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Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction-associated diseases.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI188507
Ali Shilatifard, Issam Ben-Sahra
{"title":"Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction-associated diseases.","authors":"Ali Shilatifard, Issam Ben-Sahra","doi":"10.1172/JCI188507","DOIUrl":"https://doi.org/10.1172/JCI188507","url":null,"abstract":"<p><p>Lysosome storage dysfunction plays a central role in numerous human diseases, but a lack of appropriate tools has hindered lysosomal content profiling in clinical settings. In this issue of the JCI, Saarela et al. introduce a method called tagless LysoIP that enabled rapid isolation of intact lysosomes from blood and brain cells via immunoprecipitation of the endogenous protein TMEM192. Applied to the neurodegenerative lysosomal storage disorder known as Batten disease (caused by mutations in the CLN3 gene), tagless LysoIP revealed substantial accumulation of glycerophosphodiesters (GPDs) in patient lysosomes. These findings highlight the role of CLN3 in GPD clearance and present an innovative method that will enable biomarker discovery and therapeutic advancement in lysosomal diseases.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Regulation of TTN as a mechanism of and treatment for heart failure.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI189335
Dominic E Fullenkamp
{"title":"Regulation of TTN as a mechanism of and treatment for heart failure.","authors":"Dominic E Fullenkamp","doi":"10.1172/JCI189335","DOIUrl":"https://doi.org/10.1172/JCI189335","url":null,"abstract":"<p><p>Truncation variants in the gene TTN encoding titin are the most common cause of familial dilated cardiomyopathy (DCM), with both haploinsufficiency and \"poison peptide\" implicated as contributory mechanisms of disease. In this issue of the JCI, Kim et al. identify a highly conserved enhancer element approximately 500 bp downstream of the transcriptional start site of TTN in intron 1, which they demonstrated to be critical in regulating TTN expression. This work helps to further clarify the relative role of haploinsufficiency in TTN-related DCM and provides a potential target for therapies aimed at treating TTN-related DCM.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
High IgG titers against EBV glycoprotein 42 correlate with lower risk of nasopharyngeal carcinoma.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI189207
Benjamin E Warner, Kathy Hy Shair
{"title":"High IgG titers against EBV glycoprotein 42 correlate with lower risk of nasopharyngeal carcinoma.","authors":"Benjamin E Warner, Kathy Hy Shair","doi":"10.1172/JCI189207","DOIUrl":"https://doi.org/10.1172/JCI189207","url":null,"abstract":"<p><p>Serologic biomarkers for the early diagnosis of EBV-associated nasopharyngeal carcinoma (NPC) have been identified from population studies, but a protective antibody signature in cancer-free seropositive carriers remains undefined. In this issue of the JCI, Kong et al. show that high levels of IgG against EBV glycoprotein 42 (gp42) were associated with reduced NPC risk in three independent prospective cohorts from southern China. EBV virions contain gp42, which complexes with gH-gL to facilitate fusion with B cells by binding to HLA class II (HLA-II). In this study, HLA-II was detected on non-antigen-presenting cells in a proportion of premalignant nasopharyngeal tissues, which may prime the nasopharyngeal epithelium for infection. In vitro, HLA-II expression in a nasopharyngeal cell line encouraged infection by EBV derived from B cells or epithelial cells. These findings suggest that a vaccine that stimulates gp42-IgG production may reduce the risk of EBV-associated NPC in endemic regions.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The role of TREM2 in sepsis. Reply.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI189219
Siqi Ming, Xingyu Li, Jingxian Shu, Xi Huang, Yongjian Wu
{"title":"The role of TREM2 in sepsis. Reply.","authors":"Siqi Ming, Xingyu Li, Jingxian Shu, Xi Huang, Yongjian Wu","doi":"10.1172/JCI189219","DOIUrl":"https://doi.org/10.1172/JCI189219","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The N-type calcium channel rises from the ashes.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI189308
Maria A Gandini, Gerald W Zamponi
{"title":"The N-type calcium channel rises from the ashes.","authors":"Maria A Gandini, Gerald W Zamponi","doi":"10.1172/JCI189308","DOIUrl":"https://doi.org/10.1172/JCI189308","url":null,"abstract":"<p><p>Chronic pain is a debilitating condition that affects up to 1.5 billion people globally. Advancing pain management depends on a thorough understanding of the types of pain experienced by patients and the underlying mechanisms driving it. N-type calcium channels play a crucial role as therapeutic targets for managing chronic pain. In this issue of the JCI, Tang et al. introduce C2230, an N-type calcium channel blocker that inhibited CaV2.2 channels during high frequency stimulation with little effect on other ion channels in the pain pathway across multiple models. C2230 offers a promising analgesic for use in therapeutic intervention.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The role of TREM2 in sepsis.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI188895
Jiejie Zhu, Tianyin Sun, Hanren Dai
{"title":"The role of TREM2 in sepsis.","authors":"Jiejie Zhu, Tianyin Sun, Hanren Dai","doi":"10.1172/JCI188895","DOIUrl":"https://doi.org/10.1172/JCI188895","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Microbial influencers: the airway microbiome's role in asthma.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI184316
Young Jin Kim, Supinda Bunyavanich
{"title":"Microbial influencers: the airway microbiome's role in asthma.","authors":"Young Jin Kim, Supinda Bunyavanich","doi":"10.1172/JCI184316","DOIUrl":"https://doi.org/10.1172/JCI184316","url":null,"abstract":"<p><p>Asthma is a common chronic respiratory disease affecting people of all ages globally. The airway hosts diverse microbial communities increasingly recognized as influential in the development and disease course of asthma. Here, we review recent findings on the airway microbiome in asthma. As relationships between the airway microbiome and respiratory health take root early in life, we first provide an overview of the early-life airway microbiome and asthma development, where multiple cohort studies have identified bacterial genera in the infant airway associated with risk of future wheeze and asthma. We then address current understandings of interactions between environmental factors, the airway microbiome, and asthma, including the effects of rural/urban environments, pet ownership, smoking, viral illness, and antibiotics. Next, we delve into what has been observed about the airway microbiome and asthma phenotypes and endotypes, as airway microbiota have been associated with asthma control, severity, obesity-related asthma, and treatment effects as well as with type 2 high, type 2 low, and more newly described multi-omic asthma endotypes. We then discuss emerging approaches to shape the microbiome for asthma therapy and conclude the Review with perspectives on future research directions.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI191305
Qianru Huang, Na Tian, Jianfeng Zhang, Shiyang Song, Hao Cheng, Xinnan Liu, Wenle Zhang, Youqiong Ye, Yanhua Du, Xueyu Dai, Rui Liang, Dan Li, Sheng-Ming Dai, Chuan Wang, Zhi Chen, Qianjun Zhou, Bin Li
{"title":"Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma.","authors":"Qianru Huang, Na Tian, Jianfeng Zhang, Shiyang Song, Hao Cheng, Xinnan Liu, Wenle Zhang, Youqiong Ye, Yanhua Du, Xueyu Dai, Rui Liang, Dan Li, Sheng-Ming Dai, Chuan Wang, Zhi Chen, Qianjun Zhou, Bin Li","doi":"10.1172/JCI191305","DOIUrl":"https://doi.org/10.1172/JCI191305","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Reinvigorating drug development around NGF signaling for pain.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI189029
Andi Wangzhou, Theodore J Price
{"title":"Reinvigorating drug development around NGF signaling for pain.","authors":"Andi Wangzhou, Theodore J Price","doi":"10.1172/JCI189029","DOIUrl":"https://doi.org/10.1172/JCI189029","url":null,"abstract":"<p><p>Nerve growth factor (NGF) signaling is a clinically validated target for the treatment of several prevalent types of chronic pain; however, addressing safety concerns remain a key challenge. In this issue of the JCI, Peach et al. take a major step forward in this area by deciphering complexities in the signaling of the NGF receptor TrkA, finding that neuropilin 1 (NRP1) acted as a coreceptor for NGF actions at TrkA and the receptor complex required scaffolding from GIPC1. Using a mix of techniques, including animal behavioral models, electrophysiology on mouse and human dorsal root ganglion (DRG) neurons, and elegant biochemical pharmacology, the authors demonstrated that this therapeutic target might more safely manipulate NGF signaling to achieve pain alleviation. While there are still important questions to answer, the innovative work paves the way for the development of nonopioid pain therapeutics.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Clinical Research and Public Health in the JCI.
IF 13.3 1区 医学
Journal of Clinical Investigation Pub Date : 2025-02-17 DOI: 10.1172/JCI190119
Elizabeth M McNally
{"title":"Clinical Research and Public Health in the JCI.","authors":"Elizabeth M McNally","doi":"10.1172/JCI190119","DOIUrl":"https://doi.org/10.1172/JCI190119","url":null,"abstract":"","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 4","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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