Heme oxygenase-1 alleviates allergic airway inflammation by suppressing NF-κB-mediated pyroptosis of bronchial epithelial cells.

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase-1 (HO-1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO-1-mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)-induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO-1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO-1 restrained GSDMD-mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor-Kappa B (NF-κB) p65 RHD domain and thus controlling NF-κB-dependent pyroptosis. These data provide new therapeutic indications for purposing HO-1 to counteract inflammation, which contributes to allergic inflammation control.

A Systematic Review with Meta-Analysis of Comparative Efficacy and Safety of Risankizumab and Ustekinumab for Psoriasis Treatment.

Biological targeted therapy serves as a new alternative treatment for psoriasis due to its minimal side effects. This study is aimed at examining the drug effectiveness and safety of risankizumab and ustekinumab for psoriasis treatment, so as to provide a reference for clinical decision-making. Databases from Embase, Web of Science, PubMed, and Cochrane Library were gathered, starting from inception to March 1, 2022, for randomized controlled trials regarding risankizumab and ustekinumab for psoriasis treatment. All retrieved articles were carefully selected in strict accordance with a set of inclusion and exclusion criteria. Stata 15.0 and RevMan 5.4 were applied to perform meta-analysis and risk of bias assessment. A total of two trials with three NCTs were selected, with 384 participants in the risankizumab group and 140 participants in ustekinumab. Meta-analysis showed that in the long-term and short-term PASI100, risankizumab was more effective than ustekinumab (RR = 2.27, 95% CI (1.77, 2.90), p < 0.05; RR = 2.33, 95% CI (1.75, 3.08), p < 0.05). In PASI90, RR = 1.77, 95% CI (1.54, 2.03), and p < 0.05 and RR = 1.72, 95% CI (1.48, 2.00), and p < 0.05. In short-term PASI75, RR = 1.23, 95% CI (1.13, 1.34), and p < 0.05. In sPGA of 0, the results at week-16 and week-52 showed that risankizumab was significantly more effective than ustekinumab (RR = 2.24, 95% CI (1.67, 3.01), p < 0.05; RR = 2.30, 95% CI (1.80, 2.95), p < 0.05). Risankizumab was significantly more effective than ustekinumab in improving the quality of life and PSS scores (RR = 1.48, 95% CI (1.26, 1.75), p < 0.05; RR = 2.01, 95% CI (1.41, 2.85), p < 0.05). Nevertheless, risankizumab and ustekinumab did not show significant difference in the incidence of adverse responses (RR = 1.02, 95% CI (0.75, 1.39), p > 0.05). Risankizumab was more effective than ustekinumab for the treatment of psoriasis. The adverse reactions of both risankizumab and ustekinumab were similar and could be tolerated. Risankizumab might be a better alternative option for their treatment.

Treatments in psoriasis: from standard pharmacotherapy to nanotechnology therapy.

Psoriasis is a genetic chronic disease mediated by the immune system with systemic and cutaneous manifestations that can significantly deteriorate patients' quality of life. Two-three percent of the population worldwide suffer from psoriasis and it imposes a substantial economic burden on patients. The aetiology is mainly related with genes and environmental factors. The pathophysiology of psoriasis is characterized by T cells and dendritic cells, antimicrobial peptides, genetic predispositions, lipoprotein-2, galactosin-3, fractalkine, vaspin, and human neutrophilic peptides, etc. in the progression of psoriasis. For patients with psoriasis, the traditional treatments include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, methotrexate, cyclosporine, acitretin, phototherapy, and biological agents, etc. Nanodermatology is an emerging, multidisciplinary science that is gaining increasing recognition in the treatment of psoriasis. This review provides a summary of the pathophysiology, epidemiology, clinical diagnosis, and classical pharmacotherapy of psoriasis. The review also summarizes different nanotechnology therapies for effective treatment of psoriasis.

Taraxasterol attenuates melanoma progression via inactivation of reactive oxygen species-mediated PI3K/Akt signaling pathway.

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.

Hemin-primed dendritic cells suppress allergic airway inflammation through releasing extracellular vesicles.

Hemin, a substrate of heme oxygenase (HO)-1, induces HO-1 expression on a variety of cells to exert anti-oxidant and anti-inflammatory roles. However, the role of HO-1 in allergic diseases for dendritic cells (DCs) is not fully understood. Here, we report that HO-1 modulates asthmatic airway inflammation by hemin-treated DC-released extracellular vesicles (DCEVs). Following induction of bone marrow-derived DCs by hemin and then by house dust mite (HDM) in vitro, mouse CD4+ naïve T cells were cocultured with DCEVs to determine T helper (h) cell differentiation. C57BL/6 mice were sensitized by different stimuli-induced DCEVs and challenged with HDM to analyze the changes of inflammatory cells and cytokines in the lung and bronchoalveolar lavage fluid. The results showed that hemin-treated DCEVs (hemin-DCEVs) express phosphatidylserine (PS), CD81, heat shock protein 70, and HO-1, which facilitates regulatory T (Treg) cells differentiation in vitro and in vivo. In HDM-induced asthmatic mouse model, hemin-DCEVs inhalation reduced eosinophils infiltration and mucus secretion in the airway, decreased the levels of IL-4, IL-5, and IL-13 in the lung and the number of Th2 cells in mediastinal lymph nodes (MLNs), and increased the number of Treg cells in MLNs. Thus, our study demonstrated, for the first time, that EVs from HO-1-overexpressing DCs alleviate allergic airway inflammation of eosinophilic asthma by potentiating Treg cells differentiation and limiting proinflammatory cytokine secretion, which expands our understanding of HO-1 function, opening the door for HO-1 inducer-like hemin as a novel therapeutic strategy for asthma or other allergic diseases.

Benefits and Safety of Chinese Herbal Medicine in Treating Psoriasis: An Overview of Systematic Reviews.

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.

Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell-dominant T-cell responses in asthma.

BACKGROUND: Exosomes have emerged as a vital player in cell-cell communication; however, whether airway epithelial cell (AEC)-generated exosomes participate in asthma development remains unknown. OBJECTIVE: Our aims were to characterize the AEC-secreted exosomes and the potentially functional protein(s) that may contribute to the proinflammatory effects of AEC exosomes in the dendritic cell (DC)-dominant airway allergic models and to confirm their clinical significance in patients with asthma. METHODS: Mice were treated with exosomes derived from house dust mite (HDM)-stimulated AECs (HDM-AEC-EXOs) or monocyte-derived DCs primed by HDM and/or contactin-1 (CNTN1). The numbers of DCs in the lung were determined by flow cytometry. Proteomic analysis of purified HDM-AEC-EXOs was performed. CNTN1 small interfering RNA was designed to probe its role in airway allergy, and γ-secretase inhibitor was used to determine involvement of the Notch pathway. RESULTS: HDM-AEC-EXOs facilitate the recruitment, proliferation, migration, and activation of monocyte-derived DCs in cell culture and in mice. CNTN1 in exosomes is a critical player in asthma pathology. RNA interference-mediated silencing and pharmaceutical inhibitors characterize Notch2 receptor as necessary for relaying the CNTN1 signal to activate TH2 cell/TH17 cell immune response. Studies of patients with asthma also support existence of the CNTN1-Notch2 axis that has been observed in cell and mouse models. CONCLUSION: This study's findings reveal a novel role for CNTN1 in asthma pathogenesis mediated through exosome secretion, indicating a potential strategy for the treatment of allergic airway inflammation.

Topical 0.05% clobetasol cream in the treatment of chronic hand eczema: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic hand eczema (CHE) is a recurrent, frequently disabling skin condition that requires daily skin care to prevent transepidermal water loss, posing a significant burden of society and economy. In recent years, topical 0.05% clobetasol cream is widely used for the treatment of CHE for its efficacy, tolerability and safety. Whereas, no systematic review and meta-analysis has been updated up to now. Therefore, this work aims to assess the effectiveness and safety of topical 0.05% clobetasol cream in patients with CHE. METHODS: Study on topical 0.05% clobetasol cream for CHE will be searched from their inception to December, 2020 with the language restrictions of English and Chinese in 8 databases (PubMed, Cochrane Library, Embase, the web of science, VIP, CNKI, CBM, and WAN FANG). According to the heterogeneity test, a fixed or random-effect model will be used to synthesize data. The primary outcome is the proportion of patients achieving more than 75% reduction in signs and symptoms according to the Hand Eczema Severity Index (HECSI). The secondary outcomes include: scored for 4 different characteristics of the lesions (redness, scaling, lichenification, and pruritus), QoL questionnaire, adverse events, and recurrence events. STATA 13.0 and Review Manager software 5.3 will be used for analysis and synthesis. Two or more reviewers will independently conduct the selection of studies, data extraction, and data analysis. RESULTS: The results of the study expect to provide a high-quality, evidence-based recommendation on topical 0.05% clobetasol cream in the treatment of CHE for clinicians. CONCLUSION: The study will provide scientific and useful evidence for better use of topical 0.05% clobetasol cream in treating CHE. 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/SPHVZ.

Cupping for neurodermatitis: A protocol of systematic review and meta-analysis.

BACKGROUND: Neurodermatitis is a common inflammatory and allergic disease, characterized by itching and lichenification plaque. Some studies have reported cupping therapy (CT) for the treatment of neurodermatitis. However, the effectiveness and safety are still uncertain. This study aims to evaluate the efficacy and safety of CT for the treatment of patients with neurodermatitis. METHODS: We will retrieve the following electronic databases systematically: Pubmed, Web of Science, Embase, the Cochrane Library, Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, and Wanfang database from their inception to December 2020. Other literature resources will be manually searched. Published randomized controlled trials (RCTs) and quasi-randomized controlled trials (q-RCTs) on the topic will be retrieved by 2 investigators independently. We will apply a fixed-effect model or random effect model basis on the heterogeneity test and employ with RevMan 5.3 software for data synthesis. The total clinical effective rate will be selected as the primary outcome, skin disease quality of life index score, recurrence rate, and adverse events as secondary outcomes. RESULTS: This study will comprehensively summarize the high-quality trials to determine the efficacy and safety of CT for the treatment of patients with neurodermatitis. CONCLUSION: Our systematic review will present evidence for the efficacy and safety of CT to neurodermatitis patients. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6DCM3.

Multi-center study for acupuncture combined with Chinese medicine in the treatment of chronic spontaneous urticaria based on the theory of taking shu-stream points when the disease is aggravated.

Chronic spontaneous urticaria (CSU) is a common dermatologic disease that seriously affects patient quality of life. The choice of therapy to control the disease and prevent its recurrence has always presented a difficult clinical issue. Previous studies have shown that traditional Chinese medicine is a safe and effective treatment for CSU. Recently, the temporal rhythms of CSU, a disease characterized by intermittent flares of active disease and periods of little or no disease, have attracted the attention of traditional Chinese medicine researchers. We designed a multicenter, randomized, controlled study to evaluate the efficacy and safety of combining a Chinese herbal formulation with acupuncture using shu-stream acupoints applied on the corresponding time meridians during disease exacerbations. We plan to recruit 111 outpatients with CSU aged 18 to 65 years. Participants will be randomized to 1 of the 3 groups: group A, which will be given basic acupuncture and the herbal formulation dangui yinzi; group B, which will be given danggui yinzi and shu-stream acupuncture; and a control group, which will be given danggui yinzi alone. Patients will be treated for 4 weeks and followed for 8 additional weeks. Investigators will evaluate the following parameters: the symptoms and side effects of treatment, quality of life (using the chronic urticaria quality of life questionnaire), and overall patient condition. Each week, patients will also complete the measurement of 7-day urticarial activity score. This is the first use of a combination of shu-stream acupoints and Chinese herbal medicine in the treatment of CSU. If successful, it will prove to be a simple, inexpensive, treatment strategy for solving a difficult clinical problem.

The association of Th17/Treg cells expression in peripheral blood and chronic spontaneous urticaria: A protocol of systematic review and meta-analysis.

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.

Chinese herbal medicine for psoriasis: Protocol for an overview of systematic reviews.

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.

Safety and efficacy of Chinese herbal bath for psoriasis vulgaris: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis is a common, chronic, and recurrent skin inflammatory disease, with psoriasis vulgaris considered as the most prevalent type of psoriasis. Chinese herbal bath, a type of traditional Chinese medicine, is an external therapy widely used to treat psoriasis vulgaris in China, and it has achieved satisfactory clinical effects. However, there are few studies evaluating the safety and efficacy of Chinese herbal bath compared with other external therapies administered under similar conditions. The purpose of this study is to comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris through a systematic evaluation of the literature, so as to provide a reference basis for future clinical applications. METHODS: PubMed, Embase, CENTRAL, the Web of Science, the China Biology Medicine Database (CBM), the China National Knowledge Database (CNKI), the Wan Fang Database, and the Chong Qing VIP Database will be searched to collect randomized controlled trials of Chinese herbal bath used to treat psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2019. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. Meta-analysis will be carried out with the RevMan5.3 software. The mean difference will be used as the effect index for the measurement data, and the odds ratio will be used as the effect index for the enumeration data. The 95% confidence interval will be provided for each effect. Heterogeneity among the results of each study will be evaluated by the Chi-square test. RESULTS: This study will comprehensively evaluate the clinical safety and efficacy of Chinese herbal bath in the treatment of psoriasis vulgaris, so as to provide a reference basis for future clinical applications. CONCLUSION: This study will provide a theoretical basis for the standardized administration of Chinese herbal bath. OSF REGISTRATION NUMBER:: doi: 10.17605/OSF.IO/4HRPJ.

To explore the clinical efficacy of Traditional Chinese Medicine bath in the treatment of psoriasis vulgaris with blood-heat syndrome and its effect on related cytokines based on different temperature and different concentration.

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.

Cupping for psoriasis vulgaris: A protocol of systematic review and meta-analysis.

BACKGROUND: Psoriasis vulgaris (PV) is a chronic, immune-mediated dermatological disease that significantly affects the patient's health and quality of life. At present, cupping has been widely used in the treatment of psoriasis. However, the effectiveness and safety of cupping in patients with PV are still controversial. Therefore, this review aims to evaluate the efficacy and safety of cupping therapy on PV. METHODS: The following databases will be searched from their inceptions to April 2020 with a language limitation of English and Chinese: Pubmed, Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Databas, China National Knowledge Infrastructure Database, Wanfang database and Chinese Scientific Journal Database. The reference lists of eligible studies and other resources will also be searched. Two researchers will independently perform the selection of studies, data extraction, and data analysis. A fixed or random-effect model will be applied to synthesize data depend on the heterogeneity test. The primary outcome is the proportion of patients achieving at least a 60% improvement in psoriasis area and severity index (PASI) score from baseline (PASI 60). Secondary outcomes include the proportion of patients achieving at least a 90% improvement in PASI score from baseline (PASI 90), the mean change of PASI and dermatology life quality index score, the itching index, adverse events, and recurrence rate. RevMan V.5.3 software will be used for meta-analysis. RESULTS: The study will provide a high-quality evidence-based review of cupping for PV. CONCLUSIONS: The study will be conducted to evaluate the efficacy and safety of cupping in the treatment of PV and supposed to provide clear evidence for the clinical application of cupping therapy. ETHICS AND DISSEMINATION: As the study is a protocol of systematic review and meta-analysis that does not involve individual data, ethical approval will not be required. The results will be published in a peer-reviewed journal. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KV4CJ.

Heme oxygenase-1 protects airway epithelium against apoptosis by targeting the proinflammatory NLRP3-RXR axis in asthma.

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 RXRα and RXRß 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-RXR-mediated apoptosis and inflammation.

Airway epithelial TSLP production of TLR2 drives type 2 immunity in allergic airway 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 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.