Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions.

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and ß receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

Left atrial dysfunction can independently predict exercise capacity in patients with chronic heart failure who use beta-blockers.

BACKGROUND: Beta-blockers are first-line clinical drugs for the treatment of chronic heart failure (CHF). In the guidelines for cardiac rehabilitation, patients with heart failure who do or do not receive beta-blocker therapy have different reference thresholds for maximal oxygen uptake (VO2max). It has been reported that left atrial (LA) strain can be used to predict VO2max in patients with heart failure, which can be used to assess exercise capacity. However, most existing studies included patients who did not receive beta-blocker therapy, which could have a heterogeneous influence on the conclusions. For the vast majority of CHF patients receiving beta-blockers, the exact relationship between LA strain parameters and exercise capacity is unclear. METHODS: This cross-sectional study enrolled 73 patients with CHF who received beta-blockers. All patients underwent a thorough resting echocardiogram and a cardiopulmonary exercise test to obtain VO2max, which was used to reflect exercise capacity. RESULTS: LA reservoir strain, LA maximum volume index (LAVImax), LA minimum volume index (LAVImin) (P < 0.0001) and LA booster strain (P < 0.01) were all significantly correlated with VO2max, and LA conduit strain was significantly correlated with VO2max (P < 0.05) after adjusting for sex, age, and body mass index. LA reservoir strain, LAVImax, LAVImin (P < 0.001), and LA booster strain (P < 0.05) were significantly correlated with VO2max after adjusting for left ventricular ejection fraction, the ratio of transmitral E velocity to tissue Doppler mitral annulus e' velocity (E/e'), and tricuspid annular plane systolic excursion. LA reservoir strain with a cutoff value of 24.9% had a sensitivity of 74% and specificity of 63% for the identification of patients with VO2max < 16 mL/kg/min. CONCLUSION: Among CHF patients receiving beta-blocker therapy, resting LA strain is linearly correlated with exercise capacity. LA reservoir strain is a robust independent predictor of reduced exercise capacity among all resting echocardiography parameters. CLINICAL TRIAL REGISTRATION: This study is a part of the Baduanjin-Eight-Silken-Movement with Self-efficacy Building for Patients with Chronic Heart Failure (BESMILE-HF) trial NCT03180320 (ClinicalTrials.gov, registration date: 08/06/2017).

Tongguan capsule for treating myocardial ischemia-reperfusion injury: integrating network pharmacology and mechanism study.

CONTEXT: Although Tongguan capsule (TGC) is used in the treatment of coronary atherosclerotic disease, the exact mechanism remains unclear. OBJECTIVE: Network pharmacology and experimental validation were applied to examine the mechanism of TGC for treating myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: The components and candidate targets were searched based on various databases such as TCMSP, TCMID, BATMAN-TCM. The binding ability was determined by molecular docking. The ischemia-reperfusion (I/R) model was constructed by ligating the left anterior descending (LAD) coronary artery. APOE-/- mice were divided into three groups (n = 6): Sham group, I/R group, and TGC group (1 g/kg/d). To further verification, HCAEC cells were subjected to hypoxia-reoxygenation (H/R) to establish in vitro model. RESULTS: The compounds, such as quercetin, luteolin, tanshinone IIA, kaempferol and bifendate, were obtained after screening. The affinity values of the components with GSK-3ß, mTOR, Beclin-1, and LC3 were all <-5 kcal/mol. In vivo, TGC improved LVEF and FS, reducing infarct size. In vitro, Hoechst 33258 staining result showed TGC inhibited apoptosis. Compare with the H/R model, TGC treatment increased the levels of GSK-3ß, LC3, and Beclin1, while decreasing the expression of mTOR and p62 (p < 0.05). DISCUSSION AND CONCLUSION: The findings revealed that TGC exerted a cardioprotective effect by up regulating autophagy-related proteins through the mTOR pathway, which may be a therapeutic option for MIRI. However, there are still some limitations in this research. It is necessary to search more databases to obtain information and further demonstrated through randomized controlled trials for generalization.

PCSK9 Inhibition: From Current Advances to Evolving Future.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

Incremental value of combinatorial contrast echocardiography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography in giant right atrial myxomas.

Although several studies have shown that myocardial contrast echocardiography and 18-FDG PET/CT can differentiate between benign and malignant intracardiac masses, it is rarely used in practice to evaluate myxoma. This case describes the contrast echocardiography and 18-FDG PET/CT findings of a giant myxoma with an atypical location and subclinical symptoms.

Case report: multi-modality imaging of a right ventricular fibroma in a teenager.

Background: Cardiac fibroma is a rare primary benign tumour of the heart. It often causes arrhythmia, endangers the lives of patients, and has a worse prognosis than other benign tumours. We report a 14-year-old female patient with a right ventricular fibroma. Various preoperative imaging examinations showed that the lesion was benign, and postoperative pathology confirmed that the lesions were fibroma. Case summary: A 14-year-old female patient visited her doctor for more than 5 months because of a heart murmur. Echocardiography revealed a slightly hyperechoic mass in the right ventricle, and on myocardial perfusion contrast imaging, the lesion showed equal enhancement. And the lesion also showed enhancement on contrast-enhanced gated cardiac computed tomography (CT). Contrast-enhanced magnetic resonance imaging (MRI) of the heart revealed that the lesion was isointense on T1-weighted image (T1WI), and isointense to slightly hyperintense on T2-weighted image (T2WI). The lesion was significantly homogeneously enhanced on a delayed enhancement scan. A positron emission tomography-CT (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) demonstrated that the mass showed lower levels of 18F-FDG uptake. These features suggested this lesion was a benign lesion. The postoperative pathology suggested the lesion was a right ventricular fibroma. The patient was discharged 14 days after surgery and remains disease-free and asymptomatic 14 months after surgery. Discussion: Cardiac fibromas are histologically benign, but they can cause obstruction and malignant arrhythmia. The gold standard for diagnosing fibroma is pathology. However, in the absence of pathology, it is necessary to use various imaging methods to evaluate the lesions to distinguish between benign and malignant tumours.

Salvia miltiorrhiza Bunge (Danshen) and Bioactive Compound Tanshinone IIA Alleviates Cisplatin-Induced Acute Kidney Injury Through Regulating PXR/NF-κB Signaling.

Objective: The present study aims to provide evidence on the potential protective role of Salvia miltiorrhiza Bunge (Danshen) and its bioactive compound Tanshinone IIA (TanIIA) in AKI and to reveal the specific regulatory function of PXR/NF-κB signaling in AKI-induced renal inflammation. Methods: A network pharmacological analysis was used to study target genes and regulatory networks in the treatment of Salvia miltiorrhiza on AKI. Further experiments with in vivo AKI mouse model and in vitro studies were applied to investigate the renal protective effect of TanIIA in AKI. The mechanisms of TanIIA regulating PXR/NF-κB signaling in renal inflammation were also studied. Results: Network pharmacology had suggested the nuclear receptor family as new therapeutic targets of Salvia miltiorrhiza in AKI treatment. The in vivo studies had demonstrated that TanIIA improved renal function and inflammation by reducing necrosis and promoting the proliferation of tubular epithelial cells. Improved renal arterial perfusion in AKI mice with TanIIA treatment was also recorded by ultrasonography. In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation. Conclusion: Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.

Designer Functional Nanomedicine for Myocardial Repair by Regulating the Inflammatory Microenvironment.

Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous "danger signals", which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. This review discusses the treatment and challenges of myocardial injury and describes the advantages of functional nanoparticles in regulating the myocardial inflammatory microenvironment and overcoming side effects. In addition, the role of inflammatory signals in regulating the repair and remodeling of infarcted hearts is discussed, and specific therapeutic targets are identified to provide new therapeutic ideas for the treatment of myocardial injury.

Machine learning-aided detection of heart failure (LVEF ≤ 49%) by using ballistocardiography and respiratory effort signals.

Purpose: Under the influence of COVID-19 and the in-hospital cost, the in-home detection of cardiovascular disease with smart sensing devices is becoming more popular recently. In the presence of the qualified signals, ballistocardiography (BCG) can not only reflect the cardiac mechanical movements, but also detect the HF in a non-contact manner. However, for the potential HF patients, the additional quality assessment with ECG-aided requires more procedures and brings the inconvenience to their in-home HF diagnosis. To enable the HF detection in many real applications, we proposed a machine learning-aided scheme for the HF detection in this paper, where the BCG signals recorded from the force sensor were employed without the heartbeat location, and the respiratory effort signals separated from force sensors provided more HF features due to the connection between the heart and the lung systems. Finally, the effectiveness of the proposed HF detection scheme was verified in comparative experiments. Methods: First, a piezoelectric sensor was used to record a signal sequences of the two-dimensional vital sign, which includes the BCG and the respiratory effort. Then, the linear and the non-linear features w.r.t. BCG and respiratory effort signals were extracted to serve the HF detection. Finally, the improved HF detection performance was verified through the LOO and the LOSO cross-validation settings with different machine learning classifiers. Results: The proposed machine learning-aided scheme achieved the robust performance in the HF detection by using 4 different classifiers, and yielded an accuracy of 94.97% and 87.00% in the LOO and the LOSO experiments, respectively. In addition, experimental results demonstrated that the designed respiratory and cardiopulmonary features are beneficial to the HF detection (LVEF ≤ 49 % ). Conclusion: This study proposed a machine learning-aided HF diagnostic scheme. Experimental results demonstrated that the proposed scheme can fully exploit the relationship between the heart and the lung systems to potentially improve the in-home HF detection performance by using both the BCG, the respiratory and the cardiopulmonary-related features.

Quercetin as a potential treatment for COVID-19-induced acute kidney injury: Based on network pharmacology and molecular docking study.

Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

Efficacy and safety of the Amplatzer Duct Occluder II for ventricular septal defect closure: a meta-analysis.

BACKGROUND: Transcatheter closure has become an effective and safe method to repair ventricular septal defects (VSDs). However, the devices used for VSD closure in the past frequently led to serious complications, such as complete atrioventricular block. The second­generation device, the Amplatzer Duct Occluder (ADO II), was originally designed to block small­ and medium­sized patent ductus arteriosus. Interestingly, there are some reports of the use of the ADO II to close VSD because of less complications. AIMS: A meta­analysis of the literature was performed to systematically investigate the efficacy and safety of the ADO II for VSD closure. METHODS: The Embase, PubMed, Cochrane, and Web of Science databases were searched for original studies on VSD closure with the ADO II up to March 15, 2020. The random­effects model and summary rate were employed to estimate the success and complications of VSD closure with the ADO II. RESULTS: A total of 13 articles comprising 478 patients with VSD were included. The age of the patients ranged from 0.5 to 55.7 years. The overall estimated device­implantation success rate was 99% (95% CI, 98%-100%). Residual shunts (pooled rate, 4%; 95% CI, 1%-7%) and postoperative aortic valve regurgitation (pooled rate, 0%; 95% CI, 0-1%) were common complications. Only 3 patients developed device embolism. CONCLUSIONS: The ADO II may be a safer and more effective transcatheter closure device for patients with VSD due to its higher success rate and lower complication rate, as compared with other devices.

WITHDRAWN: Application of Echocardiographic Information Technology in the Research of Infective Endocarditis and Its Neurological Complications.

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