Search

Background A component of primary innate defense of the nasal mucosa against inhaled pathogens includes continuous, low-level release of hydrogen peroxide (H2O2) into luminal secretions. Epidemiologically, an association exists between poor air quality and increased prevalence of sinonasal disease. To understand the effects of particulate matter (PM) in nasal mucosa, we studied the release of H2O2 and interleukin 8 (IL-8) after PM exposure. Methods Human nasal specimens were collected from surgery and cultured in serum-free growth medium. Cell integrity and recovery during culture was monitored by lactate dehydrogenase (LDH) release into the medium. Cultures were exposed to PM for 24 hours in the presence/absence of diphenyleneiodonium sulfate (DPI; a nicotinamide adenine dinucleotide phosphate [NADPH] oxidase inhibitor). Luminex cytokine and Amplex-Red H2O2 assays were performed. Results LDH levels dropped rapidly within 2 days, indicative of stabilization and cell recovery after harvest. All cultures released H2O2 into the medium. Exposure to PM (20 μg/cm2) increased H2O2 levels significantly (94.6 ± 7.7 nM) compared to untreated controls (55.8 ± 4.0 nM; p = 0.001). PM-induced H2O2 production was partially inhibited by DPI (80.1 ± 3.8nM), indicating that cellular NADPH oxidase may be a primary source of H2O2 production. Exposure to PM increased IL-8 levels in a dose-dependent fashion (control = 2301 ± 412 MFI; 20 μg/cm2 = 5002 ± 1327 MFI; 40 μg/cm2 = 8219 ± 1090 MFI; p = 0.022). Conclusion PM increases the quantity of H2O2 released by nasal epithelial cells, indicating that PM can contribute to oxidative stress in part by activating a normal cellular defense mechanism. Exposure to PM resulted in elevated IL-8 levels and mucin production in explants. Efforts to reduce airborne PM may lead to reduced H2O2 and mucin production in sinonasal epithelium.

Background New epithelial cells are generated through the proliferation and differentiation of resident progenitor cells in the nasal cavity. In several upper airway diseases, such as cystic fibrosis and chronic rhinosinusitis, self-renewing progenitor cells may be functionally defective, or compromised in their ability, to regenerate cells that maintain normal mucociliary clearance. Herein, we describe our early work to define and characterize a rare population of human nasal epithelial putative progenitors. Methods Single-cell suspensions of human ethmoid sinus tissues were prepared following endoscopic sinus surgery. Cell surface antibodies were analyzed as candidate markers for detecting progenitor cells. A panel of antibodies, including epithelial cell adhesion molecule (EpCAM, epithelial cells), CD45 (hematopoietic cells), nerve growth factor receptor (NGFR/CD271), intercellular adhesion molecule-1 (ICAM1/CD54), and integrin-α6 (ITGA6/CD49f) were used to resolve epithelial progenitor candidates by high-dimensional flow cytometry and the gating technique of fluorescence minus one (FMO) controls. Results A rare population of approximately 0.06% of total ethmoid cells was discriminated as EpCAM−CD45−NGFR+ICAM1+ by surface markers. Use of ITGA6 was excluded based on FMO control analysis. This lineage-negative population was purified to 99% homogeneity by cell sorting and analyzed by immunofluorescence microscopy. Sorted cells were subsequently confirmed to uniformly express the transcription factor p63. Upon in vitro culture, lineage-negative clonal cells were confirmed to spontaneously differentiate into epithelial lineage-positive cells. Conclusion Using the NGFR and ICAM1 cellular coordinates, we have identified a promising population of native human nasal epithelial progenitor cells that require more formal investigation for their role in upper airway regeneration.

Background The airway epithelium generates reactive oxygen species (ROS) as a first line of defense. Dual oxidases (DUOX1 and DUOX2) are the H2O2-producing isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family in the airway epithelium. The purpose of this study was to explore the molecular expression, function, and regulation of DUOXs in chronic rhinosinusitis (CRS).

In this paper, a new blind channel estimation method for orthogonal frequency division multiplexing systems is presented. The proposed approach based on the amplitude-phase constraints of the channel frequency response first estimates the channel amplitude-frequency response, and then calculates the channel-frequency response of the equivalent minimum phase system by its amplitude-frequency response. The zeros of the actual system and its equivalent minimum phase system are symmetric about the unit circle, and the symmetric relationships are easily determined according to the finite alphabet property of information symbols. A semi-blind estimation method based on the blind estimation method is also proposed in this paper, and it greatly reduces the numerical complexity of the blind method. Unlike existing statistical blind channel estimators, the proposed method requires short data records especially for phase-shift keying modulation. Compared with the existing finite alphabet based method, the proposed method has a lower numerical complexity. Comparison of the proposed method with training based estimation method, which is presented by computer simulations, show the effectiveness of the proposed method. Copyright © 2012 John Wiley & Sons, Ltd.

To determine if statins induce anti-inflammatory effects in upper airway inflammation. Mediators of innate and adaptive immunity regulate airway inflammation. Release of these mediators involves enzymatic conversion of polyunsaturated fatty acids into biologically active mediators, which can be blocked by statins. Although upper airway inflammation and chronic sinusitis occur in millions of patients with asthma worldwide, the anti-inflammatory effects of statins in upper airway inflammation have not been previously studied.Laboratory research.Tertiary referral center.Analysis of sinus tissues collected from patients with chronic rhinosinusitis revealed suppression of highly expressed inflammatory mediators in patients who were found to be on statins, suggesting that statins may induce anti-inflammatory effects. Therefore, the authors performed an in vitro study to determine if these anti-inflammatory effects were induced by statins. Cultured primary human airway epithelial cells were exposed to ambient air pollution particulates (PM) to trigger the inflammation, with and without statins, and the expression of inflammatory mediators was analyzed.The authors found that expression of CCL5, CCL11, and IL13RA was suppressed in patients on statins. In vitro exposure to PM enhanced the expression of these mediators, while pretreatment with statins completely blocked these effects. Furthermore, the effects of statins were blocked by inhibition of the statin pathway using isopentenyl-5-pyrophosphate. Statins did not have any significant effect on the viability of normal cells.Statins induce anti-inflammatory effects in human airway epithelial inflammation. Statins may play a role in the treatment and prevention of chronic rhinosinusitis and pulmonary exacerbation of obstructive airway diseases.

1. The current experiment was conducted to investigate the effect of zinc sulphate (ZnSO4) and zinc methionine (Zn-Met) on growth and their effect on plasma growth hormone (GH) concentration, growth hormone receptor (GHR) and insulin-like growth factor I (IGF-I) mRNA expression in mice. 2. Ninety male KunMing (KM) mice were randomly divided into three treatments. The control group was fed on a basal diet containing 11.67 mg/kg of zinc. The ZnSO4 group and Zn-Met group were fed on the diets supplemented with ZnSO4 or Zn-Met at 30 mg/kg (containing zinc of 40.05 and 40.75 mg/kg, respectively). The mice were offered the test diets for 10 days. Weight gains and food intake were measured at the end of the experiment, zinc contents in liver and serum were determined using atomic absorption spectrophotometry; GH was determined by radioimmunoassay, the levels of GHR and IGF-I mRNA were determined with reverse transcript polymerase chain reaction. 3. Both ZnSO4 and Zn-Met enhanced weight gain and food intake in the mice, Zn-Met improved the growth and food intake more effectively than ZnSO4 did (P0.05). The both forms of zinc had no effect on GH and the level of GHR mRNA expression (P0.05) and they up-regulated the expression of IGF-I mRNA (P0.05). As compared to ZnSO4, Zn-Met enhanced the level of IGF-I mRNA significantly (P0.05). 4. Both ZnSO4 and Zn-Met had no effect on plasma GH and the expression of GHR mRNA, but they enhanced the expression of IGF-I mRNA. Zinc methionine enhanced the weight gain and up-regulated IGF-I mRNA expression more effectively than ZnSO4.

Inherited predisposition to thrombosis contributes to the initiation and progression of coronary artery disease (CAD). The present study was designed to explore the relationship between genetic variation of coagulation factor V and occurrence of CAD. A total of 141 unrelated patients with CAD and 175 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) for variation detection in all 25 exons of the factor V gene. Among the study subjects, 55 CAD patients and 73 controls were evaluated at random for response to activated protein C (APC) by Coatest APC resistance test. Polymorphisms in exon 4, 10, 13 and 16 of factor V gene were documented [642G → T(S156), 1628 → A(R485K), 4070A → G(H1299R) and 5380G → A(V1736M), respectively]. The study also identified a novel polymorphism 327A → G in exon 2 which did not alter the amino acid residue. Leiden mutation (R506Q) was not detected in any of our 316 subjects. Among the five polymorphisms, the allele frequency of 1628G → A was significantly different between the CAD patients and the controls (0.36 vs. 0.21, p < 0.05). Subjects homozygous or heterozygous for the A allele of 1628G → A polymorphism had lower normalized APC ratios than those with the GG genotype in the CAD group (1.16 ± 0.13 and 1.18 ± 0.23 vs. 1.36 ± 0.33, p < 0.05) and in the controls, indicating that A 1628 allele was associated with a poor response to APC. We conclude that the 1628G → A (R485K) polymorphism of factor V is associated with a poor response to APC and increased risk for CAD.

Objective: Accumulating studies show the role of microRNAs in multiple human cancers. However, little is known about the role of microRNAs in nasopharyngeal cancers (NPC). Given the role of microRNAs in survival and death pathways in cancers, we hypothesized that the microRNAs may regulate the effects of cancer therapeutic agents.Method: Tumor specific MicroRNA expressions were studied in vitro in primary human NC cells (CCL-30) treated with statins. The effects on cell survival, cell cycle, and apoptosis were examined.Results: Recently, we showed the promising antitumor effects of statins in NPC via HMG Co-A pathway. Our new study examines the novel role of microRNAs in mediating the effects of statin in the inhibition of survival in NPC. Statins induced apoptosis and decreased survival of NPC. The regulation of tumor suppressor Let-7a was enhanced in cells treated with statins associated with decrease in the cell viability and proliferation, and increase in apoptosis in these cells. Further, we found th...