Xinming Su

[This corrects the article DOI: 10.3389/fimmu.2023.1034755.].

Background and Objectives: Histone deacetylase (HDAC) families regulate various physical processes and the development of several diseases. The role of HDACs in asthma development and progression worths further investigation. This study aims to evaluate the effect of HDACs in a mouse model of asthma. Methods: HDAC8 selective inhibitor PCI-34051 was administered to a mouse model of ovalbumin-sensitized and challenged asthma. Airway responsiveness, serum cytokines, histological changes of the airway, and expression levels of α-SMA, β-actin, VEGFR, VEGF, GAPDH, HDAC8, TGF-β3, CD 105, p-ERK 1/2, ERK 1/2, PI3K, p-AKT, AKT, and PDK1 were evaluated. The miR-381-3p level was also measured. Results: All classic histologic and cellular changes of asthma in inflammation and airway remodeling were altered by HDAC8 inhibitor PCI-34051 via regulation of the miR-381-3p level and its downstream gene, TGF-β3. Inhibition of TGF-β3 further reduced the activation of ERK, PI3K, AKT, and PDK1. Conclusion: In a mouse model, HDAC8 inhibitor PCI-34051 exhibits comprehensive control of asthmatic changes, including inflammation and airway remodeling.

Background: Histone deacetylase (HDAC) families regulate a wide range of physical processes and development of several diseases, and the role of HDACs in asthma development and progression is worth further investigation. This study aimed to evaluate HDAC effects in a mouse model of asthma. Methods: HDAC8 selective inhibitor PCI-34051 was administered to a mouse model of ovalbumin (OVA)-sensitized and challenged asthma. Airway responsiveness, serum cytokines, histological changes of the airway, and expression levels of α-SMA, b-actin, VEGFR, VEGF, GAPDH, HDAC8, TGF-b3, CD 105, p-ERK 1/2, ERK 1/2, PI3K, p-AKT, AKT, and PDK1 were evaluated. The miR-381-3p level was also measured. Results: All classic histologic and cellular changes of asthma in inflammation and airway remodeling were altered by HDAC8 inhibitor PCI-34051 via regulating the miR-381-3p level and its downstream gene TGF-b3. Inhibition of TGF-b3 further reduced the activation of ERK, PI3K, AKT and PDK1. Conclusions: HDAC8 inhibitor PCI-34051 exhibits comprehensive control of asthmatic changes, including inflammation and airway remodeling, in a mouse model.

Background: Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it’s important to find new drugs for asthma patients.Methods: Publications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR “biologic* product*” OR “biologic* therap*” OR biotherapy* OR “biologic* agent*” OR Benralizumab OR “MEDI-563” OR Fasenra OR “BIW-8405” OR Dupilumab OR SAR231893 OR “SAR-231893” OR Dupixent OR REGN668 OR “REGN-668” OR Mepolizumab OR Bosatria OR “SB-240563” OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR “SCH-55700” OR SCH55700 OR “CEP-38072” OR CEP38072 OR Cinqair OR “DCP-835” OR DCP835 OR Tezspire OR “tezepelumab-ekko” OR “AMG-157” OR tezspire OR “MEDI-9929” OR “MEDI-19929” OR MEDI9929 OR Itepekimab OR “REGN-3500”OR REGN3500 OR “SAR-440340”OR SAR440340 OR Tralokinumab OR “CAT-354” OR Anrukinzumab OR “IMA-638” OR Lebrikizumab OR “RO-5490255”OR “RG-3637”OR “TNX-650”OR “MILR1444A”OR “MILR-1444A”OR”PRO301444”OR “PRO-301444”OR Pitrakinra OR altrakincept OR “AMG-317”OR”AMG317” OR Etokimab OR Pascolizumab OR “IMA-026”OR Enokizumab OR “MEDI-528”OR “7F3COM-2H2” OR 7F3COM2H2 OR Brodalumab OR “KHK-4827” OR “KHK4827”OR “AMG-827”OR Siliq OR Ligelizumab OR “QGE-031” OR QGE031 OR Quilizumab OR Talizumab OR “TNX-901” OR TNX901 OR Infliximab OR Etanercept OR “PRS-060”) AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study.Results: This bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field.Conclusion: This study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

An abstract is unavailable. This article is available as a PDF only.

Background: Asthma is a chronic inflammatory disease featured by inflammation and remodeling of airway. Adipose-derived mesenchymal stem cell (ADSCs)-derived exosomal miRNAs have been suggested as promising therapeutic manners for diseases. Methods: ADSCs and airway smooth muscle cells (ASMCs) were isolated from SD rats. Flow cytometry was conducted to detect the surface biomarkers of isolated cells. Exosomes were extracted by sequentially centrifuge method and identified by Western blotting and nanoparticle tracking analysis (NTA). Uptake of exosomes by ASMCs was detected by confocal assay. ASMCs were treated with platelet-derived growth factor-BB (PDGF-BB) to mimic cell remodeling and inflammation. Cell counting 8 (CCK-8), Transwell, and flow cytometry were performed to determine the viability, migration, and apoptosis of ASMCs. Release of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA). Levels of RNAs and proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Interaction between miR-301a-3p and signal transducer and activator of transcription 3 (STAT3) was determined by luciferase reporter gene assay. The effect of Exosomal miR-301a-3p was analyzed in ovalbumin (OVA)-induced asthma mouse model. Results: ADSCs-derived exosomes could be effectively internalized by ASMCs. Exosomal miR-301a-3p notably suppressed the PDGF-BB-stimulated proliferation and migration of ASMCs, and enhanced apoptosis, as well as decreased the secretion of inflammatory factors. MiR-301a-3p directly targeted the 3ʹUTR region of STAT3. STAT3 overexpression reversed the suppressive effects of exosomal miR-301a-3p on ASMCs under PDGF-BB stimulation. The expression of miR-301a-3p and STAT3 was negative correlation in specimen from patients with asthma. Exosomal miR-301a-3p inhibited OVA-induced lung injury by targeting STAT3 in mice. Conclusion: This study exposed that exosomal miR-301a-3p from ADSCs could effectively alleviate PDGF-BB-stimulated remodeling and inflammation of ASMCs via targeting STAT3, presented ADSCs-derived exosomal miR-301a-3p as a promising therapeutic approach for asthma.

The pathogenesis of asthma is closely related to histone acetylation modification, but the specific acetylation sites related to this process remain indistinct. Herein, our study sought to identify differentially modified acetylation sites and their expression distribution in cells involved in asthma in lung tissues. The airway hyper-responsiveness, inflammation, and remodeling were assessed by non-invasive whole-body plethysmography, ELISA, and hematoxylin-eosin staining to confirm the successful establishment of the allergic asthma model. Afterward, the differentially modified acetylation sites in asthmatic lung tissues were identified and validated by using proteomics and western blotting, respectively. The immunohistochemistry analysis was applied to reveal the distribution of identified acetylation sites in asthmatic lung tissues. A total of 15 differentially modified acetylation sites, including 13 upregulated (H3K9ac, H3K14ac, H3K18ac, H3K23ac,H3K27ac, H3K36ac, H2B1KK120ac, H2B2BK20ac, H2BK16ac, H2BK20ac, H2BK108ac, H2BK116ac, and H2BK120ac) and 2 downregulated (H2BK5ac and H2BK11ac) sites were identified and validated. Furthermore, immunohistochemical staining of lung tissues showed that nine of the identified histone acetylation sites (H2BK5, H2BK11, H3K18, H2BK116, H2BK20, H2BK120, H3K9, H3K36, and H3K27) were differentially expressed in airway epithelial cells, and the acetylation of identified H3 histones were observed in both eosinophil and perivascular inflammatory cells. Additionally, differential expression of histone acetylation sites was also observed in nucleus of airway epithelial cells, vascular smooth muscle cells, perivascular inflammatory cells, and airway smooth muscle cells. In conclusion, we identified potential acetylation sites associated with asthma pathogenesis. These findings may contribute greatly in the search for therapeutic approaches for allergic asthma.

Background: We performed an updated meta-analysis to clarify the relationship between glutathione S-transferase Mu and theta (GSTM1 and GSTT1, respectively) null/positive genotypes and asthma. Methods: We performed a literature search using PubMed and Web of Science databases in August 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the role of GSTM1 and GSTT1 genotypes in the risk of asthma. Results: Overall, we found a significant association with asthma risk in the general population for both the GSTM1 genotype (OR = 1.21; 95% CI: 1.07–1.35; P < .001; I ² = 69.5%) and the GSTT1 genotype (OR = 1.61; 95% CI: 1.30–2.00; P < .001; I ² = 83.6%). Moreover, significant associations between both genotypes and asthma risk were also found by age stratification. Furthermore, for GSTM1 we found significant associations in populations living in Asia, Europe, and Russia, but not in Africa. Conversely, for GSTT1, we found a significantly increased risk in populations living in Asia, Europe, Africa, and Russia. In addition, a significant association was found for both genotypes with a sample size 2000. Conclusion: Our meta-analysis provides evidence that GSTM1 and GSTT1 genotypes could be used as asthma-associated biomarkers.

Asthma is a chronic inflammatory disease that has been extensively studied for many years. However, finding a complete cure remains a significant challenge. Protein acetylation, especially histone acetylation, plays a significant role in the anti-asthma process. Histone deacetylation inhibitors (HDACi) have been shown to have a curative effect on asthma in clinical practice. An asthmatic mouse model was created by ovalbumin induction. Proteome and acetylproteome analysis were performed on lung tissues. HDACi were tested in the asthmatic mice. A total of 5346 proteins and 581 acetylation sites were identified, among which 154 proteins and 68 acetylation peptides were significantly altered by asthma. Many activated and deactivated processes, pathways, and protein groups were identified through bioinformatics analysis. Sequence motif preference analysis gave rise to a novel Kac-related core histone region, -KAXXK-, which was postulated as a key regulatory unit of histone acetylation. Asthma involves a variety of proteome dynamics and is controlled by protein lysine acetylation through the core motif -KAXXK-. These findings provide novel avenues to target and treat asthma.