Pyroptosis: a double-edged sword in lung cancer and other respiratory diseases

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 15, 2024

Abstract Pyroptosis is an active cell death process mediated by gasdermin family proteins including Gasdermin A (GSDMA), B (GSDMB), C (GSDMC), D (GSDMD), E (GSDME, DFNA5), and DFNB59. Emerging evidences have shown that pyroptosis contributes to many pulmonary diseases, especially lung cancer, pneumonia. The exact roles of are tremendously intricate. Besides, there these respiratory diseases. However, it often plays a dual role in diseases which cause for concern makes difficult clinical translation. This review will focus on the multifaceted

Language: Английский

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The Burden of Multiple Myeloma in China: Trends from 1990 to 2021 and Forecasts for 2050

Cancer Letters, Journal Year: 2025, Volume and Issue: 611, P. 217440 - 217440

Published: Jan. 2, 2025

Language: Английский

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Precise targeting of lipid metabolism in the era of immuno-oncology and the latest advances in nano-based drug delivery systems for cancer therapy

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(11), P. 4717 - 4737

Published: July 27, 2024

Over the past decade, research has increasingly identified unique dysregulations in lipid metabolism within tumor microenvironment (TME). Lipids, diverse biomolecules, not only constitute biological membranes but also function as signaling molecules and energy sources. Enhanced synthesis or uptake of lipids TME significantly promotes tumorigenesis proliferation. Moreover, secreted into influence tumor-resident immune cells (TRICs), thereby aiding survival against chemotherapy immunotherapy. This review aims to highlight recent advancements understanding both TRICs, with a particular emphasis on exogenous endogenous

Language: Английский

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Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications

Frontiers of Medicine, Journal Year: 2024, Volume and Issue: 18(6), P. 945 - 968

Published: Nov. 14, 2024

Language: Английский

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The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Oct. 27, 2023

Abstract The NLRP3 inflammasome is an intracellular sensor and essential component of the innate immune system involved in danger recognition. An important hallmark activation formation a single supramolecular punctum, known as speck, per cell, which site where pro-inflammatory cytokines IL-1β IL-18 are converted into their bioactive form. Speck also provides platform for gasdermin D protein activation, whose N-terminus domain perforates plasma membrane, allowing release mature alongside with highly inflammatory form cell death, namely pyroptosis. Although controlled inflammasome-pyroptosis pathway preserves mucosal immunity homeostasis contributes to host defense, prolonged trigger deleterious could lead, genetically predisposed subjects, onset bowel disease, including Crohn's disease ulcerative colitis, well gastrointestinal cancer. Experimental evidence shows that has both protective pathogenic abilities. In this review we highlight impact NLRP3-pyroptosis axis on pathophysiology tract at molecular level, focusing newly discovered features bearing pro- anti-inflammatory neoplastic activity, targeted therapies tested preclinical clinical trials.

Language: Английский

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FABP4 as a therapeutic host target controlling SARS-CoV-2 infection

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Language: Английский

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Inflammation, microbiota, and pancreatic cancer

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 22, 2025

Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life people around world. In spite advances in treatment PC, overall survival this disease advanced stage less than 12%. Moreover, PC cells have aggressive behaviour proliferation and metastasis as well capable developing therapy resistance. Therefore, highlighting underlying molecular mechanisms pathogenesis can provide new insights for its treatment. present review, inflammation related pathways role gut microbiome regulation are highlighted. The various kinds interleukins chemokines able to regulate angiogenesis, metastasis, proliferation, resistance cells. Furthermore, number including NF-κB, TLRs TGF-β demonstrate dysregulation aggravating tumorigenesis. Therapeutic these reverse progression PC. Both chronic acute pancreatitis been shown be risk factors development further inflammation. Finally, composition microbiota factor through affecting such NF-κB mediate

Language: Английский

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GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: Feb. 25, 2025

Abstract Pyroptosis is a regulated form of inflammatory cell death in which Gasdermin D (GSDMD) plays central role as the key effector molecule. GSDMD-mediated pyroptosis characterized by complex biological features and considerable heterogeneity its expression, mechanisms, functional outcomes across various tissues, types, pathological microenvironments. This particularly pronounced inflammation-related diseases tumors. In context diseases, GSDMD expression typically upregulated, activation macrophages, neutrophils, T cells, epithelial mitochondria triggers both pyroptotic non-pyroptotic pathways, leading to release pro-inflammatory cytokines exacerbation tissue damage. However, under certain conditions, may also serve protective immune function. The tumors more manner, where it can either promote evasion or, some instances, induce tumor death. As our understanding GSDMD's continues progress, there have been advancements development inhibitors targeting pyroptosis; however, these therapeutic interventions remain preclinical phase. review systematically examines cellular molecular complexities pyroptosis, with particular emphasis on roles cancer. Furthermore, underscores substantial potential target for precision medicine, highlighting promising clinical applications.

Language: Английский

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Identifying Lipid Metabolism‐Related Therapeutic Targets and Diagnostic Markers for Lung Adenocarcinoma by Mendelian Randomization and Machine Learning Analysis

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(6)

Published: March 1, 2025

Lipid metabolic disorders are emerging as a recognized influencing factors of lung adenocarcinoma (LUAD). This study aims to investigate the influence lipid metabolism-related genes (LMRGs) on diagnosis and treatment LUAD identify significant biomarkers. DESeq2 robust rank aggregation (RRA) analyses were employed determine differential expression LMRGs from TCGA-LUAD five GEO datasets. Mendelian randomization (MR) was conducted utilizing protein quantitative trait loci (pQTLs) in deCODE, prot-a, UKB-PPP Study estimate causal relationships between plasma proteins within ieu-a-984, ieu-a-965, FinnGen R10 cohorts potential drug targets LUAD. Subsequently, an optimal machine learning model for diagnosing established by comparing four models: support vector machine, random forest (RF), glmBoost, eXtreme Gradient Boosting. Finally, diagnostic performance validated through nomogram analysis, calibration curve assessment, decision analysis (DCA), independent internal external A total biomarkers identified 1034 via MR analysis. TNFRSF21 exhibited positive association with risk; conversely, BCHE, FABP4, LPL, PLBD1 demonstrated negative correlations this risk. The RF determined be using these proteins. Ultimately, construction, DCA, well dataset validation confirmed that exhibit excellent performance. PLBD1, represent novel reliable markers therapeutic

Language: Английский

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Multi‐Omic Analysis Reveals a Lipid Metabolism Gene Signature and Predicts Prognosis and Chemotherapy Response in Thyroid Carcinoma

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(6)

Published: March 1, 2025

ABSTRACT Objective Lipid metabolic reprogramming is closely intertwined with the development and progression of thyroid carcinoma (TC); however, its specific mechanism remains elusive. This study aimed to investigate association between lipid metabolism TC progression. Methods We employed liquid chromatography‐mass spectrometry (LC/MS) for an untargeted metabolomics analysis, comparing 12 patients healthy controls (HC). Additionally, we conducted screening differentially expressed genes (DEGs) identified (LMGs). Multi‐omic findings related were integrated establish a prognostic risk model. The resulting score stratified into high‐ low‐risk groups. Overall survival (O.S.) was assessed using Kaplan–Meier (K–M) analysis. immune landscape evaluated CIBERSORT algorithm, chemotherapeutic response predicted utilizing “pRRophetic” R package. Results Our metabolomic analysis revealed heightened activity in TC, corroborated by similar transcriptomic key LMGs (FABP4, PPARGC1A, AGPAT4, ALDH1A1, TGFA, GPAT3) associated fatty acids glycerophospholipids metabolism. A novel model, incorporating these LMGs, confirmed significantly worse O.S. ( p = 0.0045) high‐risk group based on TCGA_THCA. Furthermore, exhibited lower cell infiltration, predictive outcomes indicated efficacy potential therapeutic drugs across Conclusion multi‐omic underscores utility model guiding clinical treatment improving patients.

Language: Английский

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