The current study proposes a novel technique for feature selection by inculcating robustness in the conventional Signal to noise Ratio(SNR).The proposed method utilizes the robust measures of location i.e.,the“Median...The current study proposes a novel technique for feature selection by inculcating robustness in the conventional Signal to noise Ratio(SNR).The proposed method utilizes the robust measures of location i.e.,the“Median”as well as the measures of variation i.e.,“Median absolute deviation(MAD)and Interquartile range(IQR)”in the SNR.By this way,two independent robust signal-to-noise ratios have been proposed.The proposed method selects the most informative genes/features by combining the minimum subset of genes or features obtained via the greedy search approach with top-ranked genes selected through the robust signal-to-noise ratio(RSNR).The results obtained via the proposed method are compared with wellknown gene/feature selection methods on the basis of performance metric i.e.,classification error rate.A total of 5 gene expression datasets have been used in this study.Different subsets of informative genes are selected by the proposed and all the other methods included in the study,and their efficacy in terms of classification is investigated by using the classifier models such as support vector machine(SVM),Random forest(RF)and k-nearest neighbors(k-NN).The results of the analysis reveal that the proposed method(RSNR)produces minimum error rates than all the other competing feature selection methods in majority of the cases.For further assessment of the method,a detailed simulation study is also conducted.展开更多
Objective:Metabolic dysfunction-associated steatohepatitis(MASH),a progressive subtype of metabolic dysfunction-associated steatotic liver disease(MASLD),is characterized by hepatic steatosis,lobular inflammation,and ...Objective:Metabolic dysfunction-associated steatohepatitis(MASH),a progressive subtype of metabolic dysfunction-associated steatotic liver disease(MASLD),is characterized by hepatic steatosis,lobular inflammation,and hepatocyte ballooning,and may further progress to liver fibrosis and cirrhosis.Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1),a member of the scavenger receptor family,recognizes and binds oxidized low-density lipoprotein.This study aims to investigate the role of LOX-1 in MASH progression.Methods:LOX-1 expression in MASLD mouse liver was analyzed using Gene Expression Omnibus(GEO)datasets.Immunofluorescence staining was performed to detect LOX-1 and alpha-smooth muscle actin(α-SMA)levels and co-localization in fibrotic liver tissues and LX-2 cells.LOX-1 knockout(Lox-1^(−/−))mice were generated using CRISPR/caspase-9(Cas9)and genotyped by PCR and Sanger sequencing.Wild-type(WT)and Lox-1^(−/−)mice were randomized into control and Western diet model groups.Serum and liver samples were collected for alanine aminotransferase(ALT)and aspartate aminotransferase(AST)measurement by biochemical kits,liver structure evaluation by hematoxylin and eosin(HE)staining,collagen deposition by Masson staining,lipid accumulation by Oil Red O staining,and fibrotic marker gene expression by real-time quantitative PCR(RT-qPCR).Network pharmacology and search tool for the retrieval of interacting genes/proteins(STRING)-based protein-protein interaction(PPI)with Gene Ontology(GO)enrichment were used to predict downstream targets and pathways.Results:The results from the GEO datasets GSE30552 and GSE40041 indicated LOX-1 mRNA was upregulated in high fat diet(HFD)and bile duct ligation(BDL)mouse models(both P<0.001).LOX-1 and α-SMA levels were elevated in fibrotic liver tissues.Lox-1^(−/−)mice were successfully established.Biochemical tests showed that serum AST and ALT levels were significantly elevated in WT mice fed a Western diet(both P<0.001),and these levels decreased after LOX-1 knockout(both P<0.05).HE staining revealed that WT mice on the Western diet exhibited marked hepatocellular ballooning degeneration,steatosis,inflammatory cell infiltration,and periportal fibroplasia,which were significantly ameliorated by LOX-1 knockout.Masson staining demonstrated increased blue-stained collagen fibers in the liver tissues of WT mice fed the Western diet compared with controldiet mice,and LOX-1 knockout inhibited collagen fiber deposition(all P<0.05).RT‑qPCR results showed that hepatic mRNA levels of Acta2,Col1a1,and Timp1 were significantly increased in Western diet-fed mice,and LOX-1 knockout reduced the expression of these fibrogenic marker genes.Oil Red O staining indicated that hepatocytes in WT mice fed the Western diet were notably enlarged,displayed macrovesicular steatosis,and exhibited diffusely distributed red lipid droplets,whereas LOX-1 knockout alleviated hepatic lipid accumulation(both P<0.001).RT‑qPCR results further demonstrated that knockdown of LOX-1 reduced Acta2,Col1a1,and Timp1 mRNA levels in LX‑2 cells(all P<0.05).Immunofluorescence analysis revealed co‑localization of LOX-1 and α‑SMA in LX‑2 cells,and LOX-1 silencing suppressed α‑SMA expression.Network pharmacology suggested LOX-1 may promote MASH via lipid and cholesterol metabolism networks.Conclusion:LOX-1 gene knockout ameliorates Western diet-induced MASH in mice and may serve as a potential therapeutic target.展开更多
Objective:Percutaneous coronary intervention is one of the most common procedures used for the invasive treatment of patients with coronary heart disease;the incidence of in-stent restenosis(ISR)after percutaneous cor...Objective:Percutaneous coronary intervention is one of the most common procedures used for the invasive treatment of patients with coronary heart disease;the incidence of in-stent restenosis(ISR)after percutaneous coronary intervention is 5%to 15%.In this study,a competitive endogenous RNA(ceRNA)network was constructed to investigate potential mechanisms involved in ISR.Methods:The expression data for differentially expressed microRNAs(DEmiRNAs)and messenger RNAs(mRNAs)between patients with and without ISR were obtained using limma package.Long noncoding RNAs(lncRNAs)were predicted based on the DEmiRNAs using the miRDB,miRTarBase,and TargetScan databases.An ISR-specific ceRNA network was subsequently constructed and investigated.To verify the key miRNAs of ceRNA,patients with and without ISR were enrolled from Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2018(n=8,respectively);plasma was collected from all enrolled patients.Results:Based on the raw data obtained from the Gene Expression Omnibus database,472 DEmiRNAs and 304 differentilly expressed messenger RNAs between patients with and without ISR were identified.A ceRNA network was constructed by combining 270 IncRNAs,3 miRNAs(miR-125,miR-140,and miR-206),and 4 mRNAs(STRADB,TKT,PCTP,and BTG2).The hub genes of the ceRNA network of ISR included the following:miR-125,miR-206,miR-140,PCDHB9,CASC2,BAK1P1,CSPG4P3Y,CSPG4P4Y,STRCP1,and GRIP2.Verification of miRNAs of ceRNA also showed that the expression of miR-206 was upregulated in patients with ISR vs.those without ISR(P<0.05).In contrast,the expression of miR-140 and miR-125 was downregulated in patients with ISR vs.those without ISR(P<0.05).Conclusions:This study constructed noncoding RNA-related ceRNA networks for ISR.The results indicated that miR-206,miR-125,and miR-140 may be biomarkers of ISR.展开更多
基金King Saud University for funding this work through Researchers Supporting Project Number(RSP2022R426),King Saud University,Riyadh,Saudi Arabia.
文摘The current study proposes a novel technique for feature selection by inculcating robustness in the conventional Signal to noise Ratio(SNR).The proposed method utilizes the robust measures of location i.e.,the“Median”as well as the measures of variation i.e.,“Median absolute deviation(MAD)and Interquartile range(IQR)”in the SNR.By this way,two independent robust signal-to-noise ratios have been proposed.The proposed method selects the most informative genes/features by combining the minimum subset of genes or features obtained via the greedy search approach with top-ranked genes selected through the robust signal-to-noise ratio(RSNR).The results obtained via the proposed method are compared with wellknown gene/feature selection methods on the basis of performance metric i.e.,classification error rate.A total of 5 gene expression datasets have been used in this study.Different subsets of informative genes are selected by the proposed and all the other methods included in the study,and their efficacy in terms of classification is investigated by using the classifier models such as support vector machine(SVM),Random forest(RF)and k-nearest neighbors(k-NN).The results of the analysis reveal that the proposed method(RSNR)produces minimum error rates than all the other competing feature selection methods in majority of the cases.For further assessment of the method,a detailed simulation study is also conducted.
基金supported by the Natural Science Foundation of Hunan Province,China(211142095031)。
文摘Objective:Metabolic dysfunction-associated steatohepatitis(MASH),a progressive subtype of metabolic dysfunction-associated steatotic liver disease(MASLD),is characterized by hepatic steatosis,lobular inflammation,and hepatocyte ballooning,and may further progress to liver fibrosis and cirrhosis.Lectin-like oxidized low-density lipoprotein receptor-1(LOX-1),a member of the scavenger receptor family,recognizes and binds oxidized low-density lipoprotein.This study aims to investigate the role of LOX-1 in MASH progression.Methods:LOX-1 expression in MASLD mouse liver was analyzed using Gene Expression Omnibus(GEO)datasets.Immunofluorescence staining was performed to detect LOX-1 and alpha-smooth muscle actin(α-SMA)levels and co-localization in fibrotic liver tissues and LX-2 cells.LOX-1 knockout(Lox-1^(−/−))mice were generated using CRISPR/caspase-9(Cas9)and genotyped by PCR and Sanger sequencing.Wild-type(WT)and Lox-1^(−/−)mice were randomized into control and Western diet model groups.Serum and liver samples were collected for alanine aminotransferase(ALT)and aspartate aminotransferase(AST)measurement by biochemical kits,liver structure evaluation by hematoxylin and eosin(HE)staining,collagen deposition by Masson staining,lipid accumulation by Oil Red O staining,and fibrotic marker gene expression by real-time quantitative PCR(RT-qPCR).Network pharmacology and search tool for the retrieval of interacting genes/proteins(STRING)-based protein-protein interaction(PPI)with Gene Ontology(GO)enrichment were used to predict downstream targets and pathways.Results:The results from the GEO datasets GSE30552 and GSE40041 indicated LOX-1 mRNA was upregulated in high fat diet(HFD)and bile duct ligation(BDL)mouse models(both P<0.001).LOX-1 and α-SMA levels were elevated in fibrotic liver tissues.Lox-1^(−/−)mice were successfully established.Biochemical tests showed that serum AST and ALT levels were significantly elevated in WT mice fed a Western diet(both P<0.001),and these levels decreased after LOX-1 knockout(both P<0.05).HE staining revealed that WT mice on the Western diet exhibited marked hepatocellular ballooning degeneration,steatosis,inflammatory cell infiltration,and periportal fibroplasia,which were significantly ameliorated by LOX-1 knockout.Masson staining demonstrated increased blue-stained collagen fibers in the liver tissues of WT mice fed the Western diet compared with controldiet mice,and LOX-1 knockout inhibited collagen fiber deposition(all P<0.05).RT‑qPCR results showed that hepatic mRNA levels of Acta2,Col1a1,and Timp1 were significantly increased in Western diet-fed mice,and LOX-1 knockout reduced the expression of these fibrogenic marker genes.Oil Red O staining indicated that hepatocytes in WT mice fed the Western diet were notably enlarged,displayed macrovesicular steatosis,and exhibited diffusely distributed red lipid droplets,whereas LOX-1 knockout alleviated hepatic lipid accumulation(both P<0.001).RT‑qPCR results further demonstrated that knockdown of LOX-1 reduced Acta2,Col1a1,and Timp1 mRNA levels in LX‑2 cells(all P<0.05).Immunofluorescence analysis revealed co‑localization of LOX-1 and α‑SMA in LX‑2 cells,and LOX-1 silencing suppressed α‑SMA expression.Network pharmacology suggested LOX-1 may promote MASH via lipid and cholesterol metabolism networks.Conclusion:LOX-1 gene knockout ameliorates Western diet-induced MASH in mice and may serve as a potential therapeutic target.
基金funded by the Guangdong Medical Foundation(A2021349)the Fundamental Research Funds for the Central Universities(21621062)+1 种基金the project of Traditional Chinese Medicine Bureau of Guangdong Province(20221108)the Science and Technology Projects in Guangzhou(202201010521).
文摘Objective:Percutaneous coronary intervention is one of the most common procedures used for the invasive treatment of patients with coronary heart disease;the incidence of in-stent restenosis(ISR)after percutaneous coronary intervention is 5%to 15%.In this study,a competitive endogenous RNA(ceRNA)network was constructed to investigate potential mechanisms involved in ISR.Methods:The expression data for differentially expressed microRNAs(DEmiRNAs)and messenger RNAs(mRNAs)between patients with and without ISR were obtained using limma package.Long noncoding RNAs(lncRNAs)were predicted based on the DEmiRNAs using the miRDB,miRTarBase,and TargetScan databases.An ISR-specific ceRNA network was subsequently constructed and investigated.To verify the key miRNAs of ceRNA,patients with and without ISR were enrolled from Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2018(n=8,respectively);plasma was collected from all enrolled patients.Results:Based on the raw data obtained from the Gene Expression Omnibus database,472 DEmiRNAs and 304 differentilly expressed messenger RNAs between patients with and without ISR were identified.A ceRNA network was constructed by combining 270 IncRNAs,3 miRNAs(miR-125,miR-140,and miR-206),and 4 mRNAs(STRADB,TKT,PCTP,and BTG2).The hub genes of the ceRNA network of ISR included the following:miR-125,miR-206,miR-140,PCDHB9,CASC2,BAK1P1,CSPG4P3Y,CSPG4P4Y,STRCP1,and GRIP2.Verification of miRNAs of ceRNA also showed that the expression of miR-206 was upregulated in patients with ISR vs.those without ISR(P<0.05).In contrast,the expression of miR-140 and miR-125 was downregulated in patients with ISR vs.those without ISR(P<0.05).Conclusions:This study constructed noncoding RNA-related ceRNA networks for ISR.The results indicated that miR-206,miR-125,and miR-140 may be biomarkers of ISR.
