IntroductionPreventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further.MethodsWe conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022.ResultsSeventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: −3.60,95% CI: −4.45 to −2.74, P < 0.01, I2: 84.7%, P < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, P < 0.01, I2: 82.9%, P < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, P < 0.001, I2: 81.3%, P < 0.001).DiscussionThe results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.

A variety of immune cell subsets occupy different niches in the cardiovascular system, causing changes in the structure and function of the heart and vascular system, and driving the progress of cardiovascular diseases (CVDs). The immune cells infiltrating the injury site are highly diverse and integrate into a broad dynamic immune network that controls the dynamic changes of CVDs. Due to technical limitations, the effects and molecular mechanisms of these dynamic immune networks on CVDs have not been fully revealed. With recent advances in single-cell technologies such as single-cell RNA sequencing, systematic interrogation of the immune cell subsets is feasible and will provide insights into the way we understand the integrative behavior of immune populations. We no longer lightly ignore the role of individual cells, especially certain highly heterogeneous or rare subpopulations. We summarize the phenotypic diversity of immune cell subsets and their significance in three CVDs of atherosclerosis, myocardial ischemia and heart failure. We believe that such a review could enhance our understanding of how immune heterogeneity drives the progression of CVDs, help to elucidate the regulatory roles of immune cell subsets in disease, and thus guide the development of new immunotherapies.

Background: Multiple observational studies have discovered a substantial link between obstructive sleep apnea (OSA) and ventricular dysfunction. However, conventional observational studies are vulnerable to causal reversal and confounding, making it challenging to infer the causes of effects and their direction.Methods: With the help of a bidirectional, two-sample Mendelian randomization (MR) study, we assessed the potential causality between OSA and left and right ventricular (LV, RV) structure and function. We conducted our analysis utilizing summary data from genome-wide association studies of OSA (16,761 cases and 201,194 controls) in the FinnGen Study, as well as LV (36,041 participants) and RV (29,506 participants) in the UK Biobank cardiovascular magnetic resonance research. The inverse variance weighted (IVW) was selected as the main strategy, with the MR-Egger and weighted median methods serving as supplements. Other methods were employed as sensitivity analysis tools to look at heterogeneity and pleiotropy, including MR-Egger intercept, Cochran Q statistic, MR-PRESSO, and leave-one-out analysis.Results: In the primary IVW analysis, genetically predicted OSA was strongly causative on LV end-diastolic volume (β = 0.114, 95% CI = 0.034–0.194, p = 0.006) and LV stroke volume (β = 0.111, 95% CI = 0.031–0.191, p = 0.007), and genetically predicted LV ejection fraction was linked to an increased risk of OSA (OR = 1.161, 95% CI = 1.029–1.309, p = 0.015). However, there was no connection found between OSA and any RV parameters.Conclusion: Our genetic analysis raises a potential causative link between OSA and ventricular structure and function, which may improve the knowledge of OSA as a risk factor for cardiovascular disease by demonstrating a direct impact on cardiac structure and function.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide that bears an enormous healthcare burden and aging is a major contributing factor to CVDs. Functional gene expression network during aging is regulated by mRNAs transcriptionally and by non-coding RNAs epi-transcriptionally. RNA modifications alter the stability and function of both mRNAs and non-coding RNAs and are involved in differentiation, development, and diseases. Here we review major chemical RNA modifications on mRNAs and non-coding RNAs, including N6-adenosine methylation, N1-adenosine methylation, 5-methylcytidine, pseudouridylation, 2'-O-ribose-methylation, and N7-methylguanosine, in the aging process with an emphasis on cardiovascular aging. We also summarize the currently available methods to detect RNA modifications and the bioinformatic tools to study RNA modifications. More importantly, we discussed the specific implication of the RNA modifications on mRNAs and non-coding RNAs in the pathogenesis of aging-associated CVDs, including atherosclerosis, hypertension, coronary heart diseases, congestive heart failure, atrial fibrillation, peripheral artery disease, venous insufficiency, and stroke.

Atherosclerotic cardiovascular diseases (ASCVDs) are the most important diseases that endanger people’s health, leading to high morbidity and mortality worldwide. In addition, various thrombotic events secondary to cardiovascular and cerebrovascular diseases need must be considered seriously. Therefore, the development of novel anti-platelet drugs with high efficiency, and fewer adverse effects has become a research focus for preventing of cardiovascular diseases (CVDs). Blood-activation and stasis-removal from circulation have been widely considered as principles for treating syndromes related to CVDs. Blood-activating Chinese (BAC botanical drugs, as members of traditional Chinese medicine (TCM), have shown to improve hemodynamics and hemorheology, and inhibit thrombosis and atherosclerosis. Modern medical research has identified that a combination of BAC botanical drugs and anti-platelet drugs, such as aspirin or clopidogrel, not only enhances the anti-platelet effects, but also reduces the risk of bleeding and protects the vascular endothelium. The anti-platelet mechanism of Blood-activating Chinese (BAC) botanical drugs and their compounds is not clear; therefore, their potential targets need to be explored. With the continuous development of bioinformatics and “omics” technology, some unconventional applications of BAC botanical drugs have been discovered. In this review, we will focus on the related targets and signaling pathways of anti-atherosclerotic treatments involving a combination of BAC botanical drugs and anti-platelet drugs reported in recent years.

Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, has been used in Chinese traditional medicine for over 3,000 years. BBR has been shown in both traditional and modern medicine to have a wide range of pharmacological actions, including hypoglycemic, hypolipidemic, anti-obesity, hepatoprotective, anti-inflammatory, and antioxidant activities. The unregulated reaction chain induced by oxidative stress as a crucial mechanism result in myocardial damage, which is involved in the pathogenesis and progression of many cardiovascular diseases (CVDs). Numerous researches have established that BBR protects myocardium and may be beneficial in the treatment of CVDs. Given that the pivotal role of oxidative stress in CVDs, the pharmacological effects of BBR in the treatment and/or management of CVDs have strongly attracted the attention of scholars. Therefore, this review sums up the prevention and treatment mechanisms of BBR in CVDs from in vitro, in vivo, and finally to the clinical field trials timely. We summarized the antioxidant stress of BBR in the management of coronary atherosclerosis and myocardial ischemia/reperfusion; it also analyzes the pathogenesis of oxidative stress in arrhythmia and heart failure and the therapeutic effects of BBR. In short, BBR is a hopeful drug candidate for the treatment of CVDs, which can intervene in the process of CVDs from multiple angles and different aspects. Therefore, if we want to apply it to the clinic on a large scale, more comprehensive, intensive, and detailed researches are needed to be carried out to clarify the molecular mechanism and targets of BBR.

Intermittent fasting (IF) has gained attention as a promising diet for weight loss and dysmetabolic diseases management. This systematic review aimed to investigate the effects of IF on cardiometabolic risk factors (CMRFs). A systematic literature search was carried out using three electronic databases, namely PubMed, Embase, and the Cochrane Library, until October 2020. Randomized controlled trials that compared the IF intervention with a control group diet were included. Fourteen effect sizes were expressed as weighted mean difference (WMD) using a fixed-effects model and 95% confidence intervals (CI). Compared to the ones within control groups, participants exposed to the IF intervention reduced their body weight (WMD, −1.78 kg; 95% CI, −2.21 to −1.35; p <0.05), waist circumference (WMD, −1.19 cm; 95% CI, −1.8 to −0.57; p <0.05), fat mass (WMD, −1.26 kg; 95% CI, −1.57 to −0.95; p <0.05), body mass index (WMD, −0.58 kg/m2; 95% CI, −0.8 to −0.37; p <0.05), systolic blood pressure (WMD, −2.14 mmHg; 95% CI: −3.54 to −0.73; p <0.05), diastolic blood pressure (WMD: −1.38 mmHg, 95% CI, −2.35 to −0.41, p <0.05), fasting blood glucose (WMD: −0.053 mmol/L; 95% CI: −0.105 to 0.001; p <0.05), fasting insulin (WMD, −0.8 mIU/L; 95% CI, −1.15 to −0.44; p <0.05), insulin resistance (WMD, −0.21; 95% CI, −0.36 to −0.05; p <0.05), total cholesterol (WMD, −0.10 mmol/L; 95% CI, −0.17 to −0.02; p <0.05), and triglycerides (WMD, −0.09 mmol/L; 95% CI, −0.13 to −0.04; p <0.05). No effects were observed for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or glycosylated hemoglobin. This meta-analysis supports the role of IF in improving the component composition of CMRFs, including weight, waist circumference, fat mass, BMI, blood pressure, total cholesterol, triglycerides, fasting insulin, and insulin resistance, compared to a control group diet. Further research on IF interventions should take into account long-term and well-designed administration to draw definitive conclusions.

Ischemia-reperfusion (I/R) is a pathological process that occurs in many organs and diseases. Reperfusion, recovery of blood flow, and reoxygenation often lead to reperfusion injury. Drug therapy and early reperfusion therapy can reduce tissue injury and cell necrosis caused by ischemia, leading to irreversible I/R injury. Ferroptosis was clearly defined in 2012 as a newly discovered iron-dependent, peroxide-driven, nonapoptotic form of regulated cell death. Ferroptosis is considered the cause of reperfusion injury. This discovery provides new avenues for the recognition and treatment of diseases. Ferroptosis is a key factor that leads to I/R injury and organ failure. Given the important role of ferroptosis in I/R injury, there is considerable interest in the potential role of ferroptosis as a targeted treatment for a wide range of I/R injury-related diseases. Recently, substantial progress has been made in applying ferroptosis to I/R injury in various organs and diseases. The development of ferroptosis regulators is expected to provide new opportunities for the treatment of I/R injury. Herein, we analytically review the pathological mechanism and targeted treatment of ferroptosis in I/R and related diseases from the perspectives of myocardial I/R injury, cerebral I/R injury, and ischemic renal injury.

BACKGROUND:Breast cancer is the most common cancer worldwide. Anthracyclines, alone or in combination with other chemotherapeutic agents, are the most effective chemotherapy agents against breast cancer. However, the dose-dependent cardiotoxicity of anthracyclines is a serious drawback in clinical treatment. Considerable efforts have been made to establish suggestions to avoid anthracycline-induced cardiotoxicity. Crocin extracted from saffron has potential cardioprotective effects against anthracycline-induced cardiotoxicity. The aim of this study was to estimate the cardioprotective effects and safety of saffron total glycoside tablets relative to placebo in patients with breast cancer undergoing anthracycline-based chemotherapy.METHODS:This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A sample of 200 participants (100 per group) with breast cancer will be randomly assigned to receive either saffron total glycoside tablet or placebo (four tablets each time, three times each day) for 6 months. Each participant will be interviewed three times: baseline (visit 1), after 3 months (visit 2), and after 6 months (visit 3). The primary outcome is to confirm if administration of saffron total glycoside tablets reduces the rate of cardiotoxicity relative to that with placebo. Secondary outcomes include new arrhythmic events, and cardiac troponin I and N-terminal pro-B-type natriuretic peptide levels. The quantity, quality, and severity of the adverse events will be carefully documented.DISCUSSION:We look forward to obtaining high-quality evidence that can be used to formulate clinical practice guidelines. Thus, the findings of this study are expected to help fill the current gap in cardiotoxicity prevention drugs.TRIAL REGISTRATION:This trial was published in the Chinese Clinical Trial Registry (No. ChiCTR2000041134, registered on 19th December 2020).

Abstract Background Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission. Methods Two investigators searched the PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), Wanfang, MedRxiv, and ChinaXiv databases for articles published through March 30, 2020. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. The data were extracted independently by two investigators. Results The analysis included 23 studies with 4631 total individuals. The proportions of severe disease, ICU admission, or death among patients with non-elevated TnI (or troponin T [TnT]), and those with elevated TnI (or TnT) were 12.0% and 64.5%, 11.8% and 56.0%, and 8.2% and. 59.3%, respectively. Patients with elevated TnI levels had significantly higher risks of severe disease, ICU admission, and death (RR 5.57, 95% CI 3.04 to 10.22, P < 0.001; RR 6.20, 95% CI 2.52 to 15.29, P < 0.001; RR 5.64, 95% CI 2.69 to 11.83, P < 0.001). Patients with an elevated CK level were at significantly increased risk of severe disease or ICU admission (RR 1.98, 95% CI 1.50 to 2.61, P < 0.001). Patients with elevated CK-MB levels were at a higher risk of developing severe disease or requiring ICU admission (RR 3.24, 95% CI 1.66 to 6.34, P = 0.001). Patients with newly occurring arrhythmias were at higher risk of developing severe disease or requiring ICU admission (RR 13.09, 95% CI 7.00 to 24.47, P < 0.001). An elevated IL-6 level was associated with a higher risk of developing severe disease, requiring ICU admission, or death. Conclusions COVID-19 patients with elevated TnI levels are at significantly higher risk of severe disease, ICU admission, and death. Elevated CK, CK-MB, LDH, and IL-6 levels and emerging arrhythmia are associated with the development of severe disease and need for ICU admission, and the mortality is significantly higher in patients with elevated LDH and IL-6 levels. Graphical abstract

Background: Guidelines have previously suggested that atrial fibrillation (AF) is associated with an increased risk of arrhythmic death in Brugada syndrome (BrS) patients. However, only two articles consisting of 17 AF patients with BrS supported these views. The risk stratification of BrS patients with AF remains controversial. Thus, a meta-analysis is used to estimate the risk stratification of BrS patients with AF. Methods: We searched for relevant studies published from 2000 to December 30, 2018. A total of 1712 patients with BrS from five studies were included: 200 patients (12%) were reported with AF, among whom 37 patients (19%) had arrhythmic events. Results: BrS patients with AF in all studies (OR 1.92, 95% CI:0.91 to 4.04, P = 0.09; Heterogeneity: P = 0.03, I-2 = 61%) and some European studies (OR 1.12, 95% CI: 0.18 to 6.94, P = 0.91; Heterogeneity: P = 0.006, I-2 = 80%) did not display a higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japanese studies (OR 2.32, 95% CI: 1.37 to 3.93, P = 0.002; Heterogeneity: P = 0.40, I-2 = 0%) had a higher risk of arrhythmic events than those without AF. The proportion of BrS patients with AF was greater in Japanese studies than in some European studies (16% vs. 9%, P<0.001). Conclusion: On the whole, BrS patients with AF showed no higher risk of arrhythmic events than those without AF, but BrS patients with AF in Japan had a higher risk of arrhythmic events than those without AF.

Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.

Recently, several studies have demonstrated that heart failure (HF) may increase the risk of incident cancer. However, this association has not been statistically and systematically verified by any comprehensive pooled analyses. We performed a meta-analysis on cancer morbidity and co-mortality of adults with HF in a large sample size to explore the relationship between HF and the risk of developing cancer. From inception to April 2019, we searched PubMed and EMBASE for published relevant articles on patients with HF diagnosed with cancer afterwards, with reported outcomes of morbidity and mortality. Two investigators independently reviewed these included studies. Study data were independently extracted using predefined data extraction forms. Random and fixed-effects models were fit for the study duration. This analysis consisted of 4 cohort studies comprising 5,004,251 participants. The relative risk (RR) for incident cancer was 1.22 (95% confidence interval (CI), 1.13–1.33) indicating that patients with HF may have a higher risk of developing cancer. The pooled RR of co-mortality was 2.03 (95% CI, 1.13–3.65), indicating that HF associated with cancer increases the risk of mortality. In this meta-analysis and systematic review, our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality.

We took an interest in the study by Jones et al. [(1)][1] initiating potentially cardiotoxic chemotherapy and the frequency of transitioning from stage A to more advanced heart failure (HF) stages. This study was conducted in individuals scheduled to undergo chemotherapy with potential

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As a macromolecular complex, the NLRP3 inflammasome is activated to produce downstream factors, including caspase-1, IL-1β, and IL-18, which then promote local inflammatory responses and induce pyroptosis, leading to unfavorable effects. A growing number of studies have examined the relationship between the NLRP3 inflammasome and cardiovascular diseases (CVDs). However, some studies have shown that the NLRP3 inflammasome is not involved in the occurrence of certain diseases. Therefore, identifying the mechanism of action of the NLRP3 inflammasome and its potential involvement in the pathological process of disease progression is of utmost importance. This review discusses the mechanisms of NLRP3 inflammasome activation and the relationship between the inflammasome and CVDs, including coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies, and arrhythmia, as well as CVD-related treatments.

BACKGROUND Ibrutinib is a novel antitumor drug that targets Bruton tyrosine kinase for treatment of chronic lymphocytic leukemia. Atrial fibrillation (AF) occurs in 5%-9% of patients during treatment, but the underlying mechanisms remain unclear. OBJECTIVE The purpose of this study was to develop a mouse model of ibrutinib-induced AF and investigate its proarrhythmic mechanisms. METHODS In C57BI/6 mice in the ibrutinib and control groups, ibrutinib (25 mg/kg/d) or vehicle (hydroxypropy1-beta-cyclodextrin), respectively, was administered orally for 4 weeks. Transesophageal burst stimulation then was used to induced AF. To evaluate the underlying mechanism of AF, cardiac echocardiography was performed. Ca2+ handling and action potentials in atrial myocytes were evaluated. RESULTS Compared with the control group, the ibrutinib group showed (1) a higher incidence and longer duration of AF with transesophageal burst stimulation; (2) increased left atrial mass, as indicated by echocardiography; (3) significant myocardial fibrosis in the left atrium on Masson trichrome staining; (4) Ca2+ handling disorders in atrial myocytes, such as reduced Ca2+ transient amplitude, enhanced spontaneous Ca2+ release, and reduced sarcoplasmic Ca2+ capacity; (5) enhanced delayed after-depolarization in atrial myocytes; and (6) increased CaMKII expression and phosphorylation of RyR2-Ser2814 and PLN-Thr17. CONCLUSION The present study established a mouse model of AF by oral administration of ibrutinib for 4 weeks. The arrhythmogenic mechanisms underlying this model likely are associated with structural remodeling and Ca2+ handling disorders in the atrium.

We have read with interest the paper by Guglin et al. [(1)][1] published recently in the Journal . In this trial, the study suggested that in high-risk patients who were going through an anthracycline-containing treatment, an active prevention can be used early and accurately to reduce the

Background: Xiao Yao San (XYS) is thought to be beneficial for the treatment of hypertension in China. Purpose: A systematic review and meta-analysis was performed to evaluate the efficacy and safety of XYS in hypertension. Study design: A comprehensive literature search was conducted in 7 electronic databases for randomized controlled trials from their inception until January 7, 2019. Methods: Methodological quality was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 17 trials including 1460 hypertensive patients met the selection criteria. Pooled analysis favored XYS plus antihypertensive drugs on blood pressure (BP), Hamilton anxiety scale, self-rating anxiety scale, self-rating depression scale, 9-item patient health questionnaire scale, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, homocysteine, and C-reactive protein. No significant difference between XYS plus antihypertensive drugs and antihypertensive drugs on major cardiovascular and cerebrovascular events was identified. XYS was well tolerated in the treatment of hypertension. Conclusion: XYS adjuvant to antihypertensive drugs maybe beneficial for hypertensive patients in lowering BP, improving depression, regulating blood lipids, and inhibiting inflammation. However, the efficacy and safety of XYS are still uncertain due to methodological shortcomings. More long-term, randomized, double-blinded clinical trials are needed in future studies.

Background: Ischemic stroke (IS) is a leading cause of death and long-term disability worldwide. The NaoShuanTong capsule (NSTC), a traditional Chinese patent medicine, has been extensively used in the treatment of stroke in China. However, the clinical efficacy and safety of this treatment has not been statistically and systematically verified by any comprehensive pooled analysis. We therefore performed a meta-analysis to evaluate the efficacy and safety of NSTC in the treatment of IS. Methods: Randomized controlled trials (RCTs) of NSTC in the treatment of IS conducted before September 2018 were retrieved from five databases, according to specific inclusion and exclusion criteria. Two investigators independently reviewed the included studies and extracted relevant data. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook, and analyzed using Review Manager 5.3 software. Results: Thirteen RCTs comprising a total of 1,360 participants were included in this study. NSTC was shown to significantly improve the overall response rate (OR = 3.04, 95% CI [1.76, 5.26], P < 0.00001), and neurological function (NSTC increased Modified Barthel Index (MD = 8.15, 95% CI [3.79, 12.52], P = 0.0005), Functional Independence Measure (MD = 29.61, 95% CI [10.11, 49.10], P = 0.003) and European Stroke Scale scores (MD = 8.51, 95% CI [7.00, 10.01], P = 0.03). In addition, NSTC significantly increased serum adiponectin level (MD = 0.66, 95% CI [0.23, 1.08], P = 0.002). Moreover, NSTC reduced atherosclerotic plaque area (MD = -2.24, 95% CI [-4.02, -0.46], P = 0.01) and intima-media thickness (MD = -0.09, 95% CI [-0.13, -0.05], P < 0.0001). However, there was no significant difference between NSTC treatment and conventional therapy with respect to Fugl-Meyer Assessment score (MD = 10.59, 95% CI [-1.78, 22.96], P = 0.09) or Crouse score (MD = -0.78, 95% CI [-1.79, -0.22], P = 0.13). Conclusions: The results of this meta-analysis showed that NSTC exhibits efficacy in the treatment of cerebral infarction. NSTC can improve the overall response rate and neurological function, increase blood adiponectin, reduce neurological deficits, and decrease atherosclerotic plaque area.