{"title":"Potential role of N6-methyladenosine modification in circular RNA biogenesis and function in the inflammatory responses.","authors":"Heedoo Lee, Leo Chen, Yang Jin","doi":"10.3389/fmmed.2025.1607661","DOIUrl":"10.3389/fmmed.2025.1607661","url":null,"abstract":"<p><p>N6-methyladenosine (m6A) is the best-studied post-transcriptional RNA modification. It refers to the methylation in the N6 position. M6A exists universally from viruses to mammalian cells and is highly abundant in RNA polymerase II-transcribed, protein-coding transcripts and various non-coding RNAs. M6A RNA modification influences multiple physiological and pathological processes. This RNA methylation plays a role in the pathogenesis of many human diseases, including but not limited to hematopoietic, central nervous, and reproductive systems. One of the m6A-modified non-coding RNAs is the circular form of RNA. Circular RNA (circRNA) refers to a single-stranded RNA molecule with a circular structure that exists across a wide range of organisms, including eukaryotes and prokaryotes. Its unique circular structure is formed by the covalent closure between the 3'and 5'ends of the RNA molecule. This closed-loop structure prevents the circRNA from being degraded readily by the exonucleases, resulting in more stability compared to its linear RNA counterparts. CircRNAs have been reported to regulate gene expression, protein interaction, and RNA sponging. They play important roles in many human diseases. M6A modifications of the host gene mRNAs regulate the circRNA biogenesis. Furthermore, m6A modification of circRNA itself adds additional regulation of these complicated processes. This mini-review elaborates on recent advances in m6A modification on circRNA biogenesis and function, focusing on the role of circRNA m6A modification in the development of inflammatory responses.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1607661"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610470","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":"Neural stem cells in adult neurogenesis and their therapeutic applications in neurodegenerative disorders: a concise review.","authors":"Teketay Bayleyegn Derso, Bemrew Admassu Mengistu, Yitayew Demessie, Melkie Dagnaw Fenta, Kalkidan Getnet","doi":"10.3389/fmmed.2025.1569717","DOIUrl":"10.3389/fmmed.2025.1569717","url":null,"abstract":"<p><p>The idea of using stem cell therapy to treat neurodegenerative diseases has undergone significant change over the years and has made significant progress recently. Neurotrophins, growth factors, and transcription factors regulate neural stem cell proliferation and differentiation. Disruption of these regulatory mechanisms, including negative feedback, can contribute to neurodegenerative diseases. Contemporary research highlights a growing global concern regarding diverse neurodegenerative disorders affecting both humans and animals. These conditions arise from neuronal cell death, axonal regeneration failure, and impairment of neuronal structure. Current pharmacological treatments primarily offer symptomatic relief without altering disease progression. Consequently, researchers are investigating innovative therapeutic strategies, with neural stem cell therapy emerging as a promising avenue. Adult neural stem cells, embryonic neural stem cells, and induced pluripotent stem cells represent potential cell sources, although challenges such as ethical considerations and technical limitations remain. The therapeutic application of neural stem cells holds significant promise for addressing neurodegenerative diseases, including Alzheimer's disease, stroke, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. Neural stem cell therapy aims to replenish lost neurons and promote neural regeneration in these conditions. While clinical trials have demonstrated some success in improving cognitive and motor functions in individuals with neurodegenerative impairments, challenges such as immunological rejection, the identification of compatible cell sources, ethical concerns, treatment efficacy, and potential side effects necessitate thorough investigation before widespread clinical implementation. Despite these challenges, neural stem cell-based therapy offers substantial potential for revolutionizing the treatment of neurodegenerative diseases and central nervous system injuries. This paper, therefore, explores adult neurogenesis and the therapeutic potential of neural stem cells within the dynamic field of neurodegenerative disorders.</p>","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1569717"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562245","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: Current trends in immunotherapy: from monoclonal antibodies to CAR-T cells.","authors":"Kishor Pant, Mark C Glassy","doi":"10.3389/fmmed.2025.1633469","DOIUrl":"10.3389/fmmed.2025.1633469","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1633469"},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318856","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: Epigenetics and stem cell therapy in cancer and diseases.","authors":"Sonia Coni, Roberto Schirano, Camilla Manfredi, Paola Infante, Veronica Veschi","doi":"10.3389/fmmed.2025.1621093","DOIUrl":"10.3389/fmmed.2025.1621093","url":null,"abstract":"","PeriodicalId":73090,"journal":{"name":"Frontiers in molecular medicine","volume":"5 ","pages":"1621093"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200991","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":"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}
D Y Mengistu, M Terribili, C Pellacani, L Ciapponi, M Marzullo
{"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}
Ashley King, Davis Noblitt, Olivia Sherron, Clara Kjerfve, Lydia Pless, Nicholas L Truex
{"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<sub>D</sub> = 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}