Edited by Xiao-Fan Wang Asthma is thought to be caused by malfunction of type 2 T helper cell (Th2)-mediated immunity, causing excessive inflammation, mucus overproduction, and apoptosis of airway epithelial cells. Heme oxygenase-1 (HO-1) functions in heme catabolism and is both cytoprotective and anti-inflammatory. We hypothesized that this dual function may be related to asthma's etiology. Using primary airway epithelial cells (pAECs) and an asthma mouse model, we demonstrate that severe lung inflammation is associated with rapid pAEC apoptosis. Surprisingly, NOD-like receptor protein 3 (NLRP3) inhibition, retinoid X receptor (RXR) deficiency, and HO-1 induction were associated with abrogated apoptosis. MCC950, a selective small-molecule inhibitor of canonical and noncanonical NLRP3 activation, reduced RXR expression, leading to decreased pAEC apoptosis that was reversed by the RXR agonist adapalene. Of note, HO-1 induction in a mouse model of ovalbumin-induced eosinophilic asthma suppressed Th2 responses and reduced apoptosis of pulmonary pAECs. In vitro, HO-1 induction desensitized cultured pAECs to ovalbumin-induced apoptosis, confirming the in vivo observations. Critically, the HO-1 products carbon monoxide and bilirubin suppressed the NLRP3-RXR axis in pAECs. Furthermore, HO-1 impaired production of NLRP3-RXR-induced cytokines (interleukin [IL]-25, IL-33, thymic stromal lymphopoietin, and granulocyte-macrophage colony-stimulating factor) in pAECs and lungs. Finally, we demonstrate that HO-1 binds to the NACHT domain of NLRP3 and the RXR␣ and RXR subunits and that this binding is not reversed by Sn-protoporphyrin. Our findings indicate that HO-1 and its products are essential for pAEC survival to maintain airway epithelium homeostasis during NLRP3-RXRmediated apoptosis and inflammation.
Epithelial cells (ECs)‐derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type‐2‐cell‐mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata. We found that toll‐like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C‐C chemokine ligand‐2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin (TSLP) production through the NF‐κB and JNK signaling pathways to extend the survival of recruited basophils and resident DCs in the lung, predisposing a type‐2‐cell‐mediated airway inflammation. Conversely, TLR2 deficiency impaired http://secretion of TSLP and CCL2, decreased infiltration of lung basophils, and increased resistance to Th2 response. Blocking TSLP also phenocopied these phenomena. Our findings reveal a pro‐inflammatory role of airway ECs through a TLR2‐dependent TSLP production, which may have implication for treating allergic asthma.
Background: In recent years, systematic reviews/meta-analyses (SRs/MAs) of Chinese herbal medicine (CHM) for psoriasis have continuously emerged. Their methods and evidence quality, however, are yet to be evaluated, and whether their conclusions can provide clinicians with reliable evidence is still debatable.Objectives: This overview aims to evaluate the methodological quality, risk of bias, and reporting quality of relevant SRs/MAs, as well as the current evidence of CHM for treating psoriasis.Methods: We searched nine electronic databases from their respective time of establishment to January 20, 2021, as well as the reference lists of the included SRs/MAs, protocol registries, and gray literature. Two reviewers independently used the following: A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE) to evaluate the methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs.Results: This review included 14 SRs/MAs involving 45 outcomes, of which 12 (85.71%) SRs/MAs had a very low quality evaluated by AMSTAR 2 and 7 (50.00%) SRs/MAs had a high risk of bias assessed by ROBIS. The protocol and registration and funding statements were the major reporting flaws according to the PRISMA checklist. The evaluation with the GRADE system demonstrated no outcome of high-quality evidence, and inconsistent efficacy evaluations were found in this overview. Only 15 (33.33%) outcomes were moderate-quality evidence, supporting the claim that CHM plus Western medicine (WM) was superior to WM. Generally low quality of evidence showed no difference in the incidence of adverse events between the combined therapy and WM. However, the conclusion that CHM was superior to WM cannot be drawn due to the inconsistent results.Conclusion: Despite that CHM has the potential benefit and safety in the adjuvant treatment of psoriasis, the conclusion should be treated with caution because of the generally low quality of methodology and evidence. In the future, high-quality randomized controlled trials (RCTs) should be carried out, and the quality of relevant SRs should also be improved to promote their clinical application.
Background: Chinese herbal bath has long been used in the curative treatment of psoriasis vulgaris. However, there is no unified standard protocol for Chinese herbal bath. Many factors affect the curative effect of Chinese herbal bath, such as water temperature, bath concentration, and soaking time. Most studies involving Chinese herbal bath has described the bath generally, and few studies have investigated the factors that might contribute to the efficacy of Chinese herbal bath. Here we describe a protocol to evaluate the efficacy and safety of various bathwater temperatures and herbal concentrations on psoriasis vulgaris, and their effect on serum vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), interleukin 23 (IL-23), and interleukin 17 (IL-17). These data could be useful for optimizing Chinese herbal bath treatments. Methods: In this randomized controlled trial, we planned to recruit 288 hospitalized atients with psoriasis vulgaris aged 18 to 65 years. All participants who meet the inclusion criteria will be randomly assigned to the observation group, the control group, or the basic treatment group. The observation group will be divided into 6 sub-groups according to water temperatures and bath concentrations, designated as observation groups 1 to 6. Thirty-six participants will be assigned to each group. The basic treatment group will be given co-qingdai capsule, po 2 g tid; compound glycyrrhizin tablet, po 75 mg tid; AA Skincare jojoba Oil, us.ext qd. The observation group will be given a Chinese herbal bath at the same time as the basic treatment. The control group will be given ozone hydrotherapy at the same time as the basic treatment. The entire treatment course will last for 2 weeks. The following parameters will be compared in each group, before and 2 weeks after treatment: the psoriasis area and severity index score (PASI), pruritus score, clinical efficacy, and dermatology life quality index score (DLQI); serum levels of serum VEGF, TNF-α, IL-23, and IL-17; and confocal laser scanning microscope images. Conclusion: This study will evaluate the efficacy and safety of various Chinese herbal bath conditions (water temperatures and herbal concentrations) on the treatment of psoriasis vulgaris, which will provide an important reference for the operation of Chinese herbal bath. Trial registration number: ChiCTR1900027468
Background: The pathogenesis of chronic spontaneous urticaria (CSU) is not clear, but its occurrence is closely related to the immune state of the body, that is, the balance of T cell subsets. Previous studies have confirmed that the dynamic imbalance of Th1/Th2 cells in CD4+T cell subsets of T cell subsets is closely related to the pathogenesis of CSU, but there are few studies on the relationship between the dynamic imbalance of Th17/Treg cells in CD4+T cell subsets and the pathogenesis of CSU. The purpose of this study is to evaluate the relationship between Th17/Treg cells expression in peripheral blood and CSU, so as to provide a reference basis for the pathogenesis of CSU. Methods: PubMed, Embase, CENTRAL, Web of Science, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chongqing VIP Database will be searched to collect case-control studies and cohort studies evaluating the relationship between Th17/Treg cells expression in peripheral blood and CSU. The search time limits will be from the establishment of the database to December 2020. The meta-analysis will be carried out with the RevMan V.5.3 statistical software. The quality of all included studies will be evaluated by the Newcastle-Ottawa scale. Results: The results of this study will comprehensively evaluate the Th17/Treg cells expression levels in peripheral blood of patients with CSU, and provide a reference basis for the pathogenesis of CSU. Conclusion: The findings of this study may provide new evidence for the relationship between Th17/Treg cells balance in peripheral blood and CSU. OSF registration number: DOI 10.17605/OSF.IO/S8MYW
Background: Psoriasis is a chronic recurrent dermatological disease that patents always suffer from different comorbidities. Chinese herbal medicine (CHM) has been commonly used in the treatment of psoriasis for a long history. Previous systematic reviews (SRs)/meta-analyses (MAs) have shown that CHM may benefit patients with psoriasis. This overview aims to summarize the evidence from published SRs/MAs for clinical application and to provide several directions for future researches. Methods: Nine electronic databases (Medline, Embase, Cochrane Library, AMED, CINAHL, CBM, CNKI, VIP Database, Wanfang Databases) will be searched from their inceptions to September 2020 without language restrictions. At least 2 reviewers will independently conduct the study selection, data extraction, and quality assessment. The methodological quality, risk of bias, reporting quality, and evidence quality will be respectively evaluated by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR 2), the Risk of Bias in Systematic Reviews, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results: The results of this overview will be submitted to a peer-reviewed journal for publication. Conclusions: We expect to compile current evidence from published SRs/MAs of CHM for patients with psoriasis in an accessible and useful document. Ethics and dissemination: This study is a protocol for an overview of SRs/MAs that did not involve individual data. Thus, ethical approval is not required. OSF Registration number: DOI 10.17605/OSF.IO/VC654
Background: Taraxasterol (TX), a pentacyclic triterpene, is one of the main active constituents isolated from Taraxacum officinale. A growing number of studies have reported that TX exhibits a wide range of biological activities such as anti-oxidative, anti-inflammatory, and neuro-protective effects. Recently, TX has been demonstrated to be a potential drug candidate for treatment of some types of cancers. However, the specific role of TX in melanoma remains unclear. Purpose: In this study, we aimed at exploration of the effect of TX on melanoma cell viability, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the underlying mechanisms. Research design: A375 and SK-MEL-28 cells were treated with various concentrations of TX for different times. Cell viability was measured using CCK-8 assay. Cell apoptosis was determined by flow cytometry. Transwell assays were performed to measure cell migration and invasion. The expression of E-cadherin, α-catenin, N-cadherin, vimentin, p-PI3K, PI3K, p-Akt and Akt was detected using western blot. Results: The study showed that TX induced A375 and SK-MEL-28 cell apoptosis. Furthermore, exposure to TX inhibited A375 and SK-MEL-28 cell migration and invasion. Besides, the EMT process was reversed in A375 and SK-MEL-28 cells after TX treatment. We also observed that TX reduced the protein expression of p-PI3K and p-Akt; thus, inhibiting activity of the PI3K/Akt pathway in A375 and SK-MEL-28 cells. In addition, TX treatment increased the levels of reactive oxygen species (ROS) in A375 and SK-MEL-28 cells, and treatment with the ROS scavenger NAC significantly rescued TX-induced down-regulation of p-PI3K and p-Akt in A375 and SK-MEL-28 cells. Conclusions: In conclusion, our study demonstrated that TX induced ROS accumulation followed by inactivation of the PI3K/Akt pathway and subsequently attenuated melanoma progression, suggesting that TX may be a potential candidate for treatment of melanoma.
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