GLUT1 mediates bronchial epithelial E-cadherin disruption in TDI-induced steroid-insensitive asthma.

Down-regulation of bronchial epithelial E-cadherin is an important of feature of severe asthma, including steroid-insensitive asthma. Yet, the mechanisms involved in E-cadherin disruption are not fully understood. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in dysregulation of E-cadherin in toluene diisocyanate (TDI)-induced steroid-insensitive asthma. A murine model of steroid-insensitive asthma was established by TDI sensitization and aerosol inhalation. Selective GLUT1 antagonists WZB117 and BAY876 were given to BALB/c mice after airway challenge. In vitro, primary human bronchial epithelial cells (HBECs) cultured in an airway-liquid interface (ALI) were exposed to TDI. TDI exposure markedly up-regulated GLUT1 in murine lungs and HBECs. Pharmacological inhibition of GLUT1 with BAY876 decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in vivo. Besides, the TDI-induced down-regulated expression of full-length E-cadherin was also partly recovered, accompanied by inhibited secretion of soluble E-cadherin (sE-cadherin). WZB117 also exhibited mild therapeutic effects, though not significant. In vitro, treatment with GLUT1 inhibitor relieved the TDI-induced disruption of E-cadherin in HBECs. Taken together, our data demonstrated that GLUT1 modulates bronchial epithelial E-cadherin dysfunction production in TDI-induced steroid-insensitive asthma.

Ferroptosis contributes to airway epithelial E-cadherin disruption in a mixed granulocytic asthma mouse model.

Aberrant expression of airway epithelial E-cadherin is a key feature of asthma, yet the underlying mechanisms are largely unknown. Ferroptosis is a novel form of regulated cell death involved in asthma pathogenesis. This study was aimed to evaluate the role of ferroptosis and to investigate whether ferroptosis mediates E-cadherin disruption in mixed granulocyte asthma (MGA). Two murine models of MGA were established using toluene diisocyanate (TDI) or ovalbumin with Complete Freund's Adjuvant (OVA/CFA). Specific antagonists of ferroptosis, including Liproxstatin-1 (Lip-1) and Ferrostatin-1 (Fer-1) were given to the mice. The allergen-exposed mice displayed markedly shrunk mitochondria in the airway epithelia, with decreased volume and denser staining accompanied by down-regulated GPX4 as well as up-regulated FTH1 and malondialdehyde, which are markers of ferroptosis. Decreased pulmonary expression of E-cadherin was also observed, with profound loss of membrane E-cadherin in the airway epithelia, as well as increased secretion of sE-cadherin. Treatment with Lip-1 not only showed potent protective effects against the allergen-induced airway hyperresponsiveness and inflammatory responses, but also rescued airway epithelial E-cadherin expression and inhibited the release of sE-cadherin. Taken together, our data demonstrated that ferroptosis mediates airway epithelial E-cadherin dysfunction in MGA.

GLUT1 Promotes NLRP3 Inflammasome Activation of Airway Epithelium in Lipopolysaccharide-Induced Acute Lung Injury.

Acute lung injury (ALI) is a devastating clinical disease caused by different factors, with high morbidity and mortality. It has been shown that lung injury and inflammation caused by lipopolysaccharide (LPS) can be modulated by NLRP3 inflammasome activation, yet its exact function within the airway epithelium is still unknown. Meanwhile, glucose transporter protein 1 (GLUT1) has been shown to contribute to a number of inflammatory illnesses, including ALI. The present study aimed to assess GLUT1's function in NLRP3 inflammasome activation of airway epithelium in LPS-induced acute lung injury. BALB/c mice and BEAS-2B cells were exposed to LPS (5 mg/kg and 200 µg/mL, respectively), with or without GLUT1 antagonists (WZB117 or BAY876). LPS up-regulated pulmonary expression of NLRP3 and GLUT1 in mice, which could be blocked by WZB117 or BAY876. Pharmacological inhibition of GLUT1 in vivo significantly attenuated lung tissue damage, neutrophil accumulation, and proinflammatory factors release (TNF-α, IL-6, and IL-1ß) in LPS-exposed mice. Meanwhile, the activation markers of NLRP3 inflammasome (ASC, caspase-1, IL-1ß, and IL-18) induced by LPS were also suppressed. In cultured BEAS-2B cells, LPS induced an increase in GLUT1 expression and triggered activation of the NLRP3 inflammasome, both of which were inhibited by GLUT1 antagonists. These results illustrate that GLUT1 participates in LPS-induced ALI and promotes the activation of the NLRP3 inflammasome in airway epithelial cells.

GLUT1 regulates the release of VEGF-A in the alveolar epithelium of lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis, characterized by excessive and uncontrolled inflammatory response. Vascular endothelial growth factor A (VEGF-A) contributes to the development and progression of ALI. The aim of this study was to evaluate the role of glucose transporter 1 (GLUT1) in alveolar epithelial VEGF-A production in lipopolysaccharide (LPS)-induced ALI. An ALI mouse model was induced by LPS oropharyngeal instillation. Mice were challenged with LPS and then treated with WZB117, a specific antagonist of GLUT1. For the vitro experiments, cultured A549 cells (airway epithelial cell line) were exposed to LPS, with or without the GLUT1 inhibitors WZB117 or BAY876. LPS significantly upregulated of GLUT1 and VEGF-A both in the lung from ALI mice and in cultured A549. In vivo, treatment with WZB117 not only markedly decreased LPS-induced pulmonary edema, injury, neutrophilia, as well as levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF), but also reduced VEGF-A production. Yet, the maximum tolerated concentration of WZB117 failed to suppress LPS-induced VEGF-A overexpression in vitro. While administration of BAY876 inhibited gene and protein expression as well as secretion of VEGF-A in response to LPS in A549. These results illustrated that GLUT1 upregulates VEGF-A production in alveolar epithelia from LPS-induced ALI, and inhibition of GLUT1 alleviates ALI.

GLUT1 mediates the release of HMGB1 from airway epithelial cells in mixed granulocytic asthma.

Asthma is quite heterogenous and can be categorized as eosinophilic, mixed granulocytic (presence of both eosinophils and neutrophils in the airways) and neutrophilic. Clinically, mixed granulocytic asthma (MGA) often tends to be severe and requires large doses of corticosteroids. High mobility group box 1 (HMGB1) is one of the epithelium-derived alarmins that contributes to type 2 inflammation and asthma. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in modulation of airway epithelial HMGB1 production in MGA. Induced sputum and bronchial biopsy specimens were obtained from healthy subjects and asthma patients. BALB/c mice, the airway epithelial cell line BEAS-2B, or primary human bronchial epithelial cells (HBECs) were immunized with allergens. Intracellular and extracellular HMGB1 were both detected. The role of GLUT1 was assessed by using a pharmacological antagonist BAY876. MGA patients have a significant higher sputum HMGB1 level than the health and subjects with other inflammatory phenotypes. Nuclear-to-cytoplasmic translocation of HMGB1 was also observed in the bronchial epithelia. Allergen exposure markedly induced GLUT1 expression in murine lungs and cultured epithelial cells. Pharmacological antagonism of GLUT1 with BAY876 dramatically decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in murine models of MGA. Besides, the allergen-induced up-regulation of HMGB1 was also partly recovered by BAY876, accompanied by inhibited secretion into the airway lumen. In vitro, treatment with BAY876 relieved the allergen-induced over-expression and secretion of HMGB1 in airway epithelia. Taken together, our data indicated that GLUT1 mediates bronchial epithelial HMGB1 release in MGA.

Ferroptosis mediates airway epithelial E-cadherin dysfunction in LPS-induced acute lung injury.

BACKGROUND: Loss of E-cadherin in the airway epithelial cells is a critical contributor to the development of ALI/ARDS. Yet the underlying mechanisms are largely unknown. Increasing evidences have revealed the significance of ferroptosis in the pathophysiological process of ALI/ARDS. The aim of this study was to investigate the role of ferroptosis in dysregulation of airway epithelial E-cadherin in ALI/ARDS. METHODS: BALB/c mice were subjected to intratracheal instillation of lipopolysaccharide (LPS) to establish an ALI model. Two inhibitors of ferroptosis, liproxstatin-1 (Lip-1, at the dose of 10 mg/kg and 30 mg/kg) and ferrostatin-1 (Fer-1, at the dose of 1 mg/kg and 5 mg/kg), were respectively given to the mice through intraperitoneal injection after LPS challenge. The expression of ferroptotic markers, full-length E-cadherin and soluble E-cadherin (sE-cadherin) were both detected. RESULTS: LPS exposure dramatically down-regulated pulmonary expression of E-cadherin in mice, with profound loss of membrane E-cadherin in the airway epithelial cells and increased secretion of sE-cadherin in the airway lumen. At the same time, we found that the mitochondrial of airway epithelial cells in LPS-exposed mice exhibited significant morphological alterations that are hallmark features of ferroptosis, with smaller volume and increased membrane density. Other makers of ferroptosis were also detected, including increased cytoplasmic levels of iron and lipid peroxidates (MDA), as well as decreased GPX4 expression. 30 mg/kg of Lip-1 not only showed potent protective effects against the LPS-induced injury, inflammation, edema of the lung in those mice, but also rescued airway epithelial E-cadherin expression and decreased the release of sE-cadherin through inhibiting ferroptosis. While no noticeable changes induced by LPS were observed in mice treated with Lip-1 at 10 mg/kg nor Fer-1 at 1 mg/kg or 5 mg/kg. CONCLUSIONS: Taken together, these data demonstrated that ferroptosis mediates airway epithelial E-cadherin dysfunction in LPS-induced ALI.

GLUT1 contributes to impaired epithelial tight junction in the late phase of acute lung injury.

Dysfunction of epithelial barrier is crucial for the development of acute lung injury (ALI). This study was aimed to evaluate the role of glucose transporter 1 (GLUT1) in dysregulation of epithelial tight junction in ALI. GLUT1 was inhibited with specific antagonists WZB117 or BAY876 to see the effects on epithelial tight junction in a well-established LPS-induced mouse ALI model as well as in vitro cultured epithelial cells. Pharmacological inhibition of GLUT1 with WZB117 at either a low or high dose had no effects on lung injury and inflammation 24 h after LPS challenge, but significantly decreased the pulmonary inflammatory responses induced by LPS at 72 h with a high dose, which was verified by treatment with BAY876. WZB117 or BAY876 also recovered the expression of epithelial tight junction proteins ZO-1 and occludin. In cultured BEAS-2B and A549 cells, LPS induced increased GLUT1 expression, accompanied by decreased expression of tight junction protein ZO-1 and occludin. Blockade of GLUT1 restored LPS-induced disruption of ZO-1 and occludin in BEAS-2B rather than A549. Taken together, our results showed that GLUT1 is responsible for dysfunction of epithelial tight junctions in the late phase of LPS-induced ALI.

Effects of Linpan nature therapy on health benefits in older women with and without hypertension.

Background: Nature therapy can significantly benefit the physiology and psychology of middle-aged and older people, but previous studies have focused on forest environments. The restoration potential of rural environments in urban fringe areas, which are more accessible to older people on a daily basis, has not been fully studied. This study assessed the effects of nature therapy on the physical and mental health of older women in a rural setting (locally known as Linpan) in the urban fringe area of Chengdu, China. Methods: We recruited a total of 60 older women (65.3 ± 5.5 years old) living in cities for 3 days of nature therapy in the winter (30 subjects) and spring (30 subjects), including 20 hypertensive patients. Results: The results showed that the overall blood pressure, pulse and sleep dysfunction rating scores of the participants were significantly lower than the pretest levels, and the finger blood oxygen saturation, mid-day salivary alpha-amylase and cortisol were increased post-treatment. Increases in these biomarker indicates and increase in stress. There were significant differences in the changes in systolic blood pressure between the hypertension group (HTN) and the normal group (normal) (HTN decreased by 8.8%, normal decreased by 5.4%), salivary alpha-amylase content (HTN decreased by 0.3%, normal increased by 16.9%), and sleep dysfunction rating scores (HTN decreased by 59.6%, normal decreased by 54%). The decreases in systolic blood pressure and pulse in the winter group were higher than those in the spring group by 1.8 and 4.4%, respectively, while the increases in salivary alpha-amylase content and salivary cortisol content were lower than those in the spring group by 11.7 and 11.2%, respectively, and the decrease in sleep dysfunction rating scores was lower than that in the spring group by 7.1%. Conclusion: Our study concluded that nature therapy based on various health activities in the Linpan has significant health effects on older women. It can regulate blood pressure and pulse in older women, relieve cardiovascular disease, improve sleep quality. Meanwhile, older women with high blood pressure experienced a more significant effect than the healthy group.

Case Report: An Unusual Presentation of Cardiovascular Involvement in Eosinophilic Granulomatosis With Polyangiitis.

Background: Because eosinophilic granulomatosis with polyangiitis (EGPA) is so rare and the symptoms so varied, it can be a challenge to get a correct diagnosis in clinical practice. Cardiovascular involvement is the main cause of death of EGPA. We are the first to report of cardiac magnetic resonance (CMR) findings about right-sided heart involvement in EGPA. Patient Findings: The initial abnormalities detected by CMR were Löffler endocarditis with extensive thrombosis and left ventricular (LV) dysfunction. After active treatment, LV systolic function recovered and endocarditis with thrombosis significantly improved, but there was rapidly progressive pulmonary hypertension, enlargement of right atrium and right ventricle and persistent right-sided heart failure. The patient eventually died of sudden cardiac death 6 months after hospital discharge. Conclusions: Löffler endocarditis and right-sided heart involvement are both rare presentations in patients with EGPA. CMR is a reliable non-invasive tool to precisely and comprehensively assess cardiovascular involvement in EGPA.

Comparative study on native T1 value of myocardium between using ConSept and SAX approaches in non-ischemic dilated cardiomyopathy. / ConSept法和SAXæ³•æµ‹é‡éžç¼ºè¡€æ€§æ‰©å¼ åž‹å¿ƒè‚Œç— å¿ƒè‚Œåˆå§‹T1值的对比分析.

OBJECTIVES: T1 mapping can noninvasively quantify the native longitudinal relaxation time (T1 value) of myocardium and provide more information on myocardial fibrosis based on late gadolinium enhancement (LGE). However, the traditional approach of measuring T1 value limits the popularization and application of this technology in clinic because the whole short axis (SAX) of myocardium is required in the regions of interest (ROI). This study aims to evaluate the diagnostic ability of native T1 value obtained by comparison between the midventricular septum (ConSept) and SAX approaches in diffuse myocardial lesions. METHODS: Retrospective analysis was performed on 38 patients with non-ischemic dilated cardiomyopathy (NIDCM) and 27 healthy controls who underwent T1 mapping and gadolinium delayed enhancement (LGE) scanning on a 3.0T cardiac magnetic resonance (CMR) in Xiangya Hospital of Central South University. Patients with NIDCM were divided into a LGE positive group and a LGE negative group according to the presence or absence of LGE. The native T1 value was measured by the ROI placed in the ConSept and SAX, respectively. The ability to distinguish the impaired myocardium from the healthy myocardium and the native T1 values of the myocardium measured by the 2 approaches were compared between the NIDCM group and the control group. RESULTS: The native T1 values of NIDCM group using ConSept or SAX approach were significantly higher than those in the control group (all P<0.001), and the native T1 values in the LGE positive group were greater than those in the LGE negative group (all P<0.05). There was no significant difference in T1 value of middle, basal, and apical layer between the ConSept approach and SAX approach (all P>0.05). ConSept and SAX approaches had a good consistency [concordance correlation coefficient (CCC)=0.954]. CONCLUSIONS: Comparing to the SAX approach, ConSept approach is a simple and equivalent method to measure the native T1 value of myocardium and is suitable for clinical application.

Impaired airway epithelial barrier integrity was mediated by PI3Kδ in a mouse model of lipopolysaccharide-induced acute lung injury.

Cell-cell junctions are critical for the maintenance of cellular as well as tissue polarity and integrity. Dysfunction of airway epithelial barrier has been shown to be involved in the pathogenesis of acute lung injury (ALI). Yet the role of phosphatidylinositol 3-kinase delta (PI3Kδ) in dysregulation of airway epithelial barrier integrity in ALI has not been addressed. Mice were subjected to intratracheal instillation of lipopolysaccharide (LPS) to generate a ALI model. Two pharmacological inhibitors of PI3Kδ, IC87114 and AMG319, were respectively given to the mice. Expression of p110δ and its downstream substrate phospho-AKT (Ser473) was increased in LPS-exposed lungs. These increases were inhibited by IC87114 or AMG319. LPS led to pronounced lung injury that was accompanied by significant airway neutrophil recruitment and bronchial epithelial morphological alterations 72 h after exposure. We also found compromised expression of adherens junction protein E-cadherin and tight junction protein claudin-2 in the airway epithelial cells. Treatment with either IC87114 or AMG319 not only attenuated LPS-induced edema, lung injury and neutrophilc inflammation, reduced total protein concentration and IL-6, TNF-α secretion in BALF, but also restored epithelial E-cadherin and claudin-2 expression. In summary, our results showed that LPS can induce a delayed effect on airway epithelial barrier integrity that is mediated by PI3Kδ in a mouse model of ALI.

Distinct roles of PI3Kδ and PI3Kγ in a toluene diisocyanate-induced murine asthma model.

TDI-induced asthma is characterized by neutrophil-dominated airway inflammation and often associated with poor responsiveness to steroid treatment. Both PI3Kδ and PI3Kγ have been demonstrated to play important proinflammatory roles in ovalbumin-induced asthma. We've already reported that blocking pan PI3K effectively attenuated TDI-induced allergic airway inflammation. Yet the specific functions of PI3Kδ and PI3Kγ in TDI-induced asthma are still unclear. Male BALB/c mice were first dermally sensitized and then challenged with TDI to generate an asthma model. Sellective inhibitors of PI3Kδ (IC-87114, AMG319) and PI3Kγ (AS252424, AS605240) were respectively given to the mice after each airway challenge. Treatment with IC-87114 or AMG319 after TDI exposure led to significantly decreased airway hyperresponsiveness (AHR), less neutrophil and eosinophil accumulation, attenuated airway smooth muscle (ASM) thickening, less M1 and M2 macrophages in lung, as well as lower levels of IL-4, IL-5, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) and recovered IL-10 production. While mice treated with AS252424 or AS605240 had increased AHR, more severe ASM thickening, larger numbers of neutrophils and eosinophils, more M1 but less M2 macrophages, and higher BALF levels of IL-4, IL-5, IL-6, IL-10, IL-12, IL-18 when compared with those treated with vehicle. These data revealed that pharmacological inhibition of PI3Kδ attenuates TDI-induced airway inflammation while PI3Kγ inhibition exacerbates TDI-induced asthma, indicating distinct biological functions of PI3Kδ and PI3Kγ in TDI-induced asthma.

The receptor for advanced glycation end products mediates dysfunction of airway epithelial barrier in a lipopolysaccharides-induced murine acute lung injury model.

BACKGROUND: Airway epithelial cells (AECs) act as the first barrier protecting against invasion of environment agents and maintain integrity of lung structure and function. Dysfunction of airway epithelial barrier has been shown to be involved in ALI/ARDS pathogenesis. Yet, the exact mechanism is still obscure. Our study evaluated whether the receptor for advanced glycation end products (RAGE) mediates impaired airway epithelial barrier in LPS-induced murine ALI model. METHODS: Male BALB/c mice were subjected to intratracheal instillation of LPS to generate an ALI model. Inhibitors of RAGE, FPS-ZM1 and Azeliragon were respectively given to the mice through intraperitoneal injection. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected for further analysis. RESULTS: LPS exposure led to markedly increased expression of RAGE and its ligands HMGB1, HSP70, S100b. Treatment of FPS-ZM1 or Azeliragon not only effectively descended the expression of RAGE and its ligands but also attenuated LPS-induced neutrophil-predominant airway inflammation and injury, decreased levels of IL-6, IL-1ß and TNF-α in BALF, alleviated increased alveolar-capillary permeability and pulmonary edema. LPS stimulation significantly impaired the integrity of airway epithelium, paralleled with dislocation of adheren junction (AJ) protein E-cadherin at cell-cell contacts and down-expression of both AJ and tight junction (TJ) proteins Claudin-2 and occludin, all of which were dramatically rescued by RAGE inhibition. CONCLUSION: RAGE signaling mediates airway epithelial barrier dysfunction in a LPS-induced ALI murine model.

Design, validation, and clinical practice of standardized imaging diagnostic report for COVID-19. / COVID-19规范化影像学诊断报告的设计、验证与临床实践.

OBJECTIVES: To design a standardized imaging diagnostic reporting mode for screening coronavirus disease 2019 (COVID-19), and to prospectively verify its effectiveness in clinical practice. METHODS: A new classification and standardized imaging diagnosis report mode of viral pneumonia was established by studying and summarizing the imaging findings of various kinds of viral pneumonia, combining with lesion density, interstitial changes, pleural effusion, lymph nodes, and some special signs. After systematic training, the radiologist experienced clinical practice for screening CT features. COVID-19 cases were screened retrospectively in the single-center. The confirmed cases were verified, and the diagnostic efficacy of the standardized imaging reporting system in screening COVID-19 was tested. RESULTS: There were 912 patients in this stage receiving the screening imaging examination. Of them, 190 patients were screened in the report mode and 30 patients were diagnosed as COVID-19. The CT manifestation of COVID-19 was characterized by pure ground glass lesions or with a few solid components, predominant subpleural distribution, no lymph node enlargement and pleural effusion, and often with paving-way sign and air bronchus sign. In combination with the above signs, the diagnostic efficacy of COVID-19 was 0.942. CONCLUSIONS: The standardized imaging diagnosis report mode based on COVID-19 chest image features is effective and practical, which should be popularized.

Clinical and CT imaging features between the first nucleic acid-negative and first nucleic acid-positive COVID-19 patients. / 2019å† çŠ¶ç— æ¯’ç— é¦–æ¬¡æ ¸é ¸é˜´æ€§ä¸Žé¦–æ¬¡æ ¸é ¸é˜³æ€§æ‚£è€ ä¸´åºŠåŠCT影像学表现.

OBJECTIVES: To investigate the role of chest CT for the diagnostic work-up for patients with suspected infection of coronavirus disease 2019 (COVID-19). METHODS: The clinical data and imaging findings of the first nucleic acid-negative COVID-19 patients were analyzed and compared with the first nucleic acid-positive patients. RESULTS: Compared with the first nucleic acid-positive patients, the onset time of the first nucleic acid-negative patients was shorter [(3.58±2.94) d], but the diagnosis was longer [(3.92±3.66) d]. There were no significant differences in the characteristics of the clinical data and radiological findings between the 2 groups (P>0.05). CONCLUSION: Chest CT examination is important to avoid COVID-19 missed diagnosis due to false negative nucleic acid.

A family outbreak of coronavirus disease 2019. / 一组家族暴发的2019å† çŠ¶ç— æ¯’ç— .

Although continuous outbreak of coronavirus disease 2019, it has been widely reported, there were few reports regarding family cases. We reported a group of family cluster outbreak cases confirmed in Xiangya Hospital, Central South University, China, and their clinical and image characteristics have been analyzed in order to provide reference for the prevention and early diagnosis of this disease. A total of 5 patients from one family, including 4 adults and 1 child, had a history of human contact in Wuhan, Hubei. Four adult patients showed different symptoms, including cough, fever, pharyngeal pain, and dyspnea, while the child patient had no symptoms. Laboratory examination showed no abnormality in all the patients except for slight increase in CRP in 2 patients and mild abnormal liver function index in 1 patient. The chest CT showed that all patients had abnormal images, with different degrees of manifestations.All patients were finally diagnosed by the nucleic acid test.

Structured reporting of cardiovascular magnetic resonance based on expert consensuses and guidelines.

BACKGROUND: There is a gap between China and developed countries in Europe and America as to the normalization of cardiac magnetic resonance (CMR) diagnostic reports. The aim of this study was to construct a structured CMR report template suitable for China's actual conditions. METHODS: Cardiac magnetic resonance standardized image interpretation and post-processing guidelines and CMR report guidelines are the consensus and recommendations of the Society for Cardiovascular Magnetic Resonance (SCMR) experts whose goal is to ensure the consistent quality and repeatability of CMR reports. This structured CMR report template was constructed based on the guidelines for standardized image interpretation, post processing and reporting of CMR examinations, combined with the experiences learned in Germany and the practical experiences in China. It consisted of three parts: Device and Methods, Findings (Structure and function, Tissue Characterization), Summary and Conclusion. Detailed directions were provided section by section. RESULTS: This structured CMR report template underlined the comprehensive analysis of the results of morphological, functional and tissue characteristics to provide conclusive opinions and answer the corresponding important questions raised by the clinicians. CONCLUSION: The standardization of qualitative and quantitative assessments of CMR results is the core of structured reporting of CMR.

IL-17F, rather than IL-17A, underlies airway inflammation in a steroid-insensitive toluene diisocyanate-induced asthma model.

Steroid insensitivity constitutes a major problem for asthma management. Toluene diisocyanate (TDI) is one of the leading allergens of asthma that induces both T-helper Th2 and Th17 responses, and is often associated with poor responsiveness to steroid treatment in the clinic.We sought to evaluate the effects of inhaled and systemic steroids on a TDI-induced asthma model and to find how interleukin (IL)-17A and IL-17F function in this model. BALB/c mice were exposed to TDI for generating an asthma model and were treated with inhaled fluticasone propionate, systemic prednisone, anti-IL-17A, anti-IL-17F, recombinant IL-17A or IL-17F.Both fluticasone propionate and prednisone showed no effects on TDI-induced airway hyperresponsiveness (AHR), bronchial neutrophilia and eosinophilia, and epithelial goblet cell metaplasia. TDI-induced Th2 and Th17 signatures were not suppressed by fluticasone propionate or prednisone. Treatment with anti-IL-17A after TDI exposure led to increased AHR, aggravated mucus production and airway eosinophil recruitment, accompanied by amplified Th2 responses, whereas anti-IL-17F ameliorated TDI-induced AHR and airway neutrophilia, with decreased Th17 responses. Recombinant IL-17A and IL-17F showed opposite effects to the monoclonal antibodies.IL-17A and IL-17F exert distinct biological effects during airway inflammation of a TDI-induced asthma model, which is unresponsive to both inhaled and systemic steroids.

Transient Receptor Potential Ion Channels Mediate Adherens Junctions Dysfunction in a Toluene Diisocyanate-Induced Murine Asthma Model.

Disruption of epithelial cell-cell junctions is essential for the initiation and perpetuation of airway inflammation in asthma. We've previously reported compromised epithelial barrier integrity in a toluene diisocyanate (TDI)-induced occupational asthma model. This study is aimed to explore the role of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1) in the dysfunction of adherens junctions in TDI-induced asthma. Mice were sensitized and challenged with TDI for a chemical-induced asthma model. Selective blockers of TRPV4 glycogen synthase kinase (GSK)2193874, 5 and 10 mg/kg) and TRPA1 (HC030031, 10 and 20 mg/kg) were intraperitoneally given to the mice. Immunohistochemistry revealed different expression pattern of TRPV4 and TRPA1 in lung. TDI exposure increased TRPV4 expression in the airway, which can be suppressed by GSK2193874, while treatment with neither TDI alone nor TDI together with HC030031 led to changes of TRPA1 expression in the lung. Blocking either TRPV4 or TRPA1 blunted TDI-induced airway hyperreactivity, airway neutrophilia and eosinophilia, as well as Th2 responses in a dose-dependent manner. At the same time, membrane levels of E-cadherin and ß-catenin were significantly decreased after TDI inhalation, which were inhibited by GSK2193874 or HC030031. Moreover, GSK2193874 and HC030031 also suppressed serine phosphorylation of glycogen synthase kinase 3ß, tyrosine phosphorylation of ß-catenin, as well as activation and nuclear transport of ß-catenin in mice sensitized and challenged with TDI. Our study suggested that both TRPV4 and TRPA1 contribute critically to E-cadherin and ß-catenin dysfunction in TDI-induced asthma, proposing novel therapeutic targets for asthma.