Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Objective: The present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).Methods: From May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.Results: In the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.Conclusions: mNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.

Cardiovascular diseases (CVDs) present a major social problem worldwide due to their high incidence and mortality rate. Many pathophysiological mechanisms are involved in CVDs, and oxidative stress plays a vital mediating role in most of these mechanisms. The ubiquitin–proteasome system (UPS) is the main machinery responsible for degrading cytosolic proteins in the repair system, which interacts with the mechanisms regulating endoplasmic reticulum homeostasis. Recent evidence also points to the role of UPS dysfunction in the development of CVDs. The UPS has been associated with oxidative stress and regulates reduction–oxidation homeostasis. However, the mechanisms underlying UPS-mediated oxidative stress’s contribution to CVDs are unclear, especially the role of these interactions at different disease stages. This review highlights the recent research progress on the roles of the UPS and oxidative stress, individually and in combination, in CVDs, focusing on the pathophysiology of key CVDs, including atherosclerosis, ischemia–reperfusion injury, cardiomyopathy, and heart failure. This synthesis provides new insight for continued research on the UPS–oxidative stress interaction, in turn suggesting novel targets for the treatment and prevention of CVDs.

Background: To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children’s CHD after thoracotomy. Methods: This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. Results: A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05). Conclusions: The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.

The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction (MI). A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species (ROS) to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype. In this investigation, we fabricated a ROS-sensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration. In mouse and rat models of myocardial infarction, the therapeutic gel was injected into the pericardial cavity, effectively disseminated over the heart surface, forming an in situ epicardial patch. The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium. Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1β antibodies. Moreover, the anti-IL-1β hydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1β and inducing M2-type polarization within the myocardial infarction regions, thereby facilitating therapeutic cardiac repair. Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.

Background: Trimethylamine-N-oxide (TMAO) has been proven to be a new proatherogenic compound for promoting inflammation and endothelial dysfunction. Hepatocyte-derived exosomes (Exos), including those derived from hepatocytes, play a pivotal role in the regulation of inflammation and endothelial function. As TMAO is produced in the liver, hepatocytes may be the potential target of TMAO. However, it is not yet clear whether TMAO can directly stimulate hepatocytes to produce Exos to mediate the detrimental effects of TMAO on vascular endothelial cells (VECs). Methods: Hepatocytes treated with TMAO and Exos (TMAO-Exos) were isolated from the supernatant, and added to human aortic endothelial cells (HAECs). The expressions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were detected by quantitative polymerase chain reaction (qPCR). Cell apoptosis was evaluated using Hoechst 33342 staining and flow cytometry assay, and cell migration was assessed by scratch and transwell assay. C57BL/6 mice were treated with Exos for 24 h and the thoracic aortas were isolated, then the in vitro aortic ring bioassay was conducted to determine the changes of vasodilation. The expressions of cluster of differentiation 81, tumor susceptibility gene 101, nuclear factor-kappa B (NF-κB) p65, and Phospho-NF-κB p65 were detected by western blotting. The micro ribonucleic acid (miRNA) profiles of the Exos were then identified using RNA-sequencing and validated by qPCR. The miRNA-messenger RNA networks were constructed, and the biological functions of the target genes were annotated using bioinformatics methods. Results: TMAO was found to stimulate hepatocytes to release Exos that could be taken up by HAECs, thus inducing inflammation and cell apoptosis, impairing cell migration, and inhibiting endothelium-dependent vasodilation. Additionally, the miRNAs such as miR-302d-3p carried by the TMAO-Exos were quite different to those in the TMAO-free group. A further analysis showed that the potential target genes for these miRNAs, such as mitogen-activated protein kinase 8, caspase 9 and BCL2-like 11, appeared to be involved with inflammation and endothelial function. Finally, we found that NF-κB signaling could be activated by TMAO-Exos. Conclusions: These novel findings provide evidence that TMAO can indirectly talk to VECs by promoting hepatocytes to produce Exos that carry important genetic information.