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Protein arginine deiminase 4 (PAD4) plays an important role in cancer progression by participating in gene regulation, protein modification, and neutrophil extracellular trap (NET) formation. Many reversible and irreversible PAD4 inhibitors have been reported recently. In this review, we summarize the structure-activity relationships of newly investigated PAD4 inhibitors to bring researchers up to speed by guiding and describing new scaffolds as optimization and development leads for new effective, safe, and selective cancer treatments. In addition, some recent reports have shown evidence that PAD4 inhibitors are expected to trigger antitumor immune responses, regulate immune cells and related immune factors, enhance the effects of immune checkpoint inhibitors, and enhance their antitumor efficacy. Therefore, PAD4 inhibitors may potentially change tumor immunotherapy and provide an excellent direction for the development and clinical application of immunotherapy strategies for related diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10975299 | PMC |
http://dx.doi.org/10.3390/pharmaceutics16030335 | DOI Listing |
PLoS One
September 2025
Department of Cardiac Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Background: Cardiac ischemia reperfusion (I/R) injury is a serious consequence of reperfusion therapy for myocardial infarction (MI). Peptidylarginine deiminase 4 (PAD4) is a calcium-dependent enzyme that catalyzes the citrullination of proteins. In previous studies, PAD4 inhibition protected distinct organs from I/R injury by preventing the formation of neutrophil extracellular traps (NETs) and attenuating inflammatory responses.
View Article and Find Full Text PDFRev Cardiovasc Med
August 2025
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, 453003 Xinxiang, Henan, China.
Myocarditis is a life-threatening inflammatory disorder that affects the cardiac muscle tissue. Current treatments merely regulate heart function but fail to tackle the root cause of inflammation. In myocarditis, the initial wave of inflammation is characterized by the presence of neutrophils.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China; Department of Pharmacology, School of Basic Medical Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China; State Key Laboratory for
Tacrolimus is widely used to prevent post-transplant acute kidney injury (AKI) but causes severe toxicities (e.g., nephrotoxicity, hyperglycemia).
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 2025
Intensive Care Unit, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, Hubei, China; Hubei Province Academy of Traditional Chinese Medicine, Wuhan, 430061, Hubei, China. Electronic address:
Background: Coxsackievirus B3 (CVB3) infection is a common cause of myocarditis, and the resulting inflammatory response and cellular damage can lead to severe cardiac dysfunction. Astragaloside IV (AS-IV), a natural compound with anti-inflammatory and antiviral properties, has shown potential therapeutic value in various inflammatory and immune-related diseases. Our study aims to explore the potential effects and underlying mechanisms of AS-IV in CVB3-induced viral myocarditis (VMC).
View Article and Find Full Text PDFBurns Trauma
July 2025
Department of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing 400042, China.
Sepsis, a life-threatening syndrome driven by dysregulated immune responses to infection, presents significant global health challenges with high mortality rates. Neutrophil extracellular traps (NETs), composed of deoxyribonucleic acid and antimicrobial proteins, play a dual role in sepsis pathogenesis. While NETs trap pathogens and enhance immune responses via antimicrobial activity and immune cell activation, their overproduction exacerbates tissue damage, coagulopathy, and organ dysfunction.
View Article and Find Full Text PDF