Bioinformatics combined with single-cell analysis reveals the molecular mechanism of pyroptosis in hepatocellular carcinoma DOI Creative Commons

Wei Luo,

Junxia Wang, Hongfei Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Abstract Purpose Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death, and its molecular mechanisms have not been fully elucidated. The aim this work to discover association between immune microenvironment changes pyroptosis in HCC. Methods Select gene expression profiles from comprehensive database, establish protein-protein interaction networks, perform functional enrichment analysis using databases such as Kyoto Encyclopedia Genes Genomes (KEGG). Single cell identification HCC types malignant cells, trajectory intercellular signal communication further analyze cells liver cells. Bioinformatics combined with single-cell elucidate mechanism underlying development Results key hub genes were validated through immunohistochemistry vitro experiments. Molecular biology has identified six focal death Enrichment shows that intersecting are enriched responses, chemokine mediated signaling pathways, inflammatory responses. cellular clustering single revealed infiltration especially polarization macrophages, which plays an important role. Immunohistochemistry suggests HMGB1, CYCS, GSDMD, IL-1β, NLRP3, IL18 link macrophage during development. Conclusions In summary, main pathogenesis infiltration, particularly promotes secretion factors hepatocyte pyroptosis. Our study may guide future research on pathway

Language: Английский

NLRP3 inflammasome and pyroptosis in cardiovascular diseases and exercise intervention DOI Creative Commons

Ping Ding,

Yuanming Song,

Yang Yang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 12, 2024

NOD-like receptor protein 3 (NLRP3) inflammasome is an intracellular sensing complex that possesses NACHT, leucine-rich repeat, and pyrin domain, playing a crucial role in innate immunity. Activation of the NLRP3 leads to production pro-inflammatory cellular contents, such as interleukin (IL)-1β IL-18, induction inflammatory cell death known pyroptosis, thereby amplifying or sustaining inflammation. While balanced response beneficial for resolving damage promoting tissue healing, excessive activation pyroptosis can have harmful effects. The involvement has been observed various cardiovascular diseases (CVD). Indeed, its associated are closely linked key risk factors including hyperlipidemia, diabetes, hypertension, obesity, hyperhomocysteinemia. Exercise compared with medicine highly effective measure both preventing treating CVD. Interestingly, emerging evidence suggests exercise improves CVD inhibits activity pyroptosis. In this review, mechanisms pathogenic critically discussed. Importantly, purpose emphasize managing by suppressing proposes it foundation developing novel treatment strategies.

Language: Английский

Citations

6
New Biomarkers in Liver Fibrosis: A Pass through the Quicksand? DOI Open Access

Marzia Tagliaferro,

Mariapaola Marino, Valerio Basile

et al.

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(8), P. 798 - 798

Published: July 29, 2024

Chronic liver diseases (CLD) stem from various causes and lead to a gradual progression that ultimately may result in fibrosis eventually cirrhosis. This process is typically prolonged asymptomatic, characterized by the complex interplay among cell types, signaling pathways, extracellular matrix components, immune responses. With prevalence of CLD increasing, diagnoses are often delayed, which leads poor prognoses some cases, need for transplants. Consequently, there an urgent development novel, non-invasive methods diagnosis monitoring CLD. In this context, serum biomarkers-safer, repeatable, more acceptable alternatives tissue biopsies-are attracting significant research interest, although their clinical implementation not yet widespread. review summarizes latest advancements biomarkers detecting hepatic fibrogenesis advocates concerted efforts consolidate current knowledge, thereby providing patients with early, effective, accessible facilitate personalized therapeutic strategies.

Language: Английский

Citations

5
The Emerging Role of Colchicine to Inhibit NOD-Like Receptor Family, Pyrin Domain Containing 3 Inflammasome and Interleukin-1β Expression in In Vitro Models DOI Creative Commons

Tri Astiawati,

Mohammad Saifur Rohman, Titin Andri Wihastuti

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 367 - 367

Published: March 3, 2025

While the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact cardiac fibroblast activation in context myocardial infarction (MI) remains unknown. This study aimed to investigate effect regulation NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome Interleukin-1β (IL-1β) expression fibroblasts. 3T3 fibroblasts were exposed 600 μM CoCl2 for 24 h simulate hypoxia, with normoxic cells as controls. Colchicine (1 μM) was administered h. ASC-NLRP3 colocalization IL-1β evaluated using immunofluorescence flow cytometry, respectively. Data analyzed t-tests one-way ANOVA post hoc tests. Hypoxia treatment significantly induced apoptosis-associated speck-like protein a CARD (ASC)-NLRP3 (p < 0.05). hypoxic reduced colocalization, although this reduction not statistically significant. Additionally, inhibited colchicine-treated compared those treated placebo The findings indicate that inhibits NLRP3 by disrupting ASC NLRP3, thereby reducing CoCl2-treated cells.

Language: Английский

Citations

0
“The Ameliorative Effect of Interleukin-17A Neutralization on Doxorubicin-Induced Cardiotoxicity by Modulating the NF-κB/NLRP3/Caspase-1/IL-1β Signaling Pathway in Rats” DOI Creative Commons

Mostafa D. Hassen,

Nahla O. Mousa,

Sara M. Radwan

et al.

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Doxorubicin (DOX) is used as a chemotherapeutic drug for treating cancer. Nevertheless, it causes damage to the heart by activating inflammatory pathways, resulting in cardiotoxicity. Imbalance cytokine production crucial component that might trigger initiation of processes. Inflammatory cytokines could be targeted therapies against cardiovascular diseases (CVDs). Interleukin-17A (IL-17A) promotes inflammation and stimulates harmful immunological reactions. The objective study was determine efficacy secukinumab (SEC), completely human monoclonal IgG1/κ antibody targets IL-17A, ameliorating DOX-induced cardiotoxicity (DIC). We administered 2.5 mg/kg DOX intraperitoneally male Wistar rats three times week 2 weeks simultaneously 0.9 SEC along with injection duration two weeks. findings indicated induced tissue, significant rise indicators (P < 0.001), well oxidative stress inflammation. DIC may have arisen from DOX's activation Pyrin domain containing 3 (NLRP3) inflammasome nuclear factor kappa beta (NF-κB) pathway. co-administration successfully reversed all abnormalities restoring cardiac functions their baseline levels, decreasing levels mediators such IL-17A interleukin-1β (IL-1β), improving reducing malondialdehyde (MDA) increasing reduced glutathione (GSH). Furthermore, mitigated heightened NF-κB/NLRP3 pathway caused DOX. This shows neutralization can prevent regulating NF-κB/NLRP3/Caspase-1/IL-1β potential therapeutic target CVDs.

Language: Английский

Citations

0
Ultraviolet-treated riboflavin alleviates atopic dermatitis by inhibiting NLRP3 inflammasome activation and M1 macrophage polarization via histone lactylation DOI Creative Commons
Shuang Ge,

Bingquan Qiu,

Rong Liu

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116879 - 116879

Published: March 1, 2025

Language: Английский

Citations

0
The role of NLRP3 inflammasome in multiple sclerosis: pathogenesis and pharmacological application DOI Creative Commons
Wengang Zhang,

Xiao-Rui Zheng,

Yi Yao

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

Multiple sclerosis (MS) is widely acknowledged as a chronic inflammatory autoimmune disorder characterized by central nervous system (CNS) demyelination and neurodegeneration. The hyperactivation of immune responses recognized pivotal factor contributing to the pathogenesis progression MS. Among various reactions, researchers have increasingly focused on inflammasome, complex proteins. initiation activation inflammasome are intricately involved in onset Notably, NLRP3 most extensively studied member complex, closely linked with This review will delve into roles Additionally, therapeutic strategies targeting for treatment MS, including natural compounds, autophagy regulators, other small molecular be detailed this review.

Language: Английский

Citations

0
The entrenchment of NLRP3 inflammasomes in autoimmune disease-related inflammation DOI Creative Commons

Valeria Carnazzo,

Donato Rigante, Giuliana Restante

et al.

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 103815 - 103815

Published: April 1, 2025

Autoinflammation and autoimmunity are almost "opposite" phenomena characterized by chronic activation of the immune system, 'innate' in first 'adaptive' second, leading to inflammation several tissues with specific protean effectors tissue damage. The mechanism involvement multiprotein complexes called 'inflammasomes' within autoimmune pictures, differently from autoinflammatory conditions, is yet undeciphered. In this review we provide a comprehensive overview on NLRP3 inflammasome contribution into pathogenesis some diseases. response autoantibodies against nucleic acids or tissue-specific antigens activated dendritic cells macrophages patients systemic lupus erythematosus. Crucial amplify interleukin-1 overexpression matrix metalloproteinase production at joint level rheumatoid arthritis. A deregulated occurs serous acini salivary lacrimal glands prone Sjogren's syndrome, but also inflammatory process involving endothelial cells, leucocyte recruitment, platelet plugging vasculitides. Furthermore, organ-specific diseases such as thyroiditis hepatitis may display hyperactive inflammasomes resident thyroid liver, respectively. Therefore, it not unexpected that preclinical studies have shown how inhibitors significantly overthrow severity different slow down their trend towards an ominous progression. Specific markers could reveal subclinical components escaping conventional diagnostic approaches improve monitoring personalizing treatment.

Language: Английский

Citations

0
Deep-Learning-Driven Discovery of SN3–1, a Potent NLRP3 Inhibitor with Therapeutic Potential for Inflammatory Diseases DOI
Cheng Shi,

Tongfei Gao,

Weiping Lyu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(19), P. 17833 - 17854

Published: Sept. 20, 2024

The NLRP3 inflammasome plays a central role in the pathogenesis of various intractable human diseases, making it an urgent target for therapeutic intervention. Here, we report development SN3-1, novel orally potent inhibitor, designed through lead compound strategy centered on deep-learning-based molecular generative models. Our enables rapid fragment enumeration and takes into account synthetic accessibility compounds, thereby significantly enhancing optimization compounds facilitating discovery inhibitors. X-ray crystallography provided insights SN3-1 inhibitory mechanism. has shown favorable safety profile both acute chronic toxicity assessments exhibits robust pharmacokinetic properties. Furthermore, demonstrated significant efficacy disease models characterized by activation. This study introduces candidate developing inhibitors expands repertoire tools available

Language: Английский

Citations

3
Spinosin ameliorates osteoarthritis through enhancing the Nrf2/HO-1 signaling pathway DOI Creative Commons
Peipei Lu, Shuxiang Li,

Caoyang Zhang

et al.

European Journal of Histochemistry, Journal Year: 2024, Volume and Issue: 68(2)

Published: May 22, 2024

Osteoarthritis (OA) is a common degenerative joint disease in the elderly, while oxidative stress-induced chondrocyte degeneration plays key role pathologic progression of OA. One possible reason that expression nuclear factor erythroid 2-related 2 (Nrf2), which acts as intracellular defense against stress, significantly inhibited chondrocytes. Spinosin (SPI) potent Nrf2 agonist, but its effect on OA still unknown. In this study, we found SPI can alleviate tert-Butyl hydroperoxide (TBHP)-induced extracellular matrix degradation Additionally, effectively activate Nrf2, heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) chondrocytes under TBHP environment. When was silenced by siRNA, cartilage protective also weakened. Finally, showed good alleviative effects mice. Thus, ameliorate dysfunction exhibit chondroprotective through activating Nrf2/HO-1 pathway, may provide novel promising option for treatment

Language: Английский

Citations

1
Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review DOI Creative Commons
Rafael Zubirán, Edward B. Neufeld, Amaury Dasseux

et al.

Cardiology and Therapy, Journal Year: 2024, Volume and Issue: 13(3), P. 465 - 491

Published: July 20, 2024

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role inflammation in residual risk ASCVD, emphasizing its impact on atherosclerosis progression plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), potentially other inflammatory biomarkers, can be used to identify ASCVD phenotype may serve as future targets for development more efficacious therapeutic approaches. We biological basis association with propose new strategies use inflammation-targeted treatments, discuss current challenges implementation this treatment paradigm ASCVD.

Language: Английский

Citations

1