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Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti‐inflammatory, anti‐obesity and anti‐tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF‐α‐stimulated HaCaT cells and DNCB‐induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL‐4, IL‐13, TNF‐α, IL‐5, IL‐31, IL‐33, IgE, TSLP, IL‐17, IL‐23, IL‐1β, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF‐α‐induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi‐1 (a mitochondrial fission inhibitor) and Ezrin‐specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co‐immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin‐mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are conserved noncoding small RNAs that play essential regulatory roles in gene function by regulating target genes. Pardosa pseudoannulata is an important natural predatory enemy of insect pests and plays a significant role in controlling pests in rice fields, with temperature having a significant impact on their growth and development. To understand the response of miRNAs to temperature stress in P. pseudoannulata, we performed miRNA identification analyses of adult spiders exposed to 10°C and 40°C for 12 h, as low‐temperature and high‐temperature treatment groups, respectively. We obtained 54.74 M clean reads from 69.84 M raw reads after filtering out low‐quality reads, and 78 miRNAs including 13 novel miRNAs were identified from three small RNA libraries (10°C, 25°C and 40°C). At the low temperature and the high temperature, eight (one upregulated and seven downregulated) and ten (nine upregulated and one downregulated) differentially expressed miRNAs were identified, respectively. These differentially expressed miRNAs negatively regulated 43 and 12 target mRNA (the unigenes in our previous transcriptome sequence data) in response to low‐ and high‐temperature stress, respectively. These target genes are mainly involved in translation, ribosome structure and biotransformation, as well as the generation and conversion of energy. This study represents the first report of miRNA identification related to the Araneae spider species in response to temperature stress. These results will greatly facilitate our understanding of the physiological and biochemical mechanisms of spiders in response to temperature stress, which might be beneficial for the conservation and utilization of this species as an important natural insect enemy of pests in rice ecosystems. [ABSTRACT FROM AUTHOR]

This study is to investigate the inhibitory effects and mechanisms of DEK‐targeting aptamer (DTA‐64) on epithelial mesenchymaltransition (EMT)‐mediated airway remodelling in mice and human bronchial epithelial cell line BEAS‐2B. In the ovalbumin (OVA)‐induced asthmatic mice, DTA‐64 significantly reduced the infiltration of eosinophils and neutrophils in lung tissue, attenuated the airway resistance and the proliferation of goblet cells. In addition, DTA‐64 reduced collagen deposition, transforming growth factor 1 (TGF‐β1) level in BALF and IgE levels in serum, balanced Th1/Th2/Th17 ratio, and decreased mesenchymal proteins (vimentin and α‐SMA), as well as weekend matrix metalloproteinases (MMP‐2 and MMP‐9) and NF‐κB p65 activity. In the in vitro experiments, we used TGF‐β1 to induce EMT in the human epithelial cell line BEAS‐2B. DEK overexpression (ovDEK) or silencing (shDEK) up‐regulated or down‐regulated TGF‐β1 expression, respectively, on the contrary, TGF‐β1 exposure had no effect on DEK expression. Furthermore, ovDEK and TGF‐β1 synergistically promoted EMT, whereas shDEK significantly reduced mesenchymal markers and increased epithelial markers, thus inhibiting EMT. Additionally, shDEK inhibited key proteins in TGF‐β1‐mediated signalling pathways, including Smad2/3, Smad4, p38 MAPK, ERK1/2, JNK and PI3K/AKT/mTOR. In conclusion, the effects of DTA‐64 against EMT of asthmatic mice and BEAS‐2B might partially be achieved through suppressing TGF‐β1/Smad, MAPK and PI3K signalling pathways. DTA‐64 may be a new therapeutic option for the management of airway remodelling in asthma patients. [ABSTRACT FROM AUTHOR]