Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis

Yan, Zhengzheng; Luo, Haihua; Xie, Bingyao; Tian, Tian; Li, Shan; Chen, Zhixia; Liu, Jinghua; Zhao, Xuwen; Zhang, Liyong; Deng, Yongqiang; Billiar, Timothy R.; Jiang, Yong

doi:10.1038/s41467-020-20577-3

Cited by 33 publications

(23 citation statements)

References 65 publications

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“…The study by Yan et al shed light on the development of LCP2-targeted therapeutics for sepsis and revealed the important function of LCP2 in RAGE-mediated proinflammatory signaling. 22 The immune system plays a critical role after tumor occurrence, and tumor development is a multi-gene and multi-stage process that includes important contributions of oncogenes and tumor suppressor genes. Thus, the role of LCP2 in LUAD cells and the tumor microenvironment still needs to be further explored in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

et al. 2021

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Objective Lymphocyte cytosolic protein 2 (LCP2) is often ectopically expressed in various human tumors. However, the clinical significance and role of LCP2 in lung adenocarcinoma (LUAD) remain unclear. This study explored the prognostic significance of LCP2 in LUAD patients. Methods LCP2 expression in LUAD tissues was analyzed using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Western blotting was employed to detect LCP2 expression in LUAD. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore signaling pathways mediated by LCP2 co-regulatory genes. Immunohistochemistry was used to examine levels of LCP2 and programmed death ligand 1 (PD-L1) in 68 LUAD patients. Associations between LCP2 expression and clinicopathological features, prognoses, and PD-L1 levels among the LUAD in-patients were analyzed. Results Among the 68 LUAD in-patients, LCP2 expression was correlated with clinical stage and lymph node metastasis. LUAD patients with high LCP2 expression were associated with increased overall survival. LCP2 expression may be associated with an enrichment of several immune functions. Moreover, our immunohistochemistry results demonstrated that LCP2 expression was positively correlated with PD-L1 expression in LUAD tissues. Conclusions In the study, LCP2 was found to be a favorable prognostic biomarker in LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

et al. 2021

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“…CLP was performed to induce sepsis in mice as previously described [ 23 , 24 ]. In brief, The mice were anesthetized with 2% isoflurane and fixed on a 37 °C operating platform.…”

Section: Methodsmentioning

confidence: 99%

Luteolin improves vasoconstriction function and survival of septic mice via AMPK/NF-κB pathway

Liu

Su²

2023

Heliyon

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“…The operation details for the PlexArray HT were as described previously. 65 The purified protein samples were prepared at determined concentrations in PBS running buffer, while glycine-HCl buffer (10 mmol/L, pH 2.0) was used for regeneration. Binding data were collected and analyzed by SPR Data Analysis Module software (Plexera, USA).…”

Section: Methodsmentioning

confidence: 99%

Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach

Zhang

Luo

et al. 2022

Sig Transduct Target Ther

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Effectively killing pathogenic bacteria is key for the treatment of sepsis. Although various anti-infective drugs have been used for the treatment of sepsis, the therapeutic effect is largely limited by the lack of a specific bacterium-targeting delivery system. This study aimed to develop antibacterial peptides that specifically target pathogenic bacteria for the treatment of sepsis. The lethal bacterial strain Escherichia coli MSI001 was isolated from mice of a cecal ligation and puncture (CLP) model and was used as a target to screen bacterial binding heptapeptides through an integrative bioinformatics approach based on phage display technology and high-throughput sequencing (HTS). Heptapeptides binding to E. coli MSI001 with high affinity were acquired after normalization by the heptapeptide frequency of the library. A representative heptapeptide VTKLGSL (VTK) was selected for fusion with the antibacterial peptide LL-37 to construct the specific-targeting antibacterial peptide VTK-LL37. We found that, in comparison with LL37, VTK-LL37 showed prominent bacteriostatic activity and an inhibitive effect on biofilm formation in vitro. In vivo experiments demonstrated that VTK-LL37 significantly inhibited bacterial growth, reduced HMGB1 expression, alleviated lesions of vital organs and improved the survival of mice subjected to CLP modeling. Furthermore, membrane DEGP and DEGQ were identified as VTK-binding proteins by proteomic methods. This study provides a novel strategy for targeted pathogen killing, which is helpful for the treatment of sepsis in the era of precise medicine.

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Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis

Cited by 33 publications

References 65 publications

Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma

Luteolin improves vasoconstriction function and survival of septic mice via AMPK/NF-κB pathway

Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach

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