sPLA2GIB Promotes PGD2 and IL-13 Production in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Secreted phospholipase A2 Group IB (sPLA2GIB) regulates the release of arachidonic acid, prostaglandins, and other inflammatory lipid mediators. Although it has been well involved in extensive inflammatory diseases, its specific mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. In this study, we investigated the role of sPLA2GIB in the pathophysiology of CRSwNP. METHODS: Quantitative PCR, immunofluorescence staining, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to analyze the expression of sPLA2s, phospholipase A2 receptor (PLA2R), and prostaglandin D2 (PGD2) in nasal samples. Human nasal epithelial cells (HNECs) were cultured at an air-liquid interface (ALI) and stimulated with various cytokines. The human mast cell line HMC-1 was stimulated with sPLA2GIB, and the expression of PGD2 and cytokines in the culture supernatant was detected by ELISA. RESULTS: The mRNA and protein levels of sPLA2GIB were significantly higher in eosinophilic CRSwNP than in control tissues. sPLA2GIB was predominantly expressed in the nasal epithelial cells. PLA2R mRNA and protein levels were upregulated in both eosinophilic and non-eosinophilic CRSwNP compared with the control groups. IL-4, IL-13, TNF-α, and IL-1ß upregulated the expression of sPLA2GIB in ALI-cultured HNECs. sPLA2GIB induced PGD2 and IL-13 production in HMC-1 cells in a hydrolytic activity-independent manner. PGD2 protein expression was elevated in tissue homogenates of eosinophilic CRSwNP, and PGD2 upregulated the expression of IL-13 in HMC-1 cells. CONCLUSION: Increased secretion of sPLA2GIB by epithelial cells may promote eosinophilic inflammation in CRSwNP by enhancing PGD2 and IL-13 production in mast cells via binding to PLA2R. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1107-1117, 2024.

The complete chloroplast genome and phylogenetic analysis of Lemmaphyllum carnosum var. drymoglossoides (baker) X. P. Wei, 2013.

Lemmaphyllum carnosum var. drymoglossoides (Baker) X. P. Wei, 2013 is a valuable medicinal fern in China. Its complete chloroplast genome was determined using Illumina paired-end sequencing. The genome was 157,571 bp in length with 130 genes, including 87 protein-coding genes, eight ribosomal RNA genes, and 35 tRNA genes. It displayed a quadripartite structure consisting of a small single-copy (SSC) of 21,691 bp, a large single-copy (LSC) of 81,106 bp, and two inverted repeats (IRs) of 27,387 bp, respectively. The phylogenetic results indicated that L. carnosum var. drymoglossoides exhibited the closest relationship with L. intermedium, and this study provided new information for the phylogenetic relationship of the Polypodiaceae family.

MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability.

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-ß receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-ßR3 was found to be a TGF-ß2-specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-ß2-induced phosphorylation of SMAD2 in HNECs, respectively. TGF-ßR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-ß2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-ßR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.

Sox9 mediates autophagy-dependent vascular smooth muscle cell phenotypic modulation and transplant arteriosclerosis.

Vascular smooth muscle cell (vSMC) phenotypic modulation is a dynamic pathogenesis process implicated in neointimal formation and transplant arteriosclerosis (TA). Transcription factor Sox9 functions to establish cell type and wound healing, but little is known about its transcriptional regulation in vSMCs and its roles in the development of TA. Here, we found an increased Sox9 expression in aortic allografts and in HMGB1-treated vSMCs in vitro, accompanied by the downregulation of vSMC markers. Notably, vSMC-specific Sox9 knockdown in aortic allografts attenuated neointimal formation through preventing vSMC phenotypic modulation following transplantation. We further indicated that HMGB1 induced Sox9 expression and vSMC phenotypic modulation through activating autophagy to degrade p27Kip1. Mechanistically, p27Kip1 bound to the Sox9 promoter in vSMCs together with p130/E2F4 complex, by which it restrained Sox9 transcriptional expression. These findings uncover a fundamental role of Sox9 in mediating autophagy-dependent vSMC phenotypic modulation and TA, offering a therapeutic approach for vascular pathologies.

Bves maintains vascular smooth muscle cell contractile phenotype and protects against transplant vasculopathy via Dusp1-dependent p38MAPK and ERK1/2 signaling.

BACKGROUND AND AIMS: Vascular smooth muscle cell (VSMC) plasticity is tightly associated with the pathological process of vasculopathy. Blood vessel epicardial substance (Bves) has emerged as an important regulator of intracardiac vasculogenesis and organ homeostasis. However, the involvement and role of Bves in VSMC plasticity and neointimal lesion development remain unclear. METHODS: We used an in vivo rat model of graft arteriosclerosis and in vitro PDGF-treated VSMCs and identified the novel VSMC contractile phenotype-related gene Bves using a transcriptomic analysis and literature search. In vitro knockdown and overexpression approaches were used to investigate the mechanisms underlying VSMC phenotypic plasticity. In vivo, VSMC-specific Bves overexpression in rat aortic grafts was generated to assess the physiological function of Bves in neointimal lesion development. RESULTS: Here, we found that Bves expression was negatively regulated in aortic allografts in vivo and PDGF-treated VSMCs in vitro. The genetic knockdown of Bves dramatically inhibited, whereas Bves overexpression markedly promoted, the VSMC contractile phenotype. Furthermore, RNA sequencing unraveled a positive correlation between Bves and dual-specificity protein phosphatase 1 (Dusp1) expression in VSMCs. We found that Bves knockdown restrained Dusp1 expression, but enhanced p38MAPK and ERK1/2 activation, resulting in the loss of the VSMC contractile phenotype. In vivo, an analysis of a rat graft model confirmed that VSMC-specific Bves and Dusp1 overexpression in aortic allografts significantly attenuated neointimal lesion formation. CONCLUSIONS: Bves maintains the VSMC contractile phenotype through Dusp1-dependent p38MAPK and ERK1/2 signaling, and protects against neointimal formation, underscoring the important role of Bves in preventing transplant vasculopathy.

Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis.

BACKGROUND: The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. METHODS: Real-time polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X-box binding protein 1 (sXBP-1), and phosphorylated eukaryotic initiation factor 2α (p-eIF2α), in inferior turbinate tissue samples from patients with AR and non-AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4-phenylbutyric acid (4-PBA), an ER stress inhibitor. RESULTS: Compared to those in non-AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP-1, and p-eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non-AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4-PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP-1, and p-eIF2α was significantly reduced in cultured AR-derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants. CONCLUSIONS: ER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production. LEVEL OF EVIDENCE: NA.

Defective mitochondrial function by mutation in THICK ALEURONE 1 encoding a mitochondrion-targeted single-stranded DNA-binding protein leads to increased aleurone cell layers and improved nutrition in rice.

Cereal endosperm comprises an outer aleurone and an inner starchy endosperm. Although these two tissues have the same developmental origin, they differ in morphology, cell fate, and storage product accumulation, with the mechanism largely unknown. Here, we report the identification and characterization of rice thick aleurone 1 (ta1) mutant that shows an increased number of aleurone cell layers and increased contents of nutritional factors including proteins, lipids, vitamins, dietary fibers, and micronutrients. We identified that the TA1 gene, which is expressed in embryo, aleurone, and subaleurone in caryopses, encodes a mitochondrion-targeted protein with single-stranded DNA-binding activity named OsmtSSB1. Cytological analyses revealed that the increased aleurone cell layers in ta1 originate from a developmental switch of subaleurone toward aleurone instead of starchy endosperm in the wild type. We found that TA1/OsmtSSB1 interacts with mitochondrial DNA recombinase RECA3 and DNA helicase TWINKLE, and downregulation of RECA3 or TWINKLE also leads to ta1-like phenotypes. We further showed that mutation in TA1/OsmtSSB1 causes elevated illegitimate recombinations in the mitochondrial genome, altered mitochondrial morphology, and compromised energy supply, suggesting that the OsmtSSB1-mediated mitochondrial function plays a critical role in subaleurone cell-fate determination in rice.

Clinical and Biological Markers Predict the Efficacy of Glucocorticoid- and Macrolide-Based Postoperative Therapy in Patients With Chronic Rhinosinusitis.

BACKGROUND: Although subsequent anti-inflammatory treatments are indispensable for patients with chronic rhinosinusitis (CRS) undergoing sinus surgery, few studies have explored the factors influencing the efficacy of postoperative anti-inflammatory treatment. OBJECTIVE: We aimed to develop prediction models for the response to glucocorticoid- and macrolide-based postoperative therapy in CRS patients. METHODS: We performed a post-hoc analysis of our previous study comparing the efficacy of fluticasone propionate and clarithromycin in the postoperative treatment of CRS patients. Clinical characteristics and treatment outcome information were collected. In addition, diseased sinonasal mucosal tissues obtained during surgery were processed for Bio-Plex analysis of protein levels of 34 biomarkers. Classification trees were built to predict refractory CRS based on clinical characteristics and biological markers for patients treated with fluticasone propionate or clarithromycin. A random forest algorithm was used to confirm the discriminating factors that formed the classification trees. RESULTS: One year after surgery, 22.7% of the patients (17/75) treated with fluticasone propionate, and 24.3% of those (18/74) treated with clarithromycin were diagnosed with refractory CRS. Nasal tissue IL-8 and IgG3 levels and headache VAS scores in the fluticasone propionate group, and nasal tissue IgG4 levels and overall burden of symptoms VAS scores in the clarithromycin group, were identified as discriminating factors forming the classification tree to predict refractory CRS. The overall predictive accuracy of the model was 89.3% and 87.8% for fluticasone propionate- and clarithromycin-based postsurgical treatment, respectively. CONCLUSIONS: Classification trees built using clinical and biological parameters could be helpful in identifying patients with poor response to fluticasone propionate- and clarithromycin-based postoperative treatment.

Characterizing the Neutrophilic Inflammation in Chronic Rhinosinusitis With Nasal Polyps.

The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1ß, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP.

Inflammatory features and predictors for postsurgical outcomes in patients with nasal polyps stratified by local and systemic eosinophilia.

BACKGROUND: In this study we aimed to identify inflammatory patterns and predictors associated with clinical outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different blood and tissue eosinophilia. METHODS: A total of 535 CRSwNP patients were enrolled, and the expression of 35 biomarkers, together with eosinophil and neutrophil counts in nasal polyps, were analyzed in a subset of 249 patients. Patients were stratified on the basis of blood (≥0.5 × 109 /L) and tissue (>10%) eosinophilia. Logistic regression models were applied to identify predictors of uncontrolled disease at least 1 year after surgery. Uncontrolled disease was defined according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. RESULTS: Among 535 patients, 38.5% showed inconsistent blood and tissue eosinophilia. In 249 CRSwNP patients, subjects with concomitant blood and tissue eosinophilia (group 1) showed marked mucosal type 2 inflammation, characterized by high levels of interleukin (IL)-5, IL-13, and eotaxin-1, whereas subjects with normal blood and tissue eosinophil levels (group 4) demonstrated significant local neutrophilic inflammation with high expression of granulocyte colony-stimulating factor and subjects with selective tissue eosinophilia (group 2) showed intermediate and mixed eosinophilic and neutrophilic inflammation. Subjects with isolated blood eosinophilia (group 3) showed low expression of vascular endothelial growth factor and IL-10. Asthma, prior sinus surgery, and blood eosinophilia were the top 3 predictors for postsurgical uncontrolled disease. For subgroup analysis, sex in group 1, asthma in group 2, tissue IL-10 and immunoglobulin E in group 3, and prior sinus surgery in group 4 were the strongest predictors of uncontrolled disease, respectively. CONCLUSION: Different blood and tissue eosinophilia revealed distinct tissue inflammatory patterns in CRSwNP patients.

Stromal cells and B cells orchestrate ectopic lymphoid tissue formation in nasal polyps.

BACKGROUND: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. OBJECTIVE: To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs. METHODS: The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study. RESULTS: The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 ß2 in NPs with eLTs. CXCL13 upregulated LTα1 ß2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 ß2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTßR blockage diminished nasal eLT formation in the murine model. CONCLUSION: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 ß2 in the enlargement of eLTs in NPs.

Clinical and radiologic features of the first cured Coronavirus disease 2019 (COVID-19) patient in Guangzhou City, China.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of "cough for 11 days and once fever 8 days ago" on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19.

Prevalence and transmission of antimicrobial-resistant Staphylococci and Enterococci from shared bicycles in Chengdu, China.

Shared bicycles are prevailing in China but the extent to which they contribute to maintaining and transmitting pathogens and antibiotic-resistant bacteria remain largely unknown. To fill the knowledge gap, herein, swab samples (n = 963) were collected from handlebars of shared bicycles in areas of hospital, school, metro station (n = 887) and riders (n = 76) in Chengdu, China. Staphylococci (n = 241) and Enterococci (n = 69) were widely distributed across sampling locations at a frequency of 2.3%-12.9%, and 0.08%-5.5%, respectively. Bicycle or rider-borne Gram-positive bacteria were frequently resistant to clinically important antibiotics including linezolid, fosfomycin, and vancomycin, and a significant portion of these isolates (3.4%-16.6% for Staphylococci and 0.1%-13.8% for Enterococci) indicated multidrug resistance. Nineteen Staphylococcus aureus isolates were identified in this collection and 52.6% of which were considered as methicillin-resistant S. aureus. Whole genome sequencing further characterized 26 antimicrobial resistance genes (ARGs) including fosB, fusB, and lnu(G) in S. aureus and 21 ARGs including optrA in Enterococci. Leveraging a complementary approach with conventional MLST, whole genome SNP and MLST analyses, we present that genetically closely-related bacteria were found in bicycles and riders across geographical-distinct locations suggesting bacterial transmission. Further, five new ST types 5697-5701 were firstly characterized in S. aureus. ST 942 and ST 1640 are new ST types observed in E. faecalis, and E. faecium, respectively. Our results highlighted the risk of shared bicycle system in disseminating pathogens and antibiotic resistance which warrants effective disinfections.

Genome sequence of multidrug-resistant Erysipelothrix rhusiopathiae ZJ carrying several acquired antimicrobial resistance genes.

OBJECTIVES: This study aimed to determine the genetic environment of antimicrobial resistance genes (ARGs) in Erysipelothrix rhusiopathiae strain ZJ isolated from a pig with symptoms of swine erysipelas in China. METHODS: Illumina MiSeq (200× coverage) and PacBio RS II (100× coverage) platforms were used for genome sequencing. ARGs and prophages were identified using ResFinder 3.0 and PHASTER, respectively. A conjugation experiment, induced prophage infection and long-term passage assay were performed to determine the transferability and stability of ARGs in this strain. RESULTS: The assembled circular genome of E. rhusiopathiae ZJ was 1 945 689 bp with a GC content of 36.48%; no plasmid sequence was detected. Eleven acquired ARGs were identified in the genome. A novel integrative and conjugative element (ICE) encoding a multidrug resistance (MDR) gene cluster [aadE-apt-spw-lsa(E)-lnu(B)-aadE-sat4-aphA3] was identified in strain ZJ. A prophage Φ1605 harbouring mef(A)-msr(D) and tet(M) was also found in this strain, which can take a circular form and can be induced by mitomycin C to infect E. rhusiopathiae G4T10 for ARG transfer. CONCLUSION: To our knowledge, this is the first report of a complete genome sequence of E. rhusiopathiae carrying multiple ARGs obtained from a pig farm. This is the first identification of a novel chimeric ICE carrying a MDR gene cluster and a prophage carrying ARGs in E. rhusiopathiae, which will provide a valuable reference to understand the potential transfer mechanism of MDR gene clusters carried by ICEs and prophages in Gram-positive bacteria.

B Cell-Activating Factor Promotes B Cell Survival in Ectopic Lymphoid Tissues in Nasal Polyps.

Ectopic lymphoid tissues (eLTs) characterized by B cell aggregation contribute to the local immunoglobulin production in nasal polyps (NPs). B cell-activating factor (BAFF) is vital for B cell survival, proliferation, and maturation. The purpose of this study is to investigate whether BAFF is involved in the B cell survival and eLT formation in NPs. The mRNA and protein levels of BAFF in NP tissues with and without eLTs were detected by PCR and ELISA assay, respectively. The cellular sources of BAFF and active caspase-3-positive B cells in NPs were studied by immunofluorescence staining. B cells purified from NP tissues were stimulated with BAFF and were analyzed by flow cytometry. Stromal cells purified from NP tissues were stimulated with lymphotoxin (LT) α1ß2, and BAFF levels in culture supernatants were analyzed by ELISA. Compared with those in control tissues and NPs without eLTs, the BAFF levels were elevated in NPs with eLTs. Abundant BAFF-positive cells and few active caspase-3-positive apoptotic B cells were found in NPs with eLTs, in contrast to those in NPs without eLTs. There was a negative correlation between the numbers of BAFF-positive cells and frequencies of apoptotic B cells in total B cells in NP tissues. BAFF protected nasal polyp B cells from apoptosis in vitro. Stromal cells were an important cellular source of BAFF in NPs with eLTs. LTα1ß2 induced BAFF production from nasal stromal cells in vitro. We propose that BAFF contribute to eLT formation in NPs by promoting B cell survival.

The IL-37-Mex3B-Toll-like receptor 3 axis in epithelial cells in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: The role of IL-37, an immunosuppressive cytokine, in patients with inflammatory diseases is unclear. OBJECTIVE: We sought to explore the expression and pathogenic function of IL-37 in patients with chronic rhinosinusitis (CRS). METHODS: Expression levels of IL-37, IL-18 receptor α, IL-1 receptor 8, Mex3 RNA binding family member B (Mex3B), and thymic stromal lymphopoietin (TSLP) in nasal samples were studied by using quantitative RT-PCR, immunohistochemistry, Western blotting, and ELISA. Human nasal epithelial cells (HNECs) and the BEAS-2B cell line were stimulated with various cytokines and Toll-like receptor (TLR) agonists. In some experiments BEAS-2B cells were transfected with Mex3B small interfering RNA or overexpressing lentiviruses. Genes regulated by IL-37b in HNECs were studied by using RNA sequencing analysis. IL-37b function was confirmed in mice in vivo. RESULTS: Compared with control subjects, although mRNA and protein expression of IL-37 were upregulated in diseased tissues, especially in nasal epithelial cells, in patients with CRS without nasal polyps or in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), IL-37 levels in nasal secretions were reduced in patients with eosinophilic CRSwNP. Type 2 cytokines inhibited IL-37 secretion from HNECs. HNECs expressed IL-37 receptors, IL-18 receptor α, and IL-1 receptor 8. IL-37b downregulated the expression of Mex3B, a TLR3 coreceptor, in HNECs. IL-37b suppressed polyinosinic-polycytidylic acid-induced TSLP production in HNECs in vitro and in murine nasal epithelial cells in vivo. Knocking down or overexpressing Mex3B in BEAS-2B cells abolished the inhibitory effect of IL-37b. Secreted IL-37 levels negatively correlated with Mex3B and TSLP levels and eosinophil numbers in patients with eosinophilic CRSwNP. CONCLUSIONS: The suppressed IL-37 secretion caused by a type 2 milieu can enhance Mex3B-mediated TLR3 activation and subsequent TSLP production in nasal epithelial cells and therefore promotes eosinophilic inflammation in patients with CRSwNP.

l-Arabinose Inhibits Colitis by Modulating Gut Microbiota in Mice.

l-Arabinose is a monosaccharide extracted from plants or fibers, which is known to have a variety of functional properties. In this study, we aim to investigate whether l-arabinose could inhibit colitis by modulating gut microbiota. l-Arabinose was administered in mice daily in a dextran sodium sulfate (DSS)-induced colitis model. The histological analysis, disease index, and the expression of inflammatory genes were measured. 16S-rRNA sequence analysis was performed to investigate gut microbiota. Intriguingly, we found that l-arabinose could repress DSS-induced colitis and inhibit p38-/p65-dependent inflammation activation. Besides that, our data revealed that l-arabinose-modulated DSS-induced gut microbiota were disturbed. Additionally, the perturbed gut microbiota was responsible for the suppressive effects of l-arabinose on DSS-induced colitis treated with antibiotics. Lastly, Caco-2 cells were used to confirm the protective effects of l-arabinose in colitis or inflammatory bowel disease. As expected, the protein expression levels in Caco-2 cells of pro-inflammatory genes, which were treated with l-arabinose and incubated with or without tumor necrosis factor alpha. Our work suggested that l-arabinose exerts anti-inflammation effects in DSS-induced colitis. These beneficial effects have correlations with the composition, diversity, and abundance of the gut microbiota regulated by l-arabinose. l-Arabinose could be a remarkable candidate as a functional food or novel therapeutic strategy for intestinal health.