Journal of Clinical Investigation最新文献_第8页

Intertwining clonality and resistance: Staphylococcus aureus in the antibiotic era. 克隆性与抗药性交织：抗生素时代的金黄色葡萄球菌。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI185824

Henry F Chambers, Vance G Fowler

引用次数: 0

Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury. 在急性肺损伤小鼠模型中，中性粒细胞特异性 Shp1 的缺失会导致致命的肺出血。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI183161

S Farshid Moussavi-Harami, Simon J Cleary, Mélia Magnen, Yurim Seo, Catharina Conrad, Bevin C English, Longhui Qiu, Kristin M Wang, Clare L Abram, Clifford A Lowell, Mark R Looney

{"title":"Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury.","authors":"S Farshid Moussavi-Harami, Simon J Cleary, Mélia Magnen, Yurim Seo, Catharina Conrad, Bevin C English, Longhui Qiu, Kristin M Wang, Clare L Abram, Clifford A Lowell, Mark R Looney","doi":"10.1172/JCI183161","DOIUrl":"10.1172/JCI183161","url":null,"abstract":"The acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality and neutrophils are critical to its pathogenesis. Neutrophil activation is closely regulated by inhibitory tyrosine phosphatases including Src homology region 2 domain containing phosphatase-1 (Shp1). Here, we report that loss of neutrophil Shp1 in mice produced hyperinflammation and lethal pulmonary hemorrhage in sterile inflammation and pathogen-induced models of acute lung injury (ALI) through a Syk kinase-dependent mechanism. We observed large intravascular neutrophil clusters, perivascular inflammation, and excessive neutrophil extracellular traps in neutrophil-specific Shp1 knockout mice suggesting an underlying mechanism for the observed pulmonary hemorrhage. Targeted immunomodulation through the administration of a Shp1 activator (SC43) reduced agonist-induced reactive oxygen species in vitro and ameliorated ALI-induced alveolar neutrophilia and NETs in vivo. We propose that the pharmacologic activation of Shp1 has the potential to fine-tune neutrophil hyperinflammation that is central to the pathogenesis of ARDS.","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365426","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

Ciliary localization of GPR75 promotes fat accumulation in mice. GPR75 的纤毛定位促进了小鼠的脂肪积累。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI185059

Marcelo Chávez, Anushweta Asthana, Peter K Jackson

引用次数: 0

Sleepless nights and social plights: medial septum GABAergic hyperactivity in a neuroligin 3-deficient autism model. 不眠之夜与社交困境：神经胶质蛋白 3 缺陷自闭症模型的内侧隔 GABA 能亢进。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI184795

Claire E Cho, Dahee Jung, Reesha R Patel

引用次数: 0

Endothelial YAP/TAZ activation promotes atherosclerosis in a mouse model of Hutchinson-Gilford progeria syndrome. 内皮 YAP/TAZ 激活促进 Hutchinson-Gilford progeria 综合征小鼠模型的动脉粥样硬化。

IF 4.1 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI173448

Ana Barettino, Cristina González-Gómez, Pilar Gonzalo, María J Andrés-Manzano, Carlos R Guerrero, Francisco M Espinosa, Rosa M Carmona, Yaazan Blanco, Beatriz Dorado, Carlos Torroja, Fátima Sánchez-Cabo, Ana Quintas, Alberto Benguría, Ana Dopazo, Ricardo García, Ignacio Benedicto, Vicente Andrés

{"title":"Endothelial YAP/TAZ activation promotes atherosclerosis in a mouse model of Hutchinson-Gilford progeria syndrome.","authors":"Ana Barettino, Cristina González-Gómez, Pilar Gonzalo, María J Andrés-Manzano, Carlos R Guerrero, Francisco M Espinosa, Rosa M Carmona, Yaazan Blanco, Beatriz Dorado, Carlos Torroja, Fátima Sánchez-Cabo, Ana Quintas, Alberto Benguría, Ana Dopazo, Ricardo García, Ignacio Benedicto, Vicente Andrés","doi":"10.1172/JCI173448","DOIUrl":"10.1172/JCI173448","url":null,"abstract":"Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease caused by the expression of progerin, an aberrant protein produced by a point mutation in the LMNA gene. HGPS patients show accelerated aging and die prematurely mainly from complications of atherosclerosis such as myocardial infarction, heart failure, or stroke. However, the mechanisms underlying HGPS vascular pathology remain ill-defined. We used single-cell RNA sequencing to characterize the aorta in progerin-expressing LmnaG609G/G609G mice and wild-type controls, with a special focus on endothelial cells (ECs). HGPS ECs showed gene expression changes associated with extracellular matrix alterations, increased leukocyte extravasation, and activation of the yes-associated protein 1/transcriptional activator with PDZ-binding domain (YAP/TAZ) mechanosensing pathway, all validated by different techniques. Atomic force microscopy experiments demonstrated stiffer subendothelial extracellular matrix in progeroid aortae, and ultrasound assessment of live HGPS mice revealed disturbed aortic blood flow, both key inducers of the YAP/TAZ pathway in ECs. YAP/TAZ inhibition with verteporfin reduced leukocyte accumulation in the aortic intimal layer and decreased atherosclerosis burden in progeroid mice. Our findings identify endothelial YAP/TAZ signaling as a key mechanism of HGPS vascular disease and open a new avenue for the development of YAP/TAZ-targeting drugs to ameliorate progerin-induced atherosclerosis.","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The first century of JCI and beyond. 青年商会的第一个世纪及其后。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-10-01 DOI: 10.1172/JCI186113

Elizabeth M McNally

引用次数: 0

2024 Lasker Award Recipient Zhijian Chen elucidates how DNA stimulates immunity. 2024 年拉斯克奖获得者陈志坚阐明了 DNA 如何刺激免疫力。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-09-19 DOI: 10.1172/JCI186104

Amy B Heimberger

引用次数: 0

Joel Habener, Svetlana Mojsov, and Lotte Bjerre Knudsen awarded Lasker prize for pioneering work on GLP-1. Joel Habener、Svetlana Mojsov 和 Lotte Bjerre Knudsen 因在 GLP-1 方面的开创性工作而荣获拉斯克奖。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-09-19 DOI: 10.1172/JCI186225

Hossein Ardehali

引用次数: 0

Connecting the dots: sex, depression, and musculoskeletal health. 连接点：性别、抑郁和肌肉骨骼健康。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-09-17 DOI: 10.1172/JCI180072

Mackenzie Newman, Henry J Donahue, Gretchen N Neigh

{"title":"Connecting the dots: sex, depression, and musculoskeletal health.","authors":"Mackenzie Newman, Henry J Donahue, Gretchen N Neigh","doi":"10.1172/JCI180072","DOIUrl":"https://doi.org/10.1172/JCI180072","url":null,"abstract":"Depression and multiple musculoskeletal disorders are overrepresented in women compared with men. Given that depression is a modifiable risk factor and improvement of depressive symptoms increases positive outcomes following orthopedic intervention, efforts to improve clinical recognition of depressive symptoms and increased action toward ameliorating depressive symptoms among orthopedic patients are positioned to reduce complications and positively affect patient-reported outcomes. Although psychosocial factors play a role in the manifestation and remittance of depression, it is also well appreciated that primary biochemical changes are capable of causing and perpetuating depression. Unique insight for novel treatments of depression may be facilitated by query of the bidirectional relationship between musculoskeletal health and depression. This Review aims to synthesize the diverse literature on sex, depression, and orthopedics and emphasize the potential for common underlying biological substrates. Given the overrepresentation of depression and musculoskeletal disorders among women, increased emphasis on the biological drivers of the co-occurrence of these disorders is positioned to improve women's health.","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 18","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models. 在临床前模型中，周细胞表型转换可减轻免疫抑制，并使血管化肿瘤对免疫疗法敏感。

IF 13.3 1区医学

Journal of Clinical Investigation Pub Date : 2024-09-17 DOI: 10.1172/JCI179860

Zhi-Jie Li, Bo He, Alice Domenichini, Jiulia Satiaputra, Kira H Wood, Devina D Lakhiani, Abate A Bashaw, Lisa M Nilsson, Ji Li, Edward R Bastow, Anna Johansson-Percival, Elena Denisenko, Alistair Rr Forrest, Suraj Sakaram, Rafael Carretero, Günter J Hämmerling, Jonas A Nilsson, Gabriel Yf Lee, Ruth Ganss

{"title":"Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.","authors":"Zhi-Jie Li, Bo He, Alice Domenichini, Jiulia Satiaputra, Kira H Wood, Devina D Lakhiani, Abate A Bashaw, Lisa M Nilsson, Ji Li, Edward R Bastow, Anna Johansson-Percival, Elena Denisenko, Alistair Rr Forrest, Suraj Sakaram, Rafael Carretero, Günter J Hämmerling, Jonas A Nilsson, Gabriel Yf Lee, Ruth Ganss","doi":"10.1172/JCI179860","DOIUrl":"https://doi.org/10.1172/JCI179860","url":null,"abstract":"T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"134 18","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0