Olanzapine-induced decreases of FGF21 in brown adipose tissue via histone modulations drive UCP1-dependent thermogenetic impairment.

Long-term olanzapine treatment has been associated with serious metabolism disorders, such as abnormal body weight gain, hyperglycemia, and dyslipidemia. Recently, accumulated evidence points to a link between the metabolic disorders caused by olanzapine and thermogenetic impairment. Fibroblast growth factor 21 (FGF21), a pleiotropic protein, is a potent stimulator of thermogenesis in brown adipose tissue (BAT).

Enhanced Anti-Brain Metastasis from Non-Small Cell Lung Cancer of Osimertinib and Doxorubicin Co-Delivery Targeted Nanocarrier.

Purpose: Currently, the treatment of brain metastases from non-small cell lung cancer (NSCLC) is rather difficult in the clinic. A combination of small molecule-targeted drug and chemo-drug is a promising therapeutic strategy for the treatment of NSCLC brain metastases. But the efficacy of this combination therapy is not satisfactory due to the blood-brain barrier (BBB).

Targeted drugs for pulmonary arterial hypertension: a network meta-analysis of 32 randomized clinical trials.

Background: Pulmonary arterial hypertension (PAH) is a devastating disease and ultimately leads to right heart failure and premature death. A total of four classical targeted drugs, prostanoids, endothelin receptor antagonists (ERAs), phosphodiesterase 5 inhibitors (PDE-5Is), and soluble guanylate cyclase stimulator (sGCS), have been proved to improve exercise capacity and hemodynamics compared to placebo; however, direct head-to-head comparisons of these drugs are lacking. This network meta-analysis was conducted to comprehensively compare the efficacy of these targeted drugs for PAH.

Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta-analysis of 16 Clinical Trials and 9,185 Patients.

The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation.

Resveratrol ameliorates low shear stress‑induced oxidative stress by suppressing ERK/eNOS‑Thr495 in endothelial cells.

Fluid shear stress has been revealed to differentially regulate endothelial nitric oxide synthase (eNOS) distribution in vessels. eNOS, a key enzyme in controlling nitric oxide (NO) release, has a crucial role in mediating oxidative stress, and resveratrol (RSV)‑mediated eNOS also attenuates oxidative damage and suppresses endothelial dysfunction. To observe the protective effect of RSV on low shear stress (LSS)‑induced oxidative damage and the potential mechanisms involved, a parallel‑plate flow chamber, which imposed a low level of stress of 2 dynes/cm2 to cells, was employed.

Stenting strategy for coronary artery bifurcation with drug-eluting stents: a meta-analysis of nine randomised trials and systematic review.

Aims: The present study sought to compare angiographic and clinical outcomes of a simple strategy versus a complex strategy in patients with coronary bifurcation lesions undergoing drug-eluting stent implantation.

Methods And Results: Medline, the Cochrane Library, and other internet sources were searched for randomised trials comparing simple strategy versus complex strategy for treating patients with bifurcation lesions. Nine eligible randomised trials including 2,569 patients were identified.

MAPK signaling mediates low shear stress-induced oxidative damage in human umbilical vein endothelial cells in vitro.

Objective: Atherosclerotic lesions occur preferentially in the arterial branches, bifurcations and curvatures where shear stress is low. We aimed to study the possible mechanisms involved in low shear stress (LSS)-induced oxidative damage in vascular endothelial cells.

Methods: Human umbilical vein endothelial cells (HUVECs) exposed for 60 min to simulated LSS using a parallel-plate flow chamber were examined for intracellular reactive oxygen species (ROS) and cell apoptosis with chemiluminescence assay and TUNEL staining, respectively.

Rapamycin attenuates endothelial apoptosis induced by low shear stress via mTOR and sestrin1 related redox regulation.

Background: Studies indicate the dramatic reduction of shear stress (SS) within the rapamycin eluting stent (RES) segment of coronary arteries. It remains unclear about the role of rapamycin in endothelialization of stented arteries where SS becomes low. Since mTOR (mammalian target of rapamycin) pathway is involved in the antioxidative sestrins expression, we hypothesized that rapamycin attenuated low SS (LSS) induced endothelial dysfunction through mTOR and sestrin1 associated redox regulation.

Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy.

Cardiac hypertrophy is a maladaptive change in response to pressure overload, and is also an important risk for developing heart failure. Berberine is known to have cardioprotective effects in patients with hypertension and in animal models of cardiac hypertrophy. In the current study, we observed that transverse aortic contraction (TAC) surgery induced a marked increase in heart size, the ratio of heart weight to body weight, cardiomyocyte apoptosis, myocardial fibrosis, and hypertrophic marker brain natriuretic peptide, all of which were effectively suppressed by berberine administration.