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1.
Front Chem ; 10: 867318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433636

RESUMO

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35449449

RESUMO

Klotho is a life extension factor that has the ability to regulate the function of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), whose dysfunction in the nucleus accumbens (NAc) underlies critical aspects of the pathophysiology of major depression. Here, we study the functional relevance of klotho in the pathogenesis of depression. A chronic social defeat stress paradigm, in which mice are categorized as either susceptible or unsusceptible based on their performance in a social interaction test, was used in this study. We found that the expression of klotho was largely decreased in the NAc of susceptible mice compared to control or unsusceptible mice. Genetic knockdown of klotho in the NAc induced behavioral alterations relevant to depression in naive mice, while overexpression of klotho produced an antidepressive effect in normal mice and ameliorated the behavioral responses to stress in susceptible mice. Molecularly, knockdown of klotho in the NAc resulted in selective decreases in total and synaptic GluN2B expression that were identical to those in susceptible mice. Elevation of klotho in the NAc reversed the reductions in GluN2B expressions and altered synaptic transmission and spine density in the NAc of susceptible mice. Furthermore, blockade of GluN2B with a specific antagonist abolished the beneficial effects of klotho elevation in susceptible mice. Collectively, we demonstrated that klotho in the NAc modulates behavioral responses to stress by regulating the function of GluN2B-containing NMDARs. These results reveal a novel role for klotho in the pathogenesis of depression, providing new insights into the molecular basis of major depression.

3.
J Formos Med Assoc ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35410823

RESUMO

The previously published 2017 Taiwan Lipid Guidelines for High Risk Patients becomes the standard guidance of dyslipidemia management for patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. New clinical trials of lipid lowering therapy were published successively after 2017. The study results changed the treatment concept of ASCVD. Therefore, an update focusing on the lipid treatment strategy for patients with ASCVD becomes necessary. In this focused update of the 2017 guideline, the treatment targets of low-density lipoprotein cholesterol (LDL-C) for patients with ASCVD were modified. The algorithm of LDL-C lowering therapy was revised. The recommendations in this focused update were made mainly based on the scientific evidence from recently published clinical trials and endorsed by the major medical societies in Taiwan.

4.
Cancers (Basel) ; 14(3)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35158776

RESUMO

BACKGROUND: Despite a preferred endocrine therapy for women with estrogen and progesterone receptor-positive breast cancer, aromatase inhibitors (AIs) have been reported to increase risks of cardiovascular events. Given that breast cancer patients in Asia are younger at diagnosis, it is urgent to investigate this safety concern. METHODS: Through the Taiwanese National Cohort, we identified breast cancer patients initiating selective estrogen receptor modulators (SERMs) or AIs from 2010 to 2016. Outcomes includes major adverse cardio- and cerebrovascular events (MACCEs). The average follow-up duration was five years. RESULTS: We identified 16,730 breast cancer patients treated with SERMs and 11,728 receiving AIs. The population was older and had more comorbidities in the AI group than in the SERM group. After adjusting for age, cancer stage, cancer therapies, cardiovascular drugs and comorbidities, despite similar risks of MACCEs between AI and SERM users, the risk of HF was significantly higher in patients treated with SERMs after adjusted mortality as a competing risk. When divided by the age of 50 years, despite a similar MACCEs in the younger population, MACCEs remained significantly higher in the older population who received SERMs. CONCLUSIONS: In this Asian cohort, we found that among patients of old age or with advanced cancer stage, the use of SERMs was associated with a higher risk of cardiovascular events than the use of AIs.

5.
Acta Cardiol Sin ; 37(6): 566-573, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34812229

RESUMO

Thrombolytic therapy plays an important role in treating venous thromboembolic events in patients with unstable hemodynamics or compromised limb circulation. Standard catheter-directed thrombolysis requires a lower dosage of thrombolytic agents than systemic thrombolysis, thus lowering the risk of bleeding. Pharmacomechanical catheter- directed thrombolysis further decreases the dose of thrombolytic agents and duration of infusion. Percutaneous mechanical thrombolysis may potentially become an alternative for patients not suitable for thrombolytic agents. With an increasing number of devices and ongoing trials, endovascular therapy is a promising development that may improve both safety and efficacy in treating venous thromboembolic diseases.

6.
Acta Cardiol Sin ; 37(6): 574-579, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34812230

RESUMO

Coronary artery disease (CAD) is one of the leading causes of death in Taiwan. Despite the use of current guideline-recommended therapies for secondary prevention, the residual risk of recurrent cardiovascular events remains high in CAD, warranting the need for new treatment options. Antithrombotic drugs are one of the most important medical therapies for CAD. In this article, we review the unmet needs of the current antithrombotic agents and summarize the results of clinical trials with dual antiplatelet therapy in stable CAD. We also review data from a recent study demonstrating the benefits of a dual pathway inhibition strategy with antiplatelet and anticoagulant therapy, a new option for CAD treatment. Finally, we propose a treatment algorithm for choosing different antithrombotic regimens for CAD based on current scientific evidence and expert opinions.

7.
iScience ; 24(9): 103082, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34585120

RESUMO

The new generation, i.e., second- and third-generation, drug-eluting stents (DESs) remain a risk of in-stent restenosis (ISR). We evaluated the power of a genetic risk score (GRS) model to identify high-risk populations for new generation DES ISR. We enrolled patients with coronary artery disease (CAD) treated with new generations DESs by a single-center cohort study in Taiwan and evaluated their genetic profile. After propensity score matching, there were 343 patients and 153 patients in the derivation and validation cohorts, respectively. Five selected single-nucleotide polymorphisms (SNPs), i.e., SNPs in CAMLG, GALNT2, C11orf84, THOC5, and SAMD11, were included to calculate the GRS for new generation DES ISR. In the derivation and the validation cohorts, patients with a GRS greater than or equal to 3 had significantly higher new generation DES ISR rates. We provide biological information for interventional cardiologists prior to percutaneous coronary intervention by specific five SNP-derived GRS.

8.
J Atheroscler Thromb ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497171

RESUMO

AIM: The safety concern of statins is still a major issue for Asians. The aim of this study is to compare the risk of statin-associated adverse events among potent statins. METHODS: We included patients from the Taiwan National Health Insurance Research Database who had been treated with atorvastatin, rosuvastatin, or pitavastatin and were without diabetes at baseline. They were classified into three groups: usual-dose statin (atorvastatin 10 mg/d or rosuvastatin 5-10 mg/d), high-dose statin (atorvastatin 20-40 mg/d and rosuvastatin 20 mg/d), and pitavastatin (2-4 mg/d). The primary endpoint is a composite of safety events, including hepatitis, myopathy, and new-onset diabetes mellitus (NODM). We matched age, sex, and year of recruitment among the three groups (n=50,935 in each group) and then used the multivariate Cox proportional hazards model to evaluate the relation between the safety endpoint and different statin groups. RESULTS: After a mean follow-up of 3.08±0.83 years, the safety events occurred in 9.84% in the pitavastatin group, 10.88% in the usual-dose statin group, and 10.49% in high-dose statin group. The multivariate Cox proportional hazards model indicated that usual-dose statin and high-dose statin were associated with a higher risk of the composite safety events compared with pitavastatin (adjusted hazard ratio [aHR]: 1.12, 95% confidence interval [CI]: 1.08-1.17 for usual-dose statin and aHR: 1.06, 95% CI: 1.02-1.10 for high-dose statin). The risks of hepatitis requiring hospitalization and NODM were especially lower in pitavastatin group. CONCLUSIONS: Compared with atorvastatin and rosuvastatin, pitavastatin might be associated with a lower risk of safety events in Asians.

9.
ESC Heart Fail ; 8(6): 5149-5158, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34480791

RESUMO

AIMS: In contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and most are free from traditional cardiovascular risk factors. Despite trastuzumab-related major adverse cardiac and cerebrovascular event (MACCE) being reported, its incidence and predictors remain unknown in Taiwan. METHODS AND RESULTS: Through a three-hospital retrospective cohort study, we analysed the incidence of MACCE in 386 breast cancer patients' exposure to trastuzumab from 2010 to 2018. To further reconfirm our findings, in a nationwide study using the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified 13 502 women diagnosed with breast cancer who received chemotherapy from 2010 to 2015 and found 6751 women who received initial treatment with trastuzumab. After 1:1 propensity score matching with trastuzumab non-users, the incidence of MACCE was measured with a median follow-up of 36 months. In the hospital-based study, among 386 patients receiving trastuzumab, the 5-year incidences of MACCE and heart failure (HF) were 5.4 and 2.8%, respectively. In the national cohort, the crude incidences of MACCEs and HF were 4.67 and 3.21%, respectively. After adjustment for age and comorbidities, the hazard ratio of MACCE was 1.485 (95% CI 1.246-1.769). Notably, among the endpoints, only the hazard ratio of HF was significantly higher in patients receiving trastuzumab than in nonusers. In the subgroup analysis, except for patients also using taxanes, those receiving trastuzumab had a higher risk of MACCE than non-users. CONCLUSIONS: From clinical observations in a nationwide cohort, we found an increased risk of MACCE, especially HF, in patients receiving trastuzumab. Given that its cardiotoxicity is independent of traditional cardiovascular risks, our findings highlight critical concerns regarding the cardiac safety of trastuzumab use.


Assuntos
Neoplasias da Mama , Cardiotoxicidade , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Feminino , Humanos , Estudos Retrospectivos , Taiwan/epidemiologia , Trastuzumab/efeitos adversos
10.
Neurobiol Stress ; 15: 100390, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34527794

RESUMO

Emerging evidence has shown that stress responsivity and psychiatric diseases are associated with alterations in N6-methyladenosine (m6A) mRNA epigenetic modifications. Fat mass and obesity-associated protein (FTO) is an m6A demethylase that has been linked to increased body mass and obesity. Here, we show that tricyclic antidepressants (TCAs) with weight-gain side effects, such as imipramine and amitriptyline, directly increased FTO expression and activated its epigenetic function in the ventral tegmental area (VTA). VTA-specific genetic disruption of FTO increased stress vulnerability and abolished the antidepressant activity of TCAs, whereas erasing m6A modification in the VTA by FTO overexpression or cycloleucine led to significant antidepressant activity. Mechanistically, both transcriptome sequencing and quantitative PCR revealed that overexpression of FTO in the VTA decreased the transcription of stress-related neuropeptides, such as cocaine- and amphetamine-regulated transcript peptide and urocortin, in the social defeat model, which was mimicked by imipramine, suggesting an m6A-dependent transcription mechanism of stress-related neuropeptides may underlie the responses to antidepressant. Collectively, our results demonstrate that inhibiting m6A-dependent transcription of stress-related genes may work as a novel antidepressant strategy and highlight a previously unrecognized activator of FTO-dependent epigenetic function that may be used for the treatment of other neurological diseases.

11.
Acta Cardiol Sin ; 37(4): 355-364, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34257485

RESUMO

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.

12.
Eur Cardiol ; 16: e23, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34135993

RESUMO

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.

13.
PLoS One ; 16(5): e0251109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33979377

RESUMO

Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy. The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients with early aspirin interruption and received P2Y12 inhibitor monotherapy. From January 1, 2014 to December 31, 2018, we included 498 ACS patients (age 70.18 ± 12.84 years, 71.3% men) with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The clinical outcomes between those with aspirin treatment ≤ 1 month and > 1 month were compared in 12-month follow up after PCI. Inverse probability of treatment weighting was used to balance the covariates between groups. The mean duration of aspirin treatment was 7.52 ± 8.10 days vs. 98.05 ± 56.70 days in the 2 groups (p<0.001). The primary composite endpoint of all-cause mortality, recurrent ACS or unplanned revascularization and stroke occurred in 12.6% and 14.4% in the 2 groups (adjusted HR 1.19, 95% CI 0.85-1.68). The safety outcome of BARC 3 or 5 bleeding was also similar (adjusted HR 0.69, 95% CI 0.34-1.40) between the 2 groups. In conclusion, patients with ≤ 1 month aspirin treatment had similar clinical outcomes to those with treatment > 1 month. Our results indicated that ≤ 1-month aspirin may be enough in P2Y12 inhibitor monotherapy strategy for ACS patients undergoing PCI.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Terapia Antiplaquetária Dupla/métodos , Duração da Terapia , Feminino , Humanos , Masculino , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Receptores Purinérgicos P2Y12/metabolismo , Taiwan
14.
Eur Cardiol ; 16: e02, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708263

RESUMO

The unique characteristics of patients with acute coronary syndrome in the Asia-Pacific region mean that international guidelines on the use of dual antiplatelet therapy (DAPT) cannot be routinely applied to these populations. Newer generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) have demonstrated improved clinical outcomes compared with clopidogrel. However, low numbers of Asian patients participated in pivotal studies and few regional studies comparing DAPTs have been conducted. This article aims to summarise current evidence on the use of newer generation P2Y12 inhibitors in Asian patients with acute coronary syndrome and provide recommendations to assist clinicians, especially cardiologists, in selecting a DAPT regimen. Guidance is provided on the management of ischaemic and bleeding risks, including duration of therapy, switching strategies and the management of patients with ST-elevation and non-ST-elevation MI or those requiring surgery. In particular, the need for an individualised DAPT regimen and considerations relating to switching, de-escalating, stopping or continuing DAPT beyond 12 months are discussed.

15.
Int Heart J ; 62(2): 246-255, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731521

RESUMO

Whether reduced-dose prasugrel has a better efficacy or safety than standard-dose clopidogrel remains unknown in patients undergoing percutaneous coronary intervention (PCI).A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane Library from database inception to May 1, 2020 was performed to compare the clinical outcomes in patients with acute coronary syndrome or stable coronary artery disease undergoing PCI between those treated with reduced-dose prasugrel and clopidogrel. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effect or random-effect model if significant heterogeneity was observed. The primary efficacy endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke. The primary safety endpoint was all bleeding events.Overall, seven studies with 32,951 patients with PCI were included in the analysis. Reduced-dose prasugrel was associated with a lower risk of MACE than clopidogrel (OR 0.80, 95% CI 0.67-0.97). Except for MI (OR 0.74, 95% CI 0.56-0.98), the secondary efficacy endpoints of CV death, ischemic stroke, all-cause death, and stent thrombosis were similar. For the primary safety endpoint of all bleeding events, there was no significant difference between reduced-dose prasugrel and clopidogrel (OR 1.31, 95% CI 0.87-1.98), but the risk of minor bleeding was significantly higher in reduced-dose prasugrel (OR 1.73, 95% CI 1.25-2.41).In patients undergoing PCI, a lower risk of MACE was found in patients receiving reduced-dose prasugrel than in those with clopidogrel, but a higher risk of minor bleeding events was noted.


Assuntos
Clopidogrel/administração & dosagem , Intervenção Coronária Percutânea , Cuidados Pré-Operatórios/métodos , Relação Dose-Resposta a Droga , Humanos , Estudos Observacionais como Assunto , Inibidores da Agregação Plaquetária/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Acta Cardiol Sin ; 37(1): 1-8, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33488022

RESUMO

Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor for 6-12 months is the current standard treatment for patients after percutaneous coronary intervention (PCI). However, the optimal DAPT duration is still under debate. A novel strategy with P2Y12 inhibitor monotherapy after PCI has been proposed recently. This strategy shortens the duration of DAPT to 1 to 3 months, followed by monotherapy with a P2Y12 inhibitor instead of aspirin. It has been tested in several clinical trials with promising results. In this article, we reviewed the relevant clinical trial data and the scientific rationale of P2Y12 inhibitor monotherapy with laboratory evidence of platelet inhibition. An early aspirin-free strategy with P2Y12 inhibitor monotherapy seems feasible in some of the patients after PCI.

18.
J Formos Med Assoc ; 120(1 Pt 1): 78-82, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32682701

RESUMO

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV may cause coronary plaque instability and lead to acute coronary syndrome (ACS). Management of ACS in patients with COVID-19 needs more consideration of the balance between clinical benefit and transmission risk of virus. This review provides recommendations of management strategies for ACS in patients with suspected or confirmed COVID-19 in Taiwan.


Assuntos
Síndrome Coronariana Aguda , COVID-19 , Transmissão de Doença Infecciosa/prevenção & controle , Infarto do Miocárdio , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cardiologia/métodos , Cardiologia/normas , Comorbidade , Consenso , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapia , Administração dos Cuidados ao Paciente/métodos , Medição de Risco , SARS-CoV-2/isolamento & purificação , Sociedades Médicas/normas , Taiwan
20.
Front Mol Biosci ; 8: 805594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35141279

RESUMO

Atrial fibrillation (AF) is the most common clinical sustained arrhythmia; clinical therapeutic drugs have low atrial selectivity and might cause more severe ventricle arrhythmias while stopping AF. As an anti-AF drug target with high selectivity on the atrial muscle cells, the undetermined crystal structure of Kv1.5 potassium channel impeded further new drug development. Herein, with the simulated 3D structure of Kv1.5 as the drug target, a series of 3-morpholine linked aromatic amino substituted 1H-indoles as novel Kv1.5 channel inhibitors were designed and synthesized based on target-ligand interaction analysis. The synthesis route was practical, starting from commercially available material, and the chemical structures of target compounds were characterized. It was indicated that compounds T16 and T5 (100 µM) exhibited favorable inhibitory activity against the Kv1.5 channel with an inhibition rate of 70.8 and 57.5% using a patch clamp technique. All compounds did not exhibit off-target effects against other drug targets, which denoted some selectivity on the Kv1.5 channel. Interestingly, twelve compounds exhibited favorable vasodilation activity on pre-contracted arterial rings in vitro using KCl or phenylephrine (PE) by a Myograph. The vasodilation rates of compounds T16 and T4 (100 µM) even reached over 90%, which would provide potential lead compounds for both anti-AF and anti-hypertension new drug development.

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