Asia-Pacific survey of physicians' perceptions and managements of chronic rhinosinusitis.

BACKGROUND: The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions. OBJECTIVE: Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines. METHODS: A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines. RESULTS: Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment. CONCLUSIONS: This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Time-gated iterative phase conjugation for efficient light energy delivery in scattering media.

Light waves propagating through complex biological tissues are spatially spread by multiple light scattering, and this spread limits the working depth in optical bioimaging, phototherapy, and optogenetics. Here, we propose the iterative phase conjugation of time-gated backscattered waves for enhancing the light energy delivered to a target object embedded in a scattering medium. We demonstrate the enhancement of light energy delivered to a target object hidden behind a 200-µm-thick mouse skull by more than ten times in comparison with the initial random input. The maximum enhancement was reached in only 10 iterations, more than a hundred times smaller than existing methods based on either a time-gated reflection matrix or iterative feedback optimization of the time-gated reflection intensity. Consequently, the proposed method is less sensitive to sample perturbations. Furthermore, the number of images required for optimization remained almost unchanged with an increase in the illumination area, unlike existing methods, where the convergence time scales with the illumination area. The proposed method provides high operation speed over a wide illumination area, which can facilitate the use of wavefront shaping in practical applications.

Del-1, an Endogenous Inhibitor of TGF-ß Activation, Attenuates Fibrosis.

Uncontrolled activation of transforming growth factor (TGF)-ß results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-ß signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibrosis in mice by inhibiting αv integrin-mediated activation of TGF-ß. Del-1 bound to αvß6 integrin, an important activator of TGF-ß, and inhibited the binding of αvß6 integrin to the latency-associated peptide (LAP), thereby suppressing αv integrin-mediated activation of TGF-ß. Lack of Del-1 increased colocalization of αv integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-ß activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-ß1. Del-1 supplementation improved the pathological characteristics of the mice and reduced mortality. Thus, we propose that Del-1 is a negative regulator of TGF-ß activation and a potential anti-fibrotic factor.

Relationship between Sleep Duration, Sun Exposure, and Serum 25-Hydroxyvitamin D Status: A Cross-sectional Study.

Normal-range sleep duration is an important factor for general health and metabolism, and insufficient or excessive sleep is associated with chronic metabolic disease. Among the many factors that affect sleep duration, sun exposure plays an important role in maintaining regular circadian rhythm and is also involved in the production and activation of 25-hydroxyvitamin D [25(OH)D], which regulates various functions in the body. However, 25(OH)D is available through food and various nutritional supplements without sun exposure, so it is important to find out the complex relationship among sun exposure, vitamin D status, and sleep duration. The relationship between sun exposure, vitamin D status, and sleep duration was analyzed in the nationwide survey and examination of 25,534 study populations, after adjusting for demographic characteristics, physical characteristics, lifestyle status, and socio-demographic variables. Vitamin D status alone did not show the relationship with sleep duration, although there were statistical relationships in the various factors including sun exposure with sleep duration. There was a statistical difference in 25(OH)D according to sleep duration, only in low sun exposure group. Subjects with low sun exposure and excessive sleep duration comparatively lower 25(OH)D than those with normal-range sleep, even after adjustment for potentially confounding factors. Individuals with limited exposure to sunlight should maintain adequate vitamin D status to have an appropriate sleep duration for health.

The Research Trends of Pharmacopuncture Therapy on Cervical Pain Caused by Traffic Accidents.

OBJECTIVES: The purpose of this study is to comprehensively review Korean domestic studies and investigate the research trends of pharmacopuncture therapy on cervical pain caused by traffic accidents. METHODS: Domestic studies between February 1999 and May 2020 from four Korean databases were searched with combinations of keywords 'cervical pain', 'traffic accident', 'whiplash injury', and 'pharmacopuncture'. RESULTS: 17 studies were selected for review, including 7 randomized controlled trials, 5 retrospective observational studies, 3 case reports, and 2 non-randomized controlled trials. Each study was reviewed by published year, study type, types of pharmacopuncture solutions, selected acupuncture points, dosage of pharmacopuncture solutions, frequency of treatment, concurrent treatments, outcome measurements, and the effectiveness of pharmacopuncture therapy. The results are as follows (1) It showed that the total number of published studies had increased slightly in the last 10 years compared to the previous decade. (2) The pharmacopuncture solutions used in the studies were in the following order Bee-Venom (), Jungsongouhyul (), Hwangryunhaedoktang () and Soyeom (). Frequently used acupuncture points were GB20, GV21, A-shi point, GV16, EX-B2, and SI15 in order. (3) The most commonly used total injection dosage was 1.0 cc at a time, and the frequency of treatment was twice a week. (4) Concurrent treatments such as acupuncture, herbal medication, physical therapy and Chuna manual therapy were performed in all 17 studies. (5) Pharmacopuncture therapy showed positive effects on cervical pain caused by traffic accidents in all 17 studies reviewed. CONCLUSION: Pharmacopuncture therapy was effective in cervical pain caused by traffic accidents in all 17 studies selected. Further studies will be needed using more larger scales and more objective data to confirm the effectiveness of pharmacopuncture therapy and to generalize its application.

Developmental endothelial locus-1 prevents development of peritoneal adhesions in mice.

Postoperative peritoneal adhesions, fibrous bands formed in the peritoneal cavity following surgery, represent a common, challenging and costly problem faced by surgeons and patients, for which effective therapeutic options are lacking. Since aberrant inflammation is one of the key mechanisms underlying peritoneal adhesion formation, here we set out to study the role of developmental endothelial locus-1 (Del-1), which has been recently identified as an endogenous inhibitor of inflammation, in the formation of postoperative peritoneal adhesions using a mouse model of peritoneal adhesions induced by ischemic buttons. Del-1-deficient mice had a higher incidence of adhesions, and their adhesions had higher quality and tenacity scores. Del-1 deficiency also led to enhanced inflammation mediators and collagen production. Finally, Del-1 supplementation decreased the incidence and severity of postoperative peritoneal adhesions. Taken together, these results indicate a protective role for Del-1 in postoperative peritoneal adhesion formation.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

15,16-Dihydrotanshinone I suppresses IgE-Ag stimulated mouse bone marrow-derived mast cell activation by inhibiting Syk kinase.

ETHNOPHARMACOLOGICAL RELEVANCE: 15,16-Dihydrotanshinone I (DHT-I), isolated from the dried root of Salvia miltiorrhiza Bung, which is traditionally used to treat cardiovascular and inflammatory diseases agent in Chinese medicine. DHT-I has been reported to have a broad range of biological activities, including antibacterial activity, and has been used to treat circulatory disorders, hepatitis, inflammation, cancer, and neurodegenerative diseases. AIM OF THE STUDY: The aim of this study was to evaluate the anti-allergic inflammatory effects of DHT-I on degranulation and on the generation of eicosanoids, such as, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4), in IgE/Ag-stimulated bone marrow-derived mast cells (BMMCs). MATERIALS AND METHODS: The anti-allergic inflammatory activity of DHT-I was evaluated using BMMCs. The effects of DHT-I on mast cell activation were investigated by following degranulation and eicosanoid generation using ELISA and immunoblotting and immunoprecipitation techniques. RESULTS: DHT-I at a concentration of 20µM markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of FcεRI-mediated signaling pathways demonstrated that DHT-I inhibited the phosphorylations of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT), and inhibited downstream signaling process, including [Ca(2+)]i mobilization induced by the phosphorylation of phospholipase Cγ1 (PLCγ1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-κB (NF-κB) pathway. CONCLUSIONS: DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a FcεRI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases.

Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: A pilot study.

BACKGROUND: Keloids and hypertrophic scars are prevalent and psychologically distressful dermatologic conditions. Various treatment modalities have been tried but without complete success by any one method. OBJECTIVE: We evaluated the efficacy of a combination of intense pulsed light (IPL) device and intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to the recovery of skin barrier function. METHODS: Totally 52 Korean patients were treated by the combined treatment at 4-8-week intervals. Using digital photographs, changes in scar appearance were assessed with modified Vancouver Scar Scale (MVSS), physicians' global assessment (PGA) and patient's satisfaction score. In 12 patients, the stratum corneum (SC) barrier function was assessed by measuring transepidermal water loss (TEWL) and SC capacitance. RESULTS: Most scars demonstrated significant clinical improvement in MVSS, PGA and patient's satisfaction score after the combined therapy. A significant decrease of TEWL and elevation of SC capacitance were also documented after the treatment. CONCLUSION: The combination therapy (IPL + corticosteroid injection) not only improves the appearance of keloids and hypertrophic scars but also increases the recovery level of skin hydration status in terms of the skin barrier function.

Anti-allergic effects of So-Cheong-Ryong-Tang, a traditional Korean herbal medicine, in an allergic rhinitis mouse model.

The herbal medicine, So-Cheong-Ryong-Tang (SCRT) has been empirically used for the treatment of allergic rhinitis for hundreds of years; however, its in vivo effects on allergic rhinitis have been rarely elucidated. We aimed to evaluate the anti-allergic effects of SCRT in an allergic rhinitis mouse model and to examine the underlying mechanism(s) of its anti-allergic effects. BALB/c mice were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. SCRT (1 g/kg) was given to the treatment group, and multiple parameters of allergic responses were evaluated to determine the effects of SCRT on allergic rhinitis. SCRT reduced allergic symptoms, such as rubbing and sneezing, and eosinophil infiltration into the nasal mucosa. It also suppressed serum total IgE, OVA-specific IgE, and OVA-specific IgG1 levels and increased OVA-specific IgG2a level. SCRT significantly reduced expression of the Th2 cytokine, IL-4; however, the expression of IL-5, IFN-γ, and IL-10 was unchanged in the nasal mucosa of the treatment group (by real-time RT-PCR). In splenocyte culture, levels of both IL-4 and IL-5 decreased, and IFN-γ level increased in the treatment group; however, levels of IL-10 and TGF-ß were unaffected by administration of SCRT. This study shows that SCRT induced anti-allergic effects by decreasing, locally and systemically, the Th2 cytokine IL-4, isotype switching to IgE, and eosinophilic infiltration into the nasal mucosa in an allergic rhinitis mouse model. Thus, SCRT might be considered a potential therapeutic agent in treating allergic rhinitis.

Acorus gramineus inhibits microglia mediated neuroinflammation and prevents neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders. AIM OF STUDY: The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model. MATERIALS AND METHODS: Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues. RESULTS: LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo. CONCLUSION: Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.

Inhibitory effects of Acorus calamus extracts on mast cell-dependent anaphylactic reactions using mast cell and mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Acorus calamus Linn. (Araceae) is a traditional herbal plant used for centuries to treat various allergic symptoms including asthma and bronchitis. AIM OF THE STUDY: The present study was focused to provide a pharmacological basis for the traditional use of Acorus calamus in allergic symptoms using the mast cell-dependent anaphylactic reactions in in vitro and in vivo models. MATERIALS AND METHODS: Cell viabilities were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Dinitrophenyl-human serum albumin (DNP-HSA) induced ß-hexosaminidase and interleukin (IL)-4 productions in IgE-sensitized rat basophilic leukaemia (RBL-2H3) cells were measured by enzymatic assay and enzyme-linked immunosorbent assay (ELISA). Passive cutaneous anaphylaxis (PCA) reaction mouse model was implemented for in vivo studies. RESULTS: Hot water (HW), butylene glycol (BG), hexane (HE) and steam distilled (SD) extracts of Acorus calamus showed different cytoxicity levels evaluated in RBL-2H3 cells. Sub-toxic doses of HW extract suppressed the ß-hexosaminidase secretion and IL-4 production significantly and dose dependently in DNP-HSA induced IgE-sensitized RBL-2H3 cells compared to other extracts of Acorus calamus. Further, in vivo studies also revealed that the HW extract significantly inhibited the PCA reaction in mouse compared to the normal control group. CONCLUSION: HW extract of Acorus calamus most effectively inhibited degranulation and IL-4 secretion in DNP-HSA-stimulated RBL-2H3 cells and also reduced the mast cell-mediated PCA reaction in mouse, providing a therapeutic evidence for its traditional use in ameliorating allergic reactions.

Oral administration of Uncariae rhynchophylla inhibits the development of DNFB-induced atopic dermatitis-like skin lesions via IFN-gamma down-regulation in NC/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncariae rhynchophylla (UR) is an herb which has blood pressure lowering and anti-inflammatory effects and has been prescribed traditionally to treat stroke and vascular dementia. AIM OF STUDY: In the present study, we examined whether UR suppress Atopic dermatitis (AD)-like skin lesions in NC/Nga mice treated with 2, 4-dinitrofluorobenzene (DNFB) under SPF conditions. MATERIAL AND METHODS: The effect of UR in DNFB- treated NC/Nga mice was determined by measuring the skin symptom severity, levels of serum IgE, and of the amounts of IL-4 and IFN-gamma secreted by activated T cells in draining lymph nodes. RESULTS: Oral administration of UR to DNFB-treated NC/Nga mice was found to inhibit ear thickness increases and the skin lesions induced by DNFB. IFN-gamma production by CD4+ T cells from the lymph nodes of DNFB-treated NC/Nga mice was significantly inhibited by UR treatment, although levels of IL-4 and total IgE in serum were not. CONCLUSION: UR may suppress the development of AD-like dermatitis in DNFB-treated NC/Nga mice by reducing IFN-gamma production.

Inhibition of IL-8 production by green tea polyphenols in human nasal fibroblasts and A549 epithelial cells.

The attraction of leukocytes to tissues is essential in order for inflammation and the host response to infection to occur. Airway inflammation is a very common cause illness with a substantial impact on health care. Neutrophils play an essential role in the host defense and in inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Infiltration of neutrophils occurs as a response to chemoattractant molecules by resident tissue cells. The recruitment of neutrophils in airway inflammation may account for the generation of IL-8. To evaluate the effectiveness of green tea polyphenols in the modulation of airway inflammation through the blocking of neutrophil chemokine production, nasal mucosal fibroblasts and A549 bronchial epithelial cells were analyzed for the production of IL-8. Both nasal mucosal fibroblasts and bronchial epithelial cells produced significant amounts of IL-8 through stimulation of IL-1beta. Tea polyphenols were very effective in the inhibition of IL-8 production. Among the polyphenols tested, EGCG and ECG showed strong inhibitory activity in dose-dependent manners. EGC and EC showed moderate inhibition at 48 h culture, whereas (-)catechin was not effective. Production of IL-8 after stimulation by proinflammatory cytokines in both nasal fibroblasts and bronchial epithelial cells was significantly blocked by pretreatment with green tea polyphenols.

Optimal recovery of high-purity rutin crystals from the whole plant of Fagopyrum esculentum Moench (buckwheat) by extraction, fractionation, and recrystallization.

Rutin, one of the flavonoids derived from plants, is increasingly in demand in the food, pharmaceutical, and cosmetic industries due to its various biological and physiological activities including antioxidation, anti-inflammation, and anti-hypertension. The whole plant of buckwheat (Fagopyrum esculentum Moench) is a major source of natural rutin. This study developed a low-cost process encompassing the efficient extraction, fractionation, and recrystallization to obtain high-purity rutin from buckwheat, and it could improve the economic utilization of this abundant low-value agricultural product. The sequential separation and purification procedures established in this study involved extraction with 50% (v/v) aqueous ethanol at 80 degrees C for 1 h followed by elution with water and aqueous ethanols at 20% and 30% (v/v) on a styrene-based resin column, and recrystallization at 4 degrees C for 12 h. These conditions resulted in the recovery of 92% of total rutin with over 95% purity. In the present study, high-purity rutin was obtained from whole buckwheat through low-cost processes, the separation and purification strategy established in this study could provide valuable information to the relevant industries.