The Angiotensin II Receptor Neprilysin Inhibitor LCZ696 Inhibits the NLRP3 Inflammasome By Reducing Mitochondrial Dysfunction in Macrophages and Alleviates Dextran Sulfate Sodium-induced Colitis in a Mouse Model.

The intracellular sensor protein complex known as the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome plays a crucial role in regulating inflammatory diseases by overseeing the production of interleukin (IL)-1β and IL-18. Targeting its abnormal activation with drugs holds significant promise for inflammation treatment. This study highlights LCZ696, an angiotensin receptor-neprilysin inhibitor, as an effective suppressor of NLRP3 inflammasome activation in macrophages stimulated by ATP, nigericin, and monosodium urate.

The leaves of the seasoning plant inhibit the NLRP3 inflammasome and ameliorate dextran sulfate sodium-induced colitis in mice.

The intracellular sensor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome controls caspase-1 activity and the maturation and release of the cytokines interleukin (IL)-1β and IL-18. The NLRP3 inflammasome has attracted the attention of the pharmaceutical industry because it promotes the pathogenesis of many diseases, making it a promising target for drug development. (Lour.

Repositioning of the Angiotensin II Receptor Antagonist Candesartan as an Anti-Inflammatory Agent With NLRP3 Inflammasome Inhibitory Activity.

Aberrant activation of the NLRP3 inflammasome promotes the pathogenesis of many inflammatory diseases. The development of the NLRP3 inflammasome inhibitors from existing drugs for new therapeutic purposes is becoming more important. Candesartan is an angiotensin II receptor antagonist widely used as a blood pressure-lowering drug; however, the inhibitory potential of candesartan on the NLRP3 inflammasome has not yet been investigated.

Corrigendum: A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction.

[This corrects the article DOI: 10.3389/fimmu.2020.

Changes of antithrombotic prescription in atrial fibrillation patients with acute coronary syndrome or percutaneous coronary intervention and the subsequent impact on long-term outcomes: a longitudinal cohort study.

Objectives: The choice of optimal antithrombotic therapy in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. The aim of this longitudinal cohort study is to investigate the prescribing pattern of antithrombotic regimen in different cohorts and its subsequent impact.

Setting And Design: Longitudinal data from the Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry, between January 2016 and August 2018 was screened.

Profiles of Hospitalized Patients with Angiographic Coronary Heart Disease in Taiwan during 2014-2016: Report of a Tertiary Hospital.

Background: The Taiwan Society of Cardiology (TSOC) has established multicenter registries for coronary artery disease (CAD) to investigate clinical characteristics, management and risks for mortality. However, the impacts of newly-emerged evidence-based therapies, including the use of drug-eluting stents (DESs), on patients with CAD in Taiwan remain unclear.

Methods: The Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry is a single-center, prospective, longitudinal registry in Taiwan containing data from 2014-2016.

A Synthetic Small Molecule F240B Decreases NLRP3 Inflammasome Activation by Autophagy Induction.

Conjugated polyenes are a class of widely occurring natural products with various biological functions. We previously identified 4-hydroxy auxarconjugatin B (4-HAB) as anti-inflammatory agent with an IC of ~20 µM. In this study, we synthesized a new anti-inflammatory 4-HAB analogue, F240B, which has an IC of less than 1 µM.

Association of preexisting hypertension with the morality in patients with systolic heart failure in Taiwan: The TSOC-HFrEF registry.

Purpose: To investigate the association of preexisting hypertension at admission with the mortality in patients with systolic heart failure (HF).

Method: We prospectively investigated the association of preexisting hypertension with the mortality among 1351 patients with HF in Taiwan during an average 12 months (range: 8 months-18 months) follow-up period. A multivariate cox regression analysis for the overall cohort and a subgroup analysis by age were performed.

Repositioning of the β-Blocker Carvedilol as a Novel Autophagy Inducer That Inhibits the NLRP3 Inflammasome.

The NLRP3 inflammasome is a multiprotein complex that plays a key role in the innate immune system, and aberrant activation of this complex is involved in the pathogenesis of inflammatory diseases. Carvedilol (CVL) is an α-, β-blocker used to treat high blood pressure and congestive heart failure; however, some benefits beyond decreased blood pressure were observed clinically, suggesting the potential anti-inflammatory activity of CVL. In this report, the inhibitory potential of CVL toward the NLRP3 inflammasome and the possible underlying molecular mechanisms were studied.

JNK/AP-1 activation contributes to tetrandrine resistance in T-cell acute lymphoblastic leukaemia.

T-cell acute lymphoblastic leukaemia (T-ALL) is a challenging malignancy with a high relapse rate attributed to drug resistance. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid extracted from a Chinese herb, is a potential anti-cancer and anti-leukaemic drug. In this study we investigated the mechanisms of TET resistance in T-ALL cells in vitro.

Clinical Characteristics of Patients Less than Forty Years Old with Coronary Artery Disease in Taiwan: A Cross-Sectional Study.

Background: Coronary artery disease (CAD) rarely occurs in young adults. Our objective was to investigate the baseline characteristics and outcomes of young patients with CAD.

Methods: We retrospectively enrolled patients aged < 40 years of age who underwent coronary angiography in a tertiary hospital in Taiwan between 2002 and 2015.

Prognostic impact of restored sinus rhythm in patients with sepsis and new-onset atrial fibrillation.

Background: New-onset atrial fibrillation (NeOAF) is a common type of tachyarrhythmia in critically ill patients and is associated with increased mortality in patients with sepsis. However, the prognostic impact of restored sinus rhythm (SR) in septic patients with NeOAF remains unclear.

Methods: A total of 791 patients with sepsis, who were admitted to a medical intensive care unit from January 2011 to January 2014, were screened.

Gentiana scabra Reduces SR-A Expression and Oxidized-LDL Uptake in Human Macrophages.

Background: Macrophages can imbibe low-density lipoprotein (LDL) through scavenger receptors to become foam cells, which is critical in the initiation and progression of atherosclerosis. Mounting evidence suggests that the anti-inflammatory nature of Chinese herbs have the capacity to halt the complex mechanisms underlying atherosclerosis. This study examined the effects of Chinese herbs on foam cell formation.

Chest Pain with Normal Thallium-201 Myocardial Perfusion Image - Is It Really Normal?

Background: Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI.

The Prognostic Role of QTc Interval in Acute Myocarditis.

Background: Acute myocarditis is an inflammatory disease of the myocardium. Although a fulminant course of the disease is difficult to predict, it may lead to acute heart failure and death. Previous studies have demonstrated that reduced left ventricular systolic function and prolonged QRS duration can predict the fulminant course of acute myocarditis.

Cell response on the biomimetic scaffold of silicon nano- and micro-topography.

Silicon scaffolds were synthesized in a low-pressure furnace via a vapor-liquid-solid (VLS) mechanism. Structural dimensions of silicon scaffolds were tunable in the synthesis to satisfy diverse requirements for cell culture applications. Cylindraceous SiNWs structurally resemble fibrous proteins in connective tissue and the extracellular matrix (ECM), which are main cell adhesion substrata in vivo.

Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone.

Amiodarone, a common and effective antiarrhythmic drug, has been reported to have anti-inflammatory effects such as reducing the activation and movement of neutrophils. However, its effects on human T cells remain unclear. The aim of this study was to elucidate the effects and possible underlying mechanisms of amiodarone on human T cells.

Activation of Krüppel-Like Factor 2 with Ginkgo Biloba Extract Induces eNOS Expression and Increases NO Production in Cultured Human Umbilical Endothelial Cells.

Background: The mechanisms responsible for the effects of Ginkgo biloba extract (GbE) are not fully understood. Krüppel-like factor 2 (KLF2), a zinc transcription factor, has vasculoprotective effects if activated. The present study attempted to explore whether GbE may activate KLF2 and its consequences.

A salicylate-based small molecule HS-Cm exhibits immunomodulatory effects and inhibits dipeptidyl peptidase-IV activity in human T cells.

Activated T cells are key players in chronic inflammatory diseases, including atherosclerosis. Salicylates, like aspirin, display not only anti-inflammatory, anti-thrombotic, anti-atherosclerotic activities, but also immunomodulatory effects in T cells at high dosages. Here, we aimed to identify potent immunomodulators for T cells through cell-based screening from a mini-library of 300 salicylate-based small molecules, and elucidate the mechanisms.

PKCδ signalling regulates SR-A and CD36 expression and foam cell formation.

Aims: The formation of foam cells is crucial in the initiation and progression of atherosclerosis. One of the critical steps in foam cell formation is the uptake of low-density lipoprotein (LDL) by macrophages via scavenger receptors (SRs). This study examined the role of protein kinase C (PKC) isoforms on foam cell formation.

Magnesium lithospermate B mediates anti-inflammation targeting activator protein-1 and nuclear factor-kappa B signaling pathways in human peripheral T lymphocytes.

The activation of T lymphocytes contributes to the inflammatory processes of atherosclerotic diseases. Danshen is a traditional Chinese medicine and has shown therapeutic effects in patients with cardiovascular and cerebrovascular diseases. We investigated the effects of aqueous extract of Danshen (magnesium lithospermate B (MLB)) on phorbol 12-myristate acetate+ionomycin and anti-CD3+anti-CD28 monoclonal antibody-activated T cells.

The effect of substrate topography on hFOB cell behavior and initial cell adhesion evaluated by a cytodetacher.

This study examined human fetal osteoblast (hFOB) cell morphology, adhesion force, and proliferation on a titanium-coated grooved surface. V-shaped grooves with a depth of 2.4 μm (T1) or 4.