更新于：2024-11-01

LCN2 x ICAM-1

更新于：2024-11-01

基本信息

关联

项与 LCN2 x ICAM-1 相关的药物

ICAM-Lcn2-LP

靶点

ICAM-1 x LCN2

作用机制

ICAM-1抑制剂 [+1]

在研机构

Harvard Medical School [+2]

原研机构

The Children's Hospital Corp.

在研适应症

三阴性乳腺癌

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 LCN2 x ICAM-1 相关的临床结果

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100 项与 LCN2 x ICAM-1 相关的转化医学

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0 项与 LCN2 x ICAM-1 相关的专利（医药）

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项与 LCN2 x ICAM-1 相关的文献（医药）

2024-12-01·Experimental Neurology

Reactive astrocytes generated from human iPSC are pro-inflammatory and display altered metabolism

Article

作者: Lane, Jon D. ; Boyle, Noreen T. ; McComish, Sarah F. ; Lane, Jon D ; Crompton, Lucy A. ; Caldwell, Maeve A ; O'Sullivan, Julia ; Imiolek, Magdalena ; Caldwell, Maeve A. ; Boyle, Noreen T ; O’Sullivan, Julia ; Crompton, Lucy A ; McComish, Sarah F ; Copas, Adina Mac Mahon

Astrocytes are the most abundant type of glial cell in the central nervous system and they play pivotal roles in both normal health and disease. Their dysfunction is detrimental to many brain related pathologies. Under pathological conditions, such as Alzheimer's disease, astrocytes adopt an activated reactive phenotype which can contribute to disease progression. A prominent risk factor for many neurodegenerative diseases is neuroinflammation which is the purview of glial cells, such as astrocytes and microglia. Human in vitro models have the potential to reveal relevant disease specific mechanisms, through the study of individual cell types such as astrocytes or the addition of specific factors, such as those secreted by microglia. The aim of this study was to generate human cortical astrocytes, in order to assess their protein and gene expression, examine their reactivity profile in response to exposure to the microglial secreted factors IL-1α, TNFα and C1q and assess their functionality in terms of calcium signalling and metabolism. The successfully differentiated and stimulated reactive astrocytes display increased IL-6, RANTES and GM-CSF secretion, and increased expression of genes associated with reactivity including, IL-6, ICAM1, LCN2, C3 and SERPINA3. Functional assessment of these reactive astrocytes showed a delayed and sustained calcium response to ATP and a concomitant decrease in the expression of connexin-43. Furthermore, it was demonstrated these astrocytes had an increased glycolytic capacity with no effect on oxidative phosphorylation. These findings not only increase our understanding of astrocyte reactivity but also provides a functional platform for drug discovery.

2024-08-01·MedComm

Single‐cell RNA sequencing reveals reduced intercellular adhesion molecule crosstalk between activated hepatic stellate cells and neutrophils alleviating liver fibrosis in hepatitis B virus transgenic mice post menstrual blood‐derived mesenchymal stem cell transplantation

Article

作者: Wen, Zuoshi ; Izawa, Hiromi ; Fang, Yangxin ; Yan, Huadong ; Fu, Jiamin ; Xu, Zhenyu ; Zhang, Ning ; Huang, Yuqi ; Yuan, Li ; Xiang, Charlie ; Li, Hang ; Zhang, Qi ; Yuan, Yin ; Qu, Jingjing ; Chen, Lijun ; Li, Lanjuan ; Chen, Lu ; Li, Yifei

AbstractLiver fibrosis can cause hepatitis B virus (HBV)‐associated hepatocellular carcinoma. Menstrual blood‐derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single‐cell RNA sequencing (scRNA‐seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV‐Tg) mouse model of carbon tetrachloride (CCl4)‐induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA‐bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA‐seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV‐associated liver fibrosis.

2024-02-01·Journal of Pharmacological Sciences

CU06-1004 alleviates oxidative stress and inflammation on folic acid-induced acute kidney injury in mice

Article

作者: Kwon, Young-Guen ; Kim, Yeomyeong ; Bae, Cho-Rong

PURPOSEAcute kidney injury (AKI) is characterized by reduced renal function, oxidative stress, inflammation, and renal fibrosis. CU06-1004, an endothelial cell dysfunction blocker, exhibits anti-inflammatory effects by reducing vascular permeability in pathological conditions. However, the potential effects of CU06-1004 on AKI have not been investigated. We investigated the renoprotective effect of CU06-1004 against oxidative stress, inflammation, and fibrotic changes in a folic acid-induced AKI model.METHODSAKI was induced by intraperitoneal injection of high dose (250 mg/kg) folic acid in mice. CU06-1004 was orally administered a low (10 mg/kg) or high dose (20 mg/kg).RESULTSCU06-1004 ameliorated folic acid-induced AKI by decreasing serum blood urea nitrogen and creatinine levels, mitigating histological abnormalities, and decreasing tubular injury markers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in folic acid-induced AKI mice. Additionally, CU06-1004 alleviated folic acid-induced oxidative stress by reducing 4-hydroxynonenal and malondialdehyde levels. Furthermore, it attenuated macrophage infiltration and suppressed the expression of the proinflammatory factors, including tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion protein-1. Moreover, CU06-1004 mitigated folic acid-induced tubulointerstitial fibrosis by decreasing α-smooth muscle actin and transforming growth factor-β expression.CONCLUSIONThese findings suggest CU06-1004 as a potential therapeutic agent for folic acid-induced AKI.