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...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.展开更多
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 A...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)-1αin 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.展开更多
Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a we...Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.展开更多
基金supported by the National Natural Science Foundation of China(No.82203304,82270500)Guangdong Basic and Applied Basic Research Foundation(2024B1515020113)+3 种基金High-level Hospital Construction Research Project of Maoming People’s Hospital[Yueweihan(2018)413]Science and Technology Plan Project of Maoming(No.210416154552665)Excellent Young Talent Program of Maoming People’s Hospital(NO.SY2022006)Start-up Fund of Postdoctoral Fellows to Wang Jiao Jiao(BS2021011).
文摘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.
基金supported by National Natural Science Foundation of China(Nos.82270500,82203304 and 81870324)Guangdong Basic and Applied Basic Research Foundation(No.2024B1515020113,China).
文摘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)-1αin 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.
基金This work is supported by National Natural Science Foundation of China(82270500,81870324,82203304,82070464,U1401225,U21A20419)National Mega-Project for Innovative Drugs(2019ZX09735002)+1 种基金Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China).
文摘Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
