1.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.
2.Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic,Clinical and Immunological Characteristics in Cancers
Wang JIAOJIAO ; Liao YONG ; Yang PINGLIAN ; Ye WEILE ; Liu YONG ; Xiao CHUNXIA ; Liao WEIXIONG ; Chen CHUNBO ; Liu ZHIPING ; Huang ZUNNAN
Biomedical and Environmental Sciences 2024;37(7):698-715
Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman's analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.
3.Strategy and practice of cultivating undergraduate innovative scientific research talents: taking an undergraduate research team of evidence-based medicine in Guangdong Medical University as an example
Yong CAO ; Ying WEN ; Shuhuang LIN ; Yong LIU ; Jiangbin LI ; Zunnan HUANG
Chinese Journal of Medical Education Research 2023;22(10):1505-1509
Undergraduates in colleges and universities have great academic potential. In order to cultivate undergraduate innovative scientific research talents, the key is to improve the cultivation mode of undergraduates and stimulate students' academic potential. Taking the evidence-based medicine research group of Guangdong Medical University as an example, this paper systematically analyzes the specific measures and relevant practical experiences of the research team in the cultivation of undergraduates. The research team creatively uses the methods of "student guidance system", "PBL" mode and real-time feedback mechanism, and a complete talent training system has formed to explore a group of excellent undergraduate talents. Through innovative scientific research training, these undergraduates have made many achievements in academic research. This paper hopes these strategies and experiences can provide some reference for the cultivation of undergraduates in colleges and universities all over the country.
4.Progress in association of RSK2 with malignancies and its inhibitors
Kangxing CHEN ; Ziyou WANG ; Yanxia HUANG ; Chengzhi ZHONG ; Kaiheng LI ; Zunnan HUANG
Chinese Journal of Pathophysiology 2015;(10):1772-1779
RibosomalS6kinase2(RSK2)isamemberofthep90Rsk,whichbelongstoSer/Thrkinasefami-ly.It is a downstream molecule of Ras/MAPK cascade and regulates a variety of cellular processes.RSK2 plays a key role in the cell proliferation, survival and transformation.Furthermore, the aberrant up-regulation of RSK2 was observed in dif-ferent malignancies.We here briefly review the structure and function of RSK2, the relationship between RSK2 and tumor, and the existing RSK2 inhibitors.

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