene has a prognostic role in hepatocellular carcinoma (HCC). This study aimed to identify the role of microRNAs (miRNAs) let-7c-5p by targeting EZH2 in HCC. We downloaded gene and miRNA RNA-seq data from The Cancer Genome Atlas (TCGA) database. Differences in EZH2 expression between different groups were analyzed and the association of EZH2 expression with HCC prognosis was detected using Cox regression analysis. The miRNA-EZH2-pathway network was constructed. Dual-luciferase reporter assay was performed to detect the hsa-let-7c-5p-EZH2. Cell proliferation, migration, invasion, and apoptosis were detected by CCK-8, Wound healing, Transwell, and Flow cytometry, respectively. RT-qPCR and Western blot were used to detect the expression of let-7c-5p and EZH2. EZH2 was upregulated in HCC tumors (P < 0.0001). Cox regression analysis showed that TCGA HCC patients with high EZH2 expression levels showed a short survival time [hazard ratio (HR) = 1.677, 95% confidence interval (CI) 1.316-2.137; P < 0.0001]. Seven miRNAs were negatively correlated with EZH2 expression and were significantly downregulated in HCC tumor samples (P < 0.0001), in which hsa-let-7c-5p was associated with prognosis in HCC (HR = 0.849 95% CI 0.739-0.975; P = 0.021). We identified 14 immune cells that showed significant differences in EZH2 high- and low-expression groups. Additionally, let-7c-5p inhibited HCC cell proliferation, migration, and invasion and reversed the promoted effects of EZH2 on HCC cell malignant characteristics. hsa-let-7c-5p-EZH2 significantly suppressed HCC malignant characteristics, which can be used for HCC prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/farmacologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
3.
Eur Heart J ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953786

RESUMO

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

4.
Biochem Biophys Res Commun ; 720: 150076, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-38772224

RESUMO

Chronic morphine withdrawal memory formation is a complex process influenced by various molecular mechanisms. In this study, we aimed to investigate the contributions of the basolateral amygdala (BLA) and complement component 1, q subcomponent-like 3 (C1QL3), a secreted and presynaptically targeted protein, to the formation of chronic morphine (repeat dosing of morphine) withdrawal memory using conditioned place aversion (CPA) and chemogenetic methods. We conducted experiments involving the inhibition of the BLA during naloxone-induced withdrawal to assess its impact on CPA scores, providing insights into the significance of the BLA in the chronic morphine memory formation process. We also examined changes in C1ql3/C1QL3 expression within the BLA following conditioning. Immunofluorescence analysis revealed the colocalization of C1QL3 and the G protein-coupled receptor, brain-specific angiogenesis inhibitor 3 (BAI3) in the BLA, supporting their involvement in synaptic development. Moreover, we downregulated C1QL3 expression in the BLA to investigate its role in chronic morphine withdrawal memory formation. Our findings revealed that BLA inhibition during naloxone-induced withdrawal led to a significant reduction in CPA scores, confirming the critical role of the BLA in this memory process. Additionally, the upregulation of C1ql3 expression within the BLA postconditioning suggested its participation in withdrawal memory formation. The colocalization of C1QL3 and BAI3 in the BLA further supported their involvement in synaptic development. Furthermore, downregulation of C1QL3 in the BLA effectively hindered chronic morphine withdrawal memory formation, emphasizing its pivotal role in this process. Notably, we identified postsynaptic density protein 95 (PSD95) as a potential downstream effector of C1QL3 during chronic morphine withdrawal memory formation. Blocking PSD95 led to a significant reduction in the CPA score, and it appeared that C1QL3 modulated the ubiquitination-mediated degradation of PSD95, resulting in decreased PSD95 protein levels. This study underscores the importance of the BLA, C1QL3 and PSD95 in chronic morphine withdrawal memory formation. It provides valuable insights into the underlying molecular mechanisms, emphasizing their significance in this intricate process.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Proteína 4 Homóloga a Disks-Large , Memória , Morfina , Síndrome de Abstinência a Substâncias , Animais , Morfina/farmacologia , Síndrome de Abstinência a Substâncias/metabolismo , Masculino , Camundongos , Memória/efeitos dos fármacos , Proteína 4 Homóloga a Disks-Large/metabolismo , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Complemento C1q/metabolismo , Camundongos Endogâmicos C57BL , Naloxona/farmacologia
5.
BMC Med ; 22(1): 86, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413945

RESUMO

BACKGROUND: Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. METHODS: In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. RESULTS: Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (ß = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB. CONCLUSIONS: MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica , Ponte Miocárdica , Humanos , Pessoa de Meia-Idade , Miocárdio/patologia , Meios de Contraste , Estudos Retrospectivos , Estudos de Coortes , Ponte Miocárdica/complicações , Ponte Miocárdica/diagnóstico por imagem , Ponte Miocárdica/patologia , Gadolínio , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/cirurgia , Fibrose , Fatores de Risco
6.
J Transl Med ; 21(1): 589, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660053

RESUMO

BACKGROUND: The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence. METHODS: We analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40-75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD. RESULTS: Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59-0.77) or high to non-high (HR, 0.57; 95% CI 0.41-0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29-0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26-2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84-2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69-3.42) also showed an increased risk of incident ASCVD. CONCLUSIONS: Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Incidência , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Aterosclerose/epidemiologia , Fatores de Risco de Doenças Cardíacas
7.
J Magn Reson Imaging ; 57(5): 1518-1528, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37021578

RESUMO

BACKGROUND: The identification of combined precapillary and postcapillary pulmonary hypertension (CpcPH) in patients with pulmonary hypertension (PH) due to left heart disease (LHD) can influence therapy and outcome and is currently based on invasively determined hemodynamic parameters. PURPOSE: To investigate the diagnostic value of MRI-derived corrected pulmonary transit time (PTTc) in PH-LHD sub-grouped according to hemodynamic phenotypes. STUDY TYPE: Prospective observational study. POPULATION: A total of 60 patients with PH-LHD (18 with isolated postcapillary PH [IpcPH] and 42 with CpcPH), and 33 healthy subjects. FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession cine and gradient echo-train echo planar pulse first-pass perfusion. ASSESSMENT: In patients, right heart catheterization (RHC) and MRI were performed within 30 days. Pulmonary vascular resistance (PVR) was used as the diagnostic "reference standard." The PTTc was calculated as the time interval between the peaks of the biventricular signal-intensity/time curve and corrected for heart rate. PTTc was compared between patient groups and healthy subjects and its relationship to PVR assessed. The diagnostic accuracy of PTTc for distinguishing IpcPH and CpcPH was determined. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, linear and logistic regression analysis, and receiver-operating characteristic curves. Significance level: P < 0.05. RESULTS: PTTc was significantly prolonged in CpcPH compared with IpcPH and normal controls (17.28 ± 7.67 vs. 8.82 ± 2.55 vs. 6.86 ± 2.11 seconds), and in IpcPH compared with normal controls (8.82 ± 2.55 vs. 6.86 ± 2.11 seconds). Prolonged PTTc was significantly associated with increased PVR. Furthermore, PTTc was a significantly independent predictor of CpcPH (odds ratio: 1.395, 95% confidence interval: 1.071-1.816). The area under curve was 0.852 at a cut-off value of 11.61 seconds for PTTc to distinguish between CpcPH and IpcPH (sensitivity 71.43% and specificity 94.12%). DATA CONCLUSION: PTTc may be used to identify CpcPH. Our findings have potential to improve selection for invasive RHC for PH-LHD patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Cardiopatias , Hipertensão Pulmonar , Humanos , Hemodinâmica , Resistência Vascular/fisiologia , Cateterismo Cardíaco , Imageamento por Ressonância Magnética
8.
Nutr Metab Cardiovasc Dis ; 33(6): 1134-1143, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36775706

RESUMO

BACKGROUND AND AIMS: This study aims to investigate the association of Life's Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with long-term outcomes among US adults. METHODS AND RESULTS: This population-based prospective cohort study analyzed data of 23,110 participants aged 20 years or older from the National Health and Nutrition Examination Survey from 2005 to 2014 and their linked mortality data through December 2019. LE8 score (range 0-100) was measured according to AHA definitions and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. The weighted mean age of the study population was 47.0 years (95% confidence interval [CI], 46.4-47.5 years), and 11,840 were female (weighted percentage, 51.5%; 95% CI, 50.9-52.1%). During a median follow-up period of 113 months (up to 180 months), 2942 all-cause deaths occurred, including 738 CVD deaths. The LE8 score was significantly and inversely related to mortality from all causes (adjusted hazard ratio [HR] for per 10-score increase in LE8 score, 0.86; 95% CI, 0.82-0.90) and cardiovascular disease (adjusted HR for per 10-score increase in LE8 score, 0.81; 95% CI, 0.75-0.87). Compared with participants having low CVH, those having high CVH had a reduction of 40% (adjusted HR, 0.60; 95% CI, 0.48-0.75) in the risk for all-cause mortality and 54% (adjusted HR, 0.46; 95% CI, 0.31-0.68) in the risk for cardiovascular mortality. CONCLUSIONS: Higher LE8 score was independently associated with lower risks of all-cause and cardiovascular mortality among US adults.


Assuntos
Doenças Cardiovasculares , Estados Unidos/epidemiologia , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Inquéritos Nutricionais , Fatores de Risco , Estudos Prospectivos , Doenças Cardiovasculares/epidemiologia
9.
J Transl Med ; 20(1): 616, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564799

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with Cardiovascular disease (CVD). We aim to examine the association of Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), with the presence of NAFLD among US adults. METHODS: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2017-2018 and included adults 20 years or older. LE8 score (range 0-100) was measured according to American Heart Association definitions and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. NAFLD was determined by transient elastography measured hepatic steatosis in the absence of other liver diseases and excess alcohol use. Multivariable logistic and restricted cubic spline models were used to assess the associations. RESULTS: Among 3588 participants included (weighted mean age, 48.0 years; 95% confidence interval [CI] 46.4-49.7 years), 1839 were female (weighted percentage, 51.6%; 95% CI 49.0-54.2%) and 1483 were determined to have NAFLD (weighted percentage, 36.5%; 95% CI 33.3-39.7%). The weighted mean LE8 score of the study population was 67.9 (95% CI 66.6-69.2). After the adjustment of potential confounders, higher LE8 scores were associated with reduced odds of NAFLD (odds ratio [OR] for per 10 score increase, 0.67; 95% CI 0.59-0.76) and a nonlinear dose-response relationship was observed. Similar patterns were also identified in the association of health behavior and health factor scores with NAFLD. The inversed association of LE8 score and NAFLD was significantly stronger among younger, Asian, and participants with higher education and income level. CONCLUSIONS: LE8 and its subscales scores were negatively associated with the presence of NAFLD in non-linear fashions. Promoting adherence to optimal CVH levels may be beneficial to reduce the burden of NAFLD as well as CVD.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Hepatopatia Gordurosa não Alcoólica , Estados Unidos/epidemiologia , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Doenças Cardiovasculares/epidemiologia , Fatores de Risco
10.
Eur Radiol ; 32(12): 8131-8139, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35779091

RESUMO

OBJECTIVES: The non-invasive assessment of left ventricular (LV) diastolic dysfunction remains a challenge. The role of first-pass perfusion cardiac magnetic resonance (CMR) parameters in quantitative hemodynamic analyses has been reported. We therefore aimed to validate the diagnostic ability and accuracy of such parameters against cardiac catheterization for LV diastolic dysfunction in patients with left heart disease (LHD). METHODS: We retrospectively enrolled 77 LHD patients who underwent CMR imaging and cardiac catheterization. LV diastolic dysfunction was defined as pulmonary capillary wedge pressure (PCWP) or LV end-diastolic pressure (LVEDP) > 12 mmHg on catheterization. On first-pass perfusion CMR imaging, pulmonary transit time (PTT) was measured as the time for blood to pass from the left ventricle to the right ventricle (RV) through the pulmonary vasculature. Pulmonary transit beat (PTB) was the number of cardiac cycles within the interval, and pulmonary blood volume indexed to body surface area (PBVi) was the product of PTB and RV stroke volume index (RVSVi). RESULTS: Of the 77 LHD patients, 53 (68.83%) were found to have LV diastolic dysfunction, and showed significantly higher PTTc, PTB, and PBVi (p < 0.05) compared with those without. In multivariate analyses, only PTTc and PTB were identified as independent predictors of LV diastolic dysfunction (p < 0.05). With an optimal cutoff of 11.9 s, PTTc yielded the best diagnostic performance for LV diastolic dysfunction (area under the curve = 0.83, p < 0.001). CONCLUSIONS: PTTc may represent a non-invasive quantitative surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients. KEY POINTS: • PTTc yielded the best diagnostic accuracy for diastolic dysfunction, with an optimal cutoff of 11.9 s, and a specificity of 100%. • PTTc and PTB were found to be independent predictors of LV diastolic dysfunction across different multivariate models with high reproducibility. • PTTc is a promising non-invasive surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients.


Assuntos
Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/diagnóstico por imagem , Cateterismo Cardíaco , Espectroscopia de Ressonância Magnética , Biomarcadores , Perfusão , Volume Sistólico
11.
J Magn Reson Imaging ; 52(5): 1441-1448, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32691470

RESUMO

BACKGROUND: Right ventricular (RV) dysfunction is common in patients with amyloid light-chain (AL) amyloidosis. While cardiac MRI is the reference standard tool for RV assessment, there are a number of measures of RV function that can be evaluated and it is yet unknown which of these results in the highest prognostic performance in AL amyloidosis. PURPOSE: To examine the prognostic value of various measures of RV function in a bid to find which best predicts outcome in AL amyloidosis. STUDY TYPE: Single-center, prospective. SUBJECTS: In all, 129 patients (mean age, 58 ± 11 years; 61.2% men) with biopsy-proven AL amyloidosis. FIELD STRENGTH/SEQUENCE: 3.0T / balanced steady-state free-precession cine. ASSESSMENT: RV ejection fraction (EF), RV fractional area change (FAC), RV long axis strain (LAS), RV free wall longitudinal strain (FWS), RV global longitudinal strain (GLS), and tricuspid annular plane systolic excursion (TAPSE). STATISTICAL TESTS: Mann-Whitney U-tests, Student's t-tests, receiver-operating characteristic curves, Kaplan-Meier curves, Cox proportional hazards regression models, and C-statistics. RESULTS: During the median follow-up period of 38.0 months (interquartile range, 18.5-58.0 months), all-cause mortality occurred in 95 patients (73.6%). The RVEF, RVGLS, TAPSE, RVFAC, and RVFWS were significant predictors of outcome in univariate Cox regression (all P < 0.001). After adjusting for New York Heart Association (NYHA) class, Mayo staging 2004, left ventricular (LV) EF, and LV mass index, RVFWS (HR [hazard ratio] =1.074; 95% CI [confidence interval]: 1.041-1.108; P < 0.001) was an independent predictor of all-cause mortality and had a higher C-statistic (0.753) compared to the model including RVEF (C-statistic = 0.724, P = 0.034), the model including RVFAC (C-statistic = 0.723, P = 0.033), and the model including RVGLS (C-statistic =0.733, P = 0.011). DATA CONCLUSION: RV dysfunction appears to be an independent determinant of outcome in patients with AL amyloidosis. RVFWS is a better predictor of all-cause mortality than RVEF, RVFAC, or RVGLS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 5.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Disfunção Ventricular Direita , Idoso , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Volume Sistólico , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita
12.
Phys Chem Chem Phys ; 22(7): 4096-4105, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32031546

RESUMO

LiBH4 is one of the most promising solid electrolyte materials for use in solid-state batteries because its hexagonal phase above 110 °C offers Li-ion conductivity of almost 10-3 S cm-1. However, near room temperature, its orthorhombic phase delivers Li-ion conductivity of only 10-8 S cm-1, which considerably hampers its further applications. In the present study, a highly disordered interface between LiBH4 and two-dimensional MoS2 in the composite material was formed, yielding ionic conductivity of 10-4 S cm-1 at room temperature. LiBH4 and MoS2 are found to be in close contact without the formation of any intermediate phase at the interface. First-principles calculations employing density functional theory (DFT) and the nudged elastic band (NEB) method reveal that the migration energy barrier on three specific pathways could be established via microstructure analyses. It was found that the interface between the two phases yields the lowest Li-ion diffusion barrier among all the possible Li-ion pathways; further, the superior conductivity of the composite could be attributed to the interface with high Li-ion conductivity. This study proposes a new strategy for designing solid electrolytes and provides certain possibilities for two-dimensional materials to serve as superior solid electrolytes.

13.
Molecules ; 25(11)2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32512936

RESUMO

In order to enhance the sensitivity of drug-resistant ovarian cancer cells to cisplatin (DDP), a co-delivery system was designed for simultaneous delivery of curcumin (CUR) and p53 DNA. Firstly, the bifunctional peptide K14 composed of tumor targeting peptide (tLyP-1) and nuclear localization signal (NLS) was synthesized. A nonviral carrier (PEI-K14) was synthesized by cross-linking low molecular weight polyethyleneimine (PEI) with K14. Then, CUR was coupled to PEI-K14 by matrix metalloproteinase 9 (MMP9)-cleavable peptide to prepare CUR-PEI-K14. A co-delivery system, named CUR-PEI-K14/p53, was obtained by CUR-PEI-K14 and p53 self-assembly. Furthermore, the physicochemical properties and gene transfection efficiency were evaluated. Finally, ovarian cancer cisplatin-resistant (SKOV3-DDP) cells were selected to evaluate the effect of CUR-PEI-K14/p53 on enhancing the sensitivity of drug-resistant cells to DDP. The CUR-PEI-K14/DNA complexes appeared uniformly dispersed and spherical. The particle size was around 20-150 nm and the zeta potential was around 18-37 mV. It had good stability, high transfection efficiency, and low cytotoxicity. CUR-PEI-K14/p53 could significantly increase the sensitivity of SKOV3-DDP cells to DDP, and this effect was better as combined with DDP. The sensitizing effect might be related to the upregulation of p53 messenger RNA (mRNA), the downregulation of P-glycoprotein (P-gp) mRNA, and the upregulation of BCL2-Associated X (bax) mRNA. CUR-PEI-K14/p53 can be used as an effective strategy to enhance the sensitivity of drug-resistant ovarian cancer cells to DDP.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Curcumina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas/tratamento farmacológico , Proteína Supressora de Tumor p53/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas
14.
BMC Cancer ; 19(1): 1223, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842793

RESUMO

BACKGROUND: Texture analysis of medical images has been reported to be a reliable method for differential diagnosis of neoplasms. This study was to investigate the performance of textural features and the combined performance of textural features and morphological characteristics in the differential diagnosis of pancreatic serous and mucinous cystadenomas. METHODS: We retrospectively reviewed 59 patients with pancreatic serous cystadenoma and 32 patients with pancreatic mucinous cystadenoma at our hospital. A three-dimensional region of interest (ROI) around the margin of the lesion was drawn manually in the CT images of each patient, and textural parameters were retrieved from the ROI. Textural features were extracted using the LifeX software. The least absolute shrinkage and selection operator (LASSO) method was applied to select the textural features. The differential diagnostic capabilities of morphological features, textural features, and their combination were evaluated using receiver operating characteristic (ROC) analysis, and the area under the receiver operating characteristic curve (AUC) was used as the main indicator. The diagnostic accuracy based on the AUC value is defined as follows: 0.9-1.0, excellent; 0.8-0.9, good; 0.7-0.8, moderate; 0.6-0.7, fair; 0.5-0.6, poor. RESULTS: In the differential diagnosis of pancreatic serous and mucinous cystadenomas, the combination of morphological characteristics and textural features (AUC 0.893, 95% CI 0.816-0.970) is better than morphological characteristics (AUC 0.783, 95% CI 0.665-0.900) or textural features (AUC 0.777, 95% CI 0.673-0.880) alone. CONCLUSIONS: In conclusion, our preliminary results highlighted the potential of CT texture analysis in discriminating pancreatic serous cystadenoma from mucinous cystadenoma. Furthermore, the combination of morphological characteristics and textural features can significantly improve the diagnostic performance, which may provide a reliable method for selecting patients with surgical intervention indications in consideration of the different treatment principles of the two diseases.


Assuntos
Cistadenoma Mucinoso/diagnóstico , Cistadenoma Seroso/diagnóstico , Tomografia Computadorizada Multidetectores , Neoplasias Pancreáticas/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Cistadenoma Mucinoso/diagnóstico por imagem , Cistadenoma Mucinoso/patologia , Cistadenoma Seroso/diagnóstico por imagem , Cistadenoma Seroso/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Adulto Jovem
15.
Anal Chem ; 90(21): 12930-12936, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30274510

RESUMO

Signal amplification for electrochemiluminescence (ECL) has conventionally been achieved by employing effective matrixes that can accelerate the electrochemical redox processes or carry more electrochemiluminophores. Herein, a convenient signal-amplification strategy was proposed for an ECL immunoassay with carboxylated g-C3N4 nanosheets (NSs) as tags and carcinoembryonic antigen (CEA) as the model target via electrochemically pretreating the substrate: a glassy-carbon electrode (GCE) modified with a polymerized 2-aminoterephthalic acid (ATA) film (GCE/ATA). Bioconjugates of g-C3N4 NSs and the signal CEA antibody (Ab2) (i.e., g-C3N4 NS-Ab2) were immobilized on GCE/ATA via a sandwich immunoreaction to form GCE/ATA-Ab1-Ag-Ab2-NSs. Electrochemical-impedance spectroscopy and potential-resolved ECL characterization proved that GCE/ATA plays an important role in the electron-transfer resistance ( Ret) of the GCE/ATA-Ab1-Ag-Ab2-NSs for ECL and that successively scanning GCE/ATA-Ab1-Ag-Ab2-NSs from 0 to -1.6 V in K2S2O8- and H2O2-containing medium could reduce the Ret and bring out 3.3-times-enhanced ECL at the 10th scan cycle compared with that of the 1st scan cycle, which was about 10.2 times the ECL of the GCE/ATA-Ab1-Ag-Ab2-NSs in medium containing merely K2S2O8. Inspired by this, direct and successive scanning of GCE/ATA in K2S2O8- and H2O2-containing medium was employed during fabrication, which dramatically reduced the Ret of GCE/ATA-Ab1-Ag-Ab2-NSs and brought out obviously enhanced ECL responses for selectively determining CEA from 0.1 pg/mL to 1 ng/mL, with a detection limit of 3 fg/mL.


Assuntos
Antígeno Carcinoembrionário/análise , Técnicas Eletroquímicas/métodos , Grafite/química , Imunoensaio/métodos , Medições Luminescentes/métodos , Compostos de Nitrogênio/química , Anticorpos/imunologia , Antígeno Carcinoembrionário/imunologia , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Luminescência , Nanoestruturas/química , Oxirredução , Ácidos Ftálicos/química , Polímeros/química , Compostos de Potássio/química , Sulfatos/química
16.
Nanotechnology ; 29(26): 265705, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29633716

RESUMO

Nano-dispersed Ni particles over mesoporous carbon material CMK-3 (Ni/CMK-3) was fabricated by means of impregnation-reduction strategy using precursor NiCl2 · 6H2O, which is beneficial to improving the de/rehydrogenation performances of MgH2. The dehydrogenation onset temperature of MgH2-Ni/CMK-3 is significantly lowered by 170 K from that of pristine MgH2 (around 603 K). Totally 5.9 wt% of hydrogen absorption capacity is liberated within 1 h at a temperature of 423 K under a pressure of 3 MPa. This composite can absorb 3.9 wt% hydrogen even at a temperature of 328 K under 3 MPa H2. Activation energy values of both dehydrogenation (43.4 kJ mol-1) and rehydrogenation (37.4 kJ mol-1) for MgH2-Ni/CMK-3 are greatly enhanced from those of as-milled MgH2. Ni/CMK-3 also slightly destabilizes the dehydrogenation of MgH2 by 1.5 kJ mol [Formula: see text] The enhanced performances can be attributed to the synergistic effects of both destabilization and activation from nano-dispersed Ni particles.

17.
Nanotechnology ; 29(14): 145703, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29372893

RESUMO

A novel hybrid of Cu nanoparticles/three-dimensional graphene/Ni foam (Cu NPs/3DGr/NiF) was prepared by chemical vapor deposition, followed by a galvanic displacement reaction in Ni- and Cu-ion-containing salt solution through a one-step reaction. The as-prepared Cu NPs/3DGr/NiF hybrid is uniform, stable, recyclable and exhibits an extraordinarily high catalytic efficiency for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with a reduction rate constant K = 0.056 15 s-1, required time ∼30 s and excellent sensing properties for the non-enzymatic amperometric hydrogen peroxide (H2O2) with a linear range ∼50 µM-9.65 mM, response time ∼3 s, detection limit ∼1 µM. The results indicate that the as-prepared Cu NPs/3DGr/NiF hybrid can be used to replace expensive noble metals in catalysis and sensing applications.

18.
Sensors (Basel) ; 18(7)2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30011812

RESUMO

Engineering vehicles intrusion detection is a key problem for the security of power grid operation, which can warn of the regional invasion and prevent external damage from architectural construction. In this paper, we propose an intelligent surveillance method based on the framework of Faster R-CNN for locating and identifying the invading engineering vehicles. In our detection task, the type of the objects is varied and the monitoring scene is large and complex. In order to solve these challenging problems, we modify the network structure of the object detection model by adjusting the position of the ROI pooling layer. The convolutional layer is added to the feature classification part to improve the accuracy of the detection model. We verify that increasing the depth of the feature classification part is effective for detecting engineering vehicles in realistic transmission lines corridors. We also collect plenty of scene images taken from the monitor site and label the objects to create a fine-tuned dataset. We train the modified deep detection model based on the technology of transfer learning and conduct training and test on the newly labeled dataset. Experimental results show that the proposed intelligent surveillance method can detect engineering vehicles with high accuracy and a low false alarm rate, which can be used for the early warning of power grid surveillance.

19.
ChemSusChem ; 17(19): e202400472, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-38705869

RESUMO

Hydrogen peroxide (H2O2) has been considered an energy carrier (fuel) and oxidizer for various chemical synthesis and environmental remediation processes. Biomass valorization can generate high-value-added products in a green and pollution-free way to solve the energy and environmental crisis. The biomass valorization coupled with H2O2 generation via photo-, electro-, and photoelectrocatalysis plays a positive role in sustainable targets, which can maximize energy utilization and realize the production of value-added products and fuel synthesis. Recently, catalyst design and mechanism studies in H2O2 generation coupled with biomass valorization are in the infancy stage. Herein, this review begins with a background on photo-, electro-, and photoelectrocatalytic techniques for H2O2 generation, biomass valorization, and the H2O2 generation couples with biomass valorization. Meanwhile, the progress and reaction mechanism are reviewed. Finally, the prospects and challenges of a synergistic coupled system of H2O2 synthesis and value-added biomass in achieving high conversion, selectivity, and reaction efficiency are envisioned.

20.
ESC Heart Fail ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39417989

RESUMO

AIMS: Chronic low-grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. METHODS AND RESULTS: This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9 years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean = 15.2 ± 8.1%, median = 13.0%, IQR = 9.9%-18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0 pg/mL, 3.1 vs. 3.9 pg/mL, 4.2 vs.4.7 pg/mL, respectively; all P < 0.05). In multivariate models adjusted for age, sex and other clinical features, IL-2, IL-5 and TNF-α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10-2.14; OR: 1.42, 95% CI: 1.02-1.98; OR: 1.33, 95% CI: 1.04-1.70]. After additional adjustment for imaging indicators, IL-2 and TNF-α remained significant (OR: 1.49, 95% CI: 1.06-2.09, P = 0.021; OR:1.35, 95% CI: 1.01-1.80, P = 0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE. CONCLUSIONS: Higher levels of IL-2 and TNF-α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti-inflammatory treatment in the early stages may delay its progression.

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