Frontiers in Molecular Biosciences最新文献

{"title":"Identification of ATRNL1 and WNT9A as novel key genes and drug candidates in hypertrophic cardiomyopathy: integrative bioinformatics and experimental validation","authors":"Huabin He, Yanhui Liao, Yang Chen, Hao Qin, Longlong Hu, Shucai Xiao, Huijian Wang, Renqiang Yang","doi":"10.3389/fmolb.2024.1458434","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1458434","url":null,"abstract":"BackgroundHypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies.MethodsCommonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&amp;amp;E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments.ResultWe discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only <jats:italic>ATRNL1</jats:italic> and <jats:italic>WNT9A</jats:italic> were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of <jats:italic>ATRNL1</jats:italic> in the HCM model, and all three drugs suppressed <jats:italic>WNT9A</jats:italic> expression.ConclusionWe identified several novel genes in HCM development, among which <jats:italic>ATRNL1</jats:italic> and <jats:italic>WNT9A</jats:italic> were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"56 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220152","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: Lessons from external quality control in laboratory medicine: important implications for public health!","authors":"Nathalie Weiss, Ingo Schellenberg, Klaus-Peter Hunfeld","doi":"10.3389/fmolb.2024.1485193","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1485193","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1485193"},"PeriodicalIF":3.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11424928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344654","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":"Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes","authors":"Qingyuan Yu, Yanan Xiao, Mengqi Guan, Xianshuai Zhang, Jianan Yu, Mingze Han, Zhenhua Li","doi":"10.3389/fmolb.2024.1472492","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1472492","url":null,"abstract":"Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions’ role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"55 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220142","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":"Label-free quantitative proteomic profiling reveals differential plasma protein expression in patients with obesity after treatment with liraglutide","authors":"Afshan Masood, Hicham Benabdelkamel, Salini Scaria Joy, Abdulaziz Alhossan, Bashayr Alsuwayni, Ghalia Abdeen, Madhawi Aldhwayan, Nora A. Alfadda, Alexander Dimitri Miras, Assim A. Alfadda","doi":"10.3389/fmolb.2024.1458675","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1458675","url":null,"abstract":"IntroductionTreatment and management of obesity is clinically challenging. The inclusion of GLP-1 receptor agonists (GLP1RA) in the medical management of obesity has proven to be efficacious. However, mechanisms underlying the molecular changes arising from GLP1RA treatment in patients with obesity remain to be elucidated.MethodsA single-center, prospective study was undertaken to evaluate the changes in the plasma proteins after liraglutide 3 mg therapy in twenty patients (M/F: 7/13) with obesity (mean BMI 40.65 ± 3.7 kg/m<jats:sup>2</jats:sup>). Anthropometric and laboratory parameters were measured, and blood samples were collected at two time points: baseline, before initiating treatment (pretreatment group, PT), and after three months of receiving the full dose liraglutide 3 mg (posttreatment group, PoT). An untargeted label-free LC MSMS mass spectrometric approach combined with bioinformatics and network pathway analysis was used to determine changes in the proteomic profiles.ResultsThe mean age of the study participants was 36.0 ± 11.1 years. A statistically significant change was observed in weight, BMI and HbA1c levels between the PT and PoT groups (paired t-test, <jats:italic>P</jats:italic> &amp;lt; 0.001). A significant dysregulation was noted in the abundances of 151 proteins (31 up and 120 downregulated) between the two groups. The potential biomarkers were evaluated using receiver operating characteristic (ROC) curves. The top ten proteins (area under the curve (AUC) of 0.999 (95% CI)) were identified as potential biomarkers between PT and PoT groups and included Cystatin-B, major vault protein, and plastin-3, which were upregulated, whereas multimerin-2, large ribosomal P2, and proline–rich acidic protein 1 were downregulated in the PoT group compared with the PT group. The top network pathway identified using ingenuity pathway analysis (IPA), centered around dysregulation of MAPK, AKT, and PKc signaling pathways and related to cell-to-cell signaling and interaction, cellular assembly and organization, cellular compromise and a score of 46 with 25 focus proteins.DiscussionThrough label-free quantitative proteomic analysis, our study revealed significant dysregulation of plasma proteins after liraglutide 3 mg treatment in patients with obesity. The alterations in the proteomic profile between the PT and PoT groups demonstrated a decrease in levels of proteins involved in inflammation and oxidative stress pathways. On the other hand proteins involved in the glycolytic and lipolytic metabolic pathways as well as those participating in cytoskeletal and endothelial reorganization were observed to be increased. Understanding actions of liraglutide at a molecular and proteomic levels provides a holistic look into how liraglutide impacts metabolism, induces weight loss and improves overall metabolic health.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"5 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220153","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":"Retraction: Identification of a novel ferroptosis inducer for gastric cancer treatment using drug repurposing strategy.","authors":"","doi":"10.3389/fmolb.2024.1491755","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1491755","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3389/fmolb.2022.860525.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1491755"},"PeriodicalIF":3.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344655","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":"Disease-related data patterns in cerebrospinal fluid diagnostics: medical quality versus analytical quantity","authors":"Hansotto Reiber","doi":"10.3389/fmolb.2024.1348091","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1348091","url":null,"abstract":"Cerebrospinal fluid (CSF) diagnostics is characterized by the biologically relevant combination of analytes in order to obtain disease-related data patterns that enable medically relevant interpretations. The necessary change in knowledge bases such as barrier function as a diffusion/CSF flow model and immunological networks of B-cell clones and pleiotropic cytokines is considered. The biophysical and biological principles for data combination are demonstrated using examples from neuroimmunological and dementia diagnostics. In contrast to current developments in clinical chemistry and laboratory medicine, CSF diagnostics is moving away from mega-automated systems with a constantly growing number of individual analyses toward a CSF report that integrates all patient data. Medical training in data sample interpretation in the inter-laboratory test systems (“EQA schemes”) has become increasingly important. However, the results for CSF diagnostics (EQAS from INSTAND) indicate a crucially misguided trend. The separate analysis of CSF and serum in different, non-matched assays and extreme batch variations systematically lead to misinterpretations, which are the responsibility of the test providers. The questionable role of expensive accreditation procedures and the associated false quality expectations are discussed. New concepts that reintegrate the medical expertise of the clinical chemist must be emphasized along with the positive side effect of reducing costs in the healthcare system.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"38 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220143","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":"Non-coding RNA and its network in the pathogenesis of Myasthenia Gravis","authors":"Fuqiang Wang, Xiaoli Mei, Yunhao Yang, Hanlu Zhang, Zhiyang Li, Lei Zhu, Senyi Deng, Yun Wang","doi":"10.3389/fmolb.2024.1388476","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1388476","url":null,"abstract":"Myasthenia Gravis (MG) is a chronic autoimmune disease that primarily affects the neuromuscular junction, leading to muscle weakness in patients with this condition. Previous studies have identified several dysfunctions in thymus and peripheral blood mononuclear cells (PBMCs), such as the formation of ectopic germinal centers in the thymus and an imbalance of peripheral T helper cells and regulatory T cells, that contribute to the initiation and development of MG. Recent evidences suggest that noncoding RNA, including miRNA, lncRNA and circRNA may play a significant role in MG progression. Additionally, the network between these noncoding RNAs, such as the competing endogenous RNA regulatory network, has been found to be involved in MG progression. In this review, we summarized the roles of miRNA, lncRNA, and circRNA, highlighted their potential application as biomarkers in diagnosing MG, and discussed their potential regulatory networks in the abnormal thymus and PBMCs during MG development.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220154","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":"Pathogenic role of PFKFB3 in endothelial inflammatory diseases","authors":"Ling Zhou, Juan Li, Juanjuan Wang, Xuping Niu, Junqin Li, Kaiming Zhang","doi":"10.3389/fmolb.2024.1454456","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1454456","url":null,"abstract":"The differentiation of vascular endothelial cells and the formation of new blood vessels are inseparable from the energy supply and regulation of metabolism. The budding of blood vessels is a starting point of glycolysis pathway in angiogenesis. Phosphofructokinase-2/fructose 2,6-biophosphatase 3 (PFKFB3), a key rate-limiting enzyme in glycolysis, exhibits strong kinase activity. Inhibition of PFKFB3 can reduce the rate of glycolysis, thereby inhibiting the budding of blood vessels, resulting in inhibition of pathological angiogenesis. In this review, the role of PFKFB3 in the angiogenesis of inflammatory diseases was summarized, and the endothelial inflammatory diseases associated with PFKFB3 were reviewed.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"38 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220182","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":"From in vitro to in silico: a pipeline for generating virtual tissue simulations from real image data","authors":"Elina Nürnberg, Mario Vitacolonna, Roman Bruch, Markus Reischl, Rüdiger Rudolf, Simeon Sauer","doi":"10.3389/fmolb.2024.1467366","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1467366","url":null,"abstract":"3D cell culture models replicate tissue complexity and aim to study cellular interactions and responses in a more physiologically relevant environment compared to traditional 2D cultures. However, the spherical structure of these models makes it difficult to extract meaningful data, necessitating advanced techniques for proper analysis. In silico simulations enhance research by predicting cellular behaviors and therapeutic responses, providing a powerful tool to complement experimental approaches. Despite their potential, these simulations often require advanced computational skills and significant resources, which creates a barrier for many researchers. To address these challenges, we developed an accessible pipeline using open-source software to facilitate virtual tissue simulations. Our approach employs the Cellular Potts Model, a versatile framework for simulating cellular behaviors in tissues. The simulations are constructed from real world 3D image stacks of cancer spheroids, ensuring that the virtual models are rooted in experimental data. By introducing a new metric for parameter optimization, we enable the creation of realistic simulations without requiring extensive computational expertise. This pipeline benefits researchers wanting to incorporate computational biology into their methods, even if they do not possess extensive expertise in this area. By reducing the technical barriers associated with advanced computational modeling, our pipeline enables more researchers to utilize these powerful tools. Our approach aims to foster a broader use of <jats:italic>in silico</jats:italic> methods in disease research, contributing to a deeper understanding of disease biology and the refinement of therapeutic interventions.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"290 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220183","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":"Metabolomic changes in tear fluid following zinc biofortification in the BiZiFED nutritional study: a feasibility study","authors":"Connor N. Brown, Babar Shahzad, Mukhtiar Zaman, Xiaobei Pan, Brian D. Green, Nicola M. Lowe, Imre Lengyel","doi":"10.3389/fmolb.2024.1421699","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1421699","url":null,"abstract":"BackgroundBiofortified Zinc Flour to Eliminate Deficiency in Pakistan (BiZiFED) is a nutritional research program that evaluates the impact of consuming zinc biofortified wheat flour on zinc status and associated health outcomes of vulnerable communities in northwest Pakistan. Measuring zinc status from blood samples is fraught with problems. This feasibility study evaluated whether metabolite changes in tear biofluids could be used to understand zinc status.MethodsZinc deficiency is particularly prevalent amongst the female population in Pakistan. Therefore, a crossover trial was developed in which 25 women of reproductive age received standard, wheat flour, and another 25 received zinc-biofortified wheat flour for 8 weeks. At the end of this period, the nutritional intervention was switched between the groups for another 8 weeks. Tear biofluid was collected using Schirmer strips at baseline and after 8 and 16 weeks. Metabolomic analysis was conducted using the MxP<jats:sup>®</jats:sup> Quant 500 kit on the tear biofluid from a subset of the study participants.ResultsTwo metabolites had a significantly negative correlation with plasma zinc concentration: tiglylcarnitine and valine. Compared to baseline metabolite concentrations, acetylcarnitine, glutamine, two lysophosphatidylcholines (lysoPC a C16:0 and lysoPC a C18:1), and four sphingomyelins (SM (OH) C16:1, SM C16:0, SM C16:1, and SM C24:0) were all significantly decreased post-zinc intervention, whilst a ceramide (Cer(d18:1/18:0) was significantly increased.ConclusionThese results highlight the potential of using tear biofluids as an alternative source for metabolomic biomarkers, both for the assessment of the zinc status of individuals enrolled in nutritional studies and for indicating physiological changes that arise from nutritional supplementation.","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"18 1","pages":""},"PeriodicalIF":5.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220155","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}