Identification of key genes and pathways between mild-moderate and severe asthmatics via bioinformatics analysis

Wu, Xiaolu; Li, Ran; Xu, Qin; Liu, Feng; Jiang, Yue; Zhang, Min; Tong, Meiling

doi:10.1038/s41598-022-06675-w

Cited by 4 publications

(2 citation statements)

References 61 publications

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“…The target-related proteins of carnosol in muscle cells, neither direct nor indirect target-related proteins, had not been reported before. In previous reports, carnosol had been reported to have several kinds of pharmacological effects, which includes antioxidant, anti-inflammatory, anti-cancer, and protecting effects on cells against different injuries (Johnson, 2011;Yao et al, 2014;Shi et al, 2020;Kalantar et al, 2021;Chen et al, 2022b;Ren et al, 2022;Wu et al, 2022;Ji et al, 2023). For example, lung damage in rats caused by bleomycin can be ameliorated by carnosol through bringing down oxidative stress and inflammation (Kalantar et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways

Fang,

Wang,

Zhang

et al. 2024

Front. Pharmacol.

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Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research.Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed.Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol.Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

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Section: Introductionmentioning

confidence: 99%

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways

Fang,

Wang,

Zhang

et al. 2024

Front. Pharmacol.

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“…Among all asthma cases, approximately 10% are classifed as severe asthma. Current medication regimens, while generally efective, do not control symptoms for a subset of patients [1][2][3][4]. Severe cases of asthma are often associated with refractory symptoms, glucocorticoid resistance, and death, at least 50% of which are accompanied by infltrated or increased neutrophils, rather than the eosinophilic phenotype [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Nebulized Inhaled Triptolide on Airway Inflammation in a Mouse Model of Asthma

Miao,

Wei,

Chen

et al. 2023

Canadian Respiratory Journal

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Inhalation of nebulized TP has received little attention in the past. Here, we intend to investigate the effect of nebulized inhaled TP on airway inflammation in a mouse model of asthma. 29 SPF BALB/c mice were divided into four groups: blank control (Blk, n = 5), normal saline (NS, n = 8), dexamethasone (Dex, n = 8), and TP (n = 8). During the process of sensitization, mice in the three intervention groups were treated with nebulized NS, an injection of Dex, and nebulized triptolide, respectively. Then bronchoalveolar lavage fluid (BALF), peripheral blood, and lung tissue were collected. Relevant cytokines, transcriptional factors, and CD4+Th17+ T cell proportions were assessed and compared. IL-6, IL-17, IL-23, and TGF-β1 demonstrated a significant difference between groups in the following order: Dex < TP < NS ( P ≤ 0.001 ), while IL-10 changed in the opposite direction ( P < 0.001 ). At the transcriptional level in lung tissue, the Ct value of IL-17 in the Dex group was significantly higher than in the NS and TP groups ( P < 0.001 ). Meanwhile, it was higher in the TP group than in the NS group ( P < 0.001 ). The Ct value of RORγt demonstrated a significant difference among three groups in the following order: Dex > TP > NS ( P < 0.001 ). An opposite trend of FoxP3 Ct value was revealed in the order: NS > TP > Dex. The proportion of CD4+Th17+ cells was 9.53 ± 2.74% in the NS group, 4.23 ± 2.26% in the Dex group, and 6.76 ± 2.99% in the TP group, which shows significant differences between the NS and Dex ( P < 0.001 ) or NS and TP groups ( P < 0.05 ). Inhalation of nebulized triptolide can play a role in suppressing airway inflammation with inflammatory cytokines and transcriptional factors reduced and CD4+Th17+ T cells dampened, also in a manner less than injected dexamethasone.

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Unraveling heterogeneity and treatment of asthma through integrating multi-omics data

Zhang,

et al. 2024

Front. Allergy

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Asthma has become one of the most serious chronic respiratory diseases threatening people's lives worldwide. The pathogenesis of asthma is complex and driven by numerous cells and their interactions, which contribute to its genetic and phenotypic heterogeneity. The clinical characteristic is insufficient for the precision of patient classification and therapies; thus, a combination of the functional or pathophysiological mechanism and clinical phenotype proposes a new concept called “asthma endophenotype” representing various patient subtypes defined by distinct pathophysiological mechanisms. High-throughput omics approaches including genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome enable us to investigate the pathogenetic heterogeneity of diverse endophenotypes and the underlying mechanisms from different angles. In this review, we provide a comprehensive overview of the roles of diverse cell types in the pathophysiology and heterogeneity of asthma and present a current perspective on their contribution into the bidirectional interaction between airway inflammation and airway remodeling. We next discussed how integrated analysis of multi-omics data via machine learning can systematically characterize the molecular and biological profiles of genetic heterogeneity of asthma phenotype. The current application of multi-omics approaches on patient stratification and therapies will be described. Integrating multi-omics and clinical data will provide more insights into the key pathogenic mechanism in asthma heterogeneity and reshape the strategies for asthma management and treatment.

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Identification of key genes and pathways between mild-moderate and severe asthmatics via bioinformatics analysis

Cited by 4 publications

References 61 publications

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways

Carnosol ameliorated cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways

The Effects of Nebulized Inhaled Triptolide on Airway Inflammation in a Mouse Model of Asthma

Unraveling heterogeneity and treatment of asthma through integrating multi-omics data

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