Xin-Yi-Qing-Fei-Tang and its critical components reduce asthma symptoms by suppressing GM-CSF and COX-2 expression in RBL-2H3 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) XYQFT is composed of 10 herbs. According to the NHIRD, XYQFT is one of the top ten most commonly used TCM prescriptions for asthma treatment. AIM OF THE STUDY: The aim of this study was to explore whether XYQFT reduces asthma symptoms in a mouse model of chronic asthma and determine the immunomodulatory mechanism of mast cells. MATERIALS AND METHODS: BALB/c mice were intratracheally (it) stimulated with 40 µL (2.5 µg/µL) of Dermatophagoides pteronyssinus (Der p) once a week for 6 consecutive weeks and orally administered XYQFT at 1 g/kg 30 min before Der p stimulation. Airway hypersensitivity, inflammatory cells in the BALF and total IgE in the blood were assessed in mice. In addition, RBL-2H3 cells (mast cells) were stimulated with DNP-IgE, after which different concentrations of XYQFT were added for 30 min to evaluate the effect of XYQFT on the gene expression and degranulation of DNP-stimulated RBL-2H3 cells. After the compounds in XYQFT were identified using LC‒MS/MS, the PBD method was used to identify the chemical components that inhibited the expression of the GM-CSF and COX-2 genes in mast cells. RESULTS: The airway hypersensitivity assay demonstrated that XYQFT significantly alleviated Der p-induced airway hypersensitivity. Moreover, cell counting and typing of bronchoalveolar lavage fluid revealed a significant reduction in Der p-induced inflammatory cell infiltration with XYQFT treatment. ELISA examination further indicated a significant decrease in Der p-induced total IgE levels in serum following XYQFT administration. In addition, XYQFT inhibited the degranulation and expression of genes (IL-3, IL-4, ALOX-5, IL-13, GM-CSF, COX-2, TNF-α, and MCP-1) in RBL-2H3 cells after DNP stimulation. The compounds timosaponin AIII and genkwanin in XYQFT were found to be key factors in the inhibition of COX-2 and GM-CSF gene expression in mast cells. CONCLUSION: By regulating mast cells, XYQFT inhibited inflammatory cell infiltration, airway hypersensitivity and specific immunity in a mouse model of asthma. In addition, XYQFT synergistically inhibited the expression of the GM-CSF and COX-2 genes in mast cells through timosaponin AIII and genkwanin.

Evaluation of You-Gui-Wan critical compounds inhibiting ALOX-5 and HDC gene expression in RBL-2H3 cells using a fractional factorial design.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) You-Gui-Wan (YGW) has been used to treat asthma for hundreds of years. AIM OF THE STUDY: YGW is composed of 10 types of medicinal materials. However, the immune mechanism of YGW in asthma treatment has not been elucidated. Therefore, this study investigated asthma symptoms attenuated by YGW and the underlying immune regulatory mechanism. MATERIALS AND METHODS: Intratracheal (i.t.) stimulation of BALB/c mice with Dermatophagoides pteronyssinus (Der p) was performed once per week (40 µL, 2.5 µg/µL). For six consecutive weeks, different doses of YGW (0.2 g/kg and 0.5 g/kg) were orally administered 30 min before stimulation with Der p. After the last stimulation, airway hyperreactivity, lung gene expression, and total immunoglobulin E (IgE) in blood were evaluated using a whole-body plethysmograph system, real-time PCR, and ELISA, respectively. In addition, DNP-IgE/DNP-BSA was added to stimulate mast cells (RBL-2H3), and YGW or various compound compositions (Trial) were added to RBL-2H3 cells for 30 min to evaluate the effects of the drug on mast cell degranulation and on gene expression. JMP 5.1 software was used to design and analyze YGW's critical compounds by which it inhibited ALOX-5 and HDC gene expression in RBL-2H3 cells. RESULTS: YGW significantly decreased serum total IgE levels and airway hyperresponsiveness in asthmatic mice. YGW also reduced the gene expression of IL-6, TNF-α, IL-4, IL-13, and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. YGW and the compound (Trial 21) present in YGW inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells. CONCLUSION: The experimental results indicate that YGW exhibits anti-airway hyperresponsiveness and specific immunomodulatory effects. In addition, YGW synergistically inhibits ALOX-5 and HDC gene expression in mast cells through a combination of 21 compounds, including luteolin, quercetin, and ß-carotene.

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.

Nitrogen Functionalities of Amino-Functionalized Nitrogen-Doped Graphene Quantum Dots for Highly Efficient Enhancement of Antimicrobial Therapy to Eliminate Methicillin-Resistant Staphylococcus aureus and Utilization as a Contrast Agent.

There is an urgent need for materials that can efficiently generate reactive oxygen species (ROS) and be used in photodynamic therapy (PDT) as two-photon imaging contrast probes. In this study, graphene quantum dots (GQDs) were subjected to amino group functionalization and nitrogen doping (amino-N-GQDs) via annealing and hydrothermal ammonia autoclave treatments. The synthesized dots could serve as a photosensitizer in PDT and generate more ROS than conventional GQDs under 60-s low-energy (fixed output power: 0.07 W·cm-2) excitation exerted by a 670-nm continuous-wave laser. The generated ROS were used to completely eliminate a multidrug-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA), a Gram-positive bacterium. Compared with conventional GQDs, the amino-N-GQDs had superior optical properties, including stronger absorption, higher quantum yield (0.34), stronger luminescence, and high stability under exposure. The high photostability and intrinsic luminescence of amino-N-GQDs contribute to their suitability as contrast probes for use in biomedical imaging, in addition to their bacteria tracking and localization abilities. Herein, the dual-modality amino-N-GQDs in PDT easily eliminated multidrug-resistant bacteria, ultimately revealing their potential for use in future clinical applications.

l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-ß, Production by Neonatal Regulatory T Lymphocytes.

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-ß production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.

What Taiwan contributes to the world of allergy and clinical immunology?

In commemorate the 9th Asia Pacific Congress of Allergy, Asthma, and Clinical Immunology (APCAACI) in Taipei, Taiwan in November this year, some of the seminar works and contributions by the researchers from Taiwan to the advance in the field of allergy and clinical immunology, such as DNA vaccine, traditional Chinese medicine, anti-IgE antibody, and personalized medicine for severe drug allergic reaction, are summarized in this special review.

Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation.

BACKGROUND: This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured. METHODS: LA4 cells were stimulated with 100 µg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin.Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 µg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 µl incomplete Freund's adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 µl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy. RESULTS: XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT. CONCLUSION: XQLT alleviated allergic inflammation including AHR, IgE elevation and eosinophil infiltration in Der p stimulated mice by regulating neurotrophin and reducing TARC. These results revealed the potential pharmacological targets on which the XQLT decotion exerts preventive and therapeutic effects in an allergic asthma mouse model.

Xiao-Qing-Long-Tang attenuates allergic airway inflammation and remodeling in repetitive Dermatogoides pteronyssinus challenged chronic asthmatic mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-Qing-Long-Tang (XQLT) has been used for centuries in Asia to effectively treat patients with bronchial asthma. AIM OF THE STUDY: We previously found that single and multiple doses of XQLT administered to sensitized mice before allergen challenge resulted in suppressed airway hyper-responsiveness and airway inflammation. In this study we aimed to investigate whether XQLT has the potential to attenuate the severity of asthma symptoms, and immunomodulatory mechanism of XQLT in a repetitive Dermatogoides pteronyssinus (D. pteronyssinus)-challenged chronic asthmatic mice model. MATERIALS AND METHODS: BALB/c mice were intratracheally (i.t.) inoculated with five doses of D. pteronyssinus (50 µl, 1mg/ml) and orally administered of XQLT (1 g/kg) at 1-week intervals. At three days after the last challenge, mice were sacrificed to evaluate airway remodeling, inflammation, lung histological features, and the expression profiles of cytokines and various genes. RESULTS: XQLT significantly reduced bronchial inflammatory cell infiltration and airway remodeling. It inhibited D. pteronyssinus-induced total IgE and D. pteronyssinus-specific IgG1 in serum, and changed the "T(H)2-bios" in BALF by inhibiting the activation of NF-κB. Collagen assay and Histopathology indicated that XQLT reduced airway remodeling in the lung. Simultaneously, the RT-PCR analysis showed that XQLT downregulated IL-10, IL-13, RANTES, Eotaxin, and MCP-1 mRNA expression in the lung. Moreover, EMSA and immunohistochemistry staining demonstrated that XQLT inhibited NF-κB expression in the nucleus of bronchial epithelial cells. CONCLUSIONS: These results suggest that XQLT exhibits anti-airway inflammatory, anti-airway remodeling, and specific immunoregulatory effects in a chronic asthmatic mice model.

House dust mite Dermatophagoides farinae augments proinflammatory mediator productions and accessory function of alveolar macrophages: implications for allergic sensitization and inflammation.

In this study, we examine the effects of Dermatophagoides farinae (Der f), a major source of airborne allergens, on alveolar macrophages (AMs), and we also test its contribution to allergic responses in mice. Der f activated NF-kappaB of AMs and, unlike OVA or LPS stimulation, up-regulated IL-6, TNF-alpha, and NO. In addition, it down-regulated antioxidants, but affected neither the expression nor production of IL-12. Der f-stimulated AMs expressed enhanced levels of costimulatory B7 molecules, supported T cell proliferation, and promoted Th2 cell development. The enhanced accessory function was suppressed by blockade mAbs to B7.2, IL-6, and TNF-alpha and by N-monomethyl-L-arginine, an NO synthase inhibitor, and N-acetylcysteine, a thiol antioxidant, whereas it was augmented by (+/-)-S-nitroso-N-acetylpenicillamine, an NO donor. Arg-Gly-Asp-Ser peptide and neo-glycoproteins galactose-BSA and mannose-BSA inhibited the Der f-induced IL-6 and TNF-alpha productions and enhanced accessory function of AMs. Der f was more potent than OVA for inducing pulmonary eosinophilic inflammation, NO, and serum allergen-specific IgG1 Ab production in mice. AMs from Der f-challenged mice expressed enhanced levels of B7 and augmented T cell proliferation ex vivo. In Der f-challenged mice, respiratory syncytial virus infection (5 x 10(5) pfu; 3 days before Der f instillation) augmented Der f-specific Ab production, whereas dexamethasone (50 mg/kg; 1 h before Der f instillation) diminished the allergic airway inflammation and Ab response. We conclude that AMs are sensitive targets for Der f and that the Der f-induced proinflammatory responses may represent an important mechanism in mediating the development of allergic sensitization and inflammation.