Frontiers in molecular medicine最新文献

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Neural stem cells in adult neurogenesis and their therapeutic applications in neurodegenerative disorders: a concise review. 神经干细胞在成人神经发生及其在神经退行性疾病中的治疗应用:简要综述。
Frontiers in molecular medicine Pub Date : 2025-06-19 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1569717
Teketay Bayleyegn Derso, Bemrew Admassu Mengistu, Yitayew Demessie, Melkie Dagnaw Fenta, Kalkidan Getnet
{"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":"https://doi.org/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}
引用次数: 0
Editorial: Current trends in immunotherapy: from monoclonal antibodies to CAR-T cells. 编辑:当前免疫治疗的趋势:从单克隆抗体到CAR-T细胞。
Frontiers in molecular medicine Pub Date : 2025-06-02 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1633469
Kishor Pant, Mark C Glassy
{"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}
引用次数: 0
Editorial: Epigenetics and stem cell therapy in cancer and diseases. 社论:癌症和疾病的表观遗传学和干细胞治疗。
Frontiers in molecular medicine Pub Date : 2025-05-16 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1621093
Sonia Coni, Roberto Schirano, Camilla Manfredi, Paola Infante, Veronica Veschi
{"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}
引用次数: 0
Cell surface vimentin: a natural human immune response target for immunotherapy. 细胞表面波形蛋白:一种用于免疫治疗的天然人体免疫应答靶点。
Frontiers in molecular medicine Pub Date : 2025-02-20 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1552323
Mark C Glassy
{"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}
引用次数: 0
Editorial: Tuberculosis: host immunity, diagnostics and therapeutics. 社论:结核病:宿主免疫、诊断和治疗。
Frontiers in molecular medicine Pub Date : 2025-02-18 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1568256
Anthony G Tsolaki, Amy K Barczak, Uday Kishore
{"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}
引用次数: 0
Epigenetic regulation of TDP-43: potential implications for amyotrophic lateral sclerosis. TDP-43的表观遗传调控:对肌萎缩侧索硬化症的潜在影响。
Frontiers in molecular medicine Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1530719
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}
引用次数: 0
Editorial: Neuroinflammatory aspects in neurological disorders. 社论:神经系统疾病的神经炎症方面。
Frontiers in molecular medicine Pub Date : 2025-02-11 eCollection Date: 2025-01-01 DOI: 10.3389/fmmed.2025.1557546
Pinto Alipio, Loidl C Fabián, Goldstein Jorge
{"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}
引用次数: 0
Editorial: Gene therapy and genome editing for metabolic liver disorders. 社论:代谢性肝脏疾病的基因治疗和基因组编辑。
Frontiers in molecular medicine Pub Date : 2025-01-09 eCollection Date: 2024-01-01 DOI: 10.3389/fmmed.2024.1543685
Fanny Collaud, Giulia Bortolussi
{"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}
引用次数: 0
An artificial transcription factor that activates potent interferon-γ expression in human Jurkat T Cells. 一种在人Jurkat T细胞中激活强效干扰素γ表达的人工转录因子。
Frontiers in molecular medicine Pub Date : 2025-01-08 eCollection Date: 2024-01-01 DOI: 10.3389/fmmed.2024.1492370
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}
引用次数: 0
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. 在临床前可逆性黑色素瘤小鼠模型中,针对PD-L1的免疫检查点抑制剂治疗在心脏中是耐受的,没有心脏炎症的表现。
Frontiers in molecular medicine Pub Date : 2025-01-06 eCollection Date: 2024-01-01 DOI: 10.3389/fmmed.2024.1487526
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
{"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 <sup>68</sup>Ga-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}
引用次数: 0
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