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Hypertensive and ischemic heart diseases have high morbidity all over the world, and they primarily contribute to heart failure associated with high mortality. Cardiac remodeling, as a basic pathological process in heart diseases, is mainly comprised of cardiac hypertrophy and fibrosis, as well as cell death which occurs especially in the ischemic cardiomyopathy. Myocardial remodeling has been widely investigated by a variety of animal models, including pressure overload, angiotensin II stimulation, and myocardial infarction. Pressure overload can cause compensatory cardiac hypertrophy at the early stage, followed by decompensatory hypertrophy and heart failure at the end. Recently, RNA sequencing and differentially expressed gene (DEG) analyses have been extensively employed to elucidate the molecular mechanisms of cardiac remodeling and related heart failure, which also provide potential targets for high-throughput drug screenings. In this review, we summarize recent advancements in gene expression profiling, related gene functions, and signaling pathways pertinent to myocardial remodeling induced by pressure overload at distinct stages, ischemia-reperfusion, myocardial infarction, and diabetes. We also discuss the effects of sex differences and inflammation on DEGs and their transcriptional regulatory mechanisms in cardiac remodeling. Additionally, we summarize emerging therapeutic agents and strategies aimed at modulating gene expression profiles during myocardial remodeling., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway., Methods: A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis., Results: QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01)., Conclusion: The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Breast cancer is the most common malignancy in women worldwide, and the discovery of new effective breast cancer therapies with lower toxicity is still needed. We screened a series of chalcone derivatives and found that MY11 ((E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(4-piperazinylphenyl) prop-2-en-1-one) had the strongest anti-breast cancer activity. MY11 inhibited the growth of MDA-MB-231 and MCF-7 breast cancer cells by arresting the cell cycle and promoting apoptosis, through regulation of the cell cycle and apoptosis-related proteins. PDTC (Pyrrolidinedithiocarbamate ammonium), a specific inhibitor of the NF-κB pathway, abolished the inhibitory effect of MY11 treatment. NF-κB has been shown to regulate PUMA-dependent apoptosis. Our in vitro studies demonstrated that MY11 promoted breast cancer cell apoptosis by activating the NF-κB/PUMA/mitochondrial apoptosis pathway (including Bcl-2, Bax, and Caspase-9). MY11 also inhibited tumor growth in an orthotopic breast cancer mouse model by inducing apoptosis through the NF-κB signaling pathway, importantly, with minimal toxicity. In addition, MY11 was found by docking analysis to bind to p65, which might enhance the stability of the p65 protein. Taken together, our findings indicate that MY11 exerts a significant anticancer effect in breast cancer and that it may be a potential candidate for the treatment of breast cancer., (© 2022. The Author(s).)

Prevention of premature death in patients with chronic epilepsy remains a major challenge. Multiple pathophysiologic factors have been implicated, with intense investigation of cardiorespiratory mechanisms. Up to four in five patients with chronic epilepsy exhibit cardiovascular comorbidities. These findings led us to propose the concept of an "epileptic heart," defined as "a heart and coronary vasculature damaged by chronic epilepsy as a result of repeated surges in catecholamines and hypoxemia leading to electrical and mechanical dysfunction." Among the most prominent changes documented in the literature are high incidence of myocardial infarction and arrhythmia, altered autonomic tone, diastolic dysfunction, hyperlipidemia, and accelerated atherosclerosis. This suite of pathologic changes prompted us to propose for the first time in this review a syndromic approach for improved clinical detection of the epileptic heart condition. In this review, we discuss the key pathophysiologic mechanisms underlying the candidate criteria along with standard and novel techniques that permit evaluation of each of these factors. Specifically, we present evidence of the utility of standard 12-lead, ambulatory, and multiday patch-based electrocardiograms, along with measures of cardiac electrical instability, including T-wave alternans, heart rate variability to detect altered autonomic tone, echocardiography to detect diastolic dysfunction, and plasma biomarkers for assessing hyperlipidemia and accelerated atherosclerosis. Ultimately, the proposed clinical syndromic approach is intended to improve monitoring and evaluation of cardiac risk in patients with chronic epilepsy to foster improved therapeutic strategies to reduce premature cardiac death., (© 2021 International League Against Epilepsy.)