Wolf–Hirschhorn syndrome candidate 1 facilitates alveolar macrophage pyroptosis in sepsis-induced acute lung injury through NEK7-mediated NLRP3 inflammasome activation

Liu, Caixia; Cai, Benlong; Li, Dan; Yao, Yuanxin

doi:10.1177/17534259211035426

Cited by 12 publications

(7 citation statements)

References 27 publications

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“…Additional evidence showed that either CLP or LPS caused macrophage pyroptosis ( 93 , 96 ). Activated NLRP3 forms a protein complex (NLRP3 inflammasome) consisting of NLRP3, ASC and precaspase-1, and activated caspase-1 causes macrophage pyroptosis ( 97 ). To explore how macrophages perceive intracellular LPS and function in the host at the whole body level, Kumari et al ( 98 ) constructed a conditional knockout of caspase-11 from monocytes/macrophages, neutrophils, and dendritic cells in mice, and found that macrophage/monocyte-specific caspase-11 plays a leading role in mediating the pathological manifestations of endotoxemia, including the activation of GSDMD, IL-1β and IL-18, the release of DAMPs and tissue damage, proving that caspase-11 dependent macrophage pyroptosis is pivotal in the development of sepsis.…”

Section: Types Of Programmed Cell Death In Sepsis-akimentioning

confidence: 99%

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Wang

et al. 2021

Front. Med.

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Sepsis is a systemic inflammatory response syndrome caused by infection, following with acute injury to multiple organs. Sepsis-induced acute kidney injury (AKI) is currently recognized as one of the most severe complications related to sepsis. The pathophysiology of sepsis-AKI involves multiple cell types, including macrophages, vascular endothelial cells (ECs) and renal tubular epithelial cells (TECs), etc. More significantly, programmed cell death including apoptosis, necroptosis and pyroptosis could be triggered by sepsis in these types of cells, which enhances AKI progress. Moreover, the cross-talk and connections between these cells and cell death are critical for better understanding the pathophysiological basis of sepsis-AKI. Mitochondria dysfunction and oxidative stress are traditionally considered as the leading triggers of programmed cell death. Recent findings also highlight that autophagy, mitochondria quality control and epigenetic modification, which interact with programmed cell death, participate in the damage process in sepsis-AKI. The insightful understanding of the programmed cell death in sepsis-AKI could facilitate the development of effective treatment, as well as preventive methods.

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Section: Types Of Programmed Cell Death In Sepsis-akimentioning

confidence: 99%

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Wang

et al. 2021

Front. Med.

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“…The LPS‐MH + oe‐NC group received an intratracheal injection of 15 μL of mixed oe‐NC lentivirus solution and Ma Huang‐Apricot Kernel Medicine (9 g:9 g, 4 g/kg), after which they were orally gavaged twice a day with the same mixture for 7 consecutive days. LPS‐MH + oe‐caspase‐3 group (intratracheal injection of 15 μL caspase‐3 lentivirus solution mixed with ephedrine and bitter almond medicine, 9 g: 9 g, 4 g/kg, gavage administration, twice a day for each mouse, continuously for 7 days) (Liu, Cai, et al., 2021).…”

Section: Methodsmentioning

confidence: 99%

“…Then it was stained with hematoxylin (IH0030, Beijing Solarbio Technology Co., Ltd., Beijing, China) for 2 min, followed by rinsing with tap water for 10 s and differentiation with 1% hydrochloric acid ethanol for 10 s. After washing with distilled water for 1 min, staining with eosin Y for 1 min, slightly rinsing with distilled water for 10 s, dehydrating with gradient alcohol, and clearing with xylene, neutral gum was used for sealing and slicing. After sectioning, the histological changes in tissue morphology were observed under an optical microscope (XP‐330; Shanghai Bingyu Optical Instrument Co., Ltd., Shanghai, China) and were scored by two senior pathologists (the scoring method was based on grading of bleeding and edema observed in 6 fields of view) (Liu, Cai, et al., 2021). 0 points: No damage; 1 point: <25% of the damaged area; 2 points: 25–50% of the damaged area; 3 points: 50–75% of the damaged area; 4 points: >75% of the damaged area (Beards et al., 1995; Verheij et al., 2006).…”

Section: Methodsmentioning

confidence: 99%

Mechanistic insights into targeting caspase‐3 activation and alveolar macrophage pyroptosis by Ephedra and bitter almond compounds for treating pediatric pneumonia via network pharmacology and bioinformatics

Wang,

Guo,

Sun

et al. 2024

Chem Biol Drug Des

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This study investigates the molecular mechanism of Ma Huang‐Ku Xing Ren, a traditional Chinese medicine formula, in treating pediatric pneumonia. The focus is on the regulation of caspase‐3 activation and reduction of alveolar macrophage necrosis through network pharmacology and bioinformatics analyses of Ephedra and bitter almond components. Active compounds and targets from ephedrine and bitter almond were obtained using TCMSP, TCMID, and GeneCards databases, identifying pediatric pneumonia‐related genes. A protein–protein interaction (PPI) network was constructed, and core targets were screened. GO and KEGG pathway enrichment analyses identified relevant genes and pathways. An acute pneumonia mouse model was created using the lipopolysaccharide (LPS) inhalation method, with caspase‐3 overexpression induced by a lentivirus. The mice were treated with Ephedra and bitter almond through gastric lavage. Lung tissue damage, inflammatory markers (IL‐18 and IL‐1β), and cell death‐related gene activation were assessed through H&E staining, ELISA, western blot, flow cytometry, and immunofluorescence. The study identified 128 active compounds and 121 gene targets from Ephedra and bitter almond. The PPI network revealed 13 core proteins, and pathway analysis indicated involvement in inflammation, apoptosis, and cell necrosis, particularly the caspase‐3 pathway. In vivo results showed that Ephedra and bitter almond treatment significantly mitigated LPS‐induced lung injury in mice, reducing lung injury scores and inflammatory marker levels. It also decreased caspase‐3 activity and cell death in alveolar macrophages. In conclusion, the active ingredients of Ma Huang‐Ku Xing Ren, particularly targeting caspase‐3, may effectively treat pediatric pneumonia by reducing apoptosis in alveolar macrophages, as demonstrated by both network pharmacology, bioinformatics analyses, and experimental data.

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“…Once activated, NEK7 functions to regulate the integrity of telomeres by providing them with a protective effect from oxidative DNA damage [ 46 ]. More recently, NEK7 has been identified as a mediator of NLRP3 inflammasome activation, an innate immune response pathway that promotes inflammation and apoptosis [ 47 , 48 , 49 , 50 ]. Because of NEK7’s role in mediating the inflammasome response, it is associated with the inflammatory responses of conditions such as bacterial infections, gouty arthritis, diabetes, arterial disease, and inflammatory bowel disease [ 48 , 51 , 52 , 53 , 54 , 55 ].…”

Section: Nek7mentioning

confidence: 99%

NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

Nguyen

Julia

Tran

et al. 2023

Cancers

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The Never in Mitosis Gene A (NIMA)–related kinases (NEKs) are a group of serine/threonine kinases that are involved in a wide array of cellular processes including cell cycle regulation, DNA damage repair response (DDR), apoptosis, and microtubule organization. Recent studies have identified the involvement of NEK family members in various diseases such as autoimmune disorders, malignancies, and developmental defects. Despite the existing literature exemplifying the importance of the NEK family of kinases, this family of protein kinases remains understudied. This report seeks to provide a foundation for investigating the role of different NEKs in malignancies. We do this by evaluating the 11 NEK family kinase gene expression associations with patients’ overall survival (OS) from various cancers using the Kaplan–Meier Online Tool (KMPlotter) to correlate the relationship between mRNA expression of NEK1-11 in various cancers and patient survival. Furthermore, we use the Catalog of Somatic Mutations in Cancer (COSMIC) database to identify NEK family mutations in cancers of different tissues. Overall, the data suggest that the NEK family has varying associations with patient survival in different cancers with tumor-suppressive and tumor-promoting effects being tissue-dependent.

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Wolf–Hirschhorn syndrome candidate 1 facilitates alveolar macrophage pyroptosis in sepsis-induced acute lung injury through NEK7-mediated NLRP3 inflammasome activation

Cited by 12 publications

References 27 publications

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

The Programmed Cell Death of Macrophages, Endothelial Cells, and Tubular Epithelial Cells in Sepsis-AKI

Mechanistic insights into targeting caspase‐3 activation and alveolar macrophage pyroptosis by Ephedra and bitter almond compounds for treating pediatric pneumonia via network pharmacology and bioinformatics

NEK Family Review and Correlations with Patient Survival Outcomes in Various Cancer Types

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