INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Yongchao Jia,Na Li,Haoran Wang,Ronglan Yin,Aobo Shen,Fanhua Zeng,Xueqian Liu,Jiaying Li,Yuanyuan Zhou,Jing Yuan,Ronghuan Yin
MEG3 interacts with ILF3 and downregulates its nuclear protein level. • ILF3 inhibits G. parasuis -induced apoptosis of 3D4/21 cells. • MEG3 scaffolds MDM2 to enhance ILF3 ubiquitination and degradation. • ILF3 binds the anti-apoptotic CFLAR promoter to facilitate its transcription. • MEG3 regulates G. parasuis -induced apoptosis via the MDM2/ILF3/ CFLAR axis. Glaesserella parasuis ( G. parasuis ) is an important opportunistic pathogen that poses a threat to the swine industry, and the induction of host cell apoptosis is one of the key pathogenic mechanisms by which G. parasuis invades and damages the host. Long non-coding RNAs (lncRNAs) exert diverse and crucial biological functions in cells. Maternally expressed gene 3 (MEG3), a lncRNA widely involved in cell proliferation, apoptosis, and immune responses, has been demonstrated to be associated with G. parasuis infection. However, the function and mechanism of MEG3 in regulating G. parasuis -induced apoptosis remain unclear. In this study, we found that in the porcine alveolar macrophage cell line 3D4/21, MEG3 interacts with interleukin enhancer-binding factor 3 (ILF3) and negatively regulates the protein expression of ILF3 in the nucleus. Functional analysis showed that ILF3 suppresses G. parasuis -induced apoptosis of 3D4/21 cells, whereas MEG3 participates in regulating this apoptotic process through its interaction with ILF3. Further mechanistic studies revealed that MEG3 acts as a molecular scaffold to recruit the E3 ubiquitin ligase MDM2, enhances the interaction between MDM2 and ILF3, and thereby promotes the ubiquitination and degradation of ILF3. Moreover, ILF3 binds to the promoter of the anti-apoptotic gene CFLAR to facilitate its transcription, whereas MEG3 inhibits ILF3-mediated transcriptional activation of CFLAR , consequently regulating G. parasuis -induced apoptosis of 3D4/21 cells. This study reveals a novel mechanism by which MEG3 regulates G. parasuis -induced apoptosis of 3D4/21 cells via the MDM2/ILF3/ CFLAR axis. These findings provide new insights into elucidating the molecular pathogenic mechanisms of G. parasuis . Download: Download high-res image (122KB) Download: Download full-size image
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2018
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IF 6.653
Chang Wang,Xue Yang,Qi Zheng,Birget Moe,Xing-Fang Li
The developmental toxicity of water disinfection byproducts remains unclear. Here we report the study of halobenzoquinone (HBQ)-induced in vivo developmental toxicity and oxidative stress using zebrafish embryos as a model. Embryos were exposed to 0.5–10 μM of individual HBQs and 0.5–5 mM haloacetic acids for up to 120 h postfertilization (hpf). LC50 values of the HBQs at 24 hpf were 4.6–9.8 μM, while those of three haloacetic acids were up to 200 times higher at 1900–2600 μM. HBQ exposure resulted in significant developmental malformations in larvae, including failed inflation of the gas bladder, heart malformations, and curved spines. An increase in reactive oxygen species was observed, together with a decrease in superoxide dismutase activity and glutathione content. Additionally, the antioxidant N-acetyl-l-cysteine significantly mitigated all HBQ-induced effects, supporting that oxidative stress contributes to HBQ toxicity. Further experiments examined HBQ-induced effects on DNA and genes. HBQ exposure increased 8-hydroxydeoxyguanosine levels, DNA fragmentation, and apoptosis in larvae, with apoptosis induction related to changes in the gene expression of p53 and mdm2. These results suggest that HBQs are acutely toxic, causing oxidative damage and developmental toxicity to zebrafish larvae.
研究领域:
毒理学
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环境科学
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发育生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Cao Xu,Zhang Ningyi,Chen Hening,Wang Wei,Liang Yijun,Zhang Jiaxin,Liu Ruijia,Li Shuo,Yao Yuhao,Jin Qian,Guo Ziwei,Chen Yue,Gong Yuanyuan,Li Xiaoke,Zao Xiaobin,Ye Yong’an
The JiGuCao capsule formula (JCF) has demonstrated promising curative effects in treating chronic hepatitis B (CHB) in clinical trials. Here, we aimed to investigate JCF’s function and mechanism in diseases related to the hepatitis B virus (HBV). We used mass spectrometry (MS) to identify the active metabolites of JCF and established the HBV replication mouse model by hydrodynamically injecting HBV replication plasmids into the mice’s tail vein. Liposomes were used to transfect the plasmids into the cells. The CCK-8 kit identified cell viability. We detected the levels of HBV s antigen (HBsAg) and HBV e antigen (HBeAg) by the quantitative determination kits. qRT-PCR and Western blot were used to detect the genes’ expression. The key pathways and key genes related to JCF on CHB treatment were obtained by network pharmacological analysis. Our results showed that JCF accelerated the elimination of HBsAg in mice. JCF and its medicated serum inhibited HBV replication and proliferation of HBV-replicating hepatoma cells in vitro. And the key targets of JCF in treating CHB were CASP3, CXCL8, EGFR, HSPA8, IL6, MDM2, MMP9, NR3C1, PTGS2, and VEGFA. Furthermore, these key targets were related to pathways in cancer, hepatitis B, microRNAs in cancer, PI3K-Akt signaling, and proteoglycans in cancer pathways. Finally, Cholic Acid, Deoxycholic Acid, and 3′, 4′, 7-Trihydroxyflavone were the main active metabolites of JCF that we obtained. JCF employed its active metabolites to perform an anti-HBV effect and prevent the development of HBV-related diseases.
研究领域:
药理学
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病毒学
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分子生物学
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网络药理学
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肝病学
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DOI
PubMed
高影响因子
Biomed Research International
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2021
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IF 3.411
Ling Kui,Min Li,Xiaonan Yang,Ling Yang,Qinghua Kong,Yunbing Pan,Zetan Xu,Shouling Wang,Dandan Mo,Yang Dong,Yao Liu,Jianhua Miao
Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.
研究领域:
癌症生物学
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药理学
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分子生物学
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生物信息学
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传统中药
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DOI
PubMed
高影响因子
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