Pub Date : 2025-10-29DOI: 10.1038/s12276-025-01566-2
Hui Dang, Yan Liu, Ye Zhou, Mengjun Sui, Yubo Wang, Wei Qiang, Fang Sui, Yan Zhang, Hongxin Cao, Xiaoyan Wu, Meiju Ji, Peng Hou
Ten eleven translocation 1 (TET1) is a 5-methylcytosine dioxygenase, and its altered DNA demethylation has been implicated in human diseases. However, its role in regulating thyroid function remains totally unknown. Here we first generated thyroid-specific Tet1 knockout combined with thyroid-specific BrafV600E transgenic mouse model (Thy-BrafV600E; Tet1−/−) and their control mice (Thy-BrafV600E; Tet1+/+). The latter developed severe hypothyroidism and lost reproductive ability owing to structural damages of thyroid gland, while thyroid-specific Tet1 knockout effectively restored thyroid structure and function of Thy-BrafV600E; Tet1+/+ mice and their reproductive ability. In addition, we also established thyroid-specific Tet1 knockout mouse model (Thy-Tet1−/−) and demonstrated that these mice could develop hyperthyroidism with systemic hypermetabolic symptoms such as weight loss, increased heart rate and elevated systolic blood pressure, further supporting the inhibitory effect of TET1 on thyroid function. Transcriptomic sequencing revealed that key genes related to metabolism and synthesis of thyroid hormones such as PAX8, SLC5A5 and TPO were significantly upregulated in Thy-Tet1−/− mice. Mechanistically, TET1 recruits HDAC1 to reduce the levels of H3K27Ac and H3K9Ac in the PAX8 promoter, thereby inhibiting the expression of itself and its downstream targets NIS and TPO. Further studies showed that elevated miR-29c-3p in serum exosomes enhanced thyroid function by targeting TET1, which may be one of the causes of hyperthyroidism. Thus, this study uncovers a new mechanism by which TET1 suppresses thyroid function, providing a new perspective to explore the pathogenesis of hyperthyroidism. Hyperthyroidism is a condition in which the thyroid gland produces too many hormones, leading to symptoms such as weight loss and irritability. Here scientists are exploring the role of a protein called TET1 in thyroid function. TET1 is known for its role in modifying DNA, which can affect how genes are turned on or off. In this study, researchers investigated whether TET1 influences thyroid activity. They used mice that were genetically modified to lack TET1 specifically in their thyroid glands. These mice showed signs of hyperthyroidism such as increased thyroid hormone levels and faster metabolism. The researchers found that TET1 normally helps suppress the activity of certain genes involved in thyroid hormone production by interacting with other proteins that modify DNA structure. This study suggests that TET1 plays a crucial role in regulating thyroid function and that its absence can lead to hyperthyroidism. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"TET1 loss propels the development of hyperthyroidism by remodeling histone modifications of PAX8 promoter","authors":"Hui Dang, Yan Liu, Ye Zhou, Mengjun Sui, Yubo Wang, Wei Qiang, Fang Sui, Yan Zhang, Hongxin Cao, Xiaoyan Wu, Meiju Ji, Peng Hou","doi":"10.1038/s12276-025-01566-2","DOIUrl":"10.1038/s12276-025-01566-2","url":null,"abstract":"Ten eleven translocation 1 (TET1) is a 5-methylcytosine dioxygenase, and its altered DNA demethylation has been implicated in human diseases. However, its role in regulating thyroid function remains totally unknown. Here we first generated thyroid-specific Tet1 knockout combined with thyroid-specific BrafV600E transgenic mouse model (Thy-BrafV600E; Tet1−/−) and their control mice (Thy-BrafV600E; Tet1+/+). The latter developed severe hypothyroidism and lost reproductive ability owing to structural damages of thyroid gland, while thyroid-specific Tet1 knockout effectively restored thyroid structure and function of Thy-BrafV600E; Tet1+/+ mice and their reproductive ability. In addition, we also established thyroid-specific Tet1 knockout mouse model (Thy-Tet1−/−) and demonstrated that these mice could develop hyperthyroidism with systemic hypermetabolic symptoms such as weight loss, increased heart rate and elevated systolic blood pressure, further supporting the inhibitory effect of TET1 on thyroid function. Transcriptomic sequencing revealed that key genes related to metabolism and synthesis of thyroid hormones such as PAX8, SLC5A5 and TPO were significantly upregulated in Thy-Tet1−/− mice. Mechanistically, TET1 recruits HDAC1 to reduce the levels of H3K27Ac and H3K9Ac in the PAX8 promoter, thereby inhibiting the expression of itself and its downstream targets NIS and TPO. Further studies showed that elevated miR-29c-3p in serum exosomes enhanced thyroid function by targeting TET1, which may be one of the causes of hyperthyroidism. Thus, this study uncovers a new mechanism by which TET1 suppresses thyroid function, providing a new perspective to explore the pathogenesis of hyperthyroidism. Hyperthyroidism is a condition in which the thyroid gland produces too many hormones, leading to symptoms such as weight loss and irritability. Here scientists are exploring the role of a protein called TET1 in thyroid function. TET1 is known for its role in modifying DNA, which can affect how genes are turned on or off. In this study, researchers investigated whether TET1 influences thyroid activity. They used mice that were genetically modified to lack TET1 specifically in their thyroid glands. These mice showed signs of hyperthyroidism such as increased thyroid hormone levels and faster metabolism. The researchers found that TET1 normally helps suppress the activity of certain genes involved in thyroid hormone production by interacting with other proteins that modify DNA structure. This study suggests that TET1 plays a crucial role in regulating thyroid function and that its absence can lead to hyperthyroidism. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2376-2392"},"PeriodicalIF":12.9,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01566-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145394912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1038/s12276-025-01548-4
Sunil S. Adav, Kee Woei Ng
Hair specimens are vital in precision medicine, forensics and environmental monitoring owing to their ability to retain biochemical data over time. Their noninvasive collection and long-term storage suitability make them ideal for diagnostics and investigations, offering historical insights into health and exposure records. In medicine, hair analysis provides a long-term biochemical profile, aiding in monitoring health conditions, nutritional deficiencies, toxin exposure and treatment efficacy. Advances in mass spectrometry, chromatography and spectroscopy have expanded their applications to cancer diagnostics, tuberculosis, HIV, neurological disorders and mental health assessments. In forensic science, the resistance of hair to decomposition and its ability to absorb substances help identify individuals, detect drug use and reconstruct crime scenes. Omics techniques such as genomics, proteomics and metabolomics enhance forensic accuracy by enabling precise substance detection and timeline reconstruction. Despite its potential, challenges such as hair growth variability, contamination and lack of standardized techniques limit the current impact of hair analysis. Addressing these issues could advance its role in diagnostics and forensic investigations. This review explores recent advancements and applications of hair analysis in precision medicine, infectious diseases, mental health, stress assessment and forensic science. Hair is a simple yet valuable sample used in many fields such as medicine, cosmetics and forensics. It is easy to collect and store, making it useful for studying diseases and environmental exposures. This study aims to address how hair can be better used in precision medicine and diagnostics. Researchers have found that hair can help detect diseases such as cancer and monitor drug levels in patients. They use advanced techniques including mass spectrometry (a method to measure molecules) to analyze hair samples. This helps in understanding how drugs are absorbed and how diseases progress over time. Hair analysis can also reveal exposure to toxins and stress levels by measuring substances stored in the hair over months. The study concludes that hair is a promising tool for personalized healthcare, offering insights into long-term health conditions. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"The multifaceted role of hair as a biospecimen: recent advances in precision medicine and forensic science","authors":"Sunil S. Adav, Kee Woei Ng","doi":"10.1038/s12276-025-01548-4","DOIUrl":"10.1038/s12276-025-01548-4","url":null,"abstract":"Hair specimens are vital in precision medicine, forensics and environmental monitoring owing to their ability to retain biochemical data over time. Their noninvasive collection and long-term storage suitability make them ideal for diagnostics and investigations, offering historical insights into health and exposure records. In medicine, hair analysis provides a long-term biochemical profile, aiding in monitoring health conditions, nutritional deficiencies, toxin exposure and treatment efficacy. Advances in mass spectrometry, chromatography and spectroscopy have expanded their applications to cancer diagnostics, tuberculosis, HIV, neurological disorders and mental health assessments. In forensic science, the resistance of hair to decomposition and its ability to absorb substances help identify individuals, detect drug use and reconstruct crime scenes. Omics techniques such as genomics, proteomics and metabolomics enhance forensic accuracy by enabling precise substance detection and timeline reconstruction. Despite its potential, challenges such as hair growth variability, contamination and lack of standardized techniques limit the current impact of hair analysis. Addressing these issues could advance its role in diagnostics and forensic investigations. This review explores recent advancements and applications of hair analysis in precision medicine, infectious diseases, mental health, stress assessment and forensic science. Hair is a simple yet valuable sample used in many fields such as medicine, cosmetics and forensics. It is easy to collect and store, making it useful for studying diseases and environmental exposures. This study aims to address how hair can be better used in precision medicine and diagnostics. Researchers have found that hair can help detect diseases such as cancer and monitor drug levels in patients. They use advanced techniques including mass spectrometry (a method to measure molecules) to analyze hair samples. This helps in understanding how drugs are absorbed and how diseases progress over time. Hair analysis can also reveal exposure to toxins and stress levels by measuring substances stored in the hair over months. The study concludes that hair is a promising tool for personalized healthcare, offering insights into long-term health conditions. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2234-2250"},"PeriodicalIF":12.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01548-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145379775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1038/s12276-025-01563-5
Jong-Won Kim, Mengyun Ke, Donovan Whitfield, Bin Yang, Gu Seob Roh, Wen Xie
Cysteine (Cys) posttranslational modifications play a critical role in regulating protein function, cellular signaling and redox homeostasis in various physiological and pathological conditions. Sulfiredoxin-1 (SRXN1) has emerged as a key regulator of protein redox homeostasis through its involvement in Cys sulfinylation. However, the role of SRXN1 in the pathogenesis of diseases and its therapeutic implications have yet to be fully explored. Beyond its classical function in reactive oxygen species detoxification, SRXN1 also modulates redox-sensitive signaling pathways that govern inflammation, apoptosis and cell survival, making it an essential component of cellular defense against oxidative stress-related damage. Here we highlight the significance of SRXN1 in regulating Cys sulfinylation across a broad spectrum of liver diseases. Furthermore, we emphasize the critical role of SRXN1 in regulating oxidative stress and cellular signaling through its interaction and desulfinylation of target or substrate proteins, both of which are crucial to maintaining cellular function under pathological conditions. Finally, we discuss the potential therapeutic implications of targeting SRXN1 in disease contexts where oxidative stress exacerbates pathological processes. A deeper understanding of SRXN1-mediated redox regulation may offer a novel therapeutic avenue to mitigate Cys oxidation and improve clinical outcomes in various liver disease contexts. Oxidative stress, an imbalance between harmful molecules called reactive oxygen species and the body’s defenses, contributes to many diseases. A key player in managing this stress is a protein called sulfiredoxin 1 (SRXN1). SRXN1 helps to repair proteins damaged by reactive oxygen species, particularly by reversing a process called cysteine sulfinylation, which can impair protein function. This Review explores SRXN1’s role in liver diseases, highlighting its protective effects on hepatocytes under pathological conditions such as acute liver injury, alcoholic liver disease and liver fibrosis. It does this by maintaining redox balance. Researchers used various methods to study SRXN1’s effects, including examining its interactions with other proteins and its impact on cell survival. Results show that, while SRXN1 protects against liver damage, it also aids cancer cell survival in liver cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Redox regulation by sulfiredoxin-1: bridging cysteine oxidation and liver disease therapeutics","authors":"Jong-Won Kim, Mengyun Ke, Donovan Whitfield, Bin Yang, Gu Seob Roh, Wen Xie","doi":"10.1038/s12276-025-01563-5","DOIUrl":"10.1038/s12276-025-01563-5","url":null,"abstract":"Cysteine (Cys) posttranslational modifications play a critical role in regulating protein function, cellular signaling and redox homeostasis in various physiological and pathological conditions. Sulfiredoxin-1 (SRXN1) has emerged as a key regulator of protein redox homeostasis through its involvement in Cys sulfinylation. However, the role of SRXN1 in the pathogenesis of diseases and its therapeutic implications have yet to be fully explored. Beyond its classical function in reactive oxygen species detoxification, SRXN1 also modulates redox-sensitive signaling pathways that govern inflammation, apoptosis and cell survival, making it an essential component of cellular defense against oxidative stress-related damage. Here we highlight the significance of SRXN1 in regulating Cys sulfinylation across a broad spectrum of liver diseases. Furthermore, we emphasize the critical role of SRXN1 in regulating oxidative stress and cellular signaling through its interaction and desulfinylation of target or substrate proteins, both of which are crucial to maintaining cellular function under pathological conditions. Finally, we discuss the potential therapeutic implications of targeting SRXN1 in disease contexts where oxidative stress exacerbates pathological processes. A deeper understanding of SRXN1-mediated redox regulation may offer a novel therapeutic avenue to mitigate Cys oxidation and improve clinical outcomes in various liver disease contexts. Oxidative stress, an imbalance between harmful molecules called reactive oxygen species and the body’s defenses, contributes to many diseases. A key player in managing this stress is a protein called sulfiredoxin 1 (SRXN1). SRXN1 helps to repair proteins damaged by reactive oxygen species, particularly by reversing a process called cysteine sulfinylation, which can impair protein function. This Review explores SRXN1’s role in liver diseases, highlighting its protective effects on hepatocytes under pathological conditions such as acute liver injury, alcoholic liver disease and liver fibrosis. It does this by maintaining redox balance. Researchers used various methods to study SRXN1’s effects, including examining its interactions with other proteins and its impact on cell survival. Results show that, while SRXN1 protects against liver damage, it also aids cancer cell survival in liver cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2226-2233"},"PeriodicalIF":12.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01563-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1038/s12276-025-01558-2
Kang-Min Lee, Jihun Kim, Hye Lim Jung, Young Yeon Kim, Jihoon Lee, Yeon-Ju Lee, Eunhee Yoo, Hyi-Seung Lee, Jeanho Yun
Mitophagy has been implicated in kidney function and related diseases. However, a direct analysis of mitophagy in kidney models, including disease models, remains notably lacking. Here we analyzed mitophagy levels in Drosophila Malpighian tubules, a functional analog of the human kidney, using a transgenic model of the engineered mitophagy reporter mt-Keima. We found that mitophagy is highly active in the major cell types of the Malpighian tubules, including renal stem cells, principal cells and stellate cells. Notably, the suppression of mitophagy by genetic downregulation of mitophagy-related genes, such as ATG5 and ULK1, led to a significant decrease in the secretion function of the Malpighian tubules, suggesting that mitophagy is essential for their proper function. Interestingly, a continuous high-sugar diet, which is used as a model for diabetic kidney disease, caused a reduction in mitophagy levels in principal cells before the development of mitochondrial dysfunction and defective secretion. Importantly, stimulation of mitophagy with the recently developed mitophagy inducer PDE701 rescued both mitochondrial dysfunction and defective phenotypes in a diabetic kidney disease model. Our results highlight the pivotal role of mitophagy in kidney function and suggest that modulating mitophagy could be a potential strategy for treating kidney diseases. Mitophagy is a process that removes damaged mitochondria to keep cells healthy. This study looks at how mitophagy works in the kidneys using fruit flies, which have similar kidney-like structures called Malpighian tubules. Here researchers used a special protein called mt-Keima to measure mitophagy in these tubules. They found that mitophagy is crucial for the function of the tubules. When mitophagy was reduced, the tubules did not work well, especially under conditions mimicking diabetic kidney disease (DKD). The study used a high-sugar diet to create a DKD model in flies, which led to decreased mitophagy and kidney dysfunction. However, a new compound called PDE701 increased mitophagy and improved kidney function in these flies. The findings suggest that boosting mitophagy could help treat kidney diseases such as DKD. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Exploring mitophagy levels in Drosophila Malpighian tubules unveils the pivotal role of mitophagy in kidney function and diabetic kidney disease","authors":"Kang-Min Lee, Jihun Kim, Hye Lim Jung, Young Yeon Kim, Jihoon Lee, Yeon-Ju Lee, Eunhee Yoo, Hyi-Seung Lee, Jeanho Yun","doi":"10.1038/s12276-025-01558-2","DOIUrl":"10.1038/s12276-025-01558-2","url":null,"abstract":"Mitophagy has been implicated in kidney function and related diseases. However, a direct analysis of mitophagy in kidney models, including disease models, remains notably lacking. Here we analyzed mitophagy levels in Drosophila Malpighian tubules, a functional analog of the human kidney, using a transgenic model of the engineered mitophagy reporter mt-Keima. We found that mitophagy is highly active in the major cell types of the Malpighian tubules, including renal stem cells, principal cells and stellate cells. Notably, the suppression of mitophagy by genetic downregulation of mitophagy-related genes, such as ATG5 and ULK1, led to a significant decrease in the secretion function of the Malpighian tubules, suggesting that mitophagy is essential for their proper function. Interestingly, a continuous high-sugar diet, which is used as a model for diabetic kidney disease, caused a reduction in mitophagy levels in principal cells before the development of mitochondrial dysfunction and defective secretion. Importantly, stimulation of mitophagy with the recently developed mitophagy inducer PDE701 rescued both mitochondrial dysfunction and defective phenotypes in a diabetic kidney disease model. Our results highlight the pivotal role of mitophagy in kidney function and suggest that modulating mitophagy could be a potential strategy for treating kidney diseases. Mitophagy is a process that removes damaged mitochondria to keep cells healthy. This study looks at how mitophagy works in the kidneys using fruit flies, which have similar kidney-like structures called Malpighian tubules. Here researchers used a special protein called mt-Keima to measure mitophagy in these tubules. They found that mitophagy is crucial for the function of the tubules. When mitophagy was reduced, the tubules did not work well, especially under conditions mimicking diabetic kidney disease (DKD). The study used a high-sugar diet to create a DKD model in flies, which led to decreased mitophagy and kidney dysfunction. However, a new compound called PDE701 increased mitophagy and improved kidney function in these flies. The findings suggest that boosting mitophagy could help treat kidney diseases such as DKD. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2364-2375"},"PeriodicalIF":12.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01558-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-14DOI: 10.1038/s12276-025-01560-8
Youngsuk Seo, Ji Eun Park, Jae Young Yu, Boyoung Lee, Jong Hyuk Yoon, Hyun Joo An
Glycosylation functions as a pivotal posttranslational modification in proteins and as a distinct biosynthetic process in lipids. In the brain, it plays essential roles in development, function and homeostasis by modulating protein folding, receptor trafficking and intercellular communication. Although glycans constitute less than 1% of the brain’s mass, their impact is disproportionately profound. Recent technological advances have uncovered the essential contributions of both protein- and lipid-bound glycans, including N-glycans, O-glycans and gangliosides, to brain physiology and disease. Here we explore the emerging landscape of brain glycosylation, highlighting its distinct roles in neurodevelopment, synaptic organization and immune regulation. Aberrant glycosylation has been implicated in neurodegenerative diseases (for example, Alzheimer’s and Parkinson’s), psychiatric disorders (for example, depression and schizophrenia) and neurodevelopmental conditions (for example, autism spectrum disorders, attention deficit hyperactivity disorder and dystroglycanopathies). We summarize recent breakthroughs in glycomics technologies, including glycan enrichment, liquid chromatography–tandem mass spectrometry, MALDI-based imaging mass spectrometry and high-throughput omics, which enable molecular and spatial mapping of brain glycosylation. Artificial-intelligence-driven bioinformatics and multi-omics integration are rapidly opening new avenues for deciphering glycan-mediated regulation in brain health and disease. Together, these developments position brain glycosylation as a transformative frontier in neuroscience, with the potential to yield novel diagnostic biomarkers and therapeutic strategies for complex brain disorders. The human brain is a complex organ with over 100 billion cells, including neurons and glial cells. It controls thoughts, emotions and actions through intricate communication systems. This Review explores glycosylation, a process where sugars attach to proteins and lipids, which is crucial for brain function but not well understood. Researchers have used advanced techniques such as mass spectrometry to study glycosylation in the brain. Studies have shown that glycosylation influences brain development, neuronal communication and disease mechanisms. For example, changes in glycosylation have been associated with Alzheimer’s and Parkinson’s diseases. The study highlights the importance of understanding glycosylation for developing new treatments. The researchers conclude that glycosylation is a key player in brain health and disease. Future research could lead to new diagnostic tools and therapies for brain disorders by focusing on glycosylation patterns. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"The emerging landscape of brain glycosylation: from molecular complexity to therapeutic potential","authors":"Youngsuk Seo, Ji Eun Park, Jae Young Yu, Boyoung Lee, Jong Hyuk Yoon, Hyun Joo An","doi":"10.1038/s12276-025-01560-8","DOIUrl":"10.1038/s12276-025-01560-8","url":null,"abstract":"Glycosylation functions as a pivotal posttranslational modification in proteins and as a distinct biosynthetic process in lipids. In the brain, it plays essential roles in development, function and homeostasis by modulating protein folding, receptor trafficking and intercellular communication. Although glycans constitute less than 1% of the brain’s mass, their impact is disproportionately profound. Recent technological advances have uncovered the essential contributions of both protein- and lipid-bound glycans, including N-glycans, O-glycans and gangliosides, to brain physiology and disease. Here we explore the emerging landscape of brain glycosylation, highlighting its distinct roles in neurodevelopment, synaptic organization and immune regulation. Aberrant glycosylation has been implicated in neurodegenerative diseases (for example, Alzheimer’s and Parkinson’s), psychiatric disorders (for example, depression and schizophrenia) and neurodevelopmental conditions (for example, autism spectrum disorders, attention deficit hyperactivity disorder and dystroglycanopathies). We summarize recent breakthroughs in glycomics technologies, including glycan enrichment, liquid chromatography–tandem mass spectrometry, MALDI-based imaging mass spectrometry and high-throughput omics, which enable molecular and spatial mapping of brain glycosylation. Artificial-intelligence-driven bioinformatics and multi-omics integration are rapidly opening new avenues for deciphering glycan-mediated regulation in brain health and disease. Together, these developments position brain glycosylation as a transformative frontier in neuroscience, with the potential to yield novel diagnostic biomarkers and therapeutic strategies for complex brain disorders. The human brain is a complex organ with over 100 billion cells, including neurons and glial cells. It controls thoughts, emotions and actions through intricate communication systems. This Review explores glycosylation, a process where sugars attach to proteins and lipids, which is crucial for brain function but not well understood. Researchers have used advanced techniques such as mass spectrometry to study glycosylation in the brain. Studies have shown that glycosylation influences brain development, neuronal communication and disease mechanisms. For example, changes in glycosylation have been associated with Alzheimer’s and Parkinson’s diseases. The study highlights the importance of understanding glycosylation for developing new treatments. The researchers conclude that glycosylation is a key player in brain health and disease. Future research could lead to new diagnostic tools and therapies for brain disorders by focusing on glycosylation patterns. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2214-2225"},"PeriodicalIF":12.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01560-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145294367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-10DOI: 10.1038/s12276-025-01552-8
Sultan Tousif, Daniel Minassian, Chao He, Baldeep Singh, Prachi Umbarkar, Arvind Singh Bhati, Mohammed Mohasin, Nathan Erdmann, Min Xie, Palaniappan Sethu, Carlos J. Orihuela, Hind Lal
Streptococcus pneumoniae (Spn) is the leading cause of community-acquired pneumonia (CAP). A quarter of hospitalized patients with CAP experience a major adverse cardiac event (MACE), raising their mortality by four to five times compared with pneumonia alone. Patients with CAP continue to face a significantly greater risk of MACE and cardiovascular-associated death during convalescence. However, the reasons responsible for this remain unclear. To elucidate the molecular mechanism(s) of Spn-induced MACE in convalescence, a mouse model of Spn infection and antibiotic rescue was employed. A marked decline in ejection fraction persisting at least 3 weeks after bacterial eradication with antibiotics was observed. Evidence of enduring cardiac injury was observed at the molecular, biochemical and histology levels. Blood analysis from patients with invasive pneumococcal disease confirmed unresolved inflammation in these individuals. Here we mechanistically identified that S100A8/A9-TLR4-NLRP3-mediated unresolved inflammation drives cardiac pathologies in Spn convalescent mice. This inflammation was central to the cardiac pathology because interventions with broad-spectrum immunosuppressive hydrocortisone or specific inhibitors of S100A9 (paquinimod) essentially rescued the Spn-induced cardiac pathologies. These results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing Spn-mediated cardiac pathologies in convalescence. Hospitalization for community-acquired pneumonia (CAP) can lead to serious heart problems, even after recovery. Researchers explored why this happens. They studied both humans and mice to understand the link between pneumonia and heart problems. The study involved 10 healthy adults and 7 pneumonia patients. Researchers collected blood samples to analyze immune responses. They also used mice to study heart changes after pneumonia. The focus was on inflammation and its role in heart damage. Findings showed that inflammation persists even after the infection clears, leading to heart issues. The study identified a specific inflammatory pathway (S100A8/A9-TLR4-NLRP3) as a key player in this process. The researchers concluded that targeting this inflammation could help prevent heart problems after pneumonia. Future treatments might focus on reducing inflammation to protect the heart in pneumonia survivors.
{"title":"S100A8/9-NLRP3-mediated chronic unresolved inflammation drives cardiac pathologies following invasive pneumococcal disease","authors":"Sultan Tousif, Daniel Minassian, Chao He, Baldeep Singh, Prachi Umbarkar, Arvind Singh Bhati, Mohammed Mohasin, Nathan Erdmann, Min Xie, Palaniappan Sethu, Carlos J. Orihuela, Hind Lal","doi":"10.1038/s12276-025-01552-8","DOIUrl":"10.1038/s12276-025-01552-8","url":null,"abstract":"Streptococcus pneumoniae (Spn) is the leading cause of community-acquired pneumonia (CAP). A quarter of hospitalized patients with CAP experience a major adverse cardiac event (MACE), raising their mortality by four to five times compared with pneumonia alone. Patients with CAP continue to face a significantly greater risk of MACE and cardiovascular-associated death during convalescence. However, the reasons responsible for this remain unclear. To elucidate the molecular mechanism(s) of Spn-induced MACE in convalescence, a mouse model of Spn infection and antibiotic rescue was employed. A marked decline in ejection fraction persisting at least 3 weeks after bacterial eradication with antibiotics was observed. Evidence of enduring cardiac injury was observed at the molecular, biochemical and histology levels. Blood analysis from patients with invasive pneumococcal disease confirmed unresolved inflammation in these individuals. Here we mechanistically identified that S100A8/A9-TLR4-NLRP3-mediated unresolved inflammation drives cardiac pathologies in Spn convalescent mice. This inflammation was central to the cardiac pathology because interventions with broad-spectrum immunosuppressive hydrocortisone or specific inhibitors of S100A9 (paquinimod) essentially rescued the Spn-induced cardiac pathologies. These results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing Spn-mediated cardiac pathologies in convalescence. Hospitalization for community-acquired pneumonia (CAP) can lead to serious heart problems, even after recovery. Researchers explored why this happens. They studied both humans and mice to understand the link between pneumonia and heart problems. The study involved 10 healthy adults and 7 pneumonia patients. Researchers collected blood samples to analyze immune responses. They also used mice to study heart changes after pneumonia. The focus was on inflammation and its role in heart damage. Findings showed that inflammation persists even after the infection clears, leading to heart issues. The study identified a specific inflammatory pathway (S100A8/A9-TLR4-NLRP3) as a key player in this process. The researchers concluded that targeting this inflammation could help prevent heart problems after pneumonia. Future treatments might focus on reducing inflammation to protect the heart in pneumonia survivors.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2344-2363"},"PeriodicalIF":12.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01552-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lysosomal membrane proteins play fundamental roles in the lysosomal degradation of proteins and are attractive drug targets for metabolic dysfunction-associated fatty liver disease (MAFLD). Fas apoptotic inhibitory molecule 2 (FAIM2), a lysosomal membrane protein, has been recognized as an inhibitor of apoptosis in a variety of diseases. Here we reveal that FAIM2 is an inhibitor of fatty acid synthesis and suppresses MAFLD. FAIM2 protein expression is decreased in MAFLD. Moreover, FAIM2 is degraded by the E3 ubiquitin ligase NEDD4L through the catalysis of K48-linked ubiquitination. High-fat and high-cholesterol diet-induced hepatic steatosis, inflammation and fibrosis are aggravated in Faim2-knockout mice and alleviated in mice with AAV8-mediated FAIM2 overexpression. Furthermore, in hepatocytes, FAIM2 knockout increases the expression of genes related to fatty acid synthesis, while overexpressing FAIM2 exhibits the opposite effect. Mechanistically, FAIM2 directly interacts with CREB-regulated transcription coactivator 2 (CRTC2), a prominent regulator of lipid metabolism, and mediates its degradation through autophagy. Specifically, we find that the N terminus of FAIM2, which interacts with CRTC2 and LC3, is required for autophagic degradation of CRTC2. Collectively, our findings reveal that FAIM2 acts as a fatty acid synthesis inhibitor in MAFLD by promoting the autophagic degradation of CRTC2 and that FAIM2–CRTC2 may be a promising therapeutic target. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver condition affecting many people worldwide. Researchers are looking for new ways to treat MAFLD. A recent study explored the role of a protein called FAIM2 in MAFLD. They found that FAIM2 levels are lower in people with MAFLD, and this protein helps reduce fat buildup in the liver. Researchers used mice and primary hepatocytes to study the function of FAIM2. They discovered that, when FAIM2 is missing, fat and inflammation in the liver increase. However, increasing FAIM2 levels can reduce these issues. FAIM2 works by interacting with another protein, CRTC2, and helps break it down through a process called autophagy. The study suggests that boosting FAIM2 could be a new way to treat MAFLD by reducing fat buildup in the liver. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Fas apoptotic inhibitor molecule 2 mitigates metabolic dysfunction-associated fatty liver disease through autophagic CRTC2 degradation","authors":"Yongjie Yu, Sha Hu, Tuo Zhang, Hongjie Shi, Dajun Li, Yongping Huang, Yu Zhang, Haitao Wang, Yufeng Hu, Hong Yu, Guang-Nian Zhao, Peng Zhang","doi":"10.1038/s12276-025-01559-1","DOIUrl":"10.1038/s12276-025-01559-1","url":null,"abstract":"Lysosomal membrane proteins play fundamental roles in the lysosomal degradation of proteins and are attractive drug targets for metabolic dysfunction-associated fatty liver disease (MAFLD). Fas apoptotic inhibitory molecule 2 (FAIM2), a lysosomal membrane protein, has been recognized as an inhibitor of apoptosis in a variety of diseases. Here we reveal that FAIM2 is an inhibitor of fatty acid synthesis and suppresses MAFLD. FAIM2 protein expression is decreased in MAFLD. Moreover, FAIM2 is degraded by the E3 ubiquitin ligase NEDD4L through the catalysis of K48-linked ubiquitination. High-fat and high-cholesterol diet-induced hepatic steatosis, inflammation and fibrosis are aggravated in Faim2-knockout mice and alleviated in mice with AAV8-mediated FAIM2 overexpression. Furthermore, in hepatocytes, FAIM2 knockout increases the expression of genes related to fatty acid synthesis, while overexpressing FAIM2 exhibits the opposite effect. Mechanistically, FAIM2 directly interacts with CREB-regulated transcription coactivator 2 (CRTC2), a prominent regulator of lipid metabolism, and mediates its degradation through autophagy. Specifically, we find that the N terminus of FAIM2, which interacts with CRTC2 and LC3, is required for autophagic degradation of CRTC2. Collectively, our findings reveal that FAIM2 acts as a fatty acid synthesis inhibitor in MAFLD by promoting the autophagic degradation of CRTC2 and that FAIM2–CRTC2 may be a promising therapeutic target. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver condition affecting many people worldwide. Researchers are looking for new ways to treat MAFLD. A recent study explored the role of a protein called FAIM2 in MAFLD. They found that FAIM2 levels are lower in people with MAFLD, and this protein helps reduce fat buildup in the liver. Researchers used mice and primary hepatocytes to study the function of FAIM2. They discovered that, when FAIM2 is missing, fat and inflammation in the liver increase. However, increasing FAIM2 levels can reduce these issues. FAIM2 works by interacting with another protein, CRTC2, and helps break it down through a process called autophagy. The study suggests that boosting FAIM2 could be a new way to treat MAFLD by reducing fat buildup in the liver. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2331-2343"},"PeriodicalIF":12.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01559-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The linear ubiquitin chain assembly complex (LUBAC) has been implicated in both cancer progression and viral activity; however, its role in the progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) remains unclear. Here we found that the expression of LUBAC components and Met1-linked ubiquitination was significantly upregulated and associated with poor prognosis in HCC; however, blocking the LUBAC activity with HOIPIN-1 did not affect the malignancy of HCC cells or their sensitivity to sorafenib treatment. Targeting HOIL-1 inhibited the progression of HCC in vitro and in vivo. Interestingly, we found that HOIL-1, but not other LUBAC components, was exclusively upregulated in HBV-HCC. Functionally, HOIL-1 knockdown suppressed tumor growth, metastasis and stemness in HBV-infected HCC cells. Mechanistically, HOIL-1 interacted with HBx, but not other HBV proteins, and facilitated its stabilization by recruiting deubiquitinatinase USP15, thereby reducing HBx K48-linked ubiquitination. Notably, the clinical analysis indicated that the association between high HOIL-1 expression and poor prognosis was evident only in patients with HBV-HCC with high USP15 expression and not in those with low USP15 expression. Collectively, our results demonstrated that HOIL-1 acts as an oncogene to promote HBV-HCC progression independent of LUBAC activity and may serve as a potential therapeutic target for HBV-HCC. Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide, often linked to hepatitis B virus (HBV) infection. Despite vaccines and treatments, HBV remains a key risk factor for HCC. This Article explores how HOIL-1 protein affects HCC progression in HBV-infected patients. Researchers found that HOIL-1, part of a protein complex called LUBAC, is active in HCC tissues. They studied human liver cancer cells and mice to understand HOIL-1’s role. They discovered that HOIL-1 helps stabilize another protein, HBx, which is crucial for HBV-related cancer development. HOIL-1 does this by interacting with an enzyme called USP15, preventing HBx from being broken down. The study shows that reducing HOIL-1 levels can slow down cancer growth and spread in HBV-related HCC. This suggests that targeting HOIL-1 could be a new way to treat this type of liver cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"The LUBAC subunit HOIL-1 promotes the progression of HBV-associated hepatocellular carcinoma independently of linear ubiquitination","authors":"Zheyu Dong, Qiuyue Ye, Yuxin Zhou, Yuqing Shao, Junling Chen, Jianzhong Cai, Yiyan Huang, Jiayue Yang, Yaoting Feng, Liangxing Chen, Libo Tang, Yuchuan Jiang, Peng Chen, Yu Wang, Yongyin Li","doi":"10.1038/s12276-025-01556-4","DOIUrl":"10.1038/s12276-025-01556-4","url":null,"abstract":"The linear ubiquitin chain assembly complex (LUBAC) has been implicated in both cancer progression and viral activity; however, its role in the progression of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) remains unclear. Here we found that the expression of LUBAC components and Met1-linked ubiquitination was significantly upregulated and associated with poor prognosis in HCC; however, blocking the LUBAC activity with HOIPIN-1 did not affect the malignancy of HCC cells or their sensitivity to sorafenib treatment. Targeting HOIL-1 inhibited the progression of HCC in vitro and in vivo. Interestingly, we found that HOIL-1, but not other LUBAC components, was exclusively upregulated in HBV-HCC. Functionally, HOIL-1 knockdown suppressed tumor growth, metastasis and stemness in HBV-infected HCC cells. Mechanistically, HOIL-1 interacted with HBx, but not other HBV proteins, and facilitated its stabilization by recruiting deubiquitinatinase USP15, thereby reducing HBx K48-linked ubiquitination. Notably, the clinical analysis indicated that the association between high HOIL-1 expression and poor prognosis was evident only in patients with HBV-HCC with high USP15 expression and not in those with low USP15 expression. Collectively, our results demonstrated that HOIL-1 acts as an oncogene to promote HBV-HCC progression independent of LUBAC activity and may serve as a potential therapeutic target for HBV-HCC. Hepatocellular carcinoma (HCC) is a major cause of cancer deaths worldwide, often linked to hepatitis B virus (HBV) infection. Despite vaccines and treatments, HBV remains a key risk factor for HCC. This Article explores how HOIL-1 protein affects HCC progression in HBV-infected patients. Researchers found that HOIL-1, part of a protein complex called LUBAC, is active in HCC tissues. They studied human liver cancer cells and mice to understand HOIL-1’s role. They discovered that HOIL-1 helps stabilize another protein, HBx, which is crucial for HBV-related cancer development. HOIL-1 does this by interacting with an enzyme called USP15, preventing HBx from being broken down. The study shows that reducing HOIL-1 levels can slow down cancer growth and spread in HBV-related HCC. This suggests that targeting HOIL-1 could be a new way to treat this type of liver cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2317-2330"},"PeriodicalIF":12.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01556-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1038/s12276-025-01542-w
Hee Young Kim, Won-Woo Lee
The immune system has traditionally been divided into innate and adaptive branches, with immunological memory considered a hallmark of adaptive immunity. However, recent studies reveal that innate immune cells can also exhibit memory-like properties, known as trained immunity. This phenomenon involves the long-term functional reprogramming of innate immune cells following exposure to exogenous or endogenous stimuli, mediated by epigenetic and metabolic changes. Trained immunity enhances responses to subsequent unrelated challenges and serves as a protective mechanism against reinfection. Nonetheless, it may also contribute to the development of chronic inflammatory diseases such as autoimmune disorders, allergies and atherosclerosis. Whereas much of the research has focused on pathogen-associated molecular patterns as inducers of trained immunity, emerging evidence highlights that sterile inflammation, driven by damage-associated molecular patterns and lifestyle-associated molecular patterns, can similarly induce this immune adaptation. Here we examine the molecular mechanisms underlying damage-associated molecular pattern- and lifestyle-associated molecular pattern-induced trained immunity and their roles in chronic inflammation. This Review also discusses central trained immunity, characterized by the durable reprogramming of hematopoietic stem and progenitor cells, and its implications in disease progression. Finally, potential therapeutic strategies targeting metabolic and epigenetic pathways are considered. Understanding noninfectious stimuli-induced trained immunity offers new insights into chronic inflammatory disease management. The immune system has two parts: innate and adaptive immunity. Scientists used to think only adaptive immunity had memory, but recent studies show innate immunity can also remember. Trained immunity involves long-term changes in innate immune cells, such as macrophages, due to vaccines or other stimuli, leading to better responses to future infections. Researchers have found that not just infections but also noninfectious factors such as diet and stress can trigger trained immunity. This Review reviews recent findings on how certain molecules, called damage-associated molecular patterns and lifestyle-associated molecular patterns, can induce trained immunity. These molecules are released from damaged cells or accumulated owing to poor clearance and can cause chronic inflammation, contributing to diseases such as atherosclerosis and chronic kidney disease. The Review concludes that understanding trained immunity could lead to new treatments for chronic inflammatory diseases by targeting these pathways. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
{"title":"Trained immunity induced by DAMPs and LAMPs in chronic inflammatory diseases","authors":"Hee Young Kim, Won-Woo Lee","doi":"10.1038/s12276-025-01542-w","DOIUrl":"10.1038/s12276-025-01542-w","url":null,"abstract":"The immune system has traditionally been divided into innate and adaptive branches, with immunological memory considered a hallmark of adaptive immunity. However, recent studies reveal that innate immune cells can also exhibit memory-like properties, known as trained immunity. This phenomenon involves the long-term functional reprogramming of innate immune cells following exposure to exogenous or endogenous stimuli, mediated by epigenetic and metabolic changes. Trained immunity enhances responses to subsequent unrelated challenges and serves as a protective mechanism against reinfection. Nonetheless, it may also contribute to the development of chronic inflammatory diseases such as autoimmune disorders, allergies and atherosclerosis. Whereas much of the research has focused on pathogen-associated molecular patterns as inducers of trained immunity, emerging evidence highlights that sterile inflammation, driven by damage-associated molecular patterns and lifestyle-associated molecular patterns, can similarly induce this immune adaptation. Here we examine the molecular mechanisms underlying damage-associated molecular pattern- and lifestyle-associated molecular pattern-induced trained immunity and their roles in chronic inflammation. This Review also discusses central trained immunity, characterized by the durable reprogramming of hematopoietic stem and progenitor cells, and its implications in disease progression. Finally, potential therapeutic strategies targeting metabolic and epigenetic pathways are considered. Understanding noninfectious stimuli-induced trained immunity offers new insights into chronic inflammatory disease management. The immune system has two parts: innate and adaptive immunity. Scientists used to think only adaptive immunity had memory, but recent studies show innate immunity can also remember. Trained immunity involves long-term changes in innate immune cells, such as macrophages, due to vaccines or other stimuli, leading to better responses to future infections. Researchers have found that not just infections but also noninfectious factors such as diet and stress can trigger trained immunity. This Review reviews recent findings on how certain molecules, called damage-associated molecular patterns and lifestyle-associated molecular patterns, can induce trained immunity. These molecules are released from damaged cells or accumulated owing to poor clearance and can cause chronic inflammation, contributing to diseases such as atherosclerosis and chronic kidney disease. The Review concludes that understanding trained immunity could lead to new treatments for chronic inflammatory diseases by targeting these pathways. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 10","pages":"2137-2147"},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s12276-025-01542-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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