BACKGROUND Protocadherin 8 (PCDH8) functions as a tumor-suppressor gene in many types of cancer. This study aimed to investigate the role of PCDH8 in esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Cell proliferation, apoptosis, transwell assay, tube formation assays, and tumor xenograft experiment were performed to explore the role of PCDH8 in the progression of ESCC. RESULTS PCDH8 was found to be downregulated in ESCC cells. Ectopic expression of PCDH8 blocked proliferation, invasion, and migration and induced apoptosis in ESCC cells. Furthermore, vascular endothelial growth factor A (VEGFA) secretion and the AKT signaling pathway were also inhibited when PCDH8 was upregulated. PCDH8 overexpression suppressed epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of ESCC cells. In a mouse model of ESCC xenograft tumors, PCDH8 overexpression remarkably restrained tumor cell growth, with the tumor inhibition rate of 75.2%. PCDH8 was the target of miR-200c and had a negative correlation with miR-200c. CONCLUSIONS PCDH8 exerts a tumor-suppressive effect against ESCC cells. However, further studies are required to elucidate the exact molecular mechanism underlying the antitumor activity of PCDH8 in ESCC.Lessons from the Ebola outbreak shows that it is possible to develop rapid and effective clinical research responses without relying on anecdote.Mitochondrial dysfunction is linked to age-related senescence phenotypes. We report here the pathway increasing nucleoid remodeling and biogenesis in mitochondria during the senescence of foreskin human diploid fibroblasts (fs-HDF) and WI-38 cells. Replicative senescence in fs-HDF cells increased mitochondrial nucleoid remodeling as indicated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and mitochondrial transcription factor A (TFAM) expression in enlarged and fused mitochondria. Mitochondrial nucleoid remodeling was accompanied by mitochondrial biogenesis in old cells, and the expression levels of OXPHOS complex-I, -IV and -V subunits, PGC-1α and NRF1 were greatly increased compared to young cells. Activated protein kinase C zeta (PKCζ) increased mitochondrial activity and expressed phenotypes of delayed senescence in fs-HDF cells, but not in WI-38 cells. The findings were reproduced in the doxorubicin-induced senescence of young fs-HDF and WI-38 cells via the PKCζ-LKB1-AMPK signaling pathway, which was regulated by the p53-p21WAF1 pathway when p16INK4a was silenced. The signaling enhanced PGC-1α-NRF1-TFAM axis in mitochondria, which was demonstrated by Ingenuity Pathway Analysis of young and old fs-HDF cells. Activation of the p53-p21WAF1 pathway and silencing of p16INK4a are responsible for mitochondrial reprogramming in senescent cells, which may be a compensatory mechanism to promote cell survival under senescence stress.Inflammation of the vascular microenvironment modulates distinct types of vascular cells, and plays important roles in promoting atherosclerosis, stenosis/restenosis, and vascular-related diseases. Nik-related kinase (Nrk), a member of the Ste20-type kinase family, has been reported to be selectively expressed in embryonic skeletal muscle. However, whether Nrk is expressed in adult vascular smooth muscle, and if it influences intimal hyperplasia is unclear. Here, we found that Nrk is abundantly expressed in cultured vascular smooth muscle cells (VSMC) and mouse arterial intima. Treatment of mouse VSMCs with lipopolysaccharide (LPS) or platelet-derived growth factor significantly reduced Nrk expression. In addition, expression of Nrk was significantly reduced in regions of neointimal formation caused by guide-wire carotid artery injuries in mice, as well as in human atherosclerotic tissues, when compared to normal vessels. We identified that expression of matrix metalloproteinases (MMP3, MMP8 and MMP12) and inflammatory cytokines/chemokines (CCL6, CCL8, CCL11, CXCL1, CXCL3, CXCL5 and CXCL9) are synergistically induced by Nrk siRNA in LPS-treated mouse VSMCs. Moreover, we found that resveratrol significantly impaired LPS- and Nrk siRNA-induced expression of MMP3, CCL8, CCL11, CXCL3 and CXCL5. These results suggested that Nrk may play important roles in regulating pathological progression of atherosclerosis or neointimal- hyperplasia-related vascular diseases.BACKGROUND Complex robotic percutaneous coronary intervention (R-PCI) is technically possible and leads to clinically comparable outcomes compared with the manual approach. However, there are limited data on the feasibility of chronic total occlusion (CTO) revascularization via the R-PCI approach. METHODS Ten consecutive patients undergoing R-PCI for a coronary CTO at a single tertiary academic center were analyzed. The PRECISION, PRECISION GRX, and PROGRESS CTO registries were utilized for data collection with regard to procedural/clinical details and results. RESULTS Technical success, defined as successful CTO revascularization with full or partial robotic support, occurred in 7 of 10 patients. There were no periprocedural major adverse cardiac events. https://www.selleckchem.com/products/Gemcitabine-Hydrochloride(Gemzar).html Average J-CTO score was 2; all procedures were performed from an antegrade approach. The time from robotic wire manipulation to completion of procedure regardless of method averaged 55.1 minutes; average fluoroscopy time was 29.9 minutes. CONCLUSIONS CTO revascularization via a robotic approach is feasible. Technical success may be best predicted by those patients with low J-CTO scores and lesions amenable to antegrade wire escalation technique. Given the potential benefits to both operators and patients, further research is warranted.BACKGROUND Atrial appendage (LAA) occlusion is a therapeutic option for thromboembolic prevention in atrial fibrillation (AF) patients who have contraindications to oral anticoagulation (OAC) or high risk of bleeding. Traditionally, thrombus in the LAA has been considered a contraindication for LAA occlusion. Recently, resistant thrombus formation in patients using OACs was suggested as an indication for LAA occlusion. METHODS AND RESULTS In this single-center study, we evaluated the safety and efficacy of LAA occlusion in patients with a thrombus in the LAA. Twelve non-valvular AF patients who had a thrombus in the LAA were enrolled. The mean age was 71.8 years (range, 62-83 years). Permanent AF was present in all patients. Mean CHA2DS2-VASc score was 4.9 (range, 2-8) and mean HAS-BLED score was 4.8 (range, 3-6). Thrombi in the LAA were classified as type 1 (proximal to mid) and type 2 (distal) in 3 and 9 patients, respectively. Median follow-up duration was 12 months (interquartile range, 6-24 months). LAA occlusion was performed successfully with Amplatzer Amulet device without any significant periprocedural adverse events in all 12 patients.