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Interleukin‐5 (IL‐5) has been reported to be involved in cardiovascular diseases, such as atherosclerosis and cardiac injury. This study aimed to investigate the effects of IL‐5 on cardiac remodelling. Mice were infused with angiotensin II (Ang II), and the expression and source of cardiac IL‐5 were analysed. The results showed that cardiac IL‐5 expression was time‐ and dose‐dependently decreased after Ang II infusion, and was mainly derived from cardiac macrophages. Additionally, IL‐5‐knockout (IL‐5−/−) mice were used to observe the effects of IL‐5 knockout on Ang II‐induced cardiac remodelling. We found knockout of IL‐5 significantly increased the expression of cardiac hypertrophy markers, elevated myocardial cell cross‐sectional areas and worsened cardiac dysfunction in Ang II‐infused mice. IL‐5 deletion also promoted M2 macrophage differentiation and exacerbated cardiac fibrosis. Furthermore, the effects of IL‐5 deletion on cardiac remodelling was detected after the STAT3 pathway was inhibited by S31‐201. The effects of IL‐5 on cardiac remodelling and M2 macrophage differentiation were reversed by S31‐201. Finally, the effects of IL‐5 on macrophage differentiation and macrophage‐related cardiac hypertrophy and fibrosis were analysed in vitro. IL‐5 knockout significantly increased the Ang II‐induced mRNA expression of cardiac hypertrophy markers in myocardial cells that were co‐cultured with macrophages, and this effect was reversed by S31‐201. Similar trends in the mRNA levels of fibrosis markers were observed when cardiac fibroblasts and macrophages were co‐cultured. In conclusions, IL‐5 deficiency promote the differentiation of M2 macrophages by activating the STAT3 pathway, thereby exacerbating cardiac remodelling in Ang II‐infused mice. IL‐5 may be a potential target for the clinical prevention of cardiac remodelling. [ABSTRACT FROM AUTHOR]

Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset of cardiovascular disease (CVD) but is also the fundamental cause of other ailments. The regulation of cholesterol metabolism in the human is an extremely complex process. Due to the dynamic balance between cholesterol synthesis, intake, efflux and storage, cholesterol metabolism generally remains secure. Disruption of any of these links is likely to have adverse effects on the body. At present, increasing evidence suggests that abnormal cholesterol metabolism is closely related to various systemic diseases. However, the exact mechanism by which cholesterol metabolism contributes to disease pathogenesis remains unclear, and there are still unknown factors. In this review, we outline the metabolic process of cholesterol in the human body, especially reverse cholesterol transport (RCT). Then, we discuss separately the impact of abnormal cholesterol metabolism on common diseases and potential therapeutic targets for each disease, including CVD, tumors, neurological diseases, and immune system diseases. At the end of this review, we focus on the effect of cholesterol metabolism on eye diseases. In short, we hope to provide more new ideas for the pathogenesis and treatment of diseases from the perspective of cholesterol. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation (CA) combined with left atrial appendage closure (LAAC) has emerged as a promising method to relieve symptoms while reducing the incidence of stroke in selected high‐risk patients with atrial fibrillation (AF). Hypothesis: We aimed to investigate the clinical outcomes of combined CA and LAAC in elderly patients. Methods: A total of 316 patients with symptomatic drug‐refractory AF who underwent combined CA and LAAC between January 2016 and December 2020 were retrospectively included. Baseline characteristics, periprocedural complications, and clinical events during follow‐up were recorded and compared between patients aged ≥ 75 years (n = 66) and <75 years (n = 250). Results: Pulmonary vein isolation and satisfactory LAAC were achieved in all patients. No patients experienced death or stroke/transient ischemic stroke periprocedurally. After a median follow‐up of 12.2 (6.7−24.4) months and 11.9 (5.5−23.6) months, the rate of sinus rhythm maintenance was comparable between the two groups (≥75 years: 78.8% vs. <75 years: 80.8%; log‐rank test, p = 0.674). The median follow‐up periods for clinical outcomes were 27.9 (9.3−44.8) months and 25.2 (10.8−45.7) months, respectively. In patients aged ≥ 75 years, one suffered ischemic stroke, and one experienced major bleeding event. In patients aged < 75 years, four had ischemic stroke, and eight had major bleeding events. Two patients aged < 75 years died during follow‐up, while none of the patients aged ≥ 75 years died. Conclusions: Combining CA and LAAC was feasible, safe and effective in elderly patients with AF. [ABSTRACT FROM AUTHOR]

Many terpenoids with isoprene unit(s) demonstrating critical biological activities have been isolated and characterized. In this study, we have developed a robust chem‐stamp strategy for the construction of the key isoprene unit, which consists of two steps: one‐carbon extension of aldehydes to the alkenyl boronates by the boron‐Wittig reaction and the rhodium‐catalyzed reaction of alkenyl boronates with 2,3‐allenols to yield enals. This chem‐stamp could readily be applied repeatedly and separately, enabling the modular concise synthesis of many natural and pharmaceutically active terpenoids, including retinal, β‐carotene, vitamin A, tretinoin, fenretinide, acitretin, ALRT1550, nigerapyrone C, peretinoin, and lycopene. Owing to the diversified availability of the starting materials, aldehydes and 2,3‐allenols, creation of new non‐natural terpenoids has been realized from four dimensions: the number of isoprene units, the side chain, and the two terminal groups. [ABSTRACT FROM AUTHOR]

Background: The Watchman device is the most widely used occluder but is indicated in atrial fibrillation (AF) patients with a maximal left atrial appendage (LAA) orifice diameter between 17 and 31 mm. We aimed to compare the long‐term safety and efficacy of left atrial appendage closure (LAAC) between patients with a small LAA (<17 mm) and those with an indicated LAA (17–31 mm) measured by transesophageal echocardiography (TEE). Methods: A total of 369 AF patients treated with LAAC between March 2015 and February 2019 were included and divided into two groups based on the maximal LAA orifice diameter measured by TEE: small LAA group (n = 22) and indicated LAA group (n = 347). Periprocedural complications and long‐term clinical outcomes were compared. Results: The Watchman device was successfully implanted in all patients. Mean device compression was higher in the small LAA group. Four patients (1.2%) in the indicated LAA group experienced pericardial effusion, and none experienced pericardial effusion in the small LAA group. Device‐related thrombus was detected in one (4.5%) patient in the small LAA group and five (1.4%) in the indicated LAA group (p =.310). After a mean follow‐up period of 4.1 ± 1.6 years, one patient in the small LAA group (4.5%; 1.1/100 person‐years) and four in the indicated LAA group (1.2%; 0.3/100 person‐years) suffered an ischemic stroke (p =.266). Conclusions: The safety and efficacy of LAAC with the Watchman device were comparable between patients with small and indicated LAA orifice diameters measured by TEE. [ABSTRACT FROM AUTHOR]