Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma.

BACKGROUND: The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. METHODS: House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. RESULTS: Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. CONCLUSION: Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation.

C5a enhances inflammation and chemotaxis of γδ T cells in malignant pleural effusion.

BACKGROUND: The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of γδ T cells in MPE patients and their recruitment to the pleural cavity. METHODS: We quantified γδ T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on γδ T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of γδ T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay. RESULTS: We observed a significant infiltration of γδ T cells in MPE, surpassing the levels found in blood and benign pleural effusion. γδ T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, γδ T cells in MPE showed higher levels of cytokines (IFN-γ, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the Vδ2 subtype compared to Vδ1 cells. Moreover, the complement C5a enhanced cytokine release by γδ T cells, upregulated CCR2 expression in Vδ2 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of γδ T cells. CONCLUSIONS: γδ T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.

Complement regulatory proteins: Candidate biomarkers in differentiating tuberculosis pleural effusion.

Background and aims: Complement activation is essential for tuberculosis pleural effusion. However, little is known about the value of complement regulatory protein (CD46, CD55, and CD59) in the differential diagnosis of tuberculosis. Materials and methods: Ninety-nine patients with exudative pleural effusion admitted to Xiangya Hospital of Central South University from June 1, 2021to November 14, 2022 were enrolled. The expression levels of soluble CD46 (sCD46), soluble CD55 (sCD55), and soluble CD59 (sCD59) in pleural effusion were quantified by enzyme-linked immunosorbent assay, and the receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic and co-diagnostic values. Results: The ADA level is higher in TPE patients than non-TPE patients. It is well-found that TPE patients had lower levels of sCD46, sCD55, and sCD59 compared with non-TPE patients. Moreover, the expression of sCD46, sCD55, and sCD59 in pleural effusion was negatively correlated with ADA. In addition, the diagnostic efficacy of sCD46, sCD55 and sCD59 was comparable to that of ADA, with 0.896, 0.857, 0.858 and 0.893, respectively. Furthermore, combine detection of sCD46, sCD55, sCD59 and ADA could improve the diagnostic accuracy. Conclusions: Complement regulatory factors (CD46, CD55, and CD59) were validated by this project to be promising candidate biomarkers for the diagnosis of TPE with high accuracy. The combination of the CD46, CD55, and CD59 and ADA assay exist a better diagnostic value in TPE.

Comparison of the airway complications of subtypes of laryngeal mask airway and i-gel in child patients under general anaesthesia: a protocol for systematic review and network meta-analysis of randomised control trials.

INTRODUCTION: Laryngeal mask airway (LMA), an alternative to traditional tracheal intubation, is widely used in clinical practice and is considered to be an effective device for airway management. LMA and i-gel have been widely used in anaesthesia and emergency situations in children. Some systematic reviews have evaluated the efficacy of LMA and i-gel in children, but they have not shown consistent results in clinical performance. This study aims to evaluate the airway complications of all subtypes of LMA and i-gel in child patients under general anaesthesia using a Bayesian network meta-analysis (NMA). METHODS AND ANALYSIS: PubMed, EMBASE.com, the Cochrane library, Web of Science and Chinese Biomedical Literature Database will be searched from inception to January 2019. We will include prospective randomised controlled trials (RCTs) that reported the subtypes of LMA and i-gel regardless of sample size. The risk of bias assessment of the included RCTs will be conducted according to the Cochrane Handbook V.5.1.0. A Bayesian NMA will be performed using WinBUGS V.1.4.3. Grading of Recommendations Assessment, Development and Evaluation will be used to explore the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an NMA based on published trials. The results of this NMA will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42019127668.

An overview protocol of biomarkers for breast cancer detection.

BACKGROUND: Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death over 100 countries. Generally, the prognosis of early-stage breast cancer is good. However, the prognosis is very poor when the disease is diagnosed at an advanced stage. Many screening methods have been used for early detection of breast cancer, but there are some limitations of these methods. Recently, some systematic reviews have evaluated the value of biomarkers for detecting breast cancer. However, most of the systematic reviews (SRs) only evaluated the diagnostic value of 1 biomarker, and it is unclear which biomarker is the best diagnostic test for breast cancer. This overview aims to assess the methodological and reporting quality of available systematic reviews and to compare the diagnostic value of different biomarkers. METHODS: PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched to identify published systematic reviews reporting the value of biomarkers for detecting breast cancer. Title and abstracts, as well as full texts, were screened in duplicate based on inclusion and exclusion criteria. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool and Preferred Reporting Items for Systematic Reviews and Meta-analysis diagnostic test accuracy (PRISMA-DTA) checklist will be used to assess the methodological and reporting quality, respectively. We will conduct the pairwise meta-analysis and indirect comparisons using STATA 13.0. RESULTS: The results of this study will be published in a peer-reviewed journal CONCLUSION:: This overview will provide comprehensive evidence of different biomarkers for the diagnosis of breast cancer. PROSPERO REGISTRATION NUMBER: CRD42019125880.

Diagnostic performance of biomarkers for ovarian cancer: Protocol for an overview, evidence mapping, and adjusted indirect comparisons.

BACKGROUND: Ovarian cancer is one of the deadliest gynecological diseases and the annual mortality of ovarian cancer continues to rise. The prognosis of ovarian cancer is poor because it is prone to early metastasis during progression. Therefore, early diagnosis of ovarian cancer is very important. Some systematic reviews have evaluated the diagnostic value of different biomarkers for ovarian cancer. However, there is no consensus in the conclusions, and some are even contradictory. This study aims to assess the methodological and reporting quality of available systematic reviews and to find an optimal biomarker for diagnosing ovarian cancer. METHODS: The PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched to identify relevant systematic reviews from inception to February 2019. We included systematic reviews that include randomized controlled trials, cross-sectional studies, case-control studies, or cohort studies as long as the systematic reviews evaluated the diagnostic performance of biomarkers for ovarian cancer. The methodological quality will be assessed using assessment of multiple systematic reviews-2 checklist, and the reporting quality will be assessed using preferred reporting items for systematic reviews and meta-analysis diagnostic test accuracy (PRISMA-DTA) checklist. The pairwise meta-analysis and indirect comparisons will be performed using STATA (13.0; Stata Corporation, College Station, TX). RESULTS: The results of this overview will be submitted to a peer-reviewed journal for publication. CONCLUSION: This overview will provide comprehensive evidence of different biomarkers for diagnosing ovarian cancer. PROSPERO REGISTRATION NUMBER: CRD42019125880.