Frontiers in Molecular Biosciences最新文献

{"title":"Comparative proteomics analysis of the mouse mini-gut organoid: insights into markers of gluten challenge from celiac disease intestinal biopsies","authors":"Robert Moulder, Santosh D. Bhosale, Keijo Viiri, Riitta Lahesmaa","doi":"10.3389/fmolb.2024.1446822","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1446822","url":null,"abstract":"IntroductionOrganoid models enable three-dimensional representation of cellular systems, providing flexible and accessible research tools, and can highlight key biomolecules. Such models of the intestinal epithelium can provide significant knowledge for the study of celiac disease and provide an additional context for the nature of markers observed from patient biopsy data.MethodsUsing LC–MS/MS, the proteomes of the crypt and enterocyte-like states of a mouse mini-gut organoid model were measured. The data were further compared with published biopsy data by comparing the changes induced by gluten challenge after a gluten-free diet.Results and discussionThese analyses identified 4,850 protein groups and revealed how 400 putative biomarkers of dietary challenge were differentially expressed in the organoid model. In addition to the extensive changes within the differentiated cells, the data reiterated the disruption of the crypt–villus axis after gluten challenge. The mass spectrometry data are available via ProteomeXchange with the identifier PXD025690.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"2 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma metabolites as potential markers and targets to prevent and treat urolithiasis: a Mendelian randomization study","authors":"Wuhui Zhu, Huan Li, Ming Zhang, Bing Ji, Zongtao Liu","doi":"10.3389/fmolb.2024.1426575","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1426575","url":null,"abstract":"BackgroundStudies on the relationships between diseases of the urinary system and human plasma proteomes have identified several potential biomarkers. However, none of these studies have elucidated the causal relationships between plasma proteins and urolithiasis.ObjectiveThe objective of the study was to investigate the potential risks of plasma metabolites in urolithiasis using a two-sample Mendelian randomization (MR) study.MethodsA total of 1,400 metabolites were identified in the most comprehensive genome-wide association study (GWAS) of plasma metabolomics in a European population to date, and single-nucleotide polymorphisms (SNPs) were used as the instrumental variables for the plasma metabolites. The European GWAS data for urinary calculi included 482,123 case samples and 6,223 control samples (ebi-a-GCST90018935). The associations between the plasma metabolites and risk of urolithiasis were evaluated by inverse variance weighting (IVW) and supplemented by sensitivity analyses of the MR-Egger and MR-PRESSO tests.ResultsFor the first time, we found a causal relationship between two plasma metabolites (<jats:italic>p</jats:italic> &amp;lt; 1.03 × 10<jats:sup>−4</jats:sup>) and urolithiasis (<jats:italic>p</jats:italic> &amp;lt; 0.05). The chemical 4-hydroxychlorothalonil, which is an intermediate product of the pesticide hydroxychlorothalonil, could promote urolithiasis (odds ratio (OR) = 1.12) as a risk factor. Moreover, 1-stearoyl-2-arachidonoyl-GPC, which is an important component of phospholipid metabolism in the human body, can inhibit urolithiasis (OR = 0.94).ConclusionsOur results suggest that blood metabolites can be used as blood markers and drug targets in the prevention, diagnosis, and treatment of urolithiasis; furthermore, our results can provide a basis for policy makers to formulate prevention and treatment policies for urolithiasis.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"39 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Prediction of protein-protein interactions (PPIs): the next frontier.","authors":"Amar Singh,Binh P Nguyen,Ho Leung Ng","doi":"10.3389/fmolb.2024.1479705","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1479705","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"38 1","pages":"1479705"},"PeriodicalIF":5.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNAs ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy","authors":"Amena Rezk Mohammed, Wafaa Abdelaziz Emam, Shaymaa A. Mohammed, Alshaymaa A. Abd Elalim, Eatemad Nabil Abdelhalim Mansour, Haidy Mahmoud Nasr, Aya A. Ghamry, Sabah M. Alkhawagah, Doaa Sadek Ahmed Fathy, Rasha Sobhy Elattar, Yasser Gaber Ibrahim Abish, Abdullah Hussein, Boshra Ahmed Zaghloul, Marwa K. Khairallah, Norah Alharbi, Salwa Seif Eldin, Amal Fahmy Dawood, Marwa A. Sabet, Marwa G. Gamea, Suzan Eid Elshishtawy Ibrahim, Aliaa A. Mosa, Marwa A. Dahpy","doi":"10.3389/fmolb.2024.1434023","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1434023","url":null,"abstract":"BackgroundGlobally, approximately 70 million people suffer from epilepsy. Infants constitute a significant percentage of these cases. Hence, there is a significant need for better understanding of the pathophysiology of epilepsy through laboratory and radiological methods for early detection and optimized management. Interleukin enhancer binding factor 3 antisense RNA l (ILF3AS1) is a long non-coding RNA (lncRNA) that enhances the expressions of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 9 (MMP9), which are considered to be epileptogenic.AimWe aimed to assess the serum expressions of the lncRNAs ILF3AS1, MMP3, and MMP9 along with microRNA-212 (miRNA-212) as predictive biomarkers in children with epilepsy; we also assessed their correlations with magnetic resonance imaging (MRI) findings.Subjects and MethodsFifty children with epilepsy and fifty healthy controls were considered in this study. Serum expressions of the lncRNA ILF3AS1 and miRNA-212 were estimated by quantitative real-time polymerase chain reaction (qPCR). Serum concentrations of MMP3 and MMP9 were estimated by enzyme-linked immunosorbent assay (ELISA) in parallel with MRI findings and different baseline biochemical parameters of all the subjects.ResultsThe results showed significantly higher levels of lncRNAs ILF3AS1, MMP3, and MMP9 as well as lower levels of miRNA-212 in children with epilepsy compared to the controls. The fold-change of miRNA-212 was a significant negative predictor (odds ratio = 0.153, <jats:italic>p</jats:italic> = 0.000). The receiver operating characteristic curves (Roc) showed that the areas under the curves for MMP3, MMP9, and lncRNA ILF3AS1 as well as the fold-change for miRNA-212 were 0.659, 0.738, 0.656, and 0.965, respectively. Brain lesions were detected in 15 patients (30%) with epilepsy, whereas the remaining 35 patients (70%) had normal results.ConclusionSerum levels of the lncRNA ILF3AS1 among children with epilepsy were higher than those in the control group and were associated with upregulation of both MMP3 and MMP9 as well as downregulation of miRNA-212 expressions, suggesting their predictive utility in monitoring the development of epilepsy; this also means that a treatment plan focusing on the ILF3AS1/miRNA-212/MMP3/MMP9 axis could be an effective strategy for treating epilepsy.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"3 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The diagnostic value of a nomogram based on enhanced CT radiomics for differentiating between intrahepatic cholangiocarcinoma and early hepatic abscess.","authors":"Meng-Chen Yang, Hai-Yang Liu, Yan-Ming Zhang, Yi Guo, Shang-Yu Yang, Hua-Wei Zhang, Bao Cui, Tian-Min Zhou, Hao-Xiang Guo, Dan-Wei Hou","doi":"10.3389/fmolb.2024.1409060","DOIUrl":"10.3389/fmolb.2024.1409060","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The CT-enhanced s","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1409060"},"PeriodicalIF":3.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross comparison of alternative diagnostic protocols including substitution to the clinical sample, RNA extraction method and nucleic acid amplification technology for COVID-19 diagnosis.","authors":"Ismael Segura-Ulate, Navilla Apú, Bernal Cortés, Jordi Querol-Audi, Yamitzel Zaldívar, Carlos Alexander Ortega, Fernando Flores-Mora, Andrés Gatica-Arias, Germán Madrigal-Redondo","doi":"10.3389/fmolb.2024.1445142","DOIUrl":"10.3389/fmolb.2024.1445142","url":null,"abstract":"<p><strong>Background: </strong>the gold-standard diagnostic protocol (GSDP) for COVID-19 consists of a nasopharyngeal swab (NPS) sample processed through traditional RNA extraction (TRE) and amplified with retrotranscription quantitative polymerase chain reaction (RT-qPCR). Multiple alternatives were developed to decrease time/cost of GSDP, including alternative clinical samples, RNA extraction methods and nucleic acid amplification. Thus, we carried out a cross comparison of various alternatives methods against GSDP and each other.</p><p><strong>Methods: </strong>we tested alternative diagnostic methods using saliva, heat-induced RNA release (HIRR) and a colorimetric retrotranscription loop-mediated isothermal amplification (RT-LAMP) as substitutions to the GSDP.</p><p><strong>Results: </strong>RT-LAMP using NPS processed by TRE showed high sensitivity (96%) and specificity (97%), closely matching GSDP. When saliva was processed by TRE and amplified with both RT-LAMP and RT-qPCR, RT-LAMP yielded high diagnostic parameters (88%-96% sensitivity and 95%-100% specificity) compared to RT-qPCR. Nonetheless, when saliva processed by TRE and detected by RT-LAMP was compared against the GSDP, the resulting diagnostic values for sensitivity (78%) and specificity (87%) were somewhat high but still short of those of the GSDP. Finally, saliva processed with HIRR and detected via RT-LAMP was the simplest and fastest method, but its sensitivity against GSDP was too low (56%) for any clinical application. Also, in this last method, the acidity of a large percentage of saliva samples (9%-22%) affected the pH-sensitive colorimetric indicator used in the test, requiring the exclusion of these acidic samples or an extra step for pH correction.</p><p><strong>Discussion: </strong>our comparison shows that RT-LAMP technology has diagnostic performance on par with RT-qPCR; likewise, saliva offers the same diagnostic functionality as NPS when subjected to a TRE method. Nonetheless, use of direct saliva after a HIRR and detected with RT-LAMP does not produce an acceptable diagnostic performance.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1445142"},"PeriodicalIF":3.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the roles of <i>IFIT3</i> gene and immune-metabolic pathways in psoriasis: a bioinformatics exploration for diagnostic markers and therapeutic targets.","authors":"Guangshan Chen, Xi Chen, Xingwu Duan, Runtian Zhang, Chunxiao Bai","doi":"10.3389/fmolb.2024.1439837","DOIUrl":"10.3389/fmolb.2024.1439837","url":null,"abstract":"<p><strong>Background: </strong>The functions and related signal pathways of the <i>IFIT3</i> gene in the skin lesions of patients with psoriasis were explored through bioinformatics methods to determine the potential specific molecular markers of psoriasis.</p><p><strong>Methods: </strong>The \"limma\" R package was used to analyze three datasets from the Gene Expression Omnibus database (GSE13355, GSE30999 and GSE106992), and the differential genes were screened. The STRING database was used for gene ontology (GO) enrichment analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, and protein-protein interaction network integration. Then, the <i>IFIT3</i> subnetwork was extracted and analyzed by gene set enrichment analysis (GSEA) using the Metascape database to verify the effectiveness of gene differentiation and disease tissue identification.</p><p><strong>Results: </strong>In this study, 426 differential genes were obtained, of which 322 were significantly upregulated and 104 were significantly downregulated. GO enrichment analysis showed that the differential genes were mainly involved in immunity and metabolism; the KEGG pathway enrichment analysis mainly included the chemokine signal pathway, PPAR signal pathway, and IL-17 signal pathway, among others. Based on the <i>IFIT3</i> subnetwork analysis, it was found that <i>IFIT3</i> was mainly involved in the biological processes of viruses, bacteria, and other microorganisms. The pathways obtained by GSEA were mainly related to immunity, metabolism, and antiviral activities. <i>IFIT3</i> was highly expressed in psoriatic lesions and may thus be helpful in the diagnosis of psoriasis.</p><p><strong>Conclusion: </strong>The differential genes, biological processes, and signal pathways of psoriasis, especially information related to and diagnostic efficiency of the <i>IFIT3</i> gene, were obtained by bioinformatics analysis. These results are expected to provide the theoretical basis and new directions for exploring the pathogenesis of psoriasis, in addition to helping with finding diagnostic markers and developing drug treatment targets.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1439837"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obtention of viable cell suspensions from breast cancer tumor biopsies for 3D chromatin conformation and single-cell transcriptome analysis.","authors":"Aura Stephenson-Gussinye, Luis A Rendón-Bautista, Blanca E Ruiz-Medina, Eduardo Blanco-Olais, Rosario Pérez-Molina, Cleofas Marcial-Medina, Yanin Chavarri-Guerra, Enrique Soto-Pérez-de-Celis, Andrea Morales-Alfaro, Ayerim Esquivel-López, Fernando Candanedo-González, Armando Gamboa-Domínguez, Rubén Cortes-González, Alejandro Alfaro-Goldaracena, Sara E Vázquez-Manjarrez, Guido Grajales-Figueroa, Beatriz Astudillo-Romero, Jesús Ruiz-Manriquez, A César Poot-Hernández, Paula Licona-Limón, Mayra Furlan-Magaril","doi":"10.3389/fmolb.2024.1420308","DOIUrl":"10.3389/fmolb.2024.1420308","url":null,"abstract":"<p><p>Molecular and cellular characterization of tumors is essential due to the complex and heterogeneous nature of cancer. In recent decades, many bioinformatic tools and experimental techniques have been developed to achieve personalized characterization of tumors. However, sample handling continues to be a major challenge as limitations such as prior treatments before sample acquisition, the amount of tissue obtained, transportation, or the inability to process fresh samples pose a hurdle for experimental strategies that require viable cell suspensions. Here, we present an optimized protocol that allows the recovery of highly viable cell suspensions from breast cancer primary tumor biopsies. Using these cell suspensions we have successfully characterized genome architecture through Hi-C. Also, we have evaluated single-cell gene expression and the tumor cellular microenvironment through single-cell RNAseq. Both technologies are key in the detailed and personalized molecular characterization of tumor samples. The protocol described here is a cost-effective alternative to obtain viable cell suspensions from biopsies simply and efficiently.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1420308"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clearing the JUNQ: the molecular machinery for sequestration, localization, and degradation of the JUNQ compartment.","authors":"Sarah Rolli, Chloe A Langridge, Emily M Sontag","doi":"10.3389/fmolb.2024.1427542","DOIUrl":"10.3389/fmolb.2024.1427542","url":null,"abstract":"<p><p>Cellular protein homeostasis (proteostasis) plays an essential role in regulating the folding, sequestration, and turnover of misfolded proteins via a network of chaperones and clearance factors. Previous work has shown that misfolded proteins are spatially sequestered into membrane-less compartments in the cell as part of the proteostasis process. Soluble misfolded proteins in the cytoplasm are trafficked into the juxtanuclear quality control compartment (JUNQ), and nuclear proteins are sequestered into the intranuclear quality control compartment (INQ). However, the mechanisms that control the formation, localization, and degradation of these compartments are unknown. Previously, we showed that the JUNQ migrates to the nuclear membrane adjacent to the INQ at nucleus-vacuole junctions (NVJ), and the INQ moves through the NVJ into the vacuole for clearance in an ESCRT-mediated process. Here we have investigated what mechanisms are involved in the formation, migration, and clearance of the JUNQ. We find Hsp70s Ssa1 and Ssa2 are required for JUNQ localization to the NVJ and degradation of cytoplasmic misfolded proteins. We also confirm that sequestrases Btn2 and Hsp42 sort misfolded proteins to the JUNQ or IPOD, respectively. Interestingly, proteins required for piecemeal microautophagy of the nucleus (PMN) (i.e., Nvj1, Vac8, Atg1, and Atg8) drive the formation and clearance of the JUNQ. This suggests that the JUNQ migrates to the NVJ to be cleared via microautophagy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1427542"},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11372896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of hypoxia-related genes in diagnosis and immune infiltration in acute myocardial infarction: based on bulk and single-cell RNA sequencing data.","authors":"Guoqing Liu, Wang Liao, Xiangwen Lv, Miaomiao Zhu, Xingqing Long, Jian Xie","doi":"10.3389/fmolb.2024.1448705","DOIUrl":"10.3389/fmolb.2024.1448705","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia has been found to cause cellular dysfunction and cell death, which are essential mechanisms in the development of acute myocardial infarction (AMI). However, the impact of hypoxia-related genes (HRGs) on AMI remains uncertain.</p><p><strong>Methods: </strong>The training dataset GSE66360, validation dataset GSE48060, and scRNA dataset GSE163956 were downloaded from the GEO database. We identified hub HRGs in AMI using machine learning methods. A prediction model for AMI occurrence was constructed and validated based on the identified hub HRGs. Correlations between hub HRGs and immune cells were explored using ssGSEA analysis. Unsupervised consensus clustering analysis was used to identify robust molecular clusters associated with hypoxia. Single-cell analysis was used to determine the distribution of hub HRGs in cell populations. RT-qPCR verified the expression levels of hub HRGs in the human cardiomyocyte model of AMI by oxygen-glucose deprivation (OGD) treatment in AC16 cells.</p><p><strong>Results: </strong>Fourteen candidate HRGs were identified by differential analysis, and the RF model and the nomogram based on 8 hub HRGs <i>(IRS2, ZFP36, NFIL3, TNFAIP3, SLC2A3, IER3, MAFF,</i> and <i>PLAUR)</i> were constructed, and the ROC curves verified its good prediction effect in training and validation datasets (AUC = 0.9339 and 0.8141, respectively). In addition, the interaction between hub HRGs and smooth muscle cells, immune cells was elucidated by scRNA analysis. Subsequently, the HRG pattern was constructed by consensus clustering, and the HRG gene pattern verified the accuracy of its grouping. Patients with AMI could be categorized into three HRG subclusters, and cluster A was significantly associated with immune infiltration. The RT-qPCR results showed that the hub HRGs in the OGD group were significantly overexpressed.</p><p><strong>Conclusion: </strong>A predictive model of AMI based on HRGs was developed and strongly associated with immune cell infiltration. Characterizing patients for hypoxia could help identify populations with specific molecular profiles and provide precise treatment.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1448705"},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}