Examining the contribution of Notch signaling to lung disease development

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(9), P. 6337 - 6349

Published: April 23, 2024

Language: Английский

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Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(12), P. 3109 - 3109

Published: Nov. 21, 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the IPF related genes, so as investigate potential molecular provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 obtained from Gene Expression Omnibus (GEO), differentially expressed (DEGs) were identified between normal control group. The DEGs group screened DESeq2 package R language. Ontology (GO) REACTOME pathway enrichment analyses performed. Using g:Profiler, function Then, protein-protein interaction (PPI) network constructed via Integrated Interactions Database (IID) database. Cytoscape Network Analyzer identify hub genes. miRNet NetworkAnalyst databaseswereused construct targeted microRNAs (miRNAs), transcription factors (TFs), small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis validate A total 958 out in study, including 479 up regulated down Most significantly enriched response stimulus, GPCR ligand binding, microtubule-based process, defective GALNT3 causes HFTC. combination results PPI network, miRNA-hub gene regulatory TF-hub LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, EFHC2 selected. Cyclothiazide rotigotinethe predicted molecules Our findings will contribute identification biomarkers novel strategies treatment IPF, strategy therapy.

Language: Английский

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PCSK9 inhibitor alleviates experimental pulmonary fibrosis-induced pulmonary hypertension via attenuating epithelial-mesenchymal transition by suppressing Wnt/β-catenin signaling in vivo and in vitro

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 11, 2024

Background The co-occurrence of pulmonary hypertension (PH) in patients with fibrosis (PF) is linked to a more unfavorable prognosis and increased mortality compared PF cases without PH. Early intervention comprehensive management are pivotal for improving survival outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein essential cholesterol metabolism. However, the potential PCSK9 inhibition alleviate PF-induced PH has not been previously reported. Methods A mouse model was established using intratracheal injection bleomycin (BLM), followed by administration inhibitor every other day. Data on right ventricle (RV) remodeling changes arteries were collected analyzed. Transforming growth factor-beta (TGF-β) also administered MLE-12 cells as an experimental lung model. mechanisms PCSK9’s impact examined both vivo vitro . Results Inhibition significantly reduced artery thickening RV BLM-induced Moreover, blockage effectively attenuated migration epithelial-mesenchymal transition (EMT) process TGF-β-induced cells. We observed that suppressed expression Wnt/β-catenin pathway animal cell experiments. Conclusion plays crucial role progression regulating EMT signaling. Targeting or activity could control its complication.

Language: Английский

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Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Abstract Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain intercourse and infertility. However, early diagnosis endometriosis still restricted. The purpose this investigation to identify validate key biomarkers endometriosis. Next generation sequencing (NGS) dataset GSE243039 was obtained from Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) between normal control samples were identified. After screening DEGs, gene ontology (GO) REACTOME pathway enrichment analyses performed. Furthermore, protein-protein interaction (PPI) network constructed modules analysed using Human Integrated Protein-Protein Interaction rEference (HIPIE) database Cytoscape software, hub Subsequantely, miRNAs genes, TFss miRNet NetworkAnalyst tool, possible TFs predicted. Finally, receiver operating characteristic curve (ROC) analysis used genes. A total 958 including 479 up regulated down screened samples. GO DEGs showed that they mainly involved in multicellular organismal process, developmental signaling by GPCR muscle contraction. Further PPI identified 10 VCAM1, SNCA, PRKCB, ADRB2, FOXQ1, MDFI, ACTBL2, PRKD1, DAPK1 ACTC1. Possible target miRNAs, hsa-mir-3143 hsa-mir-2110, TFs, TCF3 CLOCK, predicted constructing miRNA-hub regulatory TF-hub network. This bioinformatics techniques explore potential novel biomarkers. These might provide new ideas methods for diagnosis, treatment, monitoring

Language: Английский

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Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Aug. 13, 2024

Abstract Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators low-density lipoprotein receptor (LDLR). Information on role and regulation PCSK9 in lung very limited. Our study focuses understanding lung. levels are higher Bronchoalveolar lavage fluid (BALF) smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF nonsmokers. PCSK9-stimulated cells induce proinflammatory cytokines activation MAPKp38. transcripts highly expressed healthy individuals COPD, fibrosis systemic sclerosis. Cigarette smoke extract reduce undifferentiated bronchial epithelial (PBEC) but differentiated PBEC. inhibition affect biological pathways, induces lipid peroxidation, level apoptosis response staurosporine. results suggest that acts as an inflammatory marker. Furthermore, extracellular intracellular play different roles.

Language: Английский

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Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 29, 2023

Abstract Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Numerous proteins have been identified that are associated with occurrence and development of schizophrenia. This study aimed identify potential core genes pathways involved in schizophrenia, through exhaustive bioinformatic next generation sequencing (NGS) data analyses using GSE20966 NGS neural progenitor cells neurons obtained from healthy controls patients The were downloaded Gene Expression Omnibus database. was processed by DESeq2 package R software differentially expressed (DEGs) identified. Ontology (GO) enrichment analysis REACTOME pathway carried out biological functions DEGs. Protein-protein interaction (PPI) network, module, miRNA-hub gene regulatory network TF-hub performed hub genes, miRNA TFs. Potential analyzed receiver operating characteristic (ROC) curves (pROC). In this investigation, an overall 955 DEGs identified: 478 remarkably up regulated 477 distinctly down regulated. These enriched for GO terms mainly multicellular organismal process, GPCR ligand binding, regulation cellular process amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A BTK considered genes. constructed successfully. On whole, findings investigation enhance our understanding molecular mechanisms schizophrenia provide targets further investigation.

Language: Английский

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Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 20, 2023

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the IPF related genes, so as investigate potential molecular provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 obtained from Gene Expression Omnibus (GEO), differentially expressed (DEGs) were identified between normal control group. The DEGs group screened DESeq2 package R language. Ontology (GO) REACTOME pathway enrichment analyses performed.. Using g:Profiler, function analysis performed. Then, protein–protein interaction (PPI) network constructed via Integrated Interactions Database (IID) database. Cytoscape Network Analyzer identify hub genes. miRNet NetworkAnalyst database construct targeted microRNAs (miRNAs) transcription factors (TFs) Finally receiver operating characteristic (ROC) curve validates A total 958 out in study, including 479 up regulated down Most significantly enriched response stimulus, GPCR ligand binding, microtubule-based process defective GALNT3 causes HFTC. combination results PPI network, miRNA-hub gene regulatory TF-hub LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 EFHC2 selected. Our findings will contribute identification biomarkers novel strategies treatment IPF, strategy therapy.

Language: Английский

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Chimeric Peptide Engineered Nanomedicine for Synergistic Suppression of Tumor Growth and Therapy-Induced Hyperlipidemia by mTOR and PCSK9 Inhibition

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(10), P. 2377 - 2377

Published: Sept. 23, 2023

Chemotherapy-induced side effects restrain anti-tumor efficiency, with hyperlipidemia being the most common accompanying disease to cause treatment failure. In this work, a chimeric peptide-engineered nanomedicine (designated as PRS) was fabricated for synergistic suppression of tumor growth and therapy-induced hyperlipidemia. Within nanomedicine, matrix-targeting peptide palmitic-K(palmitic)CREKA can self-assemble into nano-micelle encapsulate Rapamycin (mTOR inhibitor) SBC-115076 (PCSK9 inhibitor). This PRS exhibits uniform nano-distribution good stability which enhances intracellular drug delivery tumor-targeting delivery. Also, found synergistically inhibit cell proliferation by interrupting mTOR pathway reducing Rapamycin-induced increasing production LDLR. vitro in vivo results demonstrate superiority systematic reduction without initiating any other toxic effects. work proposes sophisticated strategy also provides new insights cooperative management chemotherapy-induced

Language: Английский

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Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next-generation sequencing data analysis

Egyptian Journal of Medical Human Genetics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Oct. 12, 2024

Abstract Background Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain intercourse and infertility. However, early diagnosis endometriosis still restricted. The purpose this investigation to identify validate key biomarkers endometriosis. Methods Next-generation sequencing dataset GSE243039 was obtained from Gene Expression Omnibus database, differentially expressed genes (DEGs) between normal control samples were identified. After screening DEGs, gene ontology (GO) REACTOME pathway enrichment analyses performed. Furthermore, protein–protein interaction (PPI) network constructed modules analyzed using Human Integrated Protein–Protein Interaction rEference database Cytoscape software, hub Subsequently, miRNAs genes, TFs miRNet NetworkAnalyst tool, possible predicted. Finally, receiver operating characteristic curve analysis used genes. Results A total 958 including 479 upregulated downregulated screened samples. GO DEGs showed that they mainly involved in multicellular organismal process, developmental signaling by GPCR muscle contraction. Further PPI identified 10 vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 actc1. Possible target miRNAs, hsa-mir-3143 hsa-mir-2110, TFs, tcf3 (transcription factor 3) clock (clock circadian regulator), predicted constructing miRNA-hub regulatory TF-hub network. Conclusions This bioinformatics techniques explore potential novel biomarkers. These might provide new ideas methods for diagnosis, treatment monitoring

Language: Английский

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Screening of the key genes and signaling pathways for schizophrenia using bioinformatics and next generation sequencing data analysis

Italian Journal of Medicine, Journal Year: 2024, Volume and Issue: 18(4)

Published: Dec. 18, 2024

Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Researchers have identified numerous proteins associated with occurrence and development of schizophrenia. This study aimed identify potential core genes pathways involved in schizophrenia through exhaustive bioinformatics next generation sequencing (NGS) data analyses using GSE106589 NGS neural progenitor cells neurons obtained from healthy controls patients The were downloaded Gene Expression Omnibus database. was processed by DESeq2 package R software, differentially expressed (DEGs) identified. ontology (GO) enrichment analysis REACTOME pathway carried out biological functions DEGs. Protein-protein interaction network, module, micro-RNA (miRNA)-hub gene regulatory transcription factor (TF)-hub drug-hub network performed hub genes, miRNA, TFs, drug molecules. Potential analyzed receiver operating characteristic curves package. In this investigation, an overall 955 DEGs identified: 478 remarkably upregulated 477 distinctly downregulated. These enriched for GO terms mainly multicellular organismal process, G protein-coupled receptor ligand binding, regulation cellular processes, amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A, BTK considered genes. MiRNA-hub TF-hub constructed successfully predicted key miRNAs, molecules diagnosis treatment. On whole, findings investigation enhance our understanding molecular mechanisms provide targets further investigation.

Language: Английский

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