MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptional regulate gene expression in a variety of cancers. Increasing evidences indicate that miR-30 expression is down-regulated in numerous human cancers including non-small cell lung cancer (NSCLC) which hypothesizes that miR-30 may play an important role in tumorigenesis. The aim of this study was to investigate the target gene of miR-30 and its roles in tumor growth of NSCLC. Luciferase reporter assays were employed to validate regulation of a putative target of miR-30. The effect of miR-30 on endogenous levels of this target were subsequently confirmed via Western blot (WB). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-30 in NSCLC specimens and adjacent non-tumor tissues. MTT assays were conducted to explore the impact of miR-30 overexpression on the proliferation of human NSCLC cells. Both miR-30b and miR-30c (miR-30b/c) were found having target site in same region of Rab18 mRNA. Luciferase assays using a reporter carrying a putative miR-30b/c target site in the coding DNA sequence (CDS) region of Rab18 revealed that miR-30b/c directly targeted Rab18. Overexpression of miR-30b/c led to down-regulation of Rab18 in A549 and H23 cells at protein levels but not mRNA levels. Down-regulation of miR-30b/c and up-regulation of Rab18 protein levels were detected in NSCLC specimens compared with adjacent non-tumor tissues. Overexpression of miR-30b/c suppressed NSCLC cells growth. Knockdown of Rab18 by siRNA significantly inhibited the proliferation of NSCLC cells. We demonstrated that miR-30b/c was down-regulated in NSCLC specimens compared with adjacent non-tumor tissues. miR-30b/c directly targeted and down-regulated Rab18 expression and inhibited NSCLC cells proliferation. These data indicated that miR-30b/c could serve as a tumor suppressor gene involved in NSCLC pathogenesis.

Background: Diabetic cardiomyopathy (DCM) results from pathological changes in cardiac structure and function caused by diabetes. Excessive oxidative stress is an important feature of DCM pathogenesis. MicroRNAs (miRNAs) are key regulators of oxidative stress in the cardiovascular system. In the present study, we screened for the expression of oxidative stress-responsive miRNAs in the development of DCM. Furthermore, we aimed to explore the mechanism and therapeutic potential of miR-92a-2-5p in preventing diabetes-induced myocardial damage. Methods: An experimental type 2 diabetic (T2DM) rat model was induced using a high-fat diet and low-dose streptozotocin (30 mg/kg). Oxidative stress injury in cardiomyocytes was induced by high glucose (33 mmol/L). Oxidative stress-responsive miRNAs were screened by quantitative real-time PCR. Intervention with miR-92a-2-5p was accomplished by tail vein injection of agomiR in vivo or adenovirus transfection in vitro. Results: The expression of miR-92a-2-5p in the heart tissues was significantly decreased in the T2DM group. Decreased miR-92a-2-5p expression was also detected in high glucose-stimulated cardiomyocytes. Overexpression of miR-92a-2-5p attenuated cardiomyocyte oxidative stress injury, as demonstrated by increased glutathione level, and reduced reactive oxygen species accumulation, malondialdehyde and apoptosis levels. MAPK interacting serine/threonine kinase 2 (MKNK2) was verified as a novel target of miR-92a-2-5p. Overexpression of miR-92a-2-5p in cardiomyocytes significantly inhibited MKNK2 expression, leading to decreased phosphorylation of p38-MAPK signaling, which, in turn, ameliorated cardiomyocyte oxidative stress injury. Additionally, diabetes-induced myocardial damage was significantly alleviated by the injection of miR-92a-2-5p agomiR, which manifested as a significant improvement in myocardial remodeling and function. Conclusions: miR-92a-2-5p plays an important role in cardiac oxidative stress, and may serve as a therapeutic target in DCM. Graphical

Background: Dual antiplatelet therapy (DAPT) improves early post-operative graft patency, but the optimal DAPT strategy for the patients after coronary artery bypass grafting (CABG) has not been confirmed. We sought to evaluate the effect of aspirin plus ticagrelor versus aspirin plus clopidogrel on saphenous vein graft (SVG) patency within 1 year after CABG. Methods: Between October 2017 and December 2018, 147 consecutive patients undergoing elective CABG at Changhai Hospital were randomized into two groups: group AT, receiving aspirin 100 mg/d plus ticagrelor 2×90 mg/d; group AC, receiving aspirin 100 mg/d plus clopidogrel 75 mg/d. Both DAPTs should be administered within 24 h when clinical stability was ensured. 64-multislice computed tomography angiography (MSCTA) was used to assess the graft patency at 12 months after CABG.CYP2C19 gene variants were measured to assess the clopidogrel efficacy on graft patency. Results: Among the 147 participants who completed the study, one (0.7%) patient from the AC group died at 5 weeks after surgery due to severe infection. All other patients were treated with DAPT for 12 months and underwent 64-MSCTA according to schedule. There were no significant differences in pre-operative characteristics and intraoperative transit-time flow measurement findings between the two groups. Besides, no significant differences in the incidence of major adverse cardiac events (MACEs) and major bleeding were observed. A 64-MSCTA showed that SVG patency was 91.0% (141 of 155) in the AT group and 89.9% (161 of 179) in the AC group (P=0.751). No significant associations were found between different CYP2C19 genotypes and SVG patency (P>0.05). Conclusions: Either aspirin plus ticagrelor or aspirin plus clopidogrel can maintain a fairly high graft patency rate in the early phase after CABG, regardless of CYP2C19 genotypes.

Background: Calcified aortic valve disease (CAVD) is one of the most common valvular heart diseases in the elderly population. However, no effective medical treatments have been found to interfere with the progression of CAVD, and specific molecular mechanisms of CAVD remain unclear.Materials and Methods: Transcriptome sequencing data of GSE55492 and GSE148219 were downloaded from the European Nucleotide Archive, and the microarray dataset, GSE12644 was acquired from the Gene Expression Omnibus database. Software, including FastQC, HISAT2, samtools, and featureCounts was applied to generate the read count matrix. The “Limma” package in R was utilized to analyze differentially expressed genes (DEGs). Thereafter, weighted gene co-expression network analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the protein-protein interaction (PPI) network were used to identify hub genes associated with CAVD, which were further validated by receiver operating characteristic curve (ROC) analysis using GSE12644. The long non-coding RNA (LncRNA)-mediated regulatory network was established based on the differentially expressed LncRNAs and hub genes, which were detected using quantitative real-time PCR (qRT-PCR) in clinical samples and valve interstitial cells. Moreover, CIBERSORT was used to calculate the expression distribution of immune cell infiltration in CAVD.Results: A total of 126 DEGs were included in the PPI network. PI3K-Akt signaling pathway, ECM-receptor interaction, hematopoietic cell lineage, cell adhesion molecules, and focal adhesion were the most enriched pathways revealed by KEGG. Four LncRNAs, including TRHDE-AS1, LINC00092, LINC01094, and LINC00702 were considered the differentially expressed LncRNA. SPP1, TREM1, GPM6A, CCL19, CR1, NCAM1, CNTN1, TLR8, SDC1, and COL6A6 were the 10 hub genes identified to be associated with CAVD. Moreover, the calcified aortic valve samples had a greater level of Tregs, naïve B cells, and M0 macrophages than the noncalcified ones, whereas CAVD samples had a lower M2 macrophage expression compared to the noncalcified valve tissues.Conclusion: The current study identified SPP1, TREM1, TLR8, SDC1, GPM6A, and CNTN1 as hub genes that could potentially be associated with CAVD. The LINC00702–miR-181b-5p–SPP1 axis might participate in the development of CAVD. Additionally, M2 macrophages, Tregs, naïve B cells, and M0 macrophages might possibly play a role in the initiation of CAVD.

Decellularization is a promising technique to produce natural scaffolds for tissue engineering applications. However, non-crosslinked natural scaffolds disfavor application in cardiovascular surgery due to poor biomechanics and rapid degradation. Herein, we proposed a green strategy to crosslink and functionalize acellular scaffolds via the self-assembly of copper@tea polyphenol nanoparticles (Cu@TP NPs), and the resultant nanocomposite acellular scaffolds were named as Cu@TP-dBPs. The crosslinking degree, biomechanics, denaturation temperature and resistance to enzymatic degradation of Cu@TP-dBPs were comparable to those of glutaraldehyde crosslinked decellularized bovine pericardias (Glut-dBPs). Furthermore, Cu@TP-dBPs were biocompatible and had abilities to inhibit bacterial growth and promote the formation of capillary-like networks. Subcutaneous implantation models demonstrated that Cu@TP-dBPs were free of calcification and allowed for host cell infiltration at Day 21. Cardiac patch graft models confirmed that Cu@TP-dBP patches showed improved ingrowth of functional blood vessels and remodeling of extracellular matrix at Day 60. These results suggested that Cu@TP-dBPs not only had comparable biomechanics and biostability to Glut-dBPs, but also had several advantages over Glut-dBPs in terms of anticalcification, remodeling and integration capabilities. Particularly, they were functional patches possessing antibacterial and proangiogenic activities. These material properties and biological functions made Cu@TP-dBPs a promising functional acellular patch for cardiovascular applications.

Objective: Transcatheter tricuspid valve intervention (TTVI) has emerged as an alternative treatment option for high-risk and inoperable patients with symptomatic tricuspid regurgitation (TR). However, scarce data in hemodynamic profiles were available on TTVI. In this paper, we attempt to report the hemodynamic profiles of LuX-Valve.Methods: 30 patients from July 2020 to July 2021 were enrolled in this study. The patient was diagnosed with severe symptomatic TR. The clinical, invasive hemodynamic, and echocardiographic data were collected.Results: The surgical success rate was 100%. The cardiac index and stroke volume increased sharply from 2.42(2.27, 2.85) and 47.8(43.6, 62.0) to 3.04 ± 0.63 and 57.2 ± 14.7, respectively. With the elimination of TR and the increase of forward blood flow of the tricuspid valve, the extravascular lung water [798.0 (673.0, 1147.0) vs. 850.3 ± 376.1, P < 0.01] increased subsequently. The peak right atrium pressure decreased after Lux-Valve implantation (21.0 ± 6.4 vs. 19.4 ± 6.5, P < 0.05). On the contrary, the nadir right atrium pressure increased [10.0(8.0, 15.0) vs. 12.0(10.0, 17.0), P < 0.01]. Notably, the right atrium pressure difference dropped sharply from 9.0(5.0, 13.0) to 5.0(4.0, 8.0) after Lux-Valve implantation. There was no significant change in the pulmonary artery pressure. The right atrium volume decreased from 128(83, 188) to 91(67, 167) mL at 1 month and 107(66,157) mL at 6 months. With the remolding of the right heart chamber, the tricuspid annulus diameter shrank significantly from 42.5 ± 5.6 to 36.6 ± 6.3 mm at 1 month and 36.0 (33.0, 38.0) at 6 months.Conclusion: Invasive right atrium pressure may act as a potential candidate for TR evaluation and procedural guidance. Elimination of TR by LuX-Valve implantation improves the cardiac output and right atrium pressure and has no significant effect on the pulmonary artery pressure even with the increment of forward blood flow, suggesting the hemodynamic superiority of transcatheter tricuspid valve replacement but needs further study.