Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024.

BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-Oxo-ETE) is a metabolite of arachidonic acid shown to promote biological activities in different cell types. SUMMARY: 5-Oxo-ETE is synthesized from the 5-lipoxygenase product 5S-HETE (5S-hydroxy-6,8,11,14-eicosatetraenoic acid) in the presence of the nicotinamide adenine dinucleotide phosphate (NADP)+-dependent enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under some conditions that promote oxidation of NADPH to NADP+, such as the respiratory burst in phagocytic cells, eosinophils, and neutrophils, oxidative stress in monocytes and dendritic cells, and cell death, 5-Oxo-ETE synthesis can be dramatically increased. In addition, 5-Oxo-ETE can also be formed in the absence of 5-lipoxygenase in cells through transcellular biosynthesis by inflammatory cell-derived 5S-HETE. This compound performs its biological activities by the highly selective Gi/o-coupled OXE receptor, which is highly expressed on eosinophils, neutrophils, basophils, and monocytes. As such, 5-Oxo-ETE is a potent chemoattractant for these inflammatory cells, especially for eosinophils. KEY MESSAGES: Although the pathophysiological role of 5-Oxo-ETE is not clearly understood, 5-Oxo-ETE may be a significant mediator in allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis. And targeting the OXE receptor may be a novel therapy for this kind of inflammatory condition. Nowadays, selective OXE receptor antagonists are currently under investigation and could become potential therapeutic agents in allergy.

Quantitative tracing the sources and human risk assessment of complex soil pollution in an industrial park.

Pollution in industrial parks has long been characterized by complex pollution sources and difficulties in identifying pollutant origins. This study focuses on a typical industrial park consisting of 11 factories (F1-F11) including organic pigment, inorganic pigment, and chemical factories in Hunan Province, China, here, a total of 327 sample points were surveyed. Eight pollutants (Mn, Cd, As, Co, NH3-N, l, 1,2-Trichloroethane, chlorobenzene, and petroleum hydrocarbons) were classified as contaminants of concern (COCs). This study assessed the contributions of driving factors to the distribution of COCs in the soil. Pollutant source apportionment was conducted using positive matrix factorization (PMF) and random forest (RF). The results revealed that the main factors driving pollution are groundwater migration, non-compliant emissions, leaks during production, and interactions among pollutants. The primary pollution sources were four chemical factories and an inorganic pigment factory. Source 5 demonstrates significant correlations with TCA (29.6%), CB (30%), and As (31.6%). Two chemical factories (F7 and F10) are the most significant pollution source with a risk assessment contribution rate of more than 60%. The present study sheds some light on the contamination characteristics, source apportionment and source-health risk assessment of COCs in industrial park. By utilizing the proposed research framework, decision-makers can effectively prioritize and address identified pollution sources.

Effect of Local Corticosteroid Administration on CD8+CD25+Foxp3+ Tregs in Neutrophilic CRSwNP.

INTRODUCTION: CD8+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in human's immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8+CD25+Foxp3+ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs). METHODS: Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8+CD25+Foxp3+ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1ß, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures. RESULTS: CD8+CD25+Foxp3+ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1ß, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8+CD25+Foxp3+ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8+CD25+Foxp3+ Tregs treatment in vitro. CONCLUSION: The findings indicate that CD8+CD25+Foxp3+ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.

Efficacy of Budesonide Nasal Spray on Neutrophilic Chronic Rhinosinusitis with Nasal Polyps: A Combined Clinical and Experimental Study.

BACKGROUND: Neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP) occur predominantly in Asian subjects. Appropriate treatments for this endotype have not been elucidated. This study aimed to evaluate the efficacy of budesonide nasal spray on neutrophilic CRSwNP. MATERIALS AND METHODS: Fifteen neutrophilic CRSwNP patients were included, and then they received budesonide nasal spray treatment for 3 months. Biopsies of nasal polyps (NPs) were obtained from these subjects. Their clinical indexes were scored using Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT)-22, and Endoscopic Appearances (EAs). Histological analyses were used to assess numbers of neutrophils, goblet cells, and submucosal gland cells in NPs. Percentages of CD8+ T cells and CD4+CD25+Foxp3+ regulatory T cells (Tregs) were evaluated using flow cytometry. Mucin 5AC (MUC5AC), MUC5B, myeloperoxidase (MPO), interferon (IFN)-γ, and interleukin (IL)-1ß and their mRNAs were also examined. After that, we cultured NP tissues in vitro and evaluated the abovementioned inflammatory parameters before and after the administration of budesonide. RESULTS: Budesonide nasal spray did not improve clinical evaluations including VAS, SNOT-22, and EA scores. Numbers of neutrophils and goblet cells, the score of submucosal gland cells, percentages of CD8+ T cells and Tregs, MUC5AC, MUC5B, MPO, IFN-γ, and IL-1ß and their mRNAs were not decreased in NPs after the budesonide treatment. Furthermore, the administration of budesonide into NP cultures also did not reduce their levels in comparison with those before the treatment. CONCLUSION: These findings demonstrate that budesonide treatment may not alleviate the inflammatory condition in neutrophilic CRSwNP.

Efficacy of lianhuaqingwen granules in the management of chronic rhinosinusitis without nasal polyps.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a complicated disease with clinical symptoms that are impacted by the absence or presence of nasal polyps (CRSsNP or CRSwNP). Understanding of the different treatments of CRS is very significant in selecting appropriate therapies and preventing exacerbation relevant to this chronic inflammation. This study was aimed to evaluate the effect of Chinese traditional medicine lianhuaqingwen granules on CRSsNP. MATERIALS AND METHODS: CRSsNP patients were enrolled and randomized into placebo or lianhuaqingwen (LHQW) granules treatment group (placebo or LHQW group). Their clinical symptoms were scored using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT)-22. Nitric oxide (NO) from nasal cavity and sinus and nasal resistance were also examined. Then, nasal biopsy samples and nasal lavage fluid (NLF) were obtained from these patients, and histologic characteristics of nasal mucosa and T cell subpopulations patterns in the NLF were evaluated. Finally, inflammatory mediators in the NLF were assessed in both groups. RESULTS: One hundred and forty patients with CRSsNP finished this one-month study. VAS and SNOT-22 scores and nasal resistance were all decreased distinctly after the treatment of LHQW, but not after placebo. However, the nasal NO concentration was increased in LHQW administration group in comparison with placebo group. There were significant differences in above parameters between these two treatments. Histologic changes in nasal mucosa were improved only in LHQW group. CD4+ and CD8+ T cells were all downregulated in the LHQW treatment group, but not in placebo group. Inflammatory mediators from the NLF were decreased in LHQW treatment group compared to placebo group. Furthermore, there were significant changes between these two groups in CD4+ and CD8+ T cell subpopulations and concentrations of inflammatory substances. CONCLUSION: These findings demonstrate that LHQW granules treatment may control the inflammation in nasal mucosa and result in the improvement of CRSsNP. This Chinese medicine might become a promising therapy in the management of this disease.

5-Oxo-ETE from Nasal Epithelial Cells Upregulates Eosinophil Cation Protein by Eosinophils in Nasal Polyps in vitro.

BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a potent eosinophil chemoattractant and activator that is synthesized not only in inflammatory cells but also in bronchial epithelial cells. The purpose of this study is to clarify whether 5-oxo-ETE can promote the production of eosinophil cation protein (ECP) by eosinophils in nasal polyps (NP) in vitro, and whether normal nasal epithelial cells can produce this lipid mediator in response to oxidative stress. MATERIALS AND METHODS: Nasal biopsy samples were obtained from normal subjects or subjects with chronic rhinosinusitis with NP. The infiltration of eosinophil in NP was detected and cultured. After that, concentrations of ECP in eosinophil and NP cultures were evaluated after the treatment of 5-oxo-ETE or 5-oxo-ETE + its receptor (OXER) antagonist, pertussis toxin (PT). Then we studied the synthesis of 5-oxo-ETE after H2O2 stimulation by normal nasal epithelial cells and by epithelial cells of NP alone in the cultures, and also determined the OXER expression in NP. RESULTS: The number of infiltrative eosinophils in NP was increased. The ECP levels in eosinophil and NP cultures were enhanced after the administration of 5-oxo-ETE, and decreased by the PT treatment. 5-Oxo-ETE was upregulated in the cultures of nasal epithelial cells in the presence of H2O2 and of NP epithelial cells alone. The OXER was expressed in inflammatory cells, and not in epithelial cells. CONCLUSION: 5-Oxo-ETE produced by nasal epithelial cells may play a role in the formation and development of NP.

Activations of group 2 innate lymphoid cells depend on endotypes of chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a complicated disease with several variants caused by different cellular and molecular mechanisms. The characterization of this heterogeneity supports the definition that the disease consists of many endotypes, such as eosinophilic and neutrophilic CRS, and so on. This study aimed to explore group 2 innate lymphoid cells (ILC2s) in neutrophilic CRS without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP), and evaluate ILC2s across characteristics of the disease. METHODS: Nasal biopsy samples were obtained from normal subjects or subjects with CRSsNP or CRSwNP during surgery. ILC2s were sorted and purified as CD45+Lin-CD127+CD4-CD8-CRTH2+CD161+ cells through flow cytometry, and were compared among three groups of subjects. Then, these samples were cultured in vitro, and inflammatory factors were assessed in tissue cultures. After that, human recombinant (rm) interleukin (IL)-33 or IL-17 were administered into the cultures, and we again examined relevant inflammatory substances. RESULTS: ILC2s were upregulated in neutrophilic CRSsNP and CRSwNP patients, and there were no statistical differences between them. Eosinophil cation protein (ECP), myeloperoxidase (MPO), IL-25, IL-33, IL-5, IL-13, interferon (IFN)-γ and IL-17 were increased in the cultures, however, only concentrations of MPO, IFN-γ and IL-17 were enhanced in CRSwNP tissues compared to CRSsNP ones. After administration of rmIL-33, ECP, IL-5 and IL-13 were all increased in tissues from CRSsNP and CRSwNP patients, however, there were no significant differences between them. Finally, we evaluated concentrations of several above inflammatory factors after the treatment of rmIL-17, and found that MPO and IFN-γ were enhanced in these two phenotypes of patients, and were elevated significantly in CRSwNP tissue cultures. CONCLUSION: These findings show that ILC2s might be inactivated in neutrophilic CRSsNP and CRSwNP based on this pilot study.

Xylitol nasal irrigation in the treatment of chronic rhinosinusitis.

OBJECTIVE: To evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus. MATERIALS AND METHODS: Patients with CRS were enrolled and symptoms were assessed by Visual Analog Scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22). Nasal NO and iNOS mRNA in the right maxillary sinus were also examined. Then, they were treated with XNI (XNI group) or saline nasal irrigation (SNI, SNI group) for 30days, after which their symptoms were reassessed using VAS and SNOT-22, and nasal NO and iNOS mRNA in the right maxillary sinus were also reexamined. RESULTS: Twenty-five out of 30 patients completed this study. The scores of VAS and SNOT-22 were all reduced significantly after XNI treatment, but not after SNI. The concentrations of nasal NO and iNOS mRNA in the right maxillary sinus were increased significantly in XNI group. However, significant changes were not found after SNI treatment. Furthermore, there were statistical differences in the assessments of VAS and SNOT-22 and the contents of nasal NO and iNOS mRNA in the right maxillary sinus between two groups. CONCLUSIONS: XNI results in greater improvement of symptoms of CRS and greater enhancement of nasal NO and iNOS mRNA in maxillary sinus as compared to SNI.

Analysis of soil pollution characteristics and influencing factors based on ten electroplating enterprises.

The electroplating industry encompasses various processes and plating types that contribute to environmental pollution, which has led to growing public concern. To investigate related soil pollution in China, the study selected 10 sites with diverse industrial characteristics distributed across China and collected 1052 soil samples to determine the presence of industrial priority pollutants (PP) based on production process and pollutant toxicity. The factors influencing site pollution as well as proposed pollution prevention and control approaches were then evaluated. The results indicate the presence of significant pollution in the electroplating industry, with ten constituents surpassing the risk screening values (RSV). The identified PP consist of Cr(VI), zinc (Zn), nickel (Ni), total chromium (Cr), and petroleum hydrocarbons (C10-C40). PP contamination was primarily observed in production areas, liquid storage facilities, and solid zones. The vertical distribution of metal pollutants decreased with soil depth, whereas the reverse was true for petroleum hydrocarbons (C10-C40). Increase in site production time was strongly correlated with soil pollution, but strengthening anti-seepage measures in key areas can effectively reduce the soil exceedance standard ratio. This study serves as a foundation for conceptualizing site repair technology in the electroplating industry and offers a reference and methodology for pollution and source control in this and related sectors.

CD8+ Tregs ameliorate inflammatory reactions in a murine model of allergic rhinitis.

BACKGROUND: CD8+CD25+fork-head box transcription factor (Foxp3)+ regulatory T cells (CD8+ Tregs) play a role in immune tolerance. However, the role of these cells in allergic rhinitis (AR) has not been elucidated. The study aimed to evaluate influences of CD8+ Tregs on inflammatory conditions in a murine model of AR. METHODS: A murine model of AR was established. CD8+ Tregs were isolated from mice nasal mucosa and cultured in vitro. We examined interleukin (IL)-10 and transforming growth factor (TGF)-ß in cell cultures. Then, we administered CD8+ Tregs into mice nasal mucosal cultures, and examined eosinophil cation protein (ECP), IL-4, IL-5 and IL-13 in these cultures. Finally, we adoptively transferred CD8+ Tregs into mice models, and evaluated percentages of CD8+ Tregs, numbers of sneezing and nasal rubbing, and counts of eosinophils and contents of ECP, IL-4, IL-5, IL-13, IL-10 and TGF-ß in nasal lavage fluid (NLF) in mice. RESULTS: The percentage of CD8+ Tregs from AR mice was reduced. IL-10 and TGF-ß were increased in cell cultures from AR mice. ECP, IL-4, IL-5 and IL-13 were decreased after the AR mice CD8+ Tregs administration in mucosal cultures. However, their contents were not changed after normal CD8+ Tregs treatment. Additionally, the adoptive transfer of AR CD8+ Tregs enhanced the percentage of CD8+ Tregs and levels of IL-10 and TGF-ß in NLF, reduced numbers of sneezing and nasal rubbing, and counts of eosinophils and concentrations of ECP, IL-4, IL-5 and IL-13 in NLF. However, normal CD8+ Tregs could not change above parameters. CONCLUSION: These findings show that CD8+ Tregs may inhibit inflammatory responses in the AR condition.

Influences of CD8+ Tregs on Peripheral Blood Mononuclear Cells from Allergic Rhinitis Patients.

OBJECTIVES: CD8+ (or CD4+ ) CD25+ fork-head box transcription factor (Foxp3)+ regulatory T cells (CD8+ or CD4+ Tregs) all play a significant role in immune homeostasis and tolerance. However, the role of CD8+ Tregs in allergic rhinitis (AR) have not been clearly elucidated. The present study was aimed to assess the influence of CD8+ Tregs on peripheral blood mononuclear cells (PBMCs) from AR patients. STUDY DESIGN: Prospective cross-sectional study. METHODS: Patients with AR were enrolled. PBMCs were obtained, and CD4+ and CD8+ Tregs were separated from PBMCs and cultured in vitro. We examined percentages of these Tregs in total CD4+ or CD8+ T cells, respectively. After that, we evaluated levels of interleukin (IL)-10 and transforming growth factor (TGF)-ß in Tregs cultures. Finally, we administered CD4+ and CD8+ Tregs from AR patients into PBMCs cultures and examined contents of IL-4 and IL-5. RESULTS: The percentages of CD4+ or CD8+ Tregs in the total CD4+ or CD8+ T cells from PBMCs in AR patients were reduced compared to normal subjects. However, IL-10 and TGF-ß and their mRNAs were increased in CD4+ and CD8+ Tregs cultures from AR patients, and there were no significant differences in their levels between these two Tregs cultures. IL-4 and IL-5 were increased in AR subjects' PBMCs compared to normal ones and decreased after the AR CD4+ or CD8+ Tregs administration. However, there were no statistical differences in IL-4 and IL-5 concentrations between these two Tregs treatments. CONCLUSIONS: The findings demonstrate that CD8+ Tregs may alleviate inflammatory responses in AR condition. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E316-E323, 2021.

Nuocytes from mesenteric lymph node promote allergic responses in a mouse model.

INTRODUCTION: Nuocytes play an important role in Type 2 immunity. However, the contribution of ILC2s to allergic rhinitis remains to be clearly elucidated. OBJECTIVE: To evaluate the role of nuocytes from mesenteric lymph node on allergic responses in mice. METHODS: After intraperitoneal administration of interleukin IL-25 and IL-33 to wild-type and Il17br-/-Il1rl1-/- double-deficient mice, nuocytes were purified from the the nasal-associated lymphoid tissue and mesenteric lymph nodes. Then, we assessed productions of IL-5 and IL-13 in nuocytes' cultures. Finally, we adoptively transferred the mesenteric lymph node-derived nuocytes from wild-type and Il17br-/-Il1rl1-/- mice to the murine model of allergic rhinitis to evaluate their roles in nasal allergic responses. RESULTS: We showed that nuocytes in the mesenteric lymph nodes of wild-type mice were upregulated after application of IL-25 and IL-33, and were induced to produce IL-5 and IL-13. Numbers of sneezing and nasal rubbing as well as eosinophils were all enhanced after the adoptive transfer of wild-type nuocytes. Concentrations of IL-5, IL-13, IL-25 and IL-33 in nasal lavage fluid of allergic mice were also increased. However, nuocytes fromIl17br-/-Il1rl1-/- mice did not increase sneezing and nasal rubbing and eosinophilia, and upregulate the above cytokines in the nasal lavage fluid. CONCLUSION: The findings demonstrate that nuocytes from the mesenteric lymph nodes of wild-type mice promote allergic responses in a mouse model.

[The role of budesonide on CD8⁺CD25⁺Foxp3⁺ Treg cells in neutrophilic nasal polyps].

Objective:CD8⁺CD25⁺Foxp3⁺regulatory T（Treg） cells are reduced in chronic rhinosinusitis with nasal polyps（CRSwNP）. However, the role of these cells in nasal polyps（NP） has not been fully investigated. The aim of this study was to evaluate the influence of budesonide treatment on these cells and to assess their roles in neutrophilic NP. Method:Eight neutrophilic CRSwNP patients were enrolled and received budesonide nasal spray treatment for three months. Nasal samples were obtained from normal mucosa or NP and cultured in vitro. CD8⁺CD25⁺Foxp3⁺Treg cells were isolated and purified from normal or NP tissues and cultured in vitro. Then transforming growth factor-ß（TGF-ß） and its mRNA were examined in those cell cultures. After that, those cells were administered into NP cultures. Finally, the concentrations of myeloperoxidase（MPO） and interferon（IFN） -γ were evaluated in those tissue cultures. Result:CD8⁺CD25⁺Foxp3⁺Treg cells were decreased in NP compared to normal tissues. Budesonide treatment did not increase the percentage of those cells in NP. TGF-ß and its mRNA were enhanced in CD8⁺CD25⁺Foxp3⁺Treg cell cultures from NP versus those from normal tissues. In addition, levels of MPO and IFN-γ were reduced after CD8⁺CD25⁺Foxp3⁺Treg cells administration. Conclusion:These findings indicated that CD8⁺CD25⁺Foxp3⁺Treg cells may play a role in the regulation of neutrophilic inflammation, and budesonide treatment may not influence these Treg cells.

Synthesis, micellar structures and emission mechanisms of an AIE and DDED-featured fluorescent pH- and thermo-meter.

A new nanoprobe, the luminescent diblock copolymer PNIPAM(MAh-4)-b-P4VP (PN4P), with pH- and thermo-responsive deprotonation-driven emission decay (DDED) and aggregation-induced emission (AIE) features was designed and synthesized. The nanoprobe PN4P can form micellar structures in water with reversible dual-responsive fluorescence (FL) behavior within a wide pH range of 2-11. The critical solution temperature was found at about 32, 30 and 27 °C as the pH switched from 2, 7 to 11. The critical pH value of the probe was about 4.0, and the micelles showed a core-shell inversion in response to pH and thermal stimuli, accompanied by a desirable emission tunability. P4VP as the micellar shell at pH = 2 was more easily dehydrated with the increase in temperature as compared to PNIPAM as the micellar shell at pH > 4. The strongest dehydration of the P4VP shell would make PN4P the most strongly aggregated and the most AIE-active, which supports the 2.10-fold most distinguished thermal-responsive emission enhancement at pH = 2. Moreover, a dramatic acidochromic redshift of the emission band from 450 (pH > 4) to 490 nm (pH = 2) was observed, and the maximum emission at pH = 2 was enhanced by about 2.07-fold as compared with that at pH = 7. Therefore, the probe displays the desired dual responses and good reversibility. AIE and DDED are the two major mechanisms responsible for the dual-responsive emission change, with AIE playing a more important role than DDED. This work offers a promising approach to interpreting temperature (range from 28 to 40 °C) and pH changes (range from 2 to 7) in water.

Intervention of Orai1 Influences the Response of Nuocytes From Allergic Rhinitis Mice to IL-33.

OBJECTIVE: Nuocytes are essential in innate type-2 immunity and contribute to the exacerbation of allergic rhinitis (AR). This study aimed to evaluate the intervention of Orai1 on the response of nuocytes from AR mice to interleukin (IL)-33. METHODS: We established a murine model of AR. Nuocytes were obtained from the mouse nasal-associated lymphoid tissue. Then, we assessed expressions of Orai1, Ca2+ mean fluorescence intensity (MFI) in nuocytes, and their cellular response to mouse recombinant (rm) IL-33. After that, we administered rmlentivirus vectors (lenti) that encoded small hairpin RNA (shRNA) against ORAI1 (lenti-ORAI1) into nuocytes cultures and again evaluated Orai1 and Ca2+ MFI in nuocytes and their response to rmIL-33. Finally, we adoptively transferred nuocytes alone or nuocytes transfected by lenti or lenti-ORAI1 to AR models to investigate their roles during allergic inflammation. RESULTS: We showed that Orai1 and Ca2+ MFI were upregulated in AR mice nuocytes. These cells were induced to produce more IL-5 and IL-13 by rmIL-33. However, the intervention of Orai1 by lenti-ORAI1 in nuocytes decreased Orai1 and Ca2+ MFI and reduced productions of aforementioned cytokines even after the administration of rmIL-33. Numbers of sneezing, nasal rubbing, and counts of eosinophils were all enhanced after the adoptive transfer of nuocytes. Concentrations of IL-5, IL-13, and IL-33 in the nasal lavage fluid (NLF) of allergic mice were also increased. However, the adoptive transfer of nuocytes transfected by lenti-ORAI1 decreased aforementioned parameters. CONCLUSION: These findings show that the intervention of Orai1 in nuocytes influences the response of nuocytes to rmIL-33.

CD4+ T cells induce productions of IL-5 and IL-13 through MHCII on ILC2s in a murine model of allergic rhinitis.

OBJECTIVE: CD4+ T cells play an important role not only in the induction of allergy but also in allergic inflammation. Group 2 innate lymphoid cells (ILC2s) also mediate type 2 immune responses in allergic rhinitis (AR). However, the relationships between CD4+ T cells and ILC2s in allergic condition are currently not well defined. The study aimed to evaluate the potential influences of CD4+ T cells on ILC2s in the murine model of AR. METHODS: A murine model of AR was established using ovalbumin (OVA), and OVA-induced ILC2s were sorted and purified from the mouse nasal-associated lymphoid tissue (NALT), and cultured in vitro. Then, the expression of major histocompatibility complex class II (MHCII) on ILC2s was examined. CD4+ T cells were separated from AR mice peripheral blood mononuclear cells (PBMCs). After that, productions of IL-5 and IL-13 on ILC2s cultures were assessed when CD4+ T cells or plus anti-MHCII antibody or anti-CD4 antibody were administered into the cultures. Finally, we adoptively transferred ILC2s alone or ILC2s plus anti-MHCII antibody to the murine model of AR to investigate their roles in the nasal allergic inflammation. RESULTS: We showed that ILC2s could be induced by OVA in the mouse NALT. The number and percentage of ILC2s in AR mice were increased. MHCII was expressed on ILC2s, and its protein and mRNA were all enhanced in allergic condition. IL-5 and IL-13 proteins and mRNAs were elevated after CD4+ T cells administration, and were reduced after these cells plus anti-MHCII antibody or anti-CD4 antibody application. Numbers of sneezing and nasal rubbing as well as counts of eosinophils in nasal lavage fluid (NLF) were all enhanced after the adoptive transfer of ILC2s when compared to AR mice. IL-5 and IL-13 in the NLF of allergic mice were also increased in comparison with AR group. However, above parameters were all decreased after the transfer of ILC2s plus anti-MHCII antibody versus AR mice or ILC2s-treated ones. CONCLUSION: These findings show that CD4+ T cells induce productions of IL-5 and IL-13 through MHCII on ILC2s in AR mice models.

Source profiles and contributions of biofuel combustion for PM2.5, PM10 and their compositions, in a city influenced by biofuel stoves.

Source and ambient samples were collected in a city in China that uses considerable biofuel, to assess influence of biofuel combustion and other sources on particulate matter (PM). Profiles and size distribution of biofuel combustion were investigated. Higher levels in source profiles, a significant increase in heavy-biomass ambient and stronger correlations of K+, Cl-, OC and EC suggest that they can be tracers of biofuel combustion. And char-EC/soot-EC (8.5 for PM2.5 and 15.8 for PM10 of source samples) can also be used to distinguish it. In source samples, water-soluble organic carbon (WSOC) were approximately 28.0%-68.8% (PM2.5) and 27.2%-43.8% (PM10) of OC. For size distribution, biofuel combustion mainly produces smaller particles. OC1, OC2, EC1 and EC2 abundances showed two peaks with one below 1 µm and one above 2 µm. An advanced three-way factory analysis model was applied to quantify source contributions to ambient PM2.5 and PM10. Higher contributions of coal combustion, vehicular emission, nitrate and biofuel combustion occurred during the heavy-biomass period, and higher contributions of sulfate and crustal dust were observed during the light-biomass period. Mass and percentage contributions of biofuel combustion were significantly higher in heavy-biomass period. The biofuel combustion attributed above 45% of K+ and Cl-, above 30% of EC and about 20% of OC. In addition, through analysis of source profiles and contributions, they were consistently evident that biofuel combustion and crustal dust contributed more to cation than to anion, while sulfate & SOC and nitrate showed stronger influence on anion than on cation.

Nuocytes from mesenteric lymph node promote allergic responses in a mouse model / Nuócitos de linfonodo mesentérico promovem respostas alérgicas em um modelo de camundongo

Abstract Introduction: Nuocytes play an important role in Type 2 immunity. However, the contribution of ILC2s to allergic rhinitis remains to be clearly elucidated. Objective: To evaluate the role of nuocytes from mesenteric lymph node on allergic responses in mice. Methods: After intraperitoneal administration of interleukin IL-25 and IL-33 to wild-type and Il17br-/-Il1rl1-/- double-deficient mice, nuocytes were purified from the the nasal-associated lymphoid tissue and mesenteric lymph nodes. Then, we assessed productions of IL-5 and IL-13 in nuocytes' cultures. Finally, we adoptively transferred the mesenteric lymph node-derived nuocytes from wild-type and Il17br-/-Il1rl1-/- mice to the murine model of allergic rhinitis to evaluate their roles in nasal allergic responses. Results: We showed that nuocytes in the mesenteric lymph nodes of wild-type mice were upregulated after application of IL-25 and IL-33, and were induced to produce IL-5 and IL-13. Numbers of sneezing and nasal rubbing as well as eosinophils were all enhanced after the adoptive transfer of wild-type nuocytes. Concentrations of IL-5, IL-13, IL-25 and IL-33 in nasal lavage fluid of allergic mice were also increased. However, nuocytes fromIl17br-/-Il1rl1-/- mice did not increase sneezing and nasal rubbing and eosinophilia, and upregulate the above cytokines in the nasal lavage fluid. Conclusion: The findings demonstrate that nuocytes from the mesenteric lymph nodes of wildtype mice promote allergic responses in a mouse model.

Resumo Introdução: Os nuócitos desempenham um papel importante na imunidade do tipo 2. No entanto, a contribuição das interleucinas ILC2s na rinite alérgica ainda precisa ser elucidada. Objetivo: Avaliar o papel dos nuócitos de linfonodos mesentéricos nas respostas alérgicas em camundongos. Método: Após a administração intraperitoneal de interleucina (IL)-25 e IL-33 em camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- com deficiência dupla, os nuócitos foram purificados do tecido linfoide associado a mucosa nasal e linfonodos mesentéricos. Em seguida, avaliamos as produções de IL-5 e IL-13 em culturas de nuócitos. Finalmente, transferimos adotivamente os nuócitos derivados de linfonodos mesentéricos de camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- para o modelo murino de rinite alérgica para avaliar seu papel nas respostas alérgicas nasais. Resultados: Mostramos que os nuócitos nos linfonodos mesentéricos de camundongos do tipo selvagem estavam up-regulados após a aplicação de IL-25 e IL-33 e foram induzidos a produzir IL-5 e IL-13. Os espirros e friçcão nasal, bem como os eosinófilos, aumentaram após a transferência adotiva de nuócitos do tipo selvagem. As concentrações de IL-5, IL-13, IL-25 e IL-33 no líquido da lavagem nasal de camundongos alérgicos também estavam aumentadas. Entretanto, os nuócitos de camundongos Il17br-/-Il1rl1-/- não aumentaram os espirros e a friçcão nasal ou eosinofilia e up-regularam as citocinas acima no líquido de lavagem nasal. Conclusão: Os achados demonstram que os nuócitos dos linfonodos mesentéricos de camundongos selvagens promovem respostas alérgicas em um modelo de camundongo.

A de novo transcriptomic analysis to reveal functional genes in Apolygus lucorum.

The widespread planting of genetically engineered cotton producing the Cry1Ac toxin has led to significantly reduced pesticide applications since 1997. However, consequently, the number of green mirid bugs (GMB), Apolygus lucorum (Meyer-Dür) has increased. So far the GMB, instead of the cotton bollworm Helicoverpa armigera (Hübner), has become the major pest in the transgenic Bt cotton field and has influenced cotton yield. Disproportionately, only a few studies on GMB at molecular level have been reported. Libraries from both third instar nymphs and adults were sequenced using Illumina technology, producing more than 106 million short reads and assembled into 63 029 unigenes of mean length 597 nt and N50 813 nt, ranging from 300 nt to 9771 nt. BLASTx analysis against Nr, Swissprot, GO and COG was performed to annotate these unigenes. As a result, 26 478 unigenes (42.01%) matched to known proteins and 107 immune-related, 320 digestive-related and 53 metamorphosis-related genes were detected in these annotated unigenes. Additionally, we profiled gene expression using mapping based differentially expressed genes (DEGs) strategy between the two developmental stages: nymph and adult. The results demonstrated that thousands of genes were significantly differentially expressed at different developmental stages. The transcriptome and gene expression data provided comprehensive and global gene resources of GMB. This transcriptome would improve our understanding of the molecular mechanisms of various underlying biological characteristics, including development, digestion and immunity in GMB. Therefore, these findings could help elucidate the intrinsic factors of the GMB resurgence, offering novel pest management targets for future transgenic cotton breeding.

Synthesis, Anticancer Evaluation and Docking Study of 3- Benzyloxyhydantoin Derivatives.

A series of 3-benzyloxyhydantoin derivatives were designed and synthesized by introducing hydroxyurea pharmacophore into hydantoin rigid scaffold. The cytotoxic activities of the target compounds were evaluated in vitro against three cancer cell lines. Compounds 5b, 5c, 5e, 5g, 6c and 6g displayed high activity on all of the three cancer cell lines and the most promising compounds were 5g, 6g with IC50 values of 0.04 and 0.01µM. Binding of derivatives for the ribonucleotide reductase (RR) was investigated by use of molecular docking studies. Our findings show that modification at the C5 position of hydantoin with isopropyl or isobutyl was favorable to increasing binding affinity to the active site of the RR receptor and antiproliferative activity.