Long-Term Outcomes of Nasoseptal Perforation Repair Using Anterior Maxillary Sinus Wall as an Interpositional Graft.

Background: Various graft materials have been used to repair nasoseptal perforation, but there is no standardized treatment method. The anterior maxillary sinus wall is flattened in appearance and can be easily obtained in a sufficient amount for a large-sized nasoseptal perforation.

Objectives: The aim of this study is to determine whether the anterior maxillary sinus wall is suitable as an interpositional graft in the surgical repair of septal or nasoseptal perforation.

The tumor necrosis factor family molecules LIGHT and lymphotoxins in sinus mucosa of patients with chronic rhinosinusitis with or without nasal polyps.

Background: Little is known about the role of lymphotoxins (LTs) family in the sinonasal mucosa of patients with chronic rhinosinusitis (CRS). This study aims at investigating the expression of LIGHT, LTα, LTβ, and their receptors, LTβR and HVEM in normal and inflammatory sinus mucosa, and the effect of LIGHT and LTalpha1beta2 on chemokine secretion in epithelial cells, epithelial permeability, and leukocyte migration.

Material And Methods: The expression of LTs family in sinonasal mucosa was evaluated with real-time PCR, immunohistochemistry, and western blot.

The Korean Version of the Fugl-Meyer Assessment: Reliability and Validity Evaluation.

Objective: To systematically translate the Fugl-Meyer Assessment (FMA) into a Korean version of the FMA (K-FMA).

Methods: We translated the original FMA into the Korean version with three translators and a translation committee, which included physiatrists, physical therapists, and occupational therapists. Based on a test-retest method, each of 31 patients with stroke was assessed by two evaluators twice, once on recruitment, and again after a week.

Does central sensitization affect hyperalgesia after staged bilateral total knee arthroplasty? A randomized controlled trial.

Objective: Osteoarthritis (OA) patients who undergo staged bilateral total knee arthroplasty (TKA) feel postoperative hyperalgesia in the second operated knee compared with the first knee. Ketamine is an important drug for central temporal summation and inhibition of secondary mechanical hyperalgesia. This study investigated whether central sensitization has a significant effect on hyperalgesia after consecutive operations.

Batch-to-Batch Consistency of SB4 and SB2, Etanercept and Infliximab Biosimilars.

Background: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2).

Decreased expression of type I (IFN-β) and type III (IFN-λ) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without nasal polyps.

Background: Little is known about antiviral responses in the sinonasal mucosal tissue of patients with chronic rhinosinusitis (CRS).

Objective: we investigated the presence of virus and the expression of Toll-like receptor (TLR) 3, TLR7, and interferon and interferon-stimulated genes (ISGs) in healthy mucosal tissue of control subjects and the inflammatory sinus mucosal tissue of CRS patients, and evaluated whether levels of interferons and ISGs might be affected by CRS-related cytokines and by treatment with macrolides, dexamethasone, or TLR3 and TLR7 agonists.

Methods: The presence of virus in the sinonasal mucosa was evaluated with real-time PCR.

Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier.

Background: Neutrophil extracellular traps (NETs) participate in innate immunity by trapping microorganisms. Their pathophysiological implications have not been defined in chronic rhinosinusitis (CRS).

Objective: We investigated the presence of NETs in nasal secretion of patients with stable or exacerbated CRS and evaluated whether NETs participate in the secretion of chemokines in sinonasal epithelial cells, the epithelial permeability, and transendothelial leucocyte migration, and elucidate whether NETs are released by macrolides and dexamethasone.

The Dual Inhibition of Met and EGFR by ME22S, a Novel Met/EGFR Bispecific Monoclonal Antibody, Suppresses the Proliferation and Invasion of Laryngeal Cancer.

Purpose: It has been reported that the abnormal activation of receptor tyrosine kinases is associated with the development of many human carcinomas and the high activation of EGFR and Met mediates the tumorigenicity of laryngeal carcinoma. In this study, we have done the therapeutic efficacy of ME22S (a novel EGFR/Met bispecific antibody) in laryngeal carcinoma in vitro and in vivo was thoroughly evaluated.

Methods: The effects of ME22S on cell viability was assessed through MTT assays, and then Western blotting and immunocytochemistry were used to determine the expression of EGFR and Met.

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD.

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD).

The effectiveness of pregabalin for post-tonsillectomy pain control: a randomized controlled trial.

Background: Although various analgesics have been used, postoperative pain remains one of the most troublesome aspects of tonsillectomy for patients.

Objective: The aim of the present study was to evaluate the effectiveness of premedication using pregabalin compared with placebo (diazepam) on postoperative pain control in patients undergoing tonsillectomy.

Methods: Forty-eight adult patients were randomly divided into a control group and a pregabalin group.

Endogenous production of hydrogen sulfide in human sinus mucosa and its expression levels are altered in patients with chronic rhinosinusitis with and without nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNPs) or CRS without nasal polyps (CRSsNPs) is characterized by persistent inflammation of sinonasal mucosa. No one causative factor fully explains for the pathological manifestations of CRS. Endogenous hydrogen sulfide (H2S) has been shown to participate in inflammatory diseases, functioning as an inflammatory mediator in various organs.

SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD.

Sirtuin1 (SIRT1), a protein/histone deacetylase, protects against the development of pulmonary emphysema. However, the molecular mechanisms underlying this observation remain elusive. The imbalance of tissue inhibitor of matrix metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema.

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway.

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs.

Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation.

Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities.

Redox regulation of SIRT1 in inflammation and cellular senescence.

Sirtuin 1 (SIRT1) regulates inflammation, aging (life span and health span), calorie restriction/energetics, mitochondrial biogenesis, stress resistance, cellular senescence, endothelial functions, apoptosis/autophagy, and circadian rhythms through deacetylation of transcription factors and histones. SIRT1 level and activity are decreased in chronic inflammatory conditions and aging, in which oxidative stress occurs. SIRT1 is regulated by a NAD(+)-dependent DNA repair enzyme, poly(ADP-ribose) polymerase-1 (PARP1), and subsequent NAD(+) depletion by oxidative stress may have consequent effects on inflammatory and stress responses as well as cellular senescence.

High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α.

High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo.

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.

Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD+-dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown.

Expression of SOCS1 and SOCS3 is altered in the nasal mucosa of patients with mild and moderate/severe persistent allergic rhinitis.

Background: The aim of this study was to evaluate the role of suppressor of cytokine signaling (SOCS) molecules, SOCS1 and SOCS3, which act as negative regulators of cytokine signaling in various allergic diseases, in patients with mild and moderate/severe persistent allergic rhinitis.

Methods: The expression and distribution pattern of SOCS1 and SOCS3 were analyzed in nasal mucosa and peripheral blood mononuclear cells (PBMC) of healthy controls, and patients with mild and moderate/severe persistent allergic rhinitis using RT-PCR, immunohistochemistry and Western blotting. IL-4, IL-13, IL-15 and IFN-γ expression was also analyzed in the nasal mucosa of each individual using RT-PCR and Western blotting.

Mitogen- and stress-activated kinase 1 (MSK1) regulates cigarette smoke-induced histone modifications on NF-κB-dependent genes.

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes.

The expression of adiponectin receptor is altered in mild and moderate/severe persistent allergic nasal mucosa.

Background: Adiponectin, one of the adipokines, has been implicated in the inflammatory process in patients with allergic rhinitis. The level of adiponectin is affected by immunotherapy. Considering the fact that adiponectin receptors (AdipoRs) mediate intracellular signaling events in response to the binding of adiponectin, the role of AdipoRs in healthy and allergic nasal mucosa should be determined.

NF-κB inducing kinase, NIK mediates cigarette smoke/TNFα-induced histone acetylation and inflammation through differential activation of IKKs.

Background: Nuclear factor (NF)-κB inducing kinase (NIK) is a central player in the non-canonical NF κB pathway, which phosphorylates IκB kinase α (IKKα) resulting in enhancement of target gene expression. We have recently shown that IKKα responds to a variety of stimuli including oxidants and cigarette smoke (CS) regulating the histone modification in addition to its role in NF-κB activation. However, the primary signaling mechanism linking CS-mediated oxidative stress and TNFα with histone acetylation and pro-inflammatory gene transcription is not well understood.

FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease.

Forkhead box class O 3a (FOXO3) is a member of the FoxO transcription factor subfamily, which regulates the expression of target genes not only through DNA binding as a transcription factor, but also through protein-protein interaction. Although FoxO3 is a well-known transcription factor involved in diverse biological processes, the role of FoxO3 in cigarette smoke (CS)-induced lung inflammation and injury has not been studied. It is, therefore, hypothesized that deficiency of FoxO3 leads to increased susceptibility to CS-induced lung inflammatory response and airspace enlargement.

Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation.

Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response.

Nrf2 deficiency influences susceptibility to steroid resistance via HDAC2 reduction.

Abnormal lung inflammation and oxidant burden are associated with a significant reduction in histone deacetylase 2 (HDAC2) abundance and steroid resistance. We hypothesized that Nrf2 regulates steroid sensitivity via HDAC2 in response to inflammation in mouse lung. Furthermore, HDAC2 deficiency leads to steroid resistance in attenuating lung inflammatory response, which may be due to oxidant/antioxidant imbalance.

Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury.

Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H₂O₂ and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6⁻/⁻mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of proinflammatory cytokines compared to wild-type (WT) mice.