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1.
Sci Adv ; 5(9): eaax2166, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31579823

RESUMO

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

2.
Medicine (Baltimore) ; 98(38): e17283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568011

RESUMO

BACKGROUND: Cognitive-behavioral therapy has been considered as a means for internet addiction, but its long-term effect and the impact of internet addiction types and culture are still unclear. OBJECTIVE: This study aims to assess the efficacy of cognitive-behavior therapy for internet addiction symptoms and associated other psychopathological symptoms. METHOD AND ANALYSIS: We will search PubMed, Web of Knowledge, Ovid Medline, Chongqing Vip Database, Wanfang, and China National Knowledge Infrastructure database. Random-effects model in comprehensive meta-analysis software will be used to conduct main meta-analysis. Cochran Q and I are be used to assess heterogeneity while funnel plots and the Egger test are used to assess publication bias. Risk of bias for each study included is assessed by using the Cochrane risk of bias tool. The primary outcome is internet addiction symptom while secondary outcomes are psychopathological symptoms, time spent online, and dropout. TRIALS REGISTRATION NUMBER: PROSPERO CRD42019125667.

3.
Invest Ophthalmol Vis Sci ; 60(13): 4084-4096, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574534

RESUMO

Purpose: To investigate whole transcriptional differences between proliferative diabetic retinopathy (PDR) neovascular membranes (NVMs) and retinas, and the regulatory genes participating in retinal neovascularization in PDR. Methods: We used high-throughput sequencing technology to capture the whole-genome gene expression levels of all participants, including 23 patients with PDR or branch retinal vein occlusion (BRVO), 3 normal retinal samples, and 2 retinal samples from type II diabetic (T2D) eyes by donation, followed by analyses of expression patterns using bioinformatics methods, then validation of the data by in situ hybridization and Western blotting. Results: We showed that transcriptional profiles of the NVMs were distinct from those of the retinas. Angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2, and their receptors FLT4, TIE1, TIE2, and EPHB4, respectively, were overexpressed. Expression of VEGFA was highly upregulated in T2D retina, but low in the NVMs, while angiogenesis transcription factors, including ETS1 and ERG, were coordinately upregulated in NVMs. Conclusions: This study described a PDR neovascularization model in which pathological retina-secreted vascular endothelial growth factor A (VEGFA) enhanced the expression of a set of angiogenesis transcription factors and growth factors, to cooperatively induce the retinal neovascularization. Based on these results, novel potential therapeutic targets and biomarkers for PDR treatment and diagnosis are suggested.

4.
Diabetes ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597640

RESUMO

Abnormalities of methyl CpG-binding protein 2 (Mecp2) cause neurological disorders with metabolic dysfunction, however, its role in adipose tissues remains unclear. Here, we report upregulated Mecp2 in white adipose tissues (WAT) of obese humans, as well as in obese mice and during in vitro adipogenesis. Normal chow-fed adipocyte-specific Mecp2 knockout mice (Mecp2 Adi KO mice) showed a lean phenotype, with downregulated lipogenic genes and upregulated thermogenic genes identified using RNA-sequencing. Consistently, deficiency of Mecp2 in adipocytes protected mice from HFD-induced obesity and inhibited in vitro adipogenesis. Furthermore, Mecp2 Adi KO mice showed increased browning under different stimuli, including cold treatment. Mechanistically, Mecp2 bound to the promoter of secretory leukocyte protease inhibitor (Slpi) and negatively regulated its expression. Knockdown of Slpi in iWAT of Mecp2 Adi KO mice prevented cold-induced browning. Moreover, recombinant SLPI treatment reduced the HFD-induced obesity via enhancing browning. Together, our results suggest a novel non-CNS function of Mecp2 in obesity by suppressing browning, at least partially, through regulating adipokine Slpi.

5.
Nucleic Acids Res ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31598693

RESUMO

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. Here, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org). We identified a total of 311 571 RBPs with RBDs (corresponding to 6368 ortholog groups) and 3,651 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures, PPI-network and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for both the communities of RNA biology and cancer biology.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31599161

RESUMO

Gold nanorods, mesoporous silica, gadolinia, folic acid and PEG derivatives have been investigated as their own advantages in cancer theranostics. However, it remains a great challenge to assemble these components into a stable unity with the diverse and enhanced functionality for more potential applications. Herein, as inspired by the first-principle calculation, a highly stable and safe all-in-one nanoprobe is fabricated via a novel nanoassembly strategy. Multiscale calculations were performed to address atomistic bonding of a nanoprobe, heat necrosis of a tumor adjacent to vasculature, and thermal diffusion in a photothermal circumstance, respectively. The nanoprobe gains an 8-fold increase in MRI relaxivity as compared to the clinical Gd-DTPA, achieving a significant MRI signal in vivo. Conjugated with folate-PEG, the nanoprobe can be effectively absorbed by tumor cells, obtaining a vivid two-photon cells imaging. A specific multisite scheme for photothermal therapy of a solid tumor is proposed to improve low photothermal efficacy caused by thermal diffusion in a large tumor, leading to successful cure of the mice with xenograft tumor sized 10-12 mm. In vitro and in vivo toxicity, long-term excretion data and the recovery of the treated mice demonstrate that the theranostic nanoprobe possesses a good biocompatibility and metabolism efficacy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31592762

RESUMO

A facultatively anaerobic, Gram-stain-negative and non-gliding bacterium, designated F01T, was isolated from marine solar saltern in Weihai, PR China. Cells of F01T were 0.2-0.4 µm wide and 1.4-4.1 µm long, weakly catalase-positive and oxidase-negative. Growth of F01T was determined to occur at 4-40 °C (optimum, 33-37 °C), pH 6.5-8.5 (optimum, 7.0-8.0), and with 0.5-18.0 % (w/v) NaCl (optimum, 3.0-6.0 %). The 16S rRNA gene sequence analysis indicated that F01T represented a member of the genus Marinobacter within the family Alteromonadaceae. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was most closely related to Marinobacter algicola DSM 16394T, with a sequence similarity of 97.5 %. The DNA G+C content of the isolate was 57.6 mol%. The major respiratory quinone of F01T was ubiquinone-9 (Q-9) and the major fatty acids were anteiso-C15 : 0, C16 : 0 and C18 : 1ω9c. The major polar lipids were phosphoaminolipid, phosphatidylglycerol and phosphatidylethanolamine. On the basis of the results of the phylogenetic analysis and phenotypic properties, it is concluded that F01T can be considered to represent a novel species in the genus Marinobacter, for which the name Marinobacter vulgaris sp. nov. is proposed. The type strain is F01T (=MCCC 1H00290T=KCTC 52700T).

8.
Int J Nanomedicine ; 14: 7155-7171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564871

RESUMO

Background: Platelet activation and subsequent aggregation are the initial stages of thrombosis. A molecular probe that specifically targets activated platelets and remains retained under high shear stress in vivo can enhance the imaging effect to achieve early and accurate diagnosis. Methods and materials: In this study, we constructed nanoparticles (NPs) using polydopamine to carry two peptides that simultaneously bind integrin αIIbß3 and P-selectin on activated platelets to enhance the targeting of NPs to thrombus. Results: The targeting specificity and binding stability of the NPs on red and white thrombi were demonstrated in vitro using a simulated circulatory device and the targeting effect of the NPs on mixed thrombus was studied by  magnetic resonance (MR)/photoacoustic (PA) dual-modality imaging in vivo. NPs that were surface modified with both peptides have higher selectivity and retention to red and white thrombi in vitro than NPs with a single or no peptide, and the targeting effect was closely related to the number and distribution of activated platelets as well as the structure and type of thrombus. The NPs also have MR/PA dual-modality imaging functionality, significantly enhancing the imaging of mixed thrombus in vivo. Conclusion: These dual-targeted NPs have improved targeting specificity and binding stability to different thrombi under high shear stress and are beneficial for the early diagnosis of thrombosis.

9.
Food Funct ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566196

RESUMO

Decolourization of polysaccharides is one of the crucial procedures that affects their structure, which is closely related to their bioactivity. Here, Grifola frondosa polysaccharide (GFP) was decolourized with H2O2 and AB-8 macroporous resin. Then, two main fractions, named DGFP and SGFP, were obtained by purification with Sepharose CL-4B. The molecular weights of these two polysaccharides were determined to be 6.306 × 106 (±0.410%) Da and 1.174 × 107 (±0.299%) Da by HPSEC. Monosaccharide analysis indicated that DGFP was composed of glucose, mannose, and galactose (32.20 : 1.00 : 1.75), while SGFP consisted entirely of glucose. Despite a backbone →4)-α-Glcp-(1→ in two polysaccharides, reducing ends Rα →3)-α-Glcp and Rß â†’4)-ß-Glcp were observed in DGFP by 1D/2D NMR. The results suggested that decolourization with low concentrations of H2O2 might alter the structure of GFP and generate new reducing ends. In vitro antioxidant results implied that DGFP exhibited a higher ability to scavenge DPPH and hydroxyl radicals and reduced the over-generated ROS levels in a concentration-dependent manner. These results suggested that the antioxidant effects of GFP could be activated by decolourization with H2O2. Therefore, DGFP might be a more promising natural antioxidant than SGFP.

10.
J Asian Nat Prod Res ; : 1-6, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566431

RESUMO

Two new naphthoate derivatives, including a symmetrical dimer (1) and a monomer (2), were separated from the roots of Morinda officinalis var. hirsuta. Their structures were characterized on the basis of spectroscopic means especially MS and NMR methods. Biological evaluations revealed that the two compounds did not show inhibition against both cholinesterases AChE and BChE, while the dimer (1) did exhibit moderate growth inhibitory activity toward one human osteosarcoma cell line U2OS with an IC50 value of 18.5 ± 1.1 µM.

11.
Curr Eye Res ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566446

RESUMO

PURPOSE: To identify the pathogenetic mutations in a four-generation Chinese family with dominant congenital cataracts and microphthalmia. METHODS: A four-generation Chinese family with dominant congenital cataracts were recruited. Genomic DNAs were collected from their peripheral blood leukocytes and subjected to whole exome sequencing. The genetic mutations were identified by bioinformatic analyses and verified by Sanger sequencing. RESULTS: Whole exome sequencing revealed a c.279C>G point mutation in the CRYBB1 gene which was further verified by Sanger sequencing. The nucleotide replacement results in a novel mutation p.S93R in a conserved residue of ßB1 crystallin which is predicted to disrupt normal ßB1 structure and function. CONCLUSIONS: We identified a novel missense mutation p.S93R in CRYBB1 in a Chinese family with autosomal dominant congenital cataracts and microphthalmia. This serine residue is extremely conserved evolutionarily in more than 50 ßγ-crystallins of many species. These data will be very helpful to further understand the structural and functional features of crystallins.

12.
Aging (Albany NY) ; 112019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31586991

RESUMO

PURPOSE: The aim of this study was to determine the impact of analyzing age as a continuous variable on survival outcomes and treatment selection for extranodal nasal-type NK/T-cell lymphoma. RESULTS: The risk of mortality increased with increasing age, without an apparent cutoff point. Patients' age, as a continuous variable, was independently associated with overall survival after adjustment for covariates. Older early-stage patients were more likely to receive radiotherapy only whereas young-adult advanced-stage patients tended to receive non-anthracycline-based chemotherapy. A decreased risk of mortality with radiotherapy versus chemotherapy only in early-stage patients (HR, 0.347, P < 0.001) or non-anthracycline-based versus anthracycline-based chemotherapy in early-stage (HR, 0.690, P = 0.001) and advanced-stage patients (HR, 0.678, P = 0.045) was maintained in patients of all ages. CONCLUSIONS: These findings support making treatment decisions based on disease-related risk factors rather than dichotomized chronological age. PATIENTS AND METHODS: Data on 2640 patients with extranodal nasal-type NK/T-cell lymphoma from the China Lymphoma Collaborative Group database were analyzed retrospectively. Age as a continuous variable was entered into the Cox regression model using penalized spline analysis to determine the association of age with overall survival (OS) and treatment benefits.

13.
Lancet Infect Dis ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31588042

RESUMO

BACKGROUND: Non-prescription dispensing of antibiotics at community pharmacies is a major driver of antimicrobial resistance. China has regarded curbing non-prescription sales of antibiotics at community pharmacies as an important task for tackling antibiotics resistance and planned to eliminate this practice nationwide before 2020. We aimed to quantify non-prescription dispensing of antibiotics cross-sectionally at community pharmacies in China in 2017, and longitudinally (2011-17) in a single province. METHODS: A simulated client method was used to measure non-prescription antibiotic dispensing based on scenarios about paediatric diarrhoea and adult acute upper respiratory tract infection (URTI), which were presented at each pharmacy. We collected cross-sectional data for 2423 community pharmacies from 221 counties or districts in six provinces in different regions of China, in 2017. We also assessed 213 community pharmacies in Shaanxi province with a baseline survey in 2011 and subsequent follow-up surveys every 2 years until 2017. In the cross-sectional analysis, multivariate binary logistic regression with random-intercepts was used to evaluate the factors associated with non-prescription dispensing of antibiotics. We also estimated unadjusted period effects of non-prescription antibiotic dispensing using generalised estimated equations. FINDINGS: After excluding invalid interactions within 12 community pharmacies, the study included 4822 simulated interactions within 2411 community pharmacies. Non-prescription antibiotic dispensing was observed during 1169 (48·5% [95% CI 46·5-50·5]) of 2411 diarrhoea interactions and 1690 (70·1% [68·2-71·9]) of 2411 adult URTI interactions. Non-prescription antibiotic dispensing was more prevalent in rural areas and the central and western provinces, and was negatively associated with the presence of a pharmacist on-site (odds ratio 0·66 [0·56-0·78], p<0·0001) and being part of a chain pharmacy (0·75 [0·62-0·89], p=0·0012). In Shaanxi province, significant decreases of non-prescription antibiotic dispensing occurred in paediatric cases (from 154 [72·3%] of 213 community pharmacies to 107 [50·2%], p<0·0001) and adult cases (from 204 [95·8%] to 148 [69·5%], p<0·0001) between 2011 and 2017. INTERPRETATION: Non-prescription dispensing of antibiotics at community pharmacies was still prevalent nationwide in China in 2017, although a decrease was observed in Shaanxi Province since 2011. Multifaceted measures, including regulatory interventions, professional training, and public health education are needed. FUNDING: Young Talent Support Plan and High Achiever Plan of Health Science Center, Xi'an Jiaotong University, Central University Basic Research Fund, Early Career Research Start-up Plan of Xi'an Jiaotong University.

14.
Chem Commun (Camb) ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588453

RESUMO

Hollow PdO-Co3O4 nano-dodecahedrons with moderate catalytic activity were designed as electrocatalysts for Li-O2 batteries, and not only reduce the overpotentials effectively but also improve the reversibility of the ORR and OER, and cycle for more than 90 cycles stably with extremely low overpotentials.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31588648

RESUMO

Flexible Li-air battery (FLAB) with ultrahigh energy density is a hopeful candidate for the forthcoming flexible energy storage devices. However, most current FLAB operated in the pure oxygen atmosphere which limited by the safety and corrosion issues from metallic lithium anode had greatly impeded the broad application of FLAB. Herein, inspired by the protection effect of the umbrella, a stable hydrophobic composite polymer electrolyte (SHCPE) film with high flexibility, hydrophobicity, and stability was fabricated to protect the lithium anode. The SHCPE mitigated the lithium corrosions and improved the Li-air batteries with capacity, rate performance, and cycle life (from 24 cycles to 95 cycles) in the ambient air. More importantly, based on the protection of SHCPE and the catalysis of MnOOH, the prepared pouch-type FLAB displayed high flexibility, stable performances, long cycling life (180 cycles), and excellent safety which the battery can bear soaking in water, high temperature, and nail penetration.

16.
Dent Mater ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31575489

RESUMO

OBJECTIVE: To evaluate the influence of extrinsic pigmentation on the biaxial flexural strength and surface topographic of translucent Y-TZP (InCoris TZI - Sirona - USA) subjected to several surface treatments. METHODS: Sintered zirconia discs-shaped specimens (n=120) (ø:12mm; thickness:1.2mm; ISO 6872) were prepared and divided (n=15) according to various factors: "extrinsic pigmentation" (n: without; p: with) and "surface treatments" (C: control - as sintered; A: abraded with silica-coated alumina particles (30µm); G: glazed with a thin film of low-fusing porcelain glaze; GH: glazed and etched with 10% hydrofluoridric acid for 60s. Mechanical cycling (1.2×106 cycles, 200N, 3.8Hz) and flexural strength test (1mm/min - 1000kg cell) were performed. Two-way ANOVA and Tukey's were used for statistical test (α=0.05). Weibull analysis was used to evaluate the strength reliability. Samples were analyzed via (1) an optical profilometer to determine the surface roughness (Ra); (2) an X-ray diffraction (XRD) to evaluate phase transformations; and (3) a SEM equipped with an energy dispersive X-ray spectroscopy (EDX) to elucidate morphological properties and chemical compositions. RESULTS: Regardless of the surface treatment (p=0.5459) (Cn: 560.16MPa; Gn: 573.36MPa; An: 643.51MPa; GHn: 542.94MPa; Cp: 628.04MPa; Gp: 641.90MPa; Ap: 554.47MPa; GHp :602.84MPa) and extrinsic pigmentation (p=0.1280) there was no difference in the flexural strength among the experimental groups. According to the XRD analysis, phase transformations occurred in the An group (t→m) and in Ap group (t→c). Surface roughness was affected by surface treatments (An - p=0.001) and extrinsic pigmentation (Gp - p=0.001). SIGNIFICANCE: The biaxial flexural strength of the tested samples was not affected neither by surface treatments nor by pigmentation, although it can cause phase transformation and promote surface roughness.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31577560

RESUMO

INTRODUCTION: Adverse histopathological status (AHS) decreases outcomes of gastric cancer (GC). With the lack of a single factor with great reliability to preoperatively predict AHS, we developed a computational approach by integrating large-scale imaging factors, especially radiomic features at contrast-enhanced computed tomography, to predict AHS and clinical outcomes of patients with GC. METHODS: Five hundred fifty-four patients with GC (370 training and 184 test) undergoing gastrectomy were retrospectively included. Six radiomic scores (R-scores) related to pT stage, pN stage, Lauren & Borrmann (L&B) classification, World Health Organization grade, lymphatic vascular infiltration, and an overall histopathologic score (H-score) were, respectively, built from 7,000+ radiomic features. R-scores and radiographic factors were then integrated into prediction models to assess AHS. The developed AHS-based Cox model was compared with the American Joint Committee on Cancer (AJCC) eighth stage model for predicting survival outcomes. RESULTS: Radiomics related to tumor gray-level intensity, size, and inhomogeneity were top-ranked features for AHS. R-scores constructed from those features reflected significant difference between AHS-absent and AHS-present groups (P < 0.001). Regression analysis identified 5 independent predictors for pT and pN stages, 2 predictors for Lauren & Borrmann classification, World Health Organization grade, and lymphatic vascular infiltration, and 3 predictors for H-score, respectively. Area under the curve of models using those predictors was training/test 0.93/0.94, 0.85/0.83, 0.63/0.59, 0.66/0.63, 0.71/0.69, and 0.84/0.77, respectively. The AHS-based Cox model produced higher area under the curve than the eighth AJCC staging model for predicting survival outcomes. Furthermore, adding AHS-based scores to the eighth AJCC staging model enabled better net benefits for disease outcome stratification. DISCUSSION: The developed computational approach demonstrates good performance for successfully decoding AHS of GC and preoperatively predicting disease clinical outcomes.

18.
Medicine (Baltimore) ; 98(40): e17441, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577766

RESUMO

RATIONALE: Although metastatic tumor is the most common intraocular malignancy, choroidal metastasis from gastric cancer is relatively rare. We present the exact course of a spontaneous rupture of the eyeball with choroidal metastasis from gastric carcinoma (GC) and the applied surgical interventions. PATIENT CONCERNS: A 59-year-old male presented with pain and vision loss on his left eye for 6 months. He was diagnosed with GC, for which he received systemic chemotherapy for a year. DIAGNOSES: Preoperative B-scan, color fundus photography, computed tomography, and magnetic resonance imaging showed a choroidal tumor in his left eye. The spontaneous rupture of the corneoscleral limbus from 2 to 5 o'clock, combined secondary glaucoma, exudative retinal detachment and choroidal detachment were found. INTERVENTIONS: The ruptured corneoscleral limbus was sutured and the orbit was lavaged with 0.4% cisplatin during the enucleation. OUTCOMES: Histopathology confirmed high homology of the choroidal metastasis and GC. He survived for 2 months after surgery, without pain or orbital neoplasms. LESSONS: Choroidal metastasis from GC rapidly progressed to spontaneous rupture of the eyeball. Careful eyeball enucleation followed by orbital lavage with chemotherapeutics may reduce metastasis risk beyond the eyeball. Additional therapeutic interventions should be considered in patients resistant to single systemic chemotherapy.

19.
Toxicol Lett ; 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31577921

RESUMO

Toluene-diisocyanate (TDI) is mainly used in the manufacturing process of polyurethane foams, and is a potent inducer of occupational asthma characterized by airway inflammation and airway hyperreactivity. Thymic stromal lymphopoietin (TSLP) plays an important role in the development of asthma, and correlating with the differentiation of Th2 and Th17 cells. However, the role of TSLP in TDI-induced asthma remains unclear. In this study, 96 TDI-exposed workers as well as a mouse model of TDI-induced asthma were investigated. The air exposure assessment result of TDI in the workplace showed that workers were exposed to inhalation of a very high concentration of TDI, approximately 8 times the recommended level, leading to a decrease in pulmonary function and an increase in inflammatory cells, as well as TSLP and IgE levels in the supernatant of sputum obtained from exposed workers. In order to further investigate the role of TSLP in the pathogenesis of TDI-induced asthma, a mouse model of TDI-induced asthma was also employed. Histopathological analysis of mouse lung and bronchus showed an obvious infiltration of inflammatory cells around the bronchus. The levels of inflammatory cells, IFN-γ, IL-4 and IL-17 in bronchoalveolar lavage fluid (BALF), the expression levels of TSLP protein and ROR-γt and IL-17 mRNA in mouse lung tissues were also significantly increased. However, after treatment with TSLP neutralizing antibody (TSLP-Ab), the degree of pulmonary and bronchial inflammation in mice was significantly alleviated, and the levels of inflammatory cells, IFN-γ, IL-4 and IL-17 in BALF, and the expression levels of ROR-γt and IL-17 mRNA in lung tissue were significantly decreased. Our data shows that TSLP plays an important role in the pathogenesis of TDI-induced asthma, and that TSLP-Ab can effectively alleviate TDI-induced airway inflammation of asthma.

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