Alikjer8887

Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk.

To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer.

In this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD.

Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units).ated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7).

This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer.

ClinicalTrials.gov Identifier NCT03206333.

ClinicalTrials.gov Identifier NCT03206333.Wilms tumor is a rare kidney malignancy primarily developed in children. Treatment for Wilms tumor includes surgery, radiotherapy, and chemotherapy. Recent studies have demonstrated that microRNAs (miRNAs) play important roles in regulating Wilms tumor development. In this study, we aimed to elucidate the expression and function of miR-378c in Wilms tumor. https://www.selleckchem.com/products/blasticidin-s-hcl.html Quantitative real-time PCR (qRT-PCR) results showed that miR-378c was downregulated in Wilms tumor tissues and cell lines. Functionally, further CCK-8, would healing, and transwell assays revealed that overexpression of miR-378c impaired Wilms tumor cell growth and metastasis in vitro. In addition, xenograft assay showed that miR-378c overexpression inhibited Wilms tumor development in vivo. Mechanistically, luciferase reporter assay confirmed that miR-378c directly targets CAMKK2 in Wilms tumor. qRT-PCR and western blot assays demonstrated that CAMKK2 was highly expressed in Wilms tumor tissues and cell lines. Rescue experiments were performed to further evaluate the functional relationship between miR-378c and CAMKK2. Overexpression of miR-378c suppressed Wilms tumor cell metastasis via negatively regulating CAMKK2 expression. Consistently, inhibition of miR-378c enhanced Wilms tumor cell malignancy behavior via augmenting CAMKK2 expression, which could be abrogated by CAMKK2 knockdown. In summary, our findings suggest that miR-378c inhibits the development and metastasis of Wilms tumor via negatively regulating CAMKK2 expression, which could be utilized to develop new therapy strategy.

Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human induced pluripotent stem cells (iPSCs) from a family cohort with ASD.

Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modeling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) toy, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.Macroautophagy/autophagy is a conserved catabolic recycling pathway in which cytoplasmic components are sequestered, degraded, and recycled to survive various stress conditions. Autophagy dysregulation has been observed and linked with the development and progression of several pathologies, including cardiovascular diseases, the leading cause of death in the developed world. In this review, we aim to provide a broad understanding of the different molecular factors that govern autophagy regulation and how these mechanisms are involved in the development of specific cardiovascular pathologies, including ischemic and reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiac remodeling, and heart failure.Among several known RNA modifications, N6-methyladenosine (m6A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m6A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m6A methylation are termed methyltransferase or "m6A writers." The family of proteins that recognize this methylation are termed "m6A readers" and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or "m6A erasers." At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m6A methylation dynamics.