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
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)
Article
Multidisciplinary Sciences
Wenjun Li, Yuriko Terada, Yulia Y. Tyurina, Vladimir A. Tyurin, Amit Bery, Jason M. Gauthier, Ryuji Higashikubo, Alice Y. Tong, Dequan Zhou, Felix Nunez-Santana, Emilia Lecuona, Adil Hassan, Kohei Hashimoto, Davide Scozzi, Varun Puri, Ruben G. Nava, Alexander S. Krupnick, Kory J. Lavine, Andrew E. Gelman, Mark J. Miller, Valerian E. Kagan, Ankit Bharat, Daniel Kreisel
Summary: Ischemia reperfusion injury is a common pathological condition triggered by the release of endogenous ligands. In this study, the researchers discovered that necroptosis, a nonapoptotic form of cell death, triggers the recruitment of neutrophils in injured lungs. Initially, neutrophils traffic predominantly to subpleural vessels, guided by chemoattractants produced by nonclassical monocytes. The disruption of pulmonary capillaries by neutrophils leads to vascular leakage and impaired graft function. The study also found that TLR4 signaling and NADPH oxidase 4 expression mediate the arrest of neutrophils, preventing their extravasation. The formation of neutrophil extracellular traps in injured lungs can be disrupted with DNase to prevent vascular leakage and improve graft dysfunction. These findings could have important implications for the development of therapeutics to protect lungs from ischemia reperfusion injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
Immunology
Seok-Joo Kim, Agostina Carestia, Braedon McDonald, Amanda Z. Zucoloto, Heidi Grosjean, Rachelle P. Davis, Madison Turk, Victor Naumenko, Silvio Antoniak, Nigel Mackman, Mohamed Sarjoon Abdul-Cader, Mohamed Faizal Abdul-Careem, Morley D. Hollenberg, Craig N. Jenne
Summary: Influenza A virus infection leads to excessive inflammation and tissue pathology in the lungs, with platelets and neutrophils playing a key role in the pathogenesis, while protease-activated receptor 4 (PAR4) is crucial in this process.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Shijie Qiu, Xuyi Li, Jingyan Zhang, Pilong Shi, Yonggang Cao, Yongzhi Zhuang, Liquan Tong
Summary: The study prepared nano-taurine by coating taurine with neutrophil membranes, and demonstrated that nano-taurine can treat hepatic ischemia-reperfusion injury by inhibiting inflammation, oxidative stress, and ferroptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Zheng Zhang, Xiaoyan Miao, Weifeng Yao, Jie Ren, Chaojin Chen, Xiang Li, Jing Yang, Yujia You, Yuejun Lin, Tinghui Yin, Ziqing Hei
Summary: This study successfully developed a non-invasive, highly accurate, and specific method for detecting hepatic ischemia-reperfusion injury (HIRI) by creating neutrophil biomimetic microbubbles (MBneu). The MBneu retained neutrophil proteins, targeted inflamed hepatic tissue, and exhibited physicochemical properties typical of liposome-based microbubbles. The molecular ultrasound imaging of HIRI using MBneu may have promising applications in different clinical scenarios with various cell types in the future.
Article
Medicine, General & Internal
Janina Praxenthaler, Carmen Kirchner, Elke Schwier, Simon Altmann, Axel Wittmer, Dietrich Henzler, Thomas Koehler
Summary: Gut ischemia is a frequent but underdiagnosed complication. We report a case in which intravital microscopy was used for early diagnosis of mesenteric ischemia, and discuss the value and clinical perspective of this technique in intensive care.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Shaoyong Zhuang, Shengqiang Xia, Peiqi Huang, Jiajin Wu, Junwen Qu, Ruoyang Chen, Nan Sun, Dawei Li, Haoyu Wu, Ming Zhang, Jianjun Zhang, Xiaodong Yuan, Xu Wang
Summary: Renal ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury, with mechanisms not fully elucidated. Results from RNA sequencing showed disrupted mitochondrial dynamics and upregulated expression of P2RX1 in renal IRI. P2RX1 promoted the formation of NETs, leading to impairment of mitochondrial dynamics.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Nidhi Sharma, Taslim B. Shaikh, Abhisheik Eedara, Madhusudhana Kuncha, Ramakrishna Sistla, Sai Balaji Andugulapati
Summary: Dehydrozingerone (DHZ) attenuates liver fibrosis by reducing fibrotic markers and their activities through modulation of the MAPK pathway. These findings suggest that DHZ may be a potential therapeutic molecule for treating liver fibrosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
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
Gastroenterology & Hepatology
Hamza O. Yazdani, Christof Kaltenmeier, Kristin Morder, Juik Moon, Madelyn Traczek, Patricia Loughran, Ruben Zamora, Yoram Vodovotz, Feng Li, James H-C. Wang, David A. Geller, Richard L. Simmons, Samer Tohme
Summary: Exercise training preconditioning mitigates the inflammatory response to liver ischemia/reperfusion injury, protecting the liver from injury and metastases. By reducing neutrophil infiltration and NET formation, exercise training alters the complexity of hepatic inflammatory mediator networks and promotes an increase in tumor-suppressing T cells within the tumor microenvironment.
Article
Medicine, Research & Experimental
Zexin Li, Ying Wang, Yu Zhang, Xiao Wang, Baoqin Gao, Yan Li, Rong Li, Jianguo Wang
Summary: Fisetin was found to alleviate liver damage, cell apoptosis, and oxidative stress induced by liver IRI, at least through the Nrf2/HO-1 signaling pathway, suggesting its potential as a targeted drug for liver IRI treatment.
ARCHIVES OF MEDICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Carlos Andres Pantanali, Vinicius Rocha-Santos, Marcia Saldanha Kubrusly, Inar Alves Castro, Luiz Augusto Carneiro-D'Albuquerque, Flavio Henrique Galvao
Summary: Nutraceuticals are bioactive compounds found in food that can improve health, prevent diseases, and support the normal functioning of the human body. They are able to target multiple pathways, acting as antioxidants, anti-inflammatory agents, and immune response and cell death modulators. This study investigated the effect of a nutraceutical solution on liver ischemia-reperfusion injury (IRI), and found that it decreased apoptosis and histologic injury in liver tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)