Morselausen6553

The event-free group also showed higher cardiac output (CO) and cardiac index (CI) after AVT. Among the changed hemodynamic parameters during the AVT, ΔCO, ΔCO/baseline CO, ΔCI, ΔCI/baseline CI and ΔPVR/baseline PVR were significantly higher in the event-free group. Foremost, ΔPVR/baseline PVR, PVR after AVT and baseline SvO2 were independent predictors for event-free survival. Patients with SvO2 ≥ 61.65% at baseline or PVR less then 8.09 WU after AVT or ΔPVR/baseline PVR ≥ 0.054 had significantly better survival. Hemodynamic indices both at baseline and after AVT as well as the changes in these indices reflected the severity of CTEPH. Baseline SvO2, PVR after AVT, and ΔPVR/baseline PVR could be used as independent predictors to estimate the outcomes of CTEPH patients. AJTR Copyright © 2020.The essential roles of long noncoding RNA (lncRNA) have been identified by emerging literature in the non-small cell lung cancer (NSCLC). However, the role of lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) in the NSCLC tumorigenesis is not clear. Here, we investigate the role and mechanism of HAS2-AS1 in the NSCLC tumorigenesis. In the NSCLC tissue and cells, HAS2-AS1 was found to be up-regulated, which, in turn, indicated the poor prognosis of NSCLC patients. Functional experiments illustrated that HAS2-AS1 promoted the proliferation, invasion and gefitinib chemotherapy resistance of NSCLC cells. In vivo, HAS2-AS1 knockdown suppressed the tumor growth. Mechanically, HAS2-AS1 recruited the lysine-specific demethylase 1 (LSD1) to the EphB3 promoter region to inhibit its transcription. In conclusion, this finding elucidates the essential roles of HAS2-AS1 in the NSCLC tumorigenesis, providing a possible treatment strategy for the NSCLC. AJTR Copyright © 2020.Idiopathic pulmonary fibrosis (IPF) is a devastating disease, which is characterized by the progressive deterioration in lung function. In the pathogenesis of IPF, insulin-like growth factor-1 (IGF-1) has been found to be heavily involved. Metformin, a commonly used oral antidiabetic agent, is known to inhibit IGF-1 by the reversal of hyperinsulinemia. In this study, we evaluated the effects of metformin in pulmonary fibrosis in C57/BL6J mice, and further understand the role of IGF-1 signaling pathway involving in this process. Pulmonary fibrosis was induced experimentally in these mice by the intratracheal injection of bleomycin (BLM). Metformin was given orally the day before or 14 days after bleomycin injection, while pirfenidone was used as the positive control. Our study showed that intratracheal injection of bleomycin induced pulmonary fibrosis in mice, with observed elevation in collagen, fibronectin and α-SMA level, characterized by the enhanced IGF-1 and PI3K expression. Metformin was able to inhibit these effects significantly, and its antifibrotic effect had no marked difference with pirfenidone. Our results show that metformin attenuates bleomycin-induced pulmonary fibrosis via IGF-1 pathway. AJTR Copyright © 2020.Ovarian cancer is refractory in response towards platinum-based chemotherapy, and resistance frequently develops. We attempted to identify the driving pathways in cisplatin-resistant ovarian cancer and develop targeted therapies to overcome this resistance. Using an integrated bioinformatics approach, a GSE15372 database from NCBI's Gene Expression Omnibus database was obtained for identifying differentially expressed genes (DEGs), in which 535 DEGs were found (407 up-regulated and 128 down-regulated) in association with ovarian cancer cisplatin-resistance. Gene ontology and pathway enrichment analyses further found that aberrant activation of EGFR/ErbB2 signaling was the driving event in resistant cells. A network of dysregulated genes was built based on these identified DEGs and protein-protein interaction network, which led to the identification of 7 potential inhibitors based on screening a 77 small molecule natural product library. Sanguinarine, alone and in combination with cisplatin, was found to significantly suppress the proliferation of wt/resistant ovarian cancer cells in vitro and the growth of parental and resistant ovarian xenograft tumors in vivo. Our study suggests that EGFR/ErbB2 activation is one of the driving pathways in developing cisplatin-resistance in ovarian cancer, and that sanguinarine has the potential to be developed as an effective therapy to overcome this therapeutic resistance. VX-803 mouse AJTR Copyright © 2020.Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, and is frequently associated with a poor prognosis. 5-methylcytosine (m5C) is a common epigenetic modification with many critical roles in eukaryotes. However, the expression and functional roles of m5C regulators are largely unknown. In this study, we utilized The Cancer Genome Atlas (TCGA) to determine the expression, gene signatures, and prognostic values of m5C-related genes. We confirmed that the frequency of mutation events of m5C regulatory genes was high in HCC (35/363). Dysregulation of m5C-related genes was also associated with a higher HCC stage. Moreover, a strong relationship was found between the expression of m5C regulatory genes and HCC patient survival. High expression of NSUN4 and ALYREF correlated significantly with survival outcome. We developed a two-gene signature of m5C regulators with HCC prognostic value based on the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression models. Gene set enrichment analysis (GSEA) results indicated that high expression of NSUN4 was associated with methylation and demethylation processes. Meanwhile, high expression of ALYREF was clearly related to cell cycle regulation and mitosis. In conclusion, our results revealed that m5C-related genes play an essential role in tumor progression in HCC. Further detection of m5C methylation could provide a novel method for HCC targeted therapy. AJTR Copyright © 2020.The present study aimed to investigate the expression of inflammatory markers and mitochondrial function-related genes, as well as their temporal relationship with cardiac myocyte injury in a rat model of sepsis. The sepsis model was constructed using cecal ligation and puncture (CLP). Two hours after CLP, the levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and TNFα) and myocardial function markers (serum brain natriuretic peptide [BNP], cardiac troponin-I [cTNI], and procalcitonin [PCT]) were increased significantly, falling from around 9 hours postoperatively. The concentration of nitric oxide (NO) in the heart tissue was increased 6 hours after CLP. The heart rate (HR) of rats that underwent CLP decreased 2 hours after surgery and then increased to above-normal values. The left ventricular short axis shortening (FS) and left ventricular ejection fraction (LVEF) were decreased at 2 hours postoperatively and reached a minima at 6 hours. Stroke volume (SV), cardiac output (CO), and changes and heart index (CI) results indicated myocardial dysfunction.