Targeting novel regulated cell death：Ferroptosis, pyroptosis, and autophagy in sepsis-associated encephalopathy

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116453 - 116453

Опубликована: Март 20, 2024

Sepsis-associated encephalopathy (SAE), a common neurological complication of sepsis, is heterogenous complex clinical syndrome caused by the dysfunctional response host to infection. This leads excess mortality and morbidity worldwide. Despite relevance with high incidence, there lack understanding for its both acute/chronic pathogenesis therapeutic management. A better molecular mechanisms behind SAE may provide tools enhance efficacy. Mounting evidence indicates that some types non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis, autophagy, contribute SAE. Targeting these RCD meaningful targets future treatments against review summarizes core mechanism which We focus on emerging compounds can inhibit delineate their beneficial pharmacological effects Within this we suggest inhibition serve potential strategy

Язык: Английский

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Puerarin—A Promising Flavonoid: Biosynthesis, Extraction Methods, Analytical Techniques, and Biological Effects

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(10), С. 5222 - 5222

Опубликована: Май 10, 2024

Flavonoids, a variety of plant secondary metabolites, are known for their diverse biological activities. Isoflavones subgroup flavonoids that have gained attention potential health benefits. Puerarin is one the bioactive isoflavones found in Kudzu root and Pueraria genus, which widely used alternative Chinese medicine, has been to be effective treating chronic conditions like cardiovascular diseases, liver gastric respiratory diabetes, Alzheimer’s disease, cancer. extensively researched both scientific clinical studies over past few years. The purpose this review provide an up-to-date exploration puerarin biosynthesis, most common extraction methods, analytical techniques, effects, new perspective medical pharmaceutical research development.

Язык: Английский

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Fuling-Zexie formula attenuates hyperuricemia-induced nephropathy and inhibits JAK2/STAT3 signaling and NLRP3 inflammasome activation in mice

Journal of Ethnopharmacology, Год журнала: 2023, Номер 319, С. 117262 - 117262

Опубликована: Окт. 1, 2023

Язык: Английский

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The food and medicine homologous Chinese Medicine from Leguminosae species: A comprehensive review on bioactive constituents with neuroprotective effects on nervous system

Food & medicine homology., Год журнала: 2024, Номер 2(2), С. 9420033 - 9420033

Опубликована: Сен. 4, 2024

Язык: Английский

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ACE2 Rescues Sepsis-Associated Encephalopathy by Reducing Inflammation, Oxidative Stress, and Neuronal Apoptosis via the Nrf2/Sestrin2 Signaling Pathway

Molecular Neurobiology, Год журнала: 2024, Номер unknown

Опубликована: Март 27, 2024

Язык: Английский

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Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Foods, Год журнала: 2024, Номер 13(4), С. 591 - 591

Опубликована: Фев. 15, 2024

Background: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized hesperitin (Hsp)-Cu(II) complex and found that possessed strong uric acid (UA)-reducing activity vitro. In this study we further explored complex’s UA-lowering nephroprotective effects vivo. Methods: A mouse with HUA was used to investigate hypouricemic via biochemical analysis, RT-PCR, Western blot. Results: Hsp-Cu(II) markedly decreased serum UA level restored kidney tissue damage normal mice. Meanwhile, inhibited liver adenosine deaminase (ADA) xanthine oxidase (XO) activities reduce synthesis modulated protein expression urate transporters promote excretion. treatment significantly suppressed oxidative stress inflammatory kidney, reduced contents cytokines activation nucleotide-binding oligomerization domain (NOD)-like receptor thermal associated 3 (NLRP3) pathway. Conclusions: protected kidneys from renal by modulating NLRP3 may be promising dietary supplement or nutraceutical for therapy hyperuricemia.

Язык: Английский

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Dichloroacetate Prevents Sepsis Associated Encephalopathy by Inhibiting Microglia Pyroptosis through PDK4/NLRP3

Inflammation, Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

Dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, is often used to treat lactic acidosis and malignant tumors. Increasing studies have shown that DCA has neuroprotective effects. Here, we explored the role mechanism of in Sepsis associated encephalopathy (SAE). Single-cell analysis was determine important PDK4 SAE identify cell type. GO GSEA were correlation between pyroptosis. Through LPS + ATP stimulation, microglia pyroptosis model established observe expression level intracellular pyroptosis-related proteins under intervention, further detect changes ROS JC-1. Additionally, co-culture environment neuron simply constructed evaluate effect on activated microglia-mediated neuronal apoptosis. Finally, Novel object recognition test Morris water maze explore cognitive function mice from different groups after intervention. Based above experiments, this study concludes can improve ratio peripheral central M1 macrophages, inhibit NLRP3-mediated through mitochondrial membrane potential (MMP). reduce death caused by mice. In SAE, may be candidate drug for treatment neuroinflammation.

Язык: Английский

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The Circadian Clock Gene Bmal1 Regulates Microglial Pyroptosis After Spinal Cord Injury via NF‐κB/MMP9

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(12)

Опубликована: Дек. 1, 2024

ABSTRACT Background The treatment of spinal cord injury (SCI) is usually ineffective, because neuroinflammatory secondary an important cause the continuous development injury, and microglial pyroptosis step neuroinflammation. Recently, Bmal1, a core component circadian clock genes (CCGs), has been shown to play regulatory role in various tissues cells. However, it still unclear whether Bmal1 regulates after SCI. Methods In this study, we established vivo mouse model SCI using knockout (KO) mice wild‐type (WT) mice, lipopolysaccharide (LPS)‐induced BV2 cells as vitro model. A series molecular histological methods were used detect level explore mechanism respectively. Results Both results showed that inhibited NLRP3 inflammasome activation Further analysis pyroptosis‐related proteins (NLRP3, Caspase‐1, ASC, GSDMD‐N) reduced release IL‐18 IL‐1β by inhibiting NF‐κB /MMP9 pathway. It was identified transcription factor promotes expression MMP9, which turn Conclusions Our study initially pathway reduce thereby providing new promising therapeutic target for

Язык: Английский

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Protective Effects of Mdivi‐1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

Neuroinflammation is one of the essential pathogeneses cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots evidences showed microglia presented mitochondrial fragmentation during SAE. This study investigated protective effects and novel mechanisms inhibiting via division inhibitor 1 (Mdivi-1) on in The SAE model was performed by cecal ligation puncture (CLP), Mdivi-1 administrated intraperitoneal injection. Morris water maze to assess function. Mitochondrial morphology observed electron microscope or MitoTracker staining. qRT-PCR, immunofluorescence staining, western blots were used detect inflammatory factors protein content, respectively. Flow cytometry polarization hippocampal microglia. Bioinformatics analysis verify hypotheses. administration alleviated sepsis-induced fragmentation, activation, polarization, damage. neuroinflammation oxidative stress suppressed NF-κB Keap1/Nrf2/HO-1 pathways following administration; meanwhile, pyroptosis reduced, which associated with enhanced autophagosome formation p62 elevation administration. Inhibition beneficial disturbance, are related alleviating neuroinflammation, stress, pyroptosis.

Язык: Английский

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RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 1787 - 1813

Опубликована: Фев. 1, 2025

Abstract: Reversion inducing cysteine rich protein with kazal motifs (RECK), a Kazal motif-containing protein, regulates pro-inflammatory cytokines production, migration of inflammatory cells, vascular endothelial growth factor (VEGF) and Wnt pathways plays critical roles in septic storms dysfunction. Recently, RECK has been defined as the negative regulator adisintegrin metalloproteinases (ADAMs) matrix (MMPs), which are both membrane "molecular scissors" aggravate poor prognosis sepsis. To better understand related mechanisms, we make here systematic in-depth review RECK. We first summarize findings on structural characteristics regulation at transcription, post-transcription, or level Then, discuss inflammation, infection, injury by focusing function ADAMs MMPs, well VEGF, WNT, angiopoietin, notch signaling. In conclusion, participation guardian development sepsis provides insight into strategies precisely intervening dysregulationfor treatment Keywords: RECK, sepsis, regulation, inflammation

Язык: Английский

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