Frontiers in molecular medicine最新文献

{"title":"Cell surface vimentin: a natural human immune response target for immunotherapy.","authors":"Mark C Glassy","doi":"10.3389/fmmed.2025.1552323","DOIUrl":"10.3389/fmmed.2025.1552323","url":null,"abstract":"<p><p>Natural human monoclonal antibodies obtained from sentinel lymph nodes of cancer patients identify cell surface vimentin. One of these vimentin-reactive antibodies, pritumumab, has been used to treat brain cancer patients. This review summarizes data on mAbs reactive with cell surface vimentin and their origin from lymph nodes of cancer patients.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1552323"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Tuberculosis: host immunity, diagnostics and therapeutics.","authors":"Anthony G Tsolaki, Amy K Barczak, Uday Kishore","doi":"10.3389/fmmed.2025.1568256","DOIUrl":"https://doi.org/10.3389/fmmed.2025.1568256","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1568256"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143559824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of TDP-43: potential implications for amyotrophic lateral sclerosis.","authors":"D Y Mengistu, M Terribili, C Pellacani, L Ciapponi, M Marzullo","doi":"10.3389/fmmed.2025.1530719","DOIUrl":"10.3389/fmmed.2025.1530719","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease characterized by the progressive degeneration of motor neurons. One of the key pathogenic factors implicated in ALS is TDP-43 (TAR DNA-binding protein 43), an RNA-binding protein encoded by the <i>TARDBP</i> gene. Under normal physiological conditions, TDP-43 predominantly resides in the nucleus, where it plays a critical role in regulating gene expression, alternative splicing, RNA transport, and stability. In ALS, TDP-43 undergoes pathological mislocalization from the nucleus to the cytoplasm, disrupting its normal function and contributing to disease progression. The nuclear loss of TDP-43 leads to widespread dysregulation of RNA metabolism. Moreover, mislocalized TDP-43 aggregates in the cytoplasm, acquires toxic properties that sequester essential RNA molecules and proteins. Importantly, deviations in TDP-43 levels, whether excessive or reduced, can lead to cellular dysfunction, and contribute to disease progression, highlighting the delicate balance required for neuronal health. Emerging evidence suggests that epigenetic mechanisms may play a crucial role in regulating <i>TARDBP</i> expression and, consequently, TDP-43 cellular levels. Epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNAs are increasingly recognized as modulators of gene expression and cellular function in neurodegenerative diseases, including ALS. Dysregulation of these processes could contribute to aberrant <i>TARDBP</i> expression, amplifying TDP-43-associated pathologies. This review explores and summarizes the recent findings on how specific epigenetic modifications influence TDP-43 expression and discusses their possible implications for disease progression.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1530719"},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Neuroinflammatory aspects in neurological disorders.","authors":"Pinto Alipio, Loidl C Fabián, Goldstein Jorge","doi":"10.3389/fmmed.2025.1557546","DOIUrl":"10.3389/fmmed.2025.1557546","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1557546"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Gene therapy and genome editing for metabolic liver disorders.","authors":"Fanny Collaud, Giulia Bortolussi","doi":"10.3389/fmmed.2024.1543685","DOIUrl":"https://doi.org/10.3389/fmmed.2024.1543685","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1543685"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An artificial transcription factor that activates potent interferon-γ expression in human Jurkat T Cells.","authors":"Ashley King, Davis Noblitt, Olivia Sherron, Clara Kjerfve, Lydia Pless, Nicholas L Truex","doi":"10.3389/fmmed.2024.1492370","DOIUrl":"10.3389/fmmed.2024.1492370","url":null,"abstract":"<p><p>Interferon (IFN)-γ is a central regulator of cell-mediated immunity in human health and disease, but reduced expression of the target receptors impairs signaling activity and leads to immunotherapy resistance. Although intracellular expression of IFN-γ restores the signaling and downstream functions, we lack the tools to activate the <i>IFNG</i> gene instead of cell surface receptors. This paper introduces the design and characterization of an artificial transcription factor (ATF) protein that recognizes the <i>IFNG</i> gene with six zinc finger domains, which are dovetailed to a VP64 signaling domain that promotes gene transcription and translation. Biological studies with human Jurkat T cells reveal that the ATF amplifies <i>IFNG</i> gene transcription and translation, and also stimulates gene transcription for multiple class I and II HLA alleles and interferon-stimulated genes (ISGs). Biophysical characterization showed the recombinant ATF protein recognizes the human <i>IFNG</i> gene with nanomolar affinity (K_D = 5.27 ± 0.3 nM), adopts a protein secondary structure associated with the ββα-fold of zinc finger domains, and is resistant to thermal denaturation. These studies demonstrate that transcriptional targeting of cytokine genes, rather than surface receptors, activates cytokine expression and shows significant potential for directing immune function.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1492370"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-checkpoint-inhibitor therapy directed against PD-L1 is tolerated in the heart without manifestation of cardiac inflammation in a preclinical reversible melanoma mouse model.","authors":"Caroline Schoenherr, Stefan Pietzsch, Cristina Barca, Franziska E Müller, Frauke S Bahr, Martina Kasten, Andre Zeug, Sergej Erschow, Christine S Falk, Evgeni Ponimaskin, James T Thackeray, Denise Hilfiker-Kleiner, Melanie Ricke-Hoch","doi":"10.3389/fmmed.2024.1487526","DOIUrl":"10.3389/fmmed.2024.1487526","url":null,"abstract":"<p><p>Immune-checkpoint-inhibitors (ICI) target key regulators of the immune system expressed by cancer cells that mask those from recognition by the immune system. They have improved the outcome for patients with various cancer types, such as melanoma. ICI-based therapy is frequently accompanied by immune-related adverse side effects (IRAEs). The reversible melanoma cancer mouse model (B16F10 cells stably expressing a ganciclovir (GCV)-inducible suicide gene in C57BL/6N mice: B16F10-GCV) allows chemotherapy-free tumor elimination in advanced disease stage and demonstrates almost complete recovery of the mouse heart from cancer-induced atrophy, molecular impairment and heart failure. Thus, enabling the study of anti-cancer-therapy effects. Here, we analyzed potential cardiac side effects of antibody-mediated PD-L1 inhibition in the preclinical B16F10-GCV mouse model after tumor elimination and 2 weeks recovery (50 days after tumor inoculation). Anti-PD-L1 treatment was associated with improved survival as compared to isotype control (Ctrl) treated mice. Surviving anti-PD-L1 and Ctrl mice showed similar cardiac function, dimensions and the expression of cardiac stress and hypertrophy markers. Although anti-PD-L1 treatment was associated with increased troponin I type 3 cardiac (TNNI3) blood levels, cardiac mRNA expression of macrophage markers and elevated cardiac levels of secreted inflammatory factors compared to Ctrl treatment, both groups showed a comparable density of inflammatory cells in the heart (using CXCR4-ligand ⁶⁸Ga-Pentixafor in PET-CT and immunohistochemistry). Thus, anti-PD-L1 therapy improved survival in mice with advanced melanoma cancer with no major cardiac phenotype or inflammation 50 days after tumor inoculation. Without a second hit that triggers the inflammatory response, anti-PD-L1 treatment appears to be safe for the heart in the preclinical melanoma mouse model.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1487526"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human-specific gene <i>ARHGAP11B</i>-potentially an additional tool in the treatment of neurodegenerative diseases?","authors":"Wieland B Huttner","doi":"10.3389/fmmed.2024.1465647","DOIUrl":"10.3389/fmmed.2024.1465647","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1465647"},"PeriodicalIF":0.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeltaRex-G, tumor targeted retrovector encoding a CCNG1 inhibitor, for CAR-T cell therapy induced cytokine release syndrome.","authors":"Grace Haroun, Erlinda M Gordon","doi":"10.3389/fmmed.2024.1461151","DOIUrl":"10.3389/fmmed.2024.1461151","url":null,"abstract":"<p><p>Cytokine release syndrome is a serious complication of chimeric antigen receptor-T cell therapy and is triggered by excessive secretion of inflammatory cytokines by chimeric T cells which could be fatal. Following an inquiry into the molecular mechanisms orchestrating cytokine release syndrome, we hypothesize that DeltaRex-G, a tumor targeted retrovector encoding a cytocidal CCNG1 inhibitor gene, may be a viable treatment option for corticosteroid-resistant cytokine release syndrome. DeltaRex-G received United States Food and Drug Administration Emergency Use Authorization to treat Covid-19-induced acute respiratory distress syndrome, which is due to hyperactivated immune cells. A brief administration of DeltaRex-G would inhibit a certain proportion of hyperactive chimeric T cells, consequently reducing cytokine release while retaining chimeric T cell efficacy.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1461151"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy.","authors":"Armel Hervé Nwabo Kamdje, Hervet Paulain Dongmo Fogang, Patrice N Mimche","doi":"10.3389/fmmed.2024.1426454","DOIUrl":"10.3389/fmmed.2024.1426454","url":null,"abstract":"<p><p>Major epigenetic changes are associated with carcinogenesis, including aberrant DNA methylations and post-translational modifications of histone. Indeed evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-basedclinical and experimental studies, we hypothesize that factors associated with risk for developing a hematologic malignancy (HM), such as metabolic syndrome and chronic inflammation, may trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Signaling pathways associated with such risk factors include but are not limited to pro-inflammatory nuclear factor κB (NF-κB) and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways. The latter includes signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in the biology of cancer and in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"4 ","pages":"1426454"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}