Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischem...Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.展开更多
Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).Howev...Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.展开更多
The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data fro...The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data from more than 2000 sites in six human brains,we found that pairwise interactions between genes,without considering any higher-order interactions,are sufficient to predict the transcriptional pattern of the genome for individual brain regions and the transcriptional profile of the entire brain consisting of more than 200 areas.These findings suggest a quadratic complexity of transcriptional patterns in the human brain,which is much simpler than expected.In addition,using a pairwise interaction model,we revealed that the strength of gene-gene interactions in the human brain gives rise to the nearly maximal number of transcriptional clusters,which may account for the functional and structural richness of the brain.展开更多
基金Supported by Croatian Ministry of Science and Education,Josip Juraj Strossmayer University of Osijek,Faculty of Dental Medicine and Health,Osijek,Croatia,No.IP7-FDMZ-2023West-Siberian Science and Education Center,Government of Tyumen District,Decree of 20.11.2020,No.928-rpMinistry of Science and Higher Education,No.FMEN 2022-0009.
文摘Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.
基金supported by grants from the National Natural Science Foundation of China(82070588)the High Level Creative Talents from Department of Public Health in Zhejiang Proince(S2032102600032)+2 种基金Project of New Century 551 Talent Nurturing in WenzhouGT was supported in part by grants from the School of Medicine,University of Verona,Verona,ItalyCDB was supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004),UK.
文摘Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.
基金the National Key Research and Development Program of China(2017YFA0105203)the National Natural Science Foundation of China(81671855)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32040200)Beijing Academy of Artificial Intelligence,and Beijing Advanced Discipline Fund。
文摘The orchestrated expression of thousands of genes gives rise to the complexity of the human brain.However,the structures governing these myriad gene-gene interactions remain unclear.By analyzing transcription data from more than 2000 sites in six human brains,we found that pairwise interactions between genes,without considering any higher-order interactions,are sufficient to predict the transcriptional pattern of the genome for individual brain regions and the transcriptional profile of the entire brain consisting of more than 200 areas.These findings suggest a quadratic complexity of transcriptional patterns in the human brain,which is much simpler than expected.In addition,using a pairwise interaction model,we revealed that the strength of gene-gene interactions in the human brain gives rise to the nearly maximal number of transcriptional clusters,which may account for the functional and structural richness of the brain.
