Experimental and Molecular Medicine最新文献

The emerging landscape of brain glycosylation: from molecular complexity to therapeutic potential. 脑糖基化的新前景：从分子复杂性到治疗潜力。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-14 DOI: 10.1038/s12276-025-01560-8

Youngsuk Seo, Ji Eun Park, Jae Young Yu, Boyoung Lee, Jong Hyuk Yoon, Hyun Joo An

{"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":"https://doi.org/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.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

S100A8/9-NLRP3-mediated chronic unresolved inflammation drives cardiac pathologies following invasive pneumococcal disease. s100a8 /9- nlrp3介导的慢性未解决炎症驱动侵袭性肺炎球菌病后的心脏病变。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-10 DOI: 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

{"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":"https://doi.org/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.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fas apoptotic inhibitor molecule 2 mitigates metabolic dysfunction-associated fatty liver disease through autophagic CRTC2 degradation. Fas凋亡抑制剂分子2通过自噬降解CRTC2减轻代谢功能障碍相关的脂肪肝疾病。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-07 DOI: 10.1038/s12276-025-01559-1

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

{"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":"https://doi.org/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.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Ret finger protein deficiency attenuates adipogenesis in male mice with high fat diet-induced obesity. 作者更正：Ret指蛋白缺乏可减轻高脂肪饮食引起的肥胖雄性小鼠的脂肪生成。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-06 DOI: 10.1038/s12276-025-01568-0

Yun-Gyeong Lee, Anna Jeong, Yongwoon Lim, Sera Shin, Hosouk Joung, Hye Jung Cho, Su-Jin Lee, Hwang Chan Yu, Hyung-Seok Kim, Kwang-Il Nam, Gwang Hyeon Eom, Byung-Hyun Park, So-Young Park, Duk-Hwa Kwon, Hyun Kook

引用次数: 0

The LUBAC subunit HOIL-1 promotes the progression of HBV-associated hepatocellular carcinoma independently of linear ubiquitination. LUBAC亚基HOIL-1独立于线性泛素化促进hbv相关肝细胞癌的进展。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-06 DOI: 10.1038/s12276-025-01556-4

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

{"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":"https://doi.org/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.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GDF15 regulates development and growth of sympathetic neurons to enhance energy expenditure and thermogenesis. GDF15调节交感神经元的发育和生长，以增加能量消耗和产热。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-01 DOI: 10.1038/s12276-025-01543-9

Jinyoung Kim, Annie Zhao, Seo Hyun Park, Jaeseok Han, Deok-Hyeon Cheon, Sang-Hyeon Ju, Yoonhyuk Jang, Kon Chu, Hyung Jin Choi, Jiyoon Kim, Myung-Shik Lee

{"title":"GDF15 regulates development and growth of sympathetic neurons to enhance energy expenditure and thermogenesis.","authors":"Jinyoung Kim, Annie Zhao, Seo Hyun Park, Jaeseok Han, Deok-Hyeon Cheon, Sang-Hyeon Ju, Yoonhyuk Jang, Kon Chu, Hyung Jin Choi, Jiyoon Kim, Myung-Shik Lee","doi":"10.1038/s12276-025-01543-9","DOIUrl":"https://doi.org/10.1038/s12276-025-01543-9","url":null,"abstract":"Growth differentiation factor 15 (GDF15) induces weight loss and increases sympathetic activity through its receptor GFRAL. Given that RET, a GFRAL coreceptor, influences neuronal growth, we studied whether GDF15 can induce the development or growth of sympathetic neurons, in addition to its effect on sympathetic activity. Here we we used GDF15-transgenic and Gdf15-knockout mice to explore the role of GDF15 in the development and activity of sympathetic neurons. GDF15-transgenic mice exhibited increased surface area and volume of sympathetic neurite in adipose tissues. Furthermore, these mice showed heightened energy expenditure, thermogenesis, cold tolerance and an elevated sympathetic response to hypoglycemia. GFRAL was expressed in sympathetic ganglion cells, which was enhanced by GDF15. RET and its downstream signaling molecules such as AKT, ERK and CREB were activated in the sympathetic ganglia by transgenic expression of GDF15 in vivo or treatment with GDF15 in vitro, an leading to increased expression of genes related to thermogenesis, neurite growth or extension and catecholamine synthesis. An ex vivo treatment of sympathetic ganglia with GDF15 also promoted neurite growth and extension. By contrast, Gdf15-knockout mice showed opposite phenotypes, underscoring the physiological role of GDF15 in the development and activity of the sympathetic nervous system. These findings indicate that GDF15 regulates not only the sympathetic activity but also the development or growth of sympathetic neurons through GFRAL expressed in sympathetic ganglion cells, which could contribute to energy expenditure and weight loss. The modulation of GDF15 could be a therapeutic option against diseases or conditions associated with dysregulated sympathetic activity.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trained immunity induced by DAMPs and LAMPs in chronic inflammatory diseases. 慢性炎症性疾病中DAMPs和lamp诱导的训练免疫。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-01 DOI: 10.1038/s12276-025-01542-w

Hee Young Kim, Won-Woo Lee

{"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":"https://doi.org/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.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac repair and regeneration: cell therapy, in vivo reprogramming, and the promise of extracellular vesicles. 心脏修复和再生：细胞治疗、体内重编程和细胞外囊泡的前景。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-01 DOI: 10.1038/s12276-025-01549-3

R M Imtiaz Karim Rony, Joshua D Tompkins

{"title":"Cardiac repair and regeneration: cell therapy, in vivo reprogramming, and the promise of extracellular vesicles.","authors":"R M Imtiaz Karim Rony, Joshua D Tompkins","doi":"10.1038/s12276-025-01549-3","DOIUrl":"https://doi.org/10.1038/s12276-025-01549-3","url":null,"abstract":"Therapeutic interventions to replenish lost cardiomyocytes and recover myocardium functions following ischemic myocardial infarction (MI) remain major goals in the cardiac regeneration field. Clinical trials harnessing autologous or allogeneic cell therapy approaches from both cardiac and noncardiac cells sources, thus far, demonstrate marginal improvement. Moreover, complications such as arrythmias and graft rejections associated with cellular or organ-based therapies continue to prevail. Extracellular vesicles, on the other hand, are cell-derived, nano-sized, cargo-containing biomolecules that have emerged as potent alternatives to cell-based cardiac regeneration/replacement therapy. Recent studies demonstrate that most stem-cell-derived extracellular vesicles (Stem-EVs) are nonimmunogenic and carry cardioprotective therapeutic cargos. Moreover, administration of multiple Stem-EV types in animal models of acute MI results in reduced inflammation, apoptosis, smaller infarct size and improved cardiac functionality. With recent developments, engineered Stem-EVs with enhanced cardiac targeting, prolonged circulation and recombinant therapeutic cargos may tilt the cardiac regeneration field toward these novel cell-free biologics. Here we provide a brief overview of current approaches to repair and replenish damaged cardiomyocytes following MI via cell therapy and in vivo reprogramming, and we delve deeply into the therapeutic potentials of Stem-EVs in cardiac repair and regeneration.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An overview of mechanical microenvironment and mechanotransduction in intervertebral disc degeneration. 椎间盘退变的机械微环境和机械转导综述。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-01 DOI: 10.1038/s12276-025-01546-6

Wencan Ke, Hanpeng Xu, Chengyi Zhang, Zhiwei Liao, Huaizhen Liang, Bide Tong, Feijun Yuan, Kun Wang, Wenbin Hua, Bingjin Wang, Cao Yang

{"title":"An overview of mechanical microenvironment and mechanotransduction in intervertebral disc degeneration.","authors":"Wencan Ke, Hanpeng Xu, Chengyi Zhang, Zhiwei Liao, Huaizhen Liang, Bide Tong, Feijun Yuan, Kun Wang, Wenbin Hua, Bingjin Wang, Cao Yang","doi":"10.1038/s12276-025-01546-6","DOIUrl":"https://doi.org/10.1038/s12276-025-01546-6","url":null,"abstract":"Cellular mechanotransduction, essential for many biological functions, involves the conversion of mechanical signals into biochemical signals related to cell activities and metabolism. Physical factors in the local cellular microenvironment include external mechanical forces, mechanical stimulation generated by the extracellular matrix and intercellular mechanical interactions mediated through cell-cell adhesions. Intervertebral disc degeneration (IDD) is a complex pathological process involving diverse etiological contributors, such as mechanical wear, oxidative damage and nutritional deficiency. Notably, aberrant mechanical loading has been identified as a pivotal driver in both the initiation and progression of IDD. The mechanical microenvironment in intervertebral discs mainly includes pressure, tension, hydrostatic pressure, osmotic pressure and extracellular matrix stiffness. A thorough understanding of the mechanotransduction process of intervertebral disc cells in response to various mechanical stimuli and its regulatory mechanism is of great significance for the prevention and treatment of IDD. Here, therefore, we systematically review the research progress in understanding the mechanical microenvironment and mechanotransduction in IDD.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel protein-preserving passive tissue clearing approach using sodium cholate and urea for whole-organ imaging. 一种使用胆酸钠和尿素进行全器官成像的新型蛋白质保存被动组织清除方法。

IF 12.9 2区医学

Experimental and Molecular Medicine Pub Date : 2025-10-01 DOI: 10.1038/s12276-025-01550-w

Kitae Kim, Kwangbae Lee, Taehoon Kang, Jungmihn Lee, Wonseok Lee, Ji Yeoun Lee, Sunghoe Chang

{"title":"A novel protein-preserving passive tissue clearing approach using sodium cholate and urea for whole-organ imaging.","authors":"Kitae Kim, Kwangbae Lee, Taehoon Kang, Jungmihn Lee, Wonseok Lee, Ji Yeoun Lee, Sunghoe Chang","doi":"10.1038/s12276-025-01550-w","DOIUrl":"https://doi.org/10.1038/s12276-025-01550-w","url":null,"abstract":"The recent advancements in tissue-clearing techniques have opened new possibilities for non-invasive three-dimensional (3D) volumetric imaging of a wide range of biological specimens. Passive tissue-clearing methods use diffusion-based processes to infiltrate clearing reagents into samples without mechanical forces or energy input, aiming to minimize the sample disruption while preserving the tissue architecture and molecular information. Nevertheless, these methods often rely on sodium dodecyl sulfate (SDS) as a delipidating detergent, which has a risk of causing tissue damage and protein disruptions, thus necessitating the development of a reliable yet accessible approach for passive tissue clearing. Here we replaced SDS with sodium cholate (SC), combined it with urea and developed OptiMuS-prime as a novel passive tissue clearing technique to achieve a better passive infiltration of clearing reagents while retaining structural integrity. SC, a non-denaturing detergent with small micelles, enhances tissue transparency while preserving proteins in their native state, whereas urea disrupts hydrogen bonds and induces hyperhydration to enhance probe penetration. Through the optimization of composition and protocols, we found that OptiMuS-prime enables the 3D imaging of immunolabeled neural structures and vasculature networks across multiple rodent organs, including the brain, intestine and lung. The method demonstrated robust clearing and immunostaining capabilities, particularly for detecting subcellular structures in densely packed organs such as the kidney, spleen and heart, as well as in post-mortem human tissues and human induced pluripotent stem cell-derived brain organoids. Together, OptiMuS-prime offers a fully accessible and customizable solution for passive clearing and immunostaining, enabling 3D cellular connectivity analysis across whole organisms without the need for extensive tissue-clearing expertise.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0