Effects of artesunate on the malignant biological behaviors of non-small cell lung cancer in human and its mechanism.

We aimed to assess the effects of artesunate (ART) on the proliferation, migration, invasion and apoptosis of the non-small cell lung cancer cells A549 and H1299. The effects of ART and carboplatin (CBP) alone or in combination on the viability of A549 and H1299 cells were evaluated by MTT assay. The effects of 30 µg/ml ART on cell invasion, migration and apoptosis were evaluated by Transwell assay, scratch assay and flow cytometry, respectively. The protein expressions of human antigen R (HuR) and MMP-9 after treatment with 30 µg/ml ART for 48 h were detected by Western blotting. After 48 h of treatment, 9 µg/ml ART in combination with 7 µg/ml CBP exerted a mild synergistic effect on cell viability. The migration rates of cells treated with 30 µg/ml ART and number of invasive cells were significantly lower, and the apoptosis rates were higher than those of the DMSO-treated group. HuR and MMP-9 expressions in cells treated with 30 µg/ml ART for 48 h were significantly lower than those of the DMSO-treated group. ART suppresses the proliferation, migration and invasion of A549 and H1299 cells and induces their apoptosis, probably being associated with decreased expressions of HuR and MMP-9 proteins.

Gut microbes enlarged the protective effect of transplanted regulatory B cells on rejection of cardiac allografts.

BACKGROUND: Regulatory B cells (Bregs) play an important role in maintaining immune homeostasis and have the potential to induce tolerance. Previous work has found that Breg cells are involved in heart transplantation tolerance. However, the effect of Breg on the transplantation tolerance and the underlying mechanisms remain to be clarified. METHODS: Using a within-species heart transplantation model, we aimed to investigate the role of CD19+CD5+CD1dhigh Bregs isolated from transplanted mice in preventing transplant rejection in vivo. We also explored the effects of CD40 and tumor necrosis factor receptor-associated factor 6 (TRAF6) ubiquitin ligase on Breg-mediated prolongation of survival in heart transplant (HT) mice, and the regulatory effects of downstream Cdk4 and Cdk6 proteins on dendritic cells (DCs), which clarified the function and molecular mechanism of Breg cells in HT mice. RESULTS: Our data suggest that adoptive transfer of the transplanted Bregs served as an effective tolerance-inducing mechanism in HT mice and was involved in the CD40-TRAF6 signaling pathway in DCs. Moreover, DCs collected from the Breg treated HT mice also prolonged the survival of HT mice. Furthermore, DC-specific knockout of TRAF6 diminished Breg-mediated prolongation of survival in HT mice. Interestingly, gut microbes from donors increased the survival of cardiac allografts both in both the absence and presence of Bregs but were not implicated in CD40-TRAF6 signaling. CONCLUSIONS: These findings reveal a role of Breg cells in the induction of transplantation tolerance through the blockade of the CD40-TRAF6 signaling pathway, which might be used in the treatment of HT in the clinic.

Large mural thrombus in the non-aneurysmal and non-atherosclerotic ascending aorta: a case report.

BACKGROUND: The mural thrombus in the ascending aorta is rare, most of which are associated with aneurysm or atherosclerotic lesions, with high risks of causing catastrophic thrombotic events. A mural thrombus in the non-aneurysmal and non-atherosclerotic ascending aorta is exceptionally uncommon. CASE PRESENTATION: We reported a large mural thrombus in normal ascending aorta of an asymptomatic patient. Preoperative imaging confirmed the presence of the sessile thrombus located at the left anterior wall of ascending aorta. Given that it had the potential to cause fatal thrombotic complications, surgical removal and segment of ascending aorta replacement were executed. The patient had an uneventful recovery and discharged 14 days after surgery. CONCLUSIONS: Anticoagulant is the therapeutic cornerstone of ascending aortic thrombus, but surgery should be performed aggressively when the thrombus is large or floating to avoid severe embolic complications or recurrence.

Identification of key genes in calcific aortic valve disease by integrated bioinformatics analysis.

Calcific aortic valve disease (CAVD) is highly prevalent in our aging world and has no effective pharmaceutical treatment. Intense efforts have been made but the underlying molecular mechanisms of CAVD are still unclear.This study was designed to identify the critical genes and pathways in CAVD by bioinformatics analysis. Microarray datasets of GSE12644, GSE51472, and GSE83453 were obtained from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified and functional and pathway enrichment analysis was performed. Subsequently, the protein-protein interaction network (PPI) was constructed with Search Tool for the Retrieval of Interacting Genes and was visualized with Cytoscape to identify the most significant module. Hub genes were identified by Cytoscape plugin cytoHubba.A total of 179 DEGs, including 101 upregulated genes and 78 downregulated genes, were identified. The enriched functions and pathways of the DEGs include inflammatory and immune response, chemotaxis, extracellular matrix (ECM) organization, complement and coagulation cascades, ECM receptor interaction, and focal adhesion. The most significant module in the PPI network was analyzed and genes among it were mainly enriched in chemotaxis, locomotory behavior, immune response, chemokine signaling pathway, and extracellular space. In addition, DEGs, with degrees ≥ 10 and the top 10 highest Maximal Chique Centrality (MCC) score, were identified as hub genes. CCR1, MMP9, VCAM1, and ITGAX, which were of the highest degree or MCC score, were manually reviewed.The DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the pathogenesis of CAVD and might serve as candidate therapeutic targets for CAVD.

Giant right coronary artery aneurysm mimicking a right intra-ventricular mass: a case report.

BACKGROUND: Coronary artery aneurysm is a rare condition which constitutes a small proportion of coronary artery disease. Such condition mimicking an intra-cardiac mass is extremely rare and poorly understood. CASE PRESENTATION: We present an unusual case of a 53-year-old female with decreased exercise tolerance and lower extremity edema for 3 months. The echocardiography showed moderate tricuspid regurgitation and a right intra-ventricular mass below the tricuspid valve. No ventricular wall akinesia or ST segment change was found on echocardiography or electrocardiogram. Coronary computed tomographic angiography confirmed the diagnosis of intra-ventricular mass with feeding vessel originated from the right coronary artery. The patient was scheduled for tumor resection, and the mass turned out to be a thrombosed giant right coronary artery aneurysm. The patient received successful aneurysm resection and had an uneventful postoperative recovery. Unfortunately, a fistula between right coronary artery and right ventricle was detected on follow-up three months later by echocardiography. CONCLUSIONS: Coronary artery aneurysms presenting as intra-cardiac masses are extremely rare. Comprehensive preoperative evaluation is highly recommended because the surgical strategies for tumor and aneurysm are completely different. Aneurysm resection with bypass surgery is preferred rather than aneurysm repair. To our best knowledge, coronary artery aneurysms presenting as intra-ventricular masses have seldom been reported.

Effects of ANCR lncRNA on the biological behaviors of lung cancer cells A549 and the mechanism.

BACKGROUND: ANCR lncRNA has been reported to participate in many cancers, but its role in lung cancer remains unclear. FOXO1 is involved in the growth inhibition and prognosis of lung cancer. We aimed to evaluate the effects of ANCR lncRNA on the biological behaviors of lung cancer cells and the mechanism. METHODS: The lung cancer and paracancerous tissues of 50 patients were collected. The expression levels of ANCR lncRNA and FOXO1 were detected by RT-qPCR and subjected to Pearson's correlation analysis. The correlations between ANCR lncRNA expression and clinicopathological features of lung cancer patients were analyzed. The interaction between FOXO1 and ANCR lncRNA was studied by RNA pull-down and RNA immunoprecipitation assays. Human lung cancer A549 cells were transfected with lentiviral plasmids packaging ANCR lncRNA and FOXO1. The cells were divided into control group (untransfected), NC group (transfected with empty lentiviral plasmid), ANCR lncRNA group (transfected with pHRi-ANCR lncRNA), sh-ANCR lncRNA group (transfected with pHRi-sh-ANCR lncRNA), FOXO1 group (transfected with pHRi-FOXO1) and sh-ANCR lncRNA + sh-FOXO1 group (transfected with pHRi-sh-ANCR lncRNA and pHRi-sh-FOXO1). The expression levels of FOXO1 after ANCR lncRNA overexpression or inhibition were measured by RT-qPCR. Cell proliferation, cell cycle and apoptosis were detected with 5-ethynyl-2'-deoxyuridine labeling and flow cytometry respectively. Bcl-2, Bax, cyclin D1 and P27 protein expressions were detected by Western blot. RESULTS: Compared with paracancerous tissue, ANCR expression in lung cancer tissue significantly increased, and FOXO1 significantly decreased (P<0.01), being negatively correlated (P<0.01). The patients with higher TNM stage, lower differentiation degree and lymph node metastasis had higher relative expression of ANCR lncRNA. ANCR lncRNA bound FOXO1 and inhibited its expression. Compared with the NC group, sh-ANCR lncRNA and FOXO1 groups had fewer proliferative cells, more significant arrest in the G0/G1 phase, more apoptotic cells, increased expressions of Bax and P27, and reduced expressions of Bcl-2 and cyclin D1 (P<0.05). Compared with the sh-ANCR lncRNA group, the above results of the sh-ANCR lncRNA + sh-FOXO1 group were reversed (P<0.05). CONCLUSIONS: ANCR lncRNA had high expression in lung cancer, and regulated the proliferation and apoptosis of lung cancer cells by modulating FOXO1 expression.

A strongly adhesive hemostatic hydrogel for the repair of arterial and heart bleeds.

Uncontrollable bleeding is a major problem in surgical procedures and after major trauma. Existing hemostatic agents poorly control hemorrhaging from traumatic arterial and cardiac wounds because of their weak adhesion to wet and mobile tissues. Here we design a photo-reactive adhesive that mimics the extracellular matrix (ECM) composition. This biomacromolecule-based matrix hydrogel can undergo rapid gelling and fixation to adhere and seal bleeding arteries and cardiac walls after UV light irradiation. These repairs can withstand up to 290 mm Hg blood pressure, significantly higher than blood pressures in most clinical settings (systolic BP 60-160 mm Hg). Most importantly, the hydrogel can stop high-pressure bleeding from pig carotid arteries with 4~ 5 mm-long incision wounds and from pig hearts with 6 mm diameter cardiac penetration holes. Treated pigs survived after hemostatic treatments with this hydrogel, which is well-tolerated and appears to offer significant clinical advantage as a traumatic wound sealant.

Low Tidal Volume Reduces Lung Inflammation Induced by Liquid Ventilation in Piglets With Severe Lung Injury.

Total liquid ventilation (TLV) is an alternative treatment for severe lung injury. High tidal volume is usually required for TLV to maintain adequate CO2 clearance. However, high tidal volume may cause alveolar barotrauma. We aim to investigate the effect of low tidal volume on pulmonary inflammation in piglets with lung injury and under TLV. After the establishment of acute lung injury model by infusing lipopolysaccharide, 12 piglets were randomly divided into two groups, TLV with high tidal volume (25 mL/kg) or with low tidal volume (6 mL/kg) for 240 min, respectively. Extracorporeal CO2 removal was applied in low tidal volume group to improve CO2 clearance and in high tidal volume group as sham control. Gas exchange and hemodynamic status were monitored every 30 min during TLV. At the end of the study, pulmonary mRNA expression and plasmatic concentration of interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured by collecting lung tissue and blood samples from piglets. Arterial blood pressure, PaO2 , and PaCO2 showed no remarkable difference between groups during the observation period. Compared with high tidal volume strategy, low tidal volume resulted in 76% reduction of minute volume and over 80% reduction in peak inspiratory pressure during TLV. In addition, low tidal volume significantly diminished pulmonary mRNA expression and plasmatic level of IL-6 and IL-8. We conclude that during TLV, low tidal volume reduces lung inflammation in piglets with acute lung injury without compromising gas exchange.