👤 Aage Haugen

Immediately after dental implant insertion, blood will be in direct contact and interact with the implant surface and activates inflammatory responses and complement cascades within seconds. The aim of the present study was to determine the ability of fluoride-modified titanium surfaces to activate complement cascades using the human buffy coat as model. The buffy coats were exposed to hydrofluoric acid-modified surfaces for a short time and its responses were compared to controls. Identification and quantification of complement cascade biomarkers were conducted using ELISA kits and multianalyte profiling using Luminex. A lower level of C3 at 30 min and increased levels of C4, MIP-4, CRP, and pigment epithelium-derived factor at 360 min were found on modified surfaces as compared to controls. We found no significant differences in the levels of C3a, C5a, C Factor H, α2M, ApoA1, ApoC3, ApoE, Prealbumin, α1AT, and SAP in modified surfaces in the buffy coats. We conclude that titanium surfaces treated with hydrofluoric acid modify the levels of specific biomarkers related to the complement cascade and angiogenesis and, thus, tissue growth, remodeling and repair, as this may play a role in the enhanced clinical performance of fluoride-modified Ti dental implants. Show less

There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC. The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors. Associations with survival were evaluated by Cox regression and Kaplan-Meier survival analyses in two independent cohorts of 121 and 91 patients with SCC, respectively. A classifier score based on multivariable Cox regression was derived and examined in six additional publicly available data sets of stage I/II lung SCC expression profiles (n = 358). The prognostic value of this classifier was evaluated in meta-analysis of patients with stage I/II (n = 479) and stage I (n = 326) lung SCC. Dual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts. Their expression values were utilized to develop a classifier that identified patients with stage I/II lung SCC at high risk for recurrence (hazard ratio [HR] = 4.7, p = 0.018) or cancer-specific mortality (HR = 3.5, p = 0.016). This classifier also identified patients at high risk for recurrence (HR = 2.7, p = 0.008) or death (HR = 2.2, p = 0.001) in publicly available data sets of stage I/II and in meta-analysis of stage I patients. We have established and validated a prognostic classifier to inform clinical management of patients with lung SCC after surgical resection. Show less

Liver X receptor (LXR)-α and -β play a major role in lipid and glucose homeostasis. Their expression and function in the heart is not well characterized. Our aim was to describe the expression of LXRs in the murine heart, and to determine effects of cardiac LXR activation on target gene expression, lipid homeostasis and ischemia. Both LXRα and -β were expressed in heart tissues, HL-1 cells and isolated cardiomyocytes as determined by qRT-PCR. Elevated cardiac expression of LXR target genes and LXRβ was observed 24 h after in vivo permanent coronary artery ligation. The synthetic LXR agonist GW3965 induced mRNA expression of the LXR target genes in HL-1 cells and isolated cardiomyocytes. This was associated with a buildup of intracellular triglycerides and expanding lipid droplets as quantified by confocal microscopy. Mice injected with GW3965 had cardiac LXR activation as judged by increased target gene expression and lipid droplet accumulation. GW3965 in vivo and in vitro increased expression of genes inducing triglyceride synthesis, and altered expression of lipid droplet-binding protein genes. GW3965 protected HL-1 cells against hypoxia-reoxygenation induced apoptosis. LXR activation by GW3965 in vivo prior to heart isolation and perfusion with induced global ischemia and reperfusion improved left ventricular contractile function and decreased infarct size. In conclusion, LXRs are expressed in the murine heart in the basal state, and are activated by myocardial infarction. Activation of LXR by the synthetic agonist GW3965 is associated with intracardiac accumulation of lipid droplets and protection against myocardial ischemia-reperfusion injury. Show less