Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of ...allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.
Eosinophils are terminally differentiated granulocytes that have long been considered as destructive cells associated with Th2 type immune responses such as allergic inflammation and helminth ...infections. Recently, eosinophils have been actively studied as multifunctional leukocytes regulating an array of physiological responses through interaction with other immune cells. In this study, we examined the expression and function of Toll-like receptors (TLRs) in eosinophilic EoL-1 cells and demonstrated the expression of a number of immune mediators in activated EoL-1 cells and their interaction with the macrophage cell line THP-1 upon TLR4 ligand stimulation. EoL-1 cells differentiated with butyrate increased expression of TLR3, TLR4, and TLR7 at mRNA and protein level with flow cytometry analysis. Mature eosinophils derived from human cord blood CD34
cells were subjected to RNA-sequencing, and showed the expression of a panel of TLR transcripts and TLR4 was the most highly expressed TLR. Among the cognate ligands of TLR3, TLR4, and TLR7, lipopolysaccharide (LPS) or palmitic acid significantly increased mRNA expression of immune mediators in differentiated EoL-1 cells. Notably, Western blot analysis of palmitic acid-treated differentiated EoL-1 cells showed significantly up-regulated expression of Th2 type cytokines and transcription factors driving eosinophil differentiation. To evaluate functional significance of TLR4 ligand-stimulated eosinophils, we added conditioned media (CM) from EoL-1 cells to differentiated THP-1 cells and assessed the expression of M1 macrophage or M2 macrophage-related markers. M1 and M2 macrophage markers were significantly upregulated by CM from LPS and palmitic acid stimulated EoL-1 cells, respectively. In addition, the adipose tissue of obese mice, where eosinophils are decreased due to obesity-induced inflammation, showed significantly decreased frequency of M2 macrophages, despite an increase in the total macrophage numbers. Based on these collective data, we proposed that eosinophils regulate both inflammatory and anti-inflammatory polarization of macrophages through functional changes induced by different TLR4 ligands.
Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). The former sometimes can be life threatening and the latter is the most ...common reason requiring revision surgery. This study was designed to evaluate the effect of newly developed chitosan gel (8% carboxymethyl chitosan, Surgi shield) on hemostasis and wound healing after ESS.
A prospective, randomized, double-blind controlled trial was conducted in 33 patients undergoing symmetric ESS. At the conclusion of the operation, Surgi shield was randomly applied on one side of the nasal cavity, with the opposite side acting as control and the bleeding quantity of the surgical field was evaluated every 2 minutes. And then, Merocel was placed in the ethmoidectomized areas of the both sides. Five milliliters of Surgi shield was applied to the Merocel of intervention side and saline was applied to the other side. Merocel in both nasal cavities was removed and 5 mL of Surgi shield was applied again to the intervention side on the second day after surgery. The nasal cavity was examined using a nasal endoscope and the degree of adhesion, crusting, mucosal edema, infection, and granulations were graded at 1, 2, and 4 weeks after surgery.
Complete hemostasis was rapidly achieved in the Surgi shield applied side compared with the control side at 2, 4, 6, 8, and 10 minutes after application of Surgi shield (P=0.007, P=0.004, P<0.001, P=0.001, and P<0.001, respectively). There were significantly less adhesions on the Surgi shield applied side at postoperative 1, 2, and 4 weeks (P=0.001, P<0.001, and P<0.001, respectively). The degree of mucosal edema, infection, crusting, or granulation formation assessed by the endoscopic features in the Surgi shield applied side was not significantly different from that of the control side (P>0.05). No adverse effects were noted in the patient series.
Surgi shield containing chitosan can be used safely to achieve rapid hemostasis immediately after ESS and to prevent adhesion formation.
Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in ...injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.
The main objectives of engine development, given the increased environmental regulations, are performance and efficiency improvement, and emission reduction. Notably, for diesel engines, the ...significance of fuel consumption and emission reduction is increasing because they emit harmful materials (PM, NOx); however, they are characterized by relatively low CO
2
emission in comparison with gasoline engines. Various technologies have been developed to solve these problems of diesel engines; however, majority of the diesel engines are developed in a steady state, and yet their certification and evaluation include the transient state. The transient operation of diesel vehicles leads to additional fuel consumption and emission of NOx; however, the impact of transient operation has not been discussed thus far. Therefore, this study quantitively investigates the fuel consumption and NOx emission during the transient operation of a diesel vehicle. First, the engine and vehicle’s efficiency and NOx emission differences are derived and analyzed in the steady state. Subsequently, the effects of the vehicle’s transient operation are analyzed. A vehicle’s transient operation can be classified into two types: operational and thermal transient effects. Finally, the respective transient effects are quantified and analyzed.
BRAFV600E mutation and F-18 fluorodeoxyglucose (FDG) uptake are potential prognostic factors of papillary thyroid cancer (PTC). This study was performed to investigate the relationship between the ...BRAFV600E mutation and F-18 FDG uptake in PTC.We retrospectively included 169 PTC patients who underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) before thyroidectomy from May 2009 to August 2012. Subjects were classified into overt PTC (>1 cm, n = 76) and papillary thyroid microcarcinoma (PTMC, n = 93) groups. Univariate and multivariate analyses were performed to assess the relationship between maximum standardized uptake value (SUVmax) of the primary tumors and clinicopathologic variables.The BRAFV600E mutation was detected in 82.2% (139/169). In all subjects, the BRAFV600E mutation and tumor size were independently related to SUVmax by multivariate analysis (P = 0.048 and P < 0.001, respectively). SUVmax was significantly higher in tumors with the BRAFV600E mutation than in those with wild-type BRAF (9.4 ± 10.9 vs 5.0 ± 4.1, P < 0.001). Similarly, in overt PTC group, the BRAFV600E mutation and tumor size were independently correlated with SUVmax (P = 0.032 and P = 0.001, respectively). By contrast, in PTMC group, only tumor size was significantly associated with SUVmax (P = 0.010). The presence of the BRAFV600E mutation is independently associated with high F-18 FDG uptake on preoperative PET/CT in patients with overt PTC, but this relationship was not evident in PTMC. This study provides a better understanding of the relationship between F-18 FDG uptake and BRAFV600E mutation in patients with PTC.
The etiopathogenesis of infantile haemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal haemangioma capillary ...formation. The role of NDRG1, a hypoxia‐inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile haemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile haemangioma and the correlation of these proteins with proliferation and involution. Primary endothelial cells were obtained, with parental agreement, from 12 infantile haemangioma patients during surgery; 6 patients had proliferating infantile haemangiomas and 6 had involuting IHs. We compared the infantile haemangioma tissues and primary endothelial cells with human vein endothelial cells using microarrays, real‐time PCR, Western blotting and immunohistochemical staining. Our data indicated that FOXO1 expression was downregulated in proliferating infantile haemangioma tissue. We found that the expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell proliferation and downregulated c‐MYC oncoprotein levels. Our findings suggest that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation plays an important role in infantile haemangiomas pathogenesis.
Abstract In the literature, numerous trials using neuroimaging techniques have investigated brain function in patients with post-traumatic stress disorder (PTSD). However, the contrasting results ...showed that improvements, including in the study design, were required to reach consistent and convincing conclusions. This study evaluated the functional neuroimaging pattern of resting cerebral blood flow and glucose metabolism in patients with PTSD related to sexual assault. Twelve patients were enrolled for both brain single photon emission computed tomography (SPECT) and18 F-fluorodeoxyglucose positron emission tomography (PET) investigations. All data were analyzed with statistical parametric mapping 2 (SPM2). The PTSD patients showed significant relative decreases in perfusion in the left hippocampus and in the basal ganglia compared with the control group. The PTSD group also had significantly lower cerebral glucosemetabolic activity in the left hippocampus and the superior temporal and precentral gyri than in the control group. These specific patterns of perfusion and glucose metabolism may be closely related to various neurophysiologic symptoms of PTSD.
Parasitic organisms are incapable of de novo fatty acid synthesis due to a down-regulated expression of enzymes involved in the oxygen-dependent pathway. We investigated the uptake of host lipids by ...a 150-kDa hydrophobic ligand-binding protein (HLBP) of Taenia solium metacestode, an agent causative of neurocysticercosis. The protein was found to be a hetero-oligomeric complex consisting of multiple subunits (Mr 7, 10, and 15 kDa within pH 8.0-9.7), which may originate from four unique genes of 7- and 10-kDa gene families with 2-3 polymorphic alleles/paralogs. The 15-kDa protein represented glycosylated forms of the 10-kDa. With high binding affinity to lipid analogs, these subunits evidenced high-level sequence identity with other cestode HLBPs and form a novel clade associated with excretory-secretory type HLBP. In vitro experiments with viable worms suggested that the excreted 150-kDa protein might bind to lipids, and participate in the translocation of host lipids across the syncytial membrane. This process was substantially inhibited by the specific anti-150 kDa antibodies. The protein was localized in the parasite syncytium and in the lipid droplets within host granuloma wall, where significant lipase activity was expressed. HLBP-mediated uptake of the host lipid may be critical for the parasite survival and thus could be targeted by chemotherapeutics and/or vaccine.
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