Role of IL-22 in acute asthma mouse model.

Introduction: Allergic asthma is often associated with eosinophilic inflammation, which is related to the T-helper cell type 2 (Th2) cytokines and responsive to corticosteroids. However, there are also phenotypes of non-Th2-mediated asthma, which have poor responsivity to corticosteroids. The leading phenotype of non-Th2-mediated asthma is neutrophilic asthma, which is considered difficult to treat. Recently, IL-22 has been found to be involved in neutrophilic inflammation in asthma. However, studies on the role of IL-22 in asthma are still controversial as IL-22 has both pro-inflammatory and anti-inflammatory roles in asthma. This study examined whether the IL-22 level increased in acute neutrophilic asthma in the mouse model. Herein, we aimed to demonstrate increased IL-22 levels in neutrophilic asthma and elucidate the pathways leading to elevated neutrophil counts.Methods: Six-week old female BALB/c mice were sensitized and challenged with PBS, ovalbumin (OVA) or OVA + lipopolysaccharide (LPS). The mice were then assigned to one of the following five groups: (1) control (PBS/ PBS), (2) OVA/PBS, (3) OVA/OVA, (4) OVA+LPS/PBS, (5) OVA+LPS/OVA+LPS.Results: The levels of Th2 cytokines, IL-17, and IL-22 were assessed, with investigation of the neutrophil chemokines. This study showed that in the acute neutrophilic asthma, the levels of IL-17 and IL-22 were significantly higher than those in the OVA/OVA group, which represents acute eosinophilic asthma. Moreover, the level of CCL20 increased in the neutrophilic asthma group.Conclusion: Thus, this study suggests that in the acute neutrophilic asthma mouse model, IL-17 and IL-22 may increase with CCL20, resulting in neutrophilic inflammation.

Tiotropium Bromide Improves Neutrophilic Asthma by Recovering Histone Deacetylase 2 Activity.

BACKGROUND: The value of tiotropium bromide (TIO) in neutrophilic asthma was meaningful in previous study. We hypothesized that TIO's mechanism of action is associated with histone deacetylase 2 (HDAC2) activity, which is key for controlling the transcription of inflammatory cytokines and usually downregulated in neutrophilic asthma. METHODS: The effects of TIO and dexamethasone (DEX) on HDAC2 activity, nuclear factor kappa B (NF-κB), and C-X-C motif chemokine ligand 1 (CXCL1) were evaluated in neutrophilic asthma mouse model (C57BL, 6-week-old). An in-vitro study was conducted using primary human bronchial/tracheal epithelial (HBE) cells from asthma patients. Western blot analyses were performed for phospho-phospholipase Cγ-1 (PLCγ-1) and inositol trisphosphate (IP3) receptors (IP3R) with treating lipopolysaccharide (LPS) and TIO. RESULTS: Ovalbumin was used to induce eosinophilic inflammation in this study. After neutrophilic asthma was induced by LPS (O+L group), HDAC2 activity was diminished with increased NF-κB activity and CXCL1 compared to the control group. TIO significantly improved NF-κB activity, CXCL1, and HDAC2 activity compared with the O+L group in in-vivo study (P < 0.05, each). Western blot analyses showed that LPS treated HBE cells from asthma patients increased PLCγ-1 and diminished IP3 receptor levels. After TIO treatment, recovery of IP3R and improved PLCγ-1 levels were observed. CONCLUSION: These results support the hypothesis that TIO modulates inflammation by recovering HDAC2 activity from the acetylcholine-stimulated inflammation cascade in neutrophilic asthma. The detailed inflammation cascade of recovering HDAC2 activity by TIO might be associated with PLCγ-1-IP3-IP3R mediated intracellular calcium ion pathway.

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

Introduction: Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms.Methods: Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting.Results: Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production.Conclusion: These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.

Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.

BACKGROUND: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known. METHODS: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Ovalbumin (OVA) sensitization and challenges were performed for 7 weeks. The mice were injected intraperitoneally with GLP-1R agonist 5 times a week for 4 weeks after OVA sensitization. After AHR measurement, expression of Th2, Th17 cytokines, and interleukin (IL)-33 were measured in BALF and lung tissues. Moreover, IL-1ß and activity level of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were analyzed to investigate the mechanism of GLP-1R agonist on asthmatic airway inflammation. RESULTS: HFD induced significant weight gain, OVA sensitization and challenge in obese mice made eosinophilic airway inflammation, and increased AHR. Treatment with GLP-1R agonist-induced weight loss suppressed eosinophilic airway inflammation and decreased AHR. Expression of IL-4, 5, and 33 was increased in BALF of obese asthma mice followed by a decrease in response to GLP-1R agonist treatment. Moreover, lung tissue H&E stain revealed that peribronchial inflammation induced by obesity and OVA was effectively suppressed by GLP-1R agonist. Expressions of NLRP3, activated caspase-1, and IL-1ß were increased in lung tissues of obese asthma mice and demonstrated a decrease in response to GLP-1R agonist treatment. CONCLUSIONS: GLP-1R agonist effectively induced weight loss, suppressed eosinophilic bronchial airway inflammation, and AHR in obese asthma mice. These effects were mediated by suppression of NLRP3 inflammasome activity and IL-1ß. GLP-1R agonist is proposed as a novel anti-asthmatic agent targeting the obese asthmatics.

Cyclo-VEGI inhibits bronchial artery remodeling in a murine model of chronic asthma.

Purpose/Aim: In the context of asthma, airway bronchial remodeling and angiogenesis in the bronchial mucosa are well established. Cyclopeptidic-vascular endothelial growth inhibitor (cyclo-VEGI) is an inhibitor of the vascular endothelial growth factor (VEGF) receptor that increases the proliferation of endothelial cells and the formation of new vessels. However, changes in the bronchial arteries of patients with asthma have not been clearly elucidated. We investigated whether structural changes occurred in bronchial arteries, as well as the effects of cyclo-VEGI in a mouse model of chronic asthma (in vivo) and human fibroblasts (in vitro). Materials and Methods: A validated mouse model of allergic airway inflammation with ovalbumin (OVA) as the causative allergen was used for the study. Mice were treated with cyclo-VEGI or fluticasone during OVA challenge. In vitro experiments were conducted to determine whether fibroblasts proliferated following elastin exposure and the effects of cyclo-VEGI on them. Results: OVA sensitization and challenge led to greater perivascular smooth muscle area, more elastic fibers, and elevated expression of vascular cell adhesion molecule (VCAM)-1 antigen. These phenomena indicated changes to bronchial arteries. Cyclo-VEGI and fluticasone treatment both inhibited airway hyper-responsiveness and inflammation. Cyclo-VEGI-treated mice exhibited decreased perivascular smooth muscle area, elastin fibers, and VCAM-1 expression. Fluticasone-treated mice exhibited reductions in perivascular smooth muscle but not in perivascular elastin or VCAM-1 expression. In vitro, fibroblast proliferation was enhanced by elastin treatment, which was inhibited by cyclo-VEGI treatment. Eotaxin expression was elevated in elastin-treated fibroblasts and decreased with cyclo-VEGI treatment. Conclusions: Vascular remodeling occurred in our mouse model of chronic asthma. Cyclo-VEGI could reduce airway inflammation and hyper-responsiveness by inhibiting VCAM-1 expression and elastin deposition around the bronchial arteries.

Influence of dynamic neck motion on the clinical usefulness of multi-positional MRI in cervical degenerative spondylosis.

PURPOSE: The purpose of this study was to find out additional indications for multi-positional MRI in cervical degenerative spondylosis (CDS) patients. MATERIAL AND METHODS: A total of 63 patients with cervical spondylotic myelopathy that underwent multi-positional MRI and X-ray were included. Muhle's grade, C2-7 angle, and C7 slope were measured. Patients were assigned to the stenosis group (Group S) when Muhle's grades were increased by more than two or maximum grade was reached. Other patients were assigned to the maintenance group (Group M). Receiver operating characteristic (ROC) analysis was performed. Statistical significance was accepted for p values of < 0.05. RESULTS: A total of 24 patients were assigned to the S group and 39 patients to the M group. Mean C2-7 angle difference in extension (eC27A) between S and M groups was 10.97° (p = 0.002). The mean inter-group difference between C2-7 angle in extension and neutral positions (e-nC27A) was 14.39° (p = 0.000). Mean C7 slope difference in neutral position was - 6.53° (p = 0.002). Based on areas under ROC curves (AUCs), e-nC27A, eC27A, and negative C7 slope had AUCs of 0.934 (95% CI 0.876-0.992), 0.752 (95% CI 0.624-0.880), and 0.720 (95% CI 0.588-0.851), respectively. The optimal cutoff value of e-nC27A was 15.4 degrees, which had a diagnostic accuracy of 88.9%. CONCLUSION: Multi-positional MRI helps to find dynamic cord compressive lesion in CDS patients. The higher eC27A, e-nC27A values and smaller C7 slope were found to increase the likelihood of cervical dynamic stenosis. Among other factors, we recommend multi-positional MRI before surgery especially when a patient's e-nC27A is > 15.4 degrees. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Intraoperative surveillance of the vertebral artery using indocyanine green angiography and Doppler sonography in craniovertebral junction surgeries.

OBJECTIVE: The authors sought to evaluate the usefulness of indocyanine green (ICG) angiography and Doppler sonography for monitoring the vertebral artery (VA) during craniovertebral junction (CVJ) surgery and compare the incidence of VA injury (VAI) between the groups with and without the monitoring of VA using ICG angiography and Doppler sonography. METHODS: In total, 344 consecutive patients enrolled who underwent CVJ surgery. Surgery was performed without intraoperative VA monitoring tools in 262 cases (control group) and with VA monitoring tools in 82 cases (monitoring group). The authors compared the incidence of VAI between groups. The procedure times of ICG angiography, change of VA flow velocity measured by Doppler sonography, and complication were investigated. RESULTS: There were 4 VAI cases in the control group, and the incidence of VAI was 1.5%. Meanwhile, there were no VAI cases in the monitoring group. The procedure time of ICG angiography was less than 5 minutes (mean [± SD] 4.6 ± 2.1 minutes) and VA flow velocity was 11.2 ± 4.5 cm/sec. There were several cases in which the surgical method had to be changed depending on the VA monitoring. The combined use of ICG angiography and Doppler sonography was useful not only to monitor VA patency but also to assess the quality of blood flow during CVJ surgery, especially in the high-risk group of patients. CONCLUSIONS: The combined use of ICG angiography and Doppler sonography enables real-time intraoperative monitoring of the VA by detecting blood flow and flow velocity. As the arteries get closer, they provide auditory and visual feedback to the surgeon. This real-time image guidance could be a useful tool, especially for high-risk patients and inexperienced surgeons, to avoid iatrogenic VAI during any CVJ surgery.

Effect of nintedanib on airway inflammation in a mouse model of acute asthma.

Objective: New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Methods: Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Results: Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-ß1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-ß, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Conclusions: Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma.

BACKGROUND: Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (TH2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed. METHODS: Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing. RESULTS: Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in TH2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and TH2 cytokine levels. CONCLUSION: The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.

Pravastatin alleviates allergic airway inflammation in obesity-related asthma mouse model.

Background: Obesity is one of the factors associated with severe, uncontrolled asthma. The effect of pravastatin on asthmatic airway inflammation in obesity has not been evaluated. Methods: C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization and challenge. Pravastatin was administered intraperitoneally during the OVA treatment. Airway inflammation and airway hyper-responsiveness (AHR) were analyzed and lung tissues were examined. The changes in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were measured in the lung tissues. Results: HFD with OVA sensitization and challenge exacerbated eosinophilic and neutrophilic airway inflammation and increased AHR compared to lean asthma mice. The levels of cytokines examined in bronchoalveolar lavage fluid (BALF) revealed that the expressions of IL-4, 5, and 17 were elevated in the obese asthmatic group and decreased after pravastatin treatment, indicating that both the Th2 and Th17 pathways were stimulated by HFD-induced obesity and OVA challenge and suppressed by pravastatin treatment. Moreover, the serum leptin and adiponectin ratio was elevated only in obese asthmatic mice and decreased with pravastatin administration. Pravastatin successfully alleviated the airway inflammation of lung tissues and AHR in both obese and lean asthmatic mice, however, treatment with pravastatin had no effects on BALF cell counts and cytokines in lean asthma mice. In lung tissues, the phosphorylation of p38 MAPK was significantly decreased in lean as well as obese asthmatic mice. Conclusions: Pravastatin treatment in obese asthmatic mice suppressed allergic airway infiltration and AHR by inhibition of Th2 and Th17-associated signaling pathways, decreasing the leptin expression and downstream p38 MAPK signaling pathways. The effect on lean asthmatic mice was different, independent of airway cell counts and cytokines.

Comparative analysis of the intervertebral disc signal and annulus changes between immediate and 1-year postoperative MRI after transforaminal endoscopic lumbar discectomy and annuloplasty.

PURPOSE: Postoperative magnetic resonance imaging (MRI) after microdiscectomy for lumbar disc herniation frequently shows spinal canal compression by the remaining annulus, which gradually decreases over time. Transforaminal endoscopic lumbar discectomy (TELD) can remove the herniation with minimal trauma to surrounding soft tissue. We aim to identify this remodeling of annulus fibrosus and the change of disc signal after TELD. METHODS: We reviewed patients who underwent TELD. Clinical data obtained were Oswestry disability index (ODI) and visual analog scale (VAS) for back and leg pain. Residual mass signal and disc protrusion size were measured in postoperative MRI. RESULTS: Thirty-one patients were reviewed. The mean age was 38.3 ± 14.4 years (range 18 to 76 years). ODI was 18.2% at the first follow-up and 12.7% at the last follow-up (p = 0.009). VAS for back and leg pain were 2.0 and 1.0 without significant change during follow-up. Disc protrusion size was reduced by 67.7% at the 1-year follow-up (p < 0.001). The residual mass signals at postoperative day 1 were high in 12 cases, intermediate in 18 cases, and low in1 case. The signal intensity was correlated with the percentage of disc protrusion reduction (p = 0.048). The percentage of disc protrusion reduction correlated with the last follow-up ODI (p = 0.018). CONCLUSION: One year after TELD, annulus remodeling was observed with an average of 67.7% of size reduction. The high signal intensity of residual mass at day 1 correlated with disc protrusion reduction at follow-up MRI. The percentage of disc protrusion reduction associated with the ODI at the final follow-up.

The leukotriene receptor antagonist pranlukast attenuates airway remodeling by suppressing TGF-ß signaling.

BACKGROUND/OBJECTIVE: Asthma is a chronic airway disease characterized by airway eosinophilic inflammation and remodeling, which are associated with a loss in lung function. Although both contribute significantly to asthma pathogenesis, mechanistic studies and drug discovery have focused on inflammatory targets. In this study, we investigated the effect of the leukotriene receptor antagonist pranlukast on allergic airway inflammation and remodeling in vivo and in vitro. METHOD: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated OVA) were examined. Lung pathology, cytokine production, and airway hyperresponsiveness (AHR) measurements were compared among these groups. A human fetal lung fibroblast HFL-1 cell line was used in the peribranchial fibrosis analysis. RESULTS: OVA-sensitized and -challenged mice exhibited allergic airway inflammation and significant increases in Th2 cytokines. Pranlukast-treated mice showed significant attenuation of allergic airway inflammation. The pranlukast treatment decreased AHR and attenuated airway remodeling to goblet cell hyperplasia, collagen deposition, α-smooth muscle actin expression, and pro-fibrotic gene expression. We further demonstrated that pranlukast not only inhibited transforming growth factor-beta 1 (TGF-ß1)-induced Smad signaling in human fetal lung fibroblast cells but also simultaneously reduced collagen synthesis and pro-fibrotic gene expression. CONCLUSIONS: The leukotriene receptor antagonist pranlukast can reduce airway inflammation and remodeling by inhibiting TGF-ß/Smad signaling in an OVA-sensitized and -challenged asthma mouse model, thus suppressing AHR.

Dimensions of the spinous process and interspinous space: a morphometric study.

PURPOSE: To measure the morphological dimensions of the spinous process (SP) and interspinous space, and provide a basis for the development of interspinous devices for the Korean or East Asian populations. METHODS: We retrospectively analyzed the anatomical parameters of 120 patients. The parameters included height, length, and width of SP, interspinous distance (supine, standing, and dynamic), cortical thickness of SP, and spino-laminar (S-L) angle. Correlations between measurements, age, and gender were investigated. RESULTS: The largest height, length, and cortical thickness and S-L angle were noted at L3. The largest width was observed at S1. The interspinous distance decreased significantly from L2-3 to L5-S1 and was significantly larger in the supine than in standing posture for L5-S1. Cortical thickness was gradually tapered from the anterior to the posterior position. The S-L angle at L2 and L3 was similar and significantly decreased from L3 to S1. An increased trend in width with aging and a decreased trend in distance (supine) were noted. A significant increase in height, length, and distance in males compared with females was also observed. CONCLUSIONS: The interspinous space is wider at the anterior, and the cortex is thicker anteriorly. Accordingly, it appears that the optimized implant position lies in the interspinous space anteriorly. The varying interspinous space with different postures and gradually narrowing with age suggest the need for caution when sizing the device. Gender differences also need to be considered when designing implantable devices.

Effect of nintedanib on airway inflammation and remodeling in a murine chronic asthma model.

INTRODUCTION: Nintedanib is a multi-tyrosine kinase receptor inhibitor recently approved for treatment of idiopathic pulmonary fibrosis. Although angiogenesis is a key process involved in airway structural changes in patients with bronchial asthma, the effect of nintedanib targeting the angiokinase pathway on airway inflammation and remodeling has not been evaluated. METHODS: We used a 3-month ovalbumin (OVA) challenge mouse model of airway remodeling. Nintedanib was orally administrated during the challenge period, and the effects were examined based on the percentage of airway inflammatory cells, airway hyper-reactivity (AHR), peribronchial goblet cell hyperplasia, total lung collagen and smooth muscle area. The expression of growth factor receptors was analyzed in mice lung tissues. RESULTS: The OVA challenged group showed a significant increase in airway eosinophilic inflammation, elevated Th2 cytokines, AHR, and airway remodeling compared to those in the control group. The airway remodeling process, as evaluated by goblet cell hyperplasia, total lung collagen level, and airway smooth muscle area, was suppressed by nintedanib compared to that by OVA. Nintedanib effectively suppressed the phosphorylation of vascular endothelial growth factor/ platelet derived growth factor subunit2/fibroblast growth factor3 receptors in the mice lung. CONCLUSIONS: Nintedanib effectively ameliorated airway inflammation and remodeling in an OVA-induced chronic asthma model. These results suggest that nintedanib could be a new treatment agent targeting airway remodeling in patients with severe asthma.

Inhibition of MicroRNA-21 by an antagomir ameliorates allergic inflammation in a mouse model of asthma.

AIM OF THE STUDY: MicroRNA-21 (miR-21) is up-regulated during allergic airway inflammation, reflecting a Th2 immune response. We investigated the effects of an miR-21 antagomir and its mechanism of action in a mouse model of acute bronchial asthma. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered by intranasal inhalation from the day of sensitization. Changes in cell counts, Th2 cytokine levels in bronchoalveolar (BAL) fluid, and airway hyper-responsiveness (AHR) were examined. Histopathological changes and expression levels of miR-21 in lung tissues were analyzed. The mechanism of action of the antagomir was investigated by counting CD4+/CD8- T cells in splenocytes and by measuring the expression levels of transcription factors associated with T cell polarization. RESULTS: MiR-21 expression was selectively down-regulated in the lung tissues of mice treated with anti-miR-21. The antagomir suppressed AHR compared with that of the OVA-challenged and scrambled RNA-treated groups. It also reduced the total cell and eosinophil counts in BAL fluid and the levels of Th2 cytokines, including IL-4, IL-5, and IL-13. The direct target of miR-21, IL-12p35, was induced in the antagomir-treated group, decreasing the CD4+/CD8- T cell proportions in splenocytes. The levels of transcription factors involved in the Th2-signaling pathway were reduced in lung tissues on treatment with the antagomir. CONCLUSIONS: The miR-21 antagomir suppresses the development of allergic airway inflammation in a mouse model of acute bronchial asthma, inhibiting Th2 activation. These results suggest that this antagomir might be useful for treating bronchial asthma.

Oral Health in Low-Income Older Adults in Korea.

Oral diseases among older adults are prevalent and a major public health problem, but public attention regarding this matter is quite limited. Many older adults experience limited access to oral care services. The study aimed to describe characteristics of oral health conditions, perceived oral health status, and oral health practices and to examine factors related to living status and accessibility to dental health care among 9,660 low-income older adults living in a suburban city in Korea. Approximately 42% of low-income older adults lived alone; 68% perceived their oral health as either excellent or good; and 31% reported difficulty accessing dental services. Lack of accessibility to oral care services was significantly more common in older adults with low incomes, living alone, having poor oral conditions, poor self-perceived oral health, and poor tooth-brushing behavior. Strategies to promote access to dental care services for underserved older adults should be developed to prevent further oral problems and their impact on overall health conditions.

HuR represses Wnt/ß-catenin-mediated transcriptional activity by promoting cytoplasmic localization of ß-catenin.

ß-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of ß-catenin is a critical step for expressing target genes. ß-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/ß-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the ß-catenin protein in the cytoplasm. Thus, Wnt/ß-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic ß-catenin functions related to HuR-mediated RNA metabolism in cancer cells.

Prospective Comparison Study Between the Fluoroscopy-guided and Navigation Coupled With O-arm-guided Pedicle Screw Placement in the Thoracic and Lumbosacral Spines.

STUDY DESIGN: This is a prospective randomized comparison study between the fluoroscopy-guided and navigation coupled with O-arm-guided pedicle screw placement in the thoracic and lumbosacral spines. OBJECTIVE: The objective of the study was to evaluate the accuracy and clinical benefits of a navigation coupled with O-arm-guided method in the thoracic and lumbar spines by comparing with a C-arm fluoroscopy-guided method. METHODS: Under fluoroscopy guidance, 138 pedicle screws were inserted from T9 to S1 in 20 patients, and 124 pedicle screws were inserted from T9 to S1 in 20 patients using the navigation. The position of the screws within the pedicle was assessed from grade 0 (no violation cortex) to grade 3 (>4 mm violation), and the location of the violated cortex was determined. Preparation time of each equipment setting, time for screwing, and the number of x-ray shots were evaluated. RESULTS: The number of screws observed as grade 0 was 121 (87.7%) in the fluoroscopy-guided group and 114 (91.9%) in the navigation-guided group. The lateral cortex was most commonly involved in the fluoroscopy-guided group (6 cases, 35.3%), and the medial cortex was most common in the navigation-guided group (4 cases, 40%). The mean time required for preparation for screw placement was 3.7 minutes in the fluoroscopy-guided group and 14.2 minutes in the navigation-guided group. Average screwing time was 3.6 minutes in the fluoroscopy-guided group and 4.3 minutes in the navigation-guided group. The mean number of x-ray shots for each screw placement in the fluoroscopy-guided group was 6.5. Postoperatively, 2 patients with misplacement of a screw under fluoroscopy guidance presented ipsilateral leg paresthesia, possibly related to the screw position. CONCLUSIONS: The present prospective study reveals that the pedicle screw placement guided by the navigation coupled with O-arm system was more accurate and safer than that under fluoroscopy guidance.

Clinical and Radiological Outcomes in C2 Recapping Laminoplasty for the Pathologies in the Upper Cervical Spine.

OBJECTIVE: To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty. METHODS: Fourteen consecutive patients who underwent C2 recapping laminoplasty around C1-2 level were enrolled. To evaluate muscle preservation effect, the authors conducted a morphological measurement of extensor muscles between the operated and nonoperated side. Two surgeons measured the cross-sectional area (CSA) of obliquus capitis inferior (OCI) and semispinalis cervicis (SSC) muscle before and after surgery to determine atrophy rates (ARs). Additionally, we examined range of motion (ROM), sagittal vertical axis (SVA), neck visual analogue scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) score to assess potential changes in alignment and consequent clinical outcomes following posterior cervical surgery. RESULTS: We measured the CSA of OCI and SSC before surgery, and at 6 and 12 months postoperatively. Based on these measurements, the AR of the nonoperated SSC was 0.1% ± 8.5%, the AR of the operated OCI was 2.0% ± 7.2%, and the AR of the nonoperated OCI was -0.7% ± 5.1% at the 12 months after surgery. However, the AR of the operated side's SSC was 11.2% ± 12.5%, which is a relatively higher value than other measurements. Despite the atrophic change of SSC on the operated side, there were no prominent changes observed in SVA, C0-2 ROM, and C2-7 ROM between preoperative and 12 months postoperative measurements, which were 11.8 ± 10.9 mm, 16.3° ± 5.9°, and 48.7° ± 7.7° preoperatively, and 14.1 ± 11.6 mm, 16.1° ± 7.2°, and 44.0° ± 10.3° at 12 months postoperative, respectively. Improvement was also noted in VAS, NDI, and JOA scores after surgery with JOA recovery rate of 77.3% ± 29.6%. CONCLUSION: C2 recapping laminoplasty could be a useful tool for addressing pathologies around the upper cervical spine, potentially mitigating muscle atrophy and reducing postoperative neck pain, while maintaining sagittal alignment and ROM.

Association of facet tropism and progressive facet arthrosis after lumbar total disc replacement using ProDisc-L.

PURPOSE: The purpose of this retrospective study was to examine the association of facet tropism and progressive facet arthrosis (PFA) after lumbar total disc replacement (TDR) surgery using ProDisc-L. METHODS: A total of 51 segments of 42 patients who had undergone lumbar TDR using ProDisc-L between October 2003 and July 2007 and completed minimum 36-month follow-up period were retrospectively reviewed. The changes of facet arthrosis were categorized as non-PFA and PFA group. Comparison between non-PFA and PFA group was made according to age, sex, mean follow-up duration, grade of preoperative facet arthrosis, coronal and sagittal prosthetic position and degree of facet tropism. Multiple logistic regression analysis was also performed to analyze the effect of facet tropism on the progression of facet arthrosis. RESULTS: The mean age at the surgery was 44.43 ± 11.09 years and there were 16 males and 26 females. The mean follow-up period was 53.18 ± 15.79 months. Non-PFA group was composed of 19 levels and PFA group was composed of 32 levels. Age at surgery, sex proportion, mean follow-up period, level of implant, grade of preoperative facet arthrosis and coronal and sagittal prosthetic position were not significantly different between two groups (p = 0.264, 0.433, 0.527, 0.232, 0.926, 0.849 and 0.369, respectively). However, PFA group showed significantly higher degree of facet tropism (7.37 ± 6.46°) than that of non-PFA group (3.51 ± 3.53°) and p value was 0.008. After adjustment for age, sex and coronal and sagittal prosthetic position, multiple logistic regression analysis revealed that facet tropism of more than 5° was the only significant independent predictor of progression of facet arthrosis (odds ratio 5.39, 95 % confidence interval 1.251-19.343, p = 0.023). CONCLUSIONS: The data demonstrate that significant higher degree of facet tropism was seen in PFA group compared with non-PFA group and facet tropism of more than 5° had a significant association with PFA after TDR using ProDisc-L.