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1.
Nat Commun ; 15(1): 3356, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637502

RESUMO

To realize economically feasible electrochemical CO2 conversion, achieving a high partial current density for value-added products is particularly vital. However, acceleration of the hydrogen evolution reaction due to cathode flooding in a high-current-density region makes this challenging. Herein, we find that partially ligand-derived Ag nanoparticles (Ag-NPs) could prevent electrolyte flooding while maintaining catalytic activity for CO2 electroreduction. This results in a high Faradaic efficiency for CO (>90%) and high partial current density (298.39 mA cm‒2), even under harsh stability test conditions (3.4 V). The suppressed splitting/detachment of Ag particles, due to the lipid ligand, enhance the uniform hydrophobicity retention of the Ag-NP electrode at high cathodic overpotentials and prevent flooding and current fluctuations. The mass transfer of gaseous CO2 is maintained in the catalytic region of several hundred nanometers, with the smooth formation of a triple phase boundary, which facilitate the occurrence of CO2RR instead of HER. We analyze catalyst degradation and cathode flooding during CO2 electrolysis through identical-location transmission electron microscopy and operando synchrotron-based X-ray computed tomography. This study develops an efficient strategy for designing active and durable electrocatalysts for CO2 electrolysis.

2.
Sci Rep ; 14(1): 9430, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658595
3.
J Am Heart Assoc ; 13(8): e030895, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38587138

RESUMO

BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Doenças das Valvas Cardíacas , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Adolescente , Doenças das Valvas Cardíacas/epidemiologia
4.
Thromb Haemost ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574757

RESUMO

BACKGROUND: Dyspnoea is frequent during ticagrelor-based dual antiplatelet therapy (DAPT) for acute myocardial infarction (AMI). However, its clinical characteristics or management strategy remains uncertain. METHODS: The study assessed 2,617 AMI patients from the Ticagrelor versus Clopidogrel in Stabilized Patients with AMI (TALOS-AMI) trial. Dyspnoea during 1-month ticagrelor-based DAPT and following DAPT strategies with continued ticagrelor or de-escalation to clopidogrel from 1 to 12 months were evaluated for drug adherence, subsequent dyspnoea, major adverse cardiovascular events (MACE), and bleeding events. RESULTS: Dyspnoea was reported by 538 patients (20.6%) during 1 month of ticagrelor-based DAPT. Adherence to allocated DAPT over the study period was lower in the continued ticagrelor arm than the de-escalation to clopidogrel, particularly among the dyspnoeic population (81.1% vs. 91.5%, p<0.001). Among ticagrelor-treated patients with dyspnoea, those switched to clopidogrel at 1 month had a lower frequency of dyspnoea at 3 months (34.3 vs. 51.7%, p<0.001) and 6 months (25.5% vs. 38.4%, p=0.002) than those continued with ticagrelor. In patients with dyspnoea in their 1-month ticagrelor-based DAPT, de-escalation was not associated with increased MACE (1.3% vs. 3.9%, hazard ratio [HR] 0.31, 95% confidence interval [CI] =0.08-1.11, p=0.07) or clinically relevant bleeding (3.2% vs. 6.2%, HR 0.51, 95% CI 0.22-1.19, p=0.12) at 1 year. CONCLUSIONS: Dyspnoea is a common side effect among ticagrelor-based DAPT in AMI patients. Switching from ticagrelor to clopidogrel after 1 month in AMI patients may provide a reasonable option to alleviate subsequent dyspnoea in ticagrelor-relevant dyspnoeic patients, without increasing the risk of ischaemic events (NCT02018055).

5.
JAMA Cardiol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568686

RESUMO

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

6.
Front Cardiovasc Med ; 11: 1358657, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586173

RESUMO

Background: The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear. Methods: This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization. Results: Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P = 0.001) (interaction P = 0.46). Conclusions: In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men.

7.
World Neurosurg ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583568

RESUMO

OBJECTIVE: We aimed to investigate risk factors for the recurrence of distal anterior cerebral artery (DACA) aneurysms after endovascular treatment (EVT). METHODS: The clinical and radiological outcomes of DACA aneurysms treated with endovascular methods at a single tertiary hospital from September 2008 to December 2021 were retrospectively reviewed. We measured the angle between two distal branches of DACA aneurysms and categorized the angle as follows: 1) Wide-angle (≥ 180 degrees), and 2) Narrow-angle type configuration (< 180 degrees). Univariate and multivariate analyses were performed to demonstrate the relationships between characteristics of DACA aneurysm and recurrence risk. RESULTS: A total of 132 DACA aneurysms were treated in our institution. Among these, 47 DACA aneurysms after EVT were included in this study. Forty patients underwent coil embolization without stent, seven for stent-assisted coil embolization. At the last follow-up (mean 30.2 ± 24.2 months), overall recurrence rate was 23.4% (n=11). Recurrence rate of the wide-angle type (9 of 23, 39.1%) was significantly higher than narrow-angle type (2 of 24, 8.3%) (p=0.041, OR=8.174, 95% confidence interval [CI] 1.094-61.066). Irregular shape of the DACA aneurysm also showed significantly higher recurrence rate (p=0.011, OR=10.663, 95% CI 1.701-66.838) after endovascular treatment. CONCLUSION: The wide-angle between two distal branches of DACA aneurysm and irregular shape might be independent risk factors for the recurrence after endovascular treatment for DACA aneurysms.

8.
J Clin Med ; 13(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38592061

RESUMO

(1) Background: Among Korean research papers there have been studies on the correlation between tuberculosis-hypertension and diabetes and the correlation between dementia-hypertension and diabetes, but there were no analysis data specifically on tuberculosis and dementia. (2) Methods: A total of 2992 tuberculosis patients in the Gyeongbuk region were analyzed through a final analysis of integrated disease and health management system data collected from 2021 to 2022. In this selection, patients with tuberculosis under 50 years of age and 368 people diagnosed with tuberculosis were excluded. (3) Results: From 2021 to 2022, among the 2992 tuberculosis patients in Gyeongsangbuk-do aged 50 or older, 2722 (91.0%) belonged to the general tuberculosis patient group, while 270 (9.0%) belonged to the dementia-tuberculosis patient group. The average age in the dementia-tuberculosis group was 81.4 years, significantly higher than the general group's average of 75.7 years. Within the dementia-tuberculosis patient group, 235 patients (87.0%) had underlying medical conditions in addition to dementia and tuberculosis. The tuberculosis treatment cure rate was 56.3% (1477 patients) in the general group and 38.9% (105 patients) in the dementia-tuberculosis patient group. (4) Conclusions: The cure rate was notably higher in the general group. Similarly, the mortality rate (deaths due to tuberculosis) was significantly higher in the dementia-tuberculosis patient group (7.0%, 19 patients) compared to the normal group (3.0%, 81 patients). The mortality rate in the dementia group was more than twice that of the general group.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38431496

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) is linked to immune-mediated pathogenesis and a pro-inflammatory state, leading to accelerated atherosclerosis. This earlier onset of clinical cardiovascular disease poses significant morbidity and mortality. We sought to identify IHD mortality trends in individuals with IBD in the United States (US). METHODS: Mortality due to ischemic heart diseases (IHD) as the underlying cause of death with the IBD as a contributor of death were queried from death certificates using the CDC database from 1999 to 2020. Yearly crude mortality rates (CMR) were estimated by dividing the death count by the respective population size, reported per 100,000 persons. Mortality rates were adjusted for age using the Direct method and compared by demographic subpopulations. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. RESULTS: Age-adjusted mortality rates (AAMR) decreased from 0.11 in 1999 to 0.07 in 2020, primarily between 1999 and 2018 (APC -4.41, p < 0.001). AAMR was higher among male (AAMR 0.08) and White (AAMR 0.08) populations compared to female populations (AAMR 0.06) and Black (AAMR 0.04) populations, respectively. No significant differences were seen when comparing mortality between urban (AAMR 0.07) and rural (AAMR 0.08) regions. Southern US regions (AAMR 0.06) had the lowest mortality rates when compared to the other US census regions: Northeastern (AAMR 0.08), Midwestern (AAMR 0.08), and Western (AAMR 0.08). CONCLUSION: Disparities in IHD mortality exist among individuals with IBD in the US based on demographic factors, with an overall decline in mortality during the 22-year period. Further investigation is warranted to confirm these findings and evaluate for contributors to the observed disparities.

10.
Cardiorenal Med ; 14(1): 178-190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38471483

RESUMO

INTRODUCTION: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). METHODS: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. RESULTS: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. CONCLUSION: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.


Assuntos
Injúria Renal Aguda , Inibidores da Enzima Conversora de Angiotensina , Infarto do Miocárdio , Intervenção Coronária Percutânea , Sistema Renina-Angiotensina , Humanos , Injúria Renal Aguda/etiologia , Masculino , Feminino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , República da Coreia/epidemiologia , Sistema de Registros , Antagonistas de Receptores de Angiotensina/uso terapêutico , Creatinina/sangue , Resultado do Tratamento
11.
Sci Rep ; 14(1): 5568, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448443

RESUMO

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Hiperglicemia , Humanos , Feminino , Diabetes Mellitus Tipo 2/complicações , Controle Glicêmico , Hiperglicemia/complicações
12.
BMC Womens Health ; 24(1): 187, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509531

RESUMO

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.


Assuntos
Neoplasias da Mama , Calcinose , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Terapia Neoadjuvante/efeitos adversos , Prognóstico , Mama/patologia , Calcinose/diagnóstico por imagem , Calcinose/tratamento farmacológico , Calcinose/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Estudos Retrospectivos
13.
Clin Mol Hepatol ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38468561

RESUMO

Background: Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. Methods: This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. Results: This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; p=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; p<0.001). Despite the superior progression-free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, p=0.001), the overall survival (OS, 10.3 vs. 7.5 months, p=0.353) did not differ between the two PS-matched treatment groups. Conclusion: In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.

14.
EMBO Rep ; 25(3): 1233-1255, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413732

RESUMO

Accumulation of amyloid-beta (Aß) can lead to the formation of aggregates that contribute to neurodegeneration in Alzheimer's disease (AD). Despite globally reduced neural activity during AD onset, recent studies have suggested that Aß induces hyperexcitability and seizure-like activity during the early stages of the disease that ultimately exacerbate cognitive decline. However, the underlying mechanism is unknown. Here, we reveal an Aß-induced elevation of postsynaptic density protein 95 (PSD-95) in cultured neurons in vitro and in an in vivo AD model using APP/PS1 mice at 8 weeks of age. Elevation of PSD-95 occurs as a result of reduced ubiquitination caused by Akt-dependent phosphorylation of E3 ubiquitin ligase murine-double-minute 2 (Mdm2). The elevation of PSD-95 is consistent with the facilitation of excitatory synapses and the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induced by Aß. Inhibition of PSD-95 corrects these Aß-induced synaptic defects and reduces seizure activity in APP/PS1 mice. Our results demonstrate a mechanism underlying elevated seizure activity during early-stage Aß pathology and suggest that PSD-95 could be an early biomarker and novel therapeutic target for AD.


Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Animais , Camundongos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Modelos Animais de Doenças , Camundongos Transgênicos , Densidade Pós-Sináptica/metabolismo , Densidade Pós-Sináptica/patologia , Receptores de AMPA/metabolismo , Convulsões
15.
EMBO Mol Med ; 16(3): 506-522, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374465

RESUMO

Fragile X syndrome (FXS) is the leading cause of inherited autism and intellectual disabilities. Aberrant protein synthesis due to the loss of fragile X messenger ribonucleoprotein (FMRP) is the major defect in FXS, leading to a plethora of cellular and behavioral abnormalities. However, no treatments are available to date. In this study, we found that activation of metabotropic glutamate receptor 7 (mGluR7) using a positive allosteric modulator named AMN082 represses protein synthesis through ERK1/2 and eIF4E signaling in an FMRP-independent manner. We further demonstrated that treatment of AMN082 leads to a reduction in neuronal excitability, which in turn ameliorates audiogenic seizure susceptibility in Fmr1 KO mice, the FXS mouse model. When evaluating the animals' behavior, we showed that treatment of AMN082 reduces repetitive behavior and improves learning and memory in Fmr1 KO mice. This study uncovers novel functions of mGluR7 and AMN082 and suggests the activation of mGluR7 as a potential therapeutic approach for treating FXS.


Assuntos
Compostos Benzidrílicos , Síndrome do Cromossomo X Frágil , Receptores de Glutamato Metabotrópico , Camundongos , Animais , Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Síndrome do Cromossomo X Frágil/tratamento farmacológico , Síndrome do Cromossomo X Frágil/genética , Receptores de Glutamato Metabotrópico/metabolismo , Modelos Animais de Doenças , Camundongos Knockout
16.
Cancers (Basel) ; 16(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38398102

RESUMO

(1) Background: Accurate statistics on the causes of death in patients with chronic hepatitis B (CHB) are lacking. We investigated mortality rates and causes of death over time. (2) Methods: Data on patients newly diagnosed with CHB from 2007 to 2010 (cohort 1, n = 223,424) and 2012 to 2015 (cohort 2, n = 177,966) were retrieved from the Korean National Health Insurance Service. Mortality data were obtained from Statistics Korea. The causes of death were classified as liver-related (hepatic decompensation or hepatocellular carcinoma [HCC]) or extrahepatic (cardiovascular-related, cerebrovascular-related, or extrahepatic malignancy-related). (3) Results: Over a 10-year follow-up period of 223,424 patients (cohort 1) with CHB, the overall mortality was 1.54 per 100 person-years. The mortality associated with HCC was the highest (0.65 per 100 person-years), followed by mortality related to extrahepatic malignancies (0.26 per 100 person-years), and cardio/cerebrovascular diseases (0.18 per 100 person-years). In the non-cirrhotic CHB (87.4%), 70% (11,198/15,996) of patients died due to non-liver-related causes over ten years. The 10-year overall mortality was 0.86 per 100 person-years. Among these, mortality due to extrahepatic malignancies had the highest rate (0.23 per 100 person-years), followed by mortality related to HCC (0.20 per 100 person-years), and cardio/cerebrovascular diseases (0.16 per 100 person-years). The 5-year mortality associated with extrahepatic malignancies increased from 0.36 per 100 person-years (cohort 1) to 0.40 per 100 person-years (cohort 2). (4) Conclusions: Mortality related to HCC decreased, whereas mortality related to extrahepatic malignancies increased in the antiviral era. Extrahepatic malignancies were the leading cause of death among patients with CHB without cirrhosis.

19.
J Nutr Biochem ; 124: 109506, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37890708

RESUMO

There are few studies on the connection between food components and circular RNA (circRNA), a type of noncoding RNA that is significant for living organisms. (-)-Epigallocatechin-3-O-gallate (EGCG) has been reported to have various biological effects, and elucidation of the molecular mechanism is important for clarifying the functionality of EGCG. In the current study, we looked at how EGCG regulates the expression of circRNA in the liver, which expresses a lot of circRNAs. Mice were given EGCG (10 mg/kg b.w.) orally for one week before circRNA microarray testing was done on their livers. The microarray analysis revealed that mice treated with EGCG had altered expression of 35 circRNAs in their livers. To clarify the function of mmu_circRNA_011775, one of the circRNAs upregulated by EGCG, mouse liver cells after the mmu_circRNA_011775 expression vector was transfected into NMuLi cells, next-generation sequencing (NGS) was used to analyze the gene expression. NGS analysis shows that the expression of the genes responsible for liver fibrosis and inflammation. Gene ontology (GO) analysis showed that mmu_circRNA_011775 changed the meaning of GO terms associated with the cardiovascular system. In the microarray, EGCG altered 35 genes expression. Among them, pre-ribosomal RNA-derived circRNA mmu_circRNA_011775 regulated the expression of various genes related to liver fibrosis and cardiovascular system.


Assuntos
Catequina/análogos & derivados , MicroRNAs , RNA Circular , Animais , Camundongos , RNA Circular/genética , RNA Circular/metabolismo , RNA/genética , RNA/metabolismo , MicroRNAs/genética , Cirrose Hepática , Perfilação da Expressão Gênica
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