Article
Chemistry, Medicinal
Yingjun Cui, Mengyi Zhang, Honglei Xu, Tingrong Zhang, Songming Zhang, Xiuhe Zhao, Peng Jiang, Jing Li, Baijun Ye, Yuanjun Sun, Mukuo Wang, Yangping Deng, Qing Meng, Yang Liu, Qiang Fu, Jianping Lin, Liang Wang, Yue Chen
Summary: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common complication in COVID-19. The natural macrocyclic peptide CTL-A has been identified as a potential elastase inhibitor for preventing ALI/ARDS. The first total synthesis of CTL-A was achieved in 24 steps, and preliminary structure-activity relationships were elucidated. In vivo studies using an ALI mouse model demonstrated that CTL-A effectively alleviated acute lung injury, outperforming the approved elastase inhibitor sivelestat. The findings highlight the potential of CTL-A as a candidate for COVID-19 pathogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Yali Sun, Xianfei Ding, Yuqing Cui, Hongyi Li, Dong Wang, Huoyan Liang, Shaohua Liu, Xiaojuan Zhang, Haixu Wang, Tongwen Sun
Summary: This study demonstrates that the administration of Sivelestat in septic rats can improve survival, gut microbiota composition, and associated metabolites, providing new options for sepsis treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yukino Ogura, Kazuko Tajiri, Nobuyuki Murakoshi, DongZhu Xu, Saori Yonebayashi, Siqi Li, Yuta Okabe, Duo Feng, Yuzuno Shimoda, Zoughu Song, Haruka Mori, Zixun Yuan, Kazutaka Aonuma, Masaki Ieda
Summary: The study investigated the role of neutrophil elastase (NE) in the pathogenesis of myocardial infarction (MI) in mice. NE deficiency or inhibition improved survival and cardiac function post-MI, limited fibrosis, reduced heart-infiltrating neutrophils and inflammatory macrophages, and decreased apoptotic cells in the heart. NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling, suggesting that inhibition of NE could be a novel therapeutic target in the treatment of MI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Yanjun Wu, Hongmei Huang, Jiayun Wu, Yiru Qin, Na Zhao, Baowei Chen, Qiying Nong, Yongshun Huang, Ligang Hu
Summary: This study investigates the mechanism of lead-induced myocardial injury and finds that neutrophil degranulation plays a significant role in this process. The findings suggest that lead exposure can initiate early myocardial injury by promoting neutrophil degranulation.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Medicine, Research & Experimental
Baoer Liu, Brice Korkmaz, Patricia Kraft, Tobias Mayer, Alex A. Sayour, Marc A. Grundl, Roxane Domain, Matthias Karck, Gabor Szabo, Sevil Korkmaz-Icoez
Summary: This study demonstrated that the pharmacological inhibition of cathepsin C (CatC) with BI-9740 improves graft function after heart transplantation in rats. By reducing the proteolytic activity of neutrophil elastase, ameliorating histopathological lesions and inflammatory cell infiltration, improvements were observed in both systolic and diastolic function of the transplanted hearts. Additionally, BI-9740 also shortened the graft re-beating time.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Chun-Lian Wang, Yan Wang, Qi-Lan Jiang, Yang Zeng, Qing-Ping Yao, Xing Liu, Tao Li, Jun Jiang
Summary: The study aimed to investigate the effects of recombinant DNase I and sivelestat on the elimination of NETs and their impact on IRI in hindlimbs. The results showed that both DNase I and moderate doses of sivelestat could eliminate IRI-induced NETs, improve hindlimb perfusion and angiogenesis, prevent muscle fibrosis, and enhance motor function. Appropriate administration mode and dosage are crucial for the prevention of IRI by eliminating NETs, with topical administration of DNase I being more effective and intravenous administration of sivelestat being more beneficial. These findings provide a better treatment strategy for IRI in clinical practice.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Review
Cell Biology
Nan Zhang, Xiahenazi Aiyasiding, Wen-jing Li, Hai-han Liao, Qi-zhu Tang
Summary: Myocardial infarction is a common and life-threatening cardiac emergency. Neutrophils, through the release of granule proteins, play an important role in the inflammation and immune response associated with myocardial infarction.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Chemistry, Multidisciplinary
Angelique Rivot, Natacha Jugniot, Samuel Jacoutot, Nicolas Vanthuyne, Philippe Massot, Philippe Mellet, Sylvain R. A. Marque, Gerard Audran, Pierre Voisin, Marie Delles, Gilles Devouassoux, Eric Thiaudiere, Abderrazzak Bentaher, Elodie Parzy
Summary: The study suggests using OMRI in mice to evaluate protease activity in the lungs, finding an increase in proteolysis in LPS-induced inflammation. This preclinical detection method may open new avenues for diagnosis and in vivo antiprotease testing.
Article
Medicine, Research & Experimental
Kunsheng Li, Pengyu Zhou, Jie Li, Yongqing Cheng, Shiliang Li, Yumeng Wang, Weipeng Jiang, Yang Bai, Hailong Cao, Dongjin Wang
Summary: The expression and function of P2Y14 receptor in neutrophils after myocardial infarction/reperfusion (MIR) injury were investigated. The results showed that P2Y14 receptor is involved in the regulation of inflammation in the infarct area after MIR, and it establishes a novel signaling pathway concerning the interplay between cardiomyocytes and neutrophils in the heart tissue.
Article
Urology & Nephrology
Aykut Colakerol, Serhat Suzan, Mustafa Zafer Temiz, Serkan Gonultas, Serdar Aykan, Sule Ozsoy, Suat Hayri Kucuk, Emrah Yuruk, Engin Kandirali, Atilla Semercioz
Summary: The study investigated the impact of extracorporeal shock wave lithotripsy (ESWL) on rat kidney damage, revealing significant tissue inflammation and damage in the early stage, with the use of the NE inhibitor sivelestat significantly reducing the ESWL-induced kidney injury.
Article
Biochemistry & Molecular Biology
Lorenza Marinaccio, Azzurra Stefanucci, Giuseppe Scioli, Alice Della Valle, Gokhan Zengin, Angelo Cichelli, Adriano Mollica
Summary: This review provides an overview of the latest advancements in peptide human neutrophil elastase inhibitors isolated from natural sources, including their identification, structures, and mechanisms of action. These inhibitors play a significant role in the development of potent bioactive compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Min Liu, Siyi Liu, Lin Liu, Jingya Xiu, Tian Zhang, Dawei Chen, Mingxi Qiao, Haiyang Hu, Jiulong Zhang, Xiuli Zhao
Summary: Rheumatoid arthritis (RA) is characterized by inflammation outbreak and joint destruction. Neutrophils play a crucial role in RA by releasing excess neutrophil extracellular traps (NETs), but preventing NETs formation is still challenging. In this study, a method using sivelestat-conjugated bovine serum albumin nanoparticles (BTST NPs) was established to selectively inhibit neutrophil elastase (NE) and prevent NETs production. Additionally, the BTST NPs were loaded with dexamethasone palmitate (DP) for synergistic treatment of RA. The results showed that DP/BTST NPs could effectively target inflamed neutrophils, hinder NETs generation, and improve RA symptoms.
Article
Gastroenterology & Hepatology
Qin Tan, Xiao Ma, Bing Yang, Ye Liu, Yibin Xie, Xijun Wang, Wei Yuan, Jie Ma
Summary: This study reveals the pathogenic mechanism of the periodontal pathogen P. gingivalis in pancreatic cancer. The study found that P. gingivalis is present in both the oral cavity and tumor tissues of PC patients. When exposed to P. gingivalis, tumor development is accelerated and the cancerous pancreas exhibits a neutrophils-dominated inflammatory environment.
Article
Chemistry, Multidisciplinary
Maria R. Rios, Gloria Garoffolo, Giulia Rinaldi, Alicia Megia-Fernandez, Silvia Ferrari, Calum T. Robb, Adriano G. Rossi, Maurizio Pesce, Mark Bradley
Summary: A highly sensitive optical probe for the detection of activated neutrophils and NETs was reported in this study. This probe, based on a triple-quenched, super-silent tri-branched structure, showed a >20 fold increase in fluorescence upon cleavage. It was highly specific for human neutrophil elastase and successfully detected NETosis and neutrophil activation in in vitro differentiated neutrophils and isolated human neutrophils.
CHEMICAL COMMUNICATIONS
(2021)
Article
Neurosciences
Ichiro Horinokita, Hideki Hayashi, Rihona Yoshizawa, Mika Ichiyanagi, Yui Imamura, Yui Iwatani, Norio Takagi
Summary: The study found that the inhibition of PGRN cleavage, rather than direct action, can suppress post-ischemic inflammation, potentially establishing a new approach for cerebral ischemia treatment.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)