Xiao Qing Long Tang ameliorates neutrophil extracellular trap-dendritic cells-T helper 17 cell axis in Neutrophilic Asthma

by Xiaoying Ji, Hongda Chen, Sheng-dong He, Min Huang, Xiaoli You, Chuan Xiao, Zhifeng Chen, Jinwen Cai

Neutrophilic asthma (NA) is an allergic airway inflammation disease featuring heterogeneous neutrophil infiltration, which is driven by the interactions between dendritic cells (DCs) and T helper (Th) 17 cells. Neutrophils release neutrophil extracellular traps (Nets), which promote disease progression and glucocorticoid resistance. Therefore, targeting the interaction among Nets, DC and Th17 is a promising pathway for preventing organ damage. Traditional Chinese Medicine (TCM), especially Xiao-qing-long-tang (XQLT), has shown potential in managing eosinophilic asthma by modulating Th2 cell-mediated inflammation, reducing eosinophilic infiltration, and airway remodeling. However, XQLT’s effect on Nets and DCs-Th17 interactions in NA remains unclear.

We developed two models: an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced NA mouse model with interventions using either XQLT or sivelestat, and a series of bone marrow-derived dendritic cells (BMDCs)-Th17 cell differentiation models induced by Nets, OVA/LPS, OVA/LPS/Nets, XQLT, OVA/LPS/Nets/XQLT, or corresponding inhibitors. The chemical composition of XQLT was analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Key parameters were evaluated via histopathology, immunohistochemistry, immunofluorescence scanning, flow cytometry, Western blot (WB) analysis, and enzyme-linked immunosorbent assay (ELISA).

In OVA/LPS-induced mice, treatment with sivelestat in OVA/LPS-induced mice reduced airway inflammation, Nets formation characterized by citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) expressions, Th2/17 cell proportions in lungs, and interleukin (IL)-4, 6, 17, and 23 levels in bronchoalveolar lavage fluid (BALF). In vitro, OVA/LPS/Nets promoted IL-6/23 secretions and Th17 differentiation through increased p38 mitogen-activated protein kinase (MAPK)/nuclear factor κB (NF-κB) signaling phosphorylation in DCs. Fifty-one compounds were identified in XQLT, with 11 predicted to bind MAPK proteins with high affinity. XQLT significantly inhibited Nets-DCs-Th17 Axis and p38MAPK/NF-κB signaling in both NA mouse and cell models.

XQLT offered a promising treatment strategy for regulating the Nets-DCs-Th17 axis in NA.

The effectiveness of interventions to reduce cancer‐related stigma: An integrative review

Abstract

Aims

The clinical significance of cancer-related stigma on patients' well-being has been widely established. Stigma can be perceived and internalised by cancer patients or implemented by the general population and healthcare workers. Various interventions have been carried out to reduce cancer-related stigma, but their effectiveness is not well-understood. This review aims to synthesise evidence on the effectiveness of interventions to reduce cancer-related stigma.

Design

An integrative review.

Methods

This integrative review combined both qualitative and quantitative studies and followed five steps to identify problems, search for the literature, appraise the literature quality, analyse data, and present data. Mixed Methods Appraisal Tool (version 2018) was applied to evaluate the quality of the included studies.

Data Sources

Databases included Web of Science, MEDLINE, SpringerLink, Wiley Online Journals, Cochrane Library, ScienceDirect, OVID, and China National Knowledge Infrastructure (from the inception of each database to 30 April 2021).

Results

Eighteen quantitative, six qualitative, and five mixed-methods studies were included in this review. Cultural factors should be considered when conducting interventions to reduce cancer-related stigma. For cancer patients, multi-component interventions have demonstrated a positive effect on their perceived stigma. For general population, interactive interventions show promise to reduce their implemented stigma towards cancer patients. For healthcare workers, there is a paucity of studies to reduce their implemented stigma. Existing studies reported inconclusive evidence, partially due to the lack of a robust study design with an adequate sample size.

Conclusions

Multi-component and interactive interventions show promise to relieve cancer-related stigma. More methodologically robust studies should be conducted in different cultures to elucidate the most appropriate interventions for different populations to reduce cancer-related stigma.

Implication for the Profession and Patient Care

These findings will facilitate healthcare workers to design and implement interventions to reduce cancer-related stigma, thus improving the quality of life for cancer patients.

Patient and Public Contribution

No patient and public contribution.