Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice

Wu, Yi‐Long; Ou, Weijie; Zhong, Ming; Lin, Su; Zhu, Yueyong

doi:10.14218/jcth.2021.00560

Cited by 14 publications

(12 citation statements)

References 32 publications

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“…aureus and E. coli, employing necrosulfonamide (NSA) as a GSDMD-NT protein inhibitor, to evaluate the antimicrobial effect of GSDMD-NT protein . The results obtained from SPM for assessing CFUs revealed significant antimicrobial effects in the PCZs and PCZs + NIR treatment groups, while the addition of NSA diminished the antimicrobial effect but still remained higher than that of the Control group (Figure j,k).…”

Section: Results and Discussionmentioning

confidence: 98%

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery

Wang,

Zhang,

Liu

et al. 2024

ACS Nano

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There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a proefferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.

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Section: Results and Discussionmentioning

confidence: 98%

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery

Wang,

Zhang,

Liu

et al. 2024

ACS Nano

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“…Another study indicates that NSA inhibits the pyroptosis pathway in ALF, leading to an increased survival rate in ALF mice. However, the study did not determine whether these pyroptotic cells are primarily hepatocytes or macrophages ( 116 ). Therefore, targeting GSDMD-NT oligomerization has shown promising results in inflammatory and autoimmune liver diseases.…”

Section: Targeted Inhibition Of Macrophage Pyroptosis In the Treatmen...mentioning

confidence: 99%

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Ni,

Chen,

Zhao

et al. 2024

Front. Immunol.

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Macrophages play a critical role in innate immunity, with approximately 90% of the total macrophage population in the human body residing in the liver. This population encompasses both resident and infiltrating macrophages. Recent studies highlight the pivotal role of liver macrophages in various aspects such as liver inflammation, regeneration, and immune regulation. A novel pro-inflammatory programmed cell death, pyroptosis, initially identified in macrophages, has garnered substantial attention since its discovery. Studies investigating pyroptosis and inflammation progression have particularly centered around macrophages. In liver diseases, pyroptosis plays an important role in driving the inflammatory response, facilitating the fibrotic process, and promoting tumor progression. Notably, the role of macrophage pyroptosis cannot be understated. This review primarily focuses on the role of macrophage pyroptosis in liver diseases. Additionally, it underscores the therapeutic potential inherent in targeting macrophage pyroptosis.

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“…Recent evidence has challenged the specificity of necrosulfonamide by showing that in addition to MLKL-mediated necroptosis, necrosulfonamide also inhibits GSDMD-induced pyroptosis (144). Following this report, several studies showed that necrosulfonamide prevented disease outcomes in mouse models of diseases such as acute brain injury, colitis, acute liver failure, and myocardial dysfunction due to its pyroptosis inhibitory effects (144)(145)(146)(147). Recently, a new class of xanthine and uracil derivatives has been reported to stabilize the inactive state of MLKL, thereby inhibiting MLKL oligomerization and membrane translocation, but their precise mechanism of action, in vivo safety, and off-target effects remain to be elucidated (148,149).…”

Section: Mlkl As a Potential Future Therapeutic Targetmentioning

confidence: 99%

Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases

et al. 2023

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A delicate balance between programmed cell death and proliferation of intestinal epithelial cells (IEC) exists in the gut to maintain homeostasis. Homeostatic cell death programs such as anoikis and apoptosis ensure the replacement of dead epithelia without overt immune activation. In infectious and chronic inflammatory diseases of the gut, this balance is invariably disturbed by increased levels of pathologic cell death. Pathological forms of cell death such as necroptosis trigger immune activation barrier dysfunction, and perpetuation of inflammation. A leaky and inflamed gut can thus become a cause of persistent low-grade inflammation and cell death in other organs of the gastrointestinal (GI) tract, such as the liver and the pancreas. In this review, we focus on the advances in the molecular and cellular understanding of programmed necrosis (necroptosis) in tissues of the GI tract. In this review, we will first introduce the reader to the basic molecular aspects of the necroptosis machinery and discuss the pathways leading to necroptosis in the GI system. We then highlight the clinical significance of the preclinical findings and finally evaluate the different therapeutic approaches that attempt to target necroptosis against various GI diseases. Finally, we review the recent advances in understanding the biological functions of the molecules involved in necroptosis and the potential side effects that may occur due to their systemic inhibition. This review is intended to introduce the reader to the core concepts of pathological necroptotic cell death, the signaling pathways involved, its immuno-pathological implications, and its relevance to GI diseases. Further advances in our ability to control the extent of pathological necroptosis will provide better therapeutic opportunities against currently intractable GI and other diseases.

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Gasdermin D Inhibitor Necrosulfonamide Alleviates Lipopolysaccharide/D-galactosamine-induced Acute Liver Failure in Mice

Cited by 14 publications

References 32 publications

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery

Unveiling the flames: macrophage pyroptosis and its crucial role in liver diseases

Breaking bad: necroptosis in the pathogenesis of gastrointestinal diseases

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