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Sepsis is a complex disorder related to dysregulation of the host response to infection and is a major health problem worldwide owing to its high mortality rates. However, the exact mechanisms causing sepsis remains unclear because of the complexity of the underlying pathways. Dysregulation of non-canonical NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation induces septic shock by promoting pyroptosis and pro-inflammatory cytokine production (e.g., interleukin-1β) via caspase-11 and Gasdermin-D. Herein, we describe a rapid, simple method for evaluation of the degree of sepsis by investigating non-canonical inflammasome activation in both in vitro and in vivo models. The method is expected to be useful for testing and screening drugs for the treatment of sepsis.
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http://dx.doi.org/10.1007/978-1-0716-2144-8_14 | DOI Listing |
J Biochem Mol Toxicol
September 2025
Department of Anesthesiology, Qianjiang Maternal and Child Health and Family Planning Service Centre, Qianjiang, Hubei, China.
Acute lung injury (ALI) is a major contributor to the high morbidity and mortality associated with intestinal ischemia-reperfusion (II/R). Despite its severity, current clinical management of ALI remains limited to supportive care without addressing the cause of the disease, underscoring the urgent need to investigate the underlying mechanism and develop targeted therapies. In this study, we employed both in vitro and in vivo models to explore ALI in the setting of II/R.
View Article and Find Full Text PDFRSC Med Chem
September 2025
NodThera Ltd. Suite 8, The Mansion, Chesterford Research Park, Little Chesterford, Saffron Walden Essex CB10 1XL UK
Inhibition of the NLRP3 inflammasome has emerged as a high potential treatment paradigm for the treatment of neuroinflammation, with demonstrated anti-neuroinflammatory effects in Parkinson's disease patients and a strong rationale in Alzheimer's disease and amyotrophic lateral sclerosis. To facilitate further progress in this field, brain penetrant NLRP3 inflammasome inhibitors as leads and tool compounds are required. We discovered a small molecule NLRP3 inflammasome inhibitor, NT-0527 (11), and extensively profiled this to reveal a highly potent, selective and brain penetrant compound.
View Article and Find Full Text PDFFerroptosis, an iron-dependent cell death pathway driven by lipid peroxidation, has emerged as a critical pathophysiological mechanism linking cancer and inflammatory diseases. The seemingly distinct pathologies exhibit shared microenvironmental hallmarks-oxidative stress, immune dysregulation, and metabolic reprogramming-that converge on ferroptosis regulation. This review synthesizes how ferroptosis operates at the intersection of these diseases, acting as both a tumor-suppressive mechanism and a driver of inflammatory tissue damage.
View Article and Find Full Text PDFMedComm (2020)
September 2025
The activation of nucleotide oligomerization domain-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is implicated in the pathogenesis of various inflammatory diseases. The natural product oridonin possesses a novel mechanism for NLRP3 inhibition and a unique binding mode with NLRP3, but its poor anti-inflammatory activity limits further application. After virtual screening of diverse natural product libraries, dehydrocostus lactone (DCL) was considered as a potential NLRP3 inhibitor.
View Article and Find Full Text PDFFront Pharmacol
August 2025
The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
Hyperuricemia (HUA) is a prevalent metabolic disorder driven by dysregulated purine metabolism and impaired urate excretion, and robust animal models are critical for elucidating its pathophysiology and guiding therapy development. This review systematically examines chemically induced, gene-edited, environmental, exercise and microbiota-based HUA models across rodents, poultry, primates, zebrafish and silkworms, highlighting each model's strengths and limitations in mimicking human uric acid handling. We discuss how these models have validated standard urate-lowering treatments-such as xanthine oxidase inhibitors and uricosurics-and uncovered emerging therapeutic targets, including the gut-NLRP3 inflammasome axis and SIRT1-mediated ABCG2 regulation.
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