Life sciences最新文献

{"title":"Chronic hyperglycemia induces hepatocyte pyroptosis via Gα₁₂/Gα₁₃-associated endoplasmic reticulum stress: Effect of pharmacological intervention.","authors":"Muhammad Sohaib Khan, Jihoon Tak, Yun Seok Kim, Sang Gil Lee, Eun Byul Lee, Sang Geon Kim","doi":"10.1016/j.lfs.2024.123180","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123180","url":null,"abstract":"<p><strong>Aims: </strong>Hyperglycemia induces pathophysiological changes. Endoplasmic reticulum (ER) stress with Gα₁₂ overexpression may promote hepatocyte death. This study investigated whether sustained hyperglycemia triggers ER stress-associated pyroptosis and fibrosis in the liver alongside an overexpression of Gα₁₂, and examined the potential link with VEGF-A levels.</p><p><strong>Main methods: </strong>Mice were subjected to a high-fat diet (60 kcal% fat) with streptozotocin (50 mg/kg body weight, three consecutive times, between 12-13th weeks). AZ2 (a functional Gα₁₂ inhibitor) was treated at 10 mg/kg body weight (5 times/week, 3 weeks). Immunoblotting and immunohistochemistry analyses were performed.</p><p><strong>Key findings: </strong>Hepatic Gα₁₂/Gα₁₃ were overexpressed in the diabetic mice. The following proteins downstream from the Gα₁₂ axis were upregulated: PGC1α, PPARα, and SIRT1. Sustained hyperglycemia promoted ER stress marker levels. Histopathological and biochemical assays showed large-sized lipid droplet accumulation, hepatocyte degeneration, and damage as blood transaminase activities increased. Moreover, the diabetic condition increased IL-1β, caspase-1, and NLRP3 levels, which were supportive of pyroptosis. Consistently, the intensities of Masson's trichrome, collagen-1A1, α-SMA, vimentin, and fibronectin all increased. VEGF-A and VEGFR2 levels also increased in the liver and/or sera. The levels of hepatic pigment epithelial-derived factor (PEDF), a physiological antagonist of VEGF-A, decreased with its reciprocal increase in serum. These events were reversed by AZ2 treatment, supporting the role of Gα₁₂ in hyperglycemic stress in the liver.</p><p><strong>Significance: </strong>Chronic hyperglycemia causes hepatic pyroptosis and fibrosis related to ER stress with Gα₁₂/Gα₁₃ and VEGF overexpression, which may be overcome by AZ2 treatments.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123180"},"PeriodicalIF":5.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of ABCG2 in health and disease: Linking cancer therapy resistance and other disorders.","authors":"Nahla E El-Ashmawy, Ghada M Al-Ashmawy, Omnia B Hamada, Naglaa F Khedr","doi":"10.1016/j.lfs.2024.123245","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123245","url":null,"abstract":"<p><p>All biological systems have adenosine triphosphate (ATP) binding cassette (ABC) transporters, one of the significant protein superfamilies involved in transport across membranes. ABC transporters have been implicated in the etiology of diseases like metabolic disorders, cancer, and Alzheimer's disease. ATP-binding cassette superfamily G member 2 (ABCG2), one of the ABC transporters, is necessary for the ATP-dependent efflux of several endogenous and exogenous substances. Consequently, it maintained cellular homeostasis and shielded tissue from xenobiotic substances. ABCG2 was initially identified in an Adriamycin-selected breast cancer cell line (MCF-7/AdrVp) and was linked to the emergence of multidrug resistance (MDR) in cancerous cells. Under many pathophysiological conditions, including inflammation, disease pathology, tissue injury, infection, and in response to xenobiotics and endogenous substances, the expression of ABCG2 undergoes alterations that result in modifications in its function and activity. Genetic variants in the ABCG2 transporter can potentially impact its expression and function, contributing to the development of many disorders. This review aimed to illustrate the impact of ABCG2 expression and its variants on oral drug bioavailability, MDR in specific cancer cells, explore the relationship between ABCG2 expression and other disorders such as gout, Alzheimer's disease, epilepsy, and erythropoietic protoporphyria, and demonstrate the influence of various synthetic and natural compounds in regulating ABCG2 expression.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123245"},"PeriodicalIF":5.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic vs. inorganic nitrates: Metabolic and vascular outcomes in STZ-induced diabetes in mice.","authors":"Francineide Fernandes-Costa, Rayanelle Tissiane Gomes da Silva, Arthur José Pontes Oliveira de Almeida, Isac Almeida de Medeiros, Luciene Simões de Assis Tafuri, Gustavo Jorge Dos Santos, Mattias Carlstrom, Josiane Campos Cruz","doi":"10.1016/j.lfs.2024.123257","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123257","url":null,"abstract":"<p><strong>Background: </strong>Diabetic animals often display dysregulated nitric oxide (NO) metabolism, contributing to vascular dysfunction. This study evaluates the metabolic and vascular effects of organic nitrate isosorbide mononitrate (ISMN) versus inorganic sodium nitrate (NaNO3) in mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ).</p><p><strong>Experimental approach: </strong>T1DM was induced in male C57Bl6 mice with STZ ip and confirmed by fasting glucose. Mice were treated with ISMN (10 mg·kg^-1) or NaNO3 (85 mg·L^-1) for 14 days. A combination of in vivo, in vitro, and ex vivo studies assessed cardiometabolic benefits.</p><p><strong>Results: </strong>Both nitrates reduced blood and urinary hyperglycemia in T1DM mice, with ISMN exhibiting more significant reductions in blood glucose. ISMN and NaNO3 similarly reduced water and food intake, urinary volume, glucose intolerance, and insulin resistance while increasing insulin and nitrite levels in serum and urine. Both nitrates improved endothelium-independent vascular function and attenuated reactive oxygen species (ROS) while increasing NO levels in the aortic rings of T1DM mice. Furthermore, both nitrates similarly reduced mean arterial pressure in T1DM mice.</p><p><strong>Conclusion and implications: </strong>ISMN and NaNO₃ have demonstrated comparable hypotensive and antioxidant effects, offering metabolic and vascular benefits in STZ-TDM1 mice. The more pronounced reduction in blood glucose with ISMN treatment compared to NaNO₃ is particularly promising. The antihyperglycemic effects of both nitrates were linked to increased serum insulin levels and enhanced insulin sensitivity. These results provide a foundation for future clinical studies to evaluate the potential of ISMN or NaNO3 as antidiabetogenic and antihypertensive adjuvant therapies in diabetic patients.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123257"},"PeriodicalIF":5.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel selenoglycoside compound GlcSeCys alleviates diets-induced obesity and metabolic dysfunctions with the modulation of Galectin-1 and selenoproteins.","authors":"Ruhui Zhang, Xinni Xie, Jun Liu, Ruiying Pan, Yu Huang, Yuguo Du","doi":"10.1016/j.lfs.2024.123259","DOIUrl":"10.1016/j.lfs.2024.123259","url":null,"abstract":"<p><p>Selenium, an essential trace element in human, has been shown to play protective roles in obesity and metabolic disorders despite insufficient understanding of mechanisms. Moreover, it's well known that biological actions of selenium compounds differed greatly due to divergent chemical forms. Selenoglycoside is a type of organoselenium compounds with excellent hydrophilicity, but biological activity of which in vivo are almost unknown. We have designed and synthesized Se-β-d-glucopyranosyl-D-selenocysteine, a novel selenoglycoside compound named GlcSeCys. Herein, GlcSeCys was given to high fat high cholesterol (HFHC) fed mice to determine its actions as well as relevant molecular mechanisms using transcriptome and multiple molecular biological methods. It was revealed that GlcSeCys displayed pronounced anti-obesity effect and significantly alleviated hyperglycemia, hyperinsulinemia along with hepatic steatosis in HFHC diets-induced mice. Mechanistically, GlcSeCys was found to inhibit lipogenesis, lipid uptake and inflammation in liver, along with attenuation of Galectin-1 and induction of selenoprotein S (SELENOS). With regard to adipose tissues, GlcSeCys ameliorated hypertrophy of adipocytes, suppressed lipids biosynthesis and stimulated WAT browning along with abrogated WAT inflammation activation, which were in line with repression of Galectin-1 and increase of GPx3. Collectively, our results uncovered, for the first time, that selenoglycoside compound GlcSeCys possessed excellent protective effects against obesity and metabolic disorders, and the mechanisms were correlated with modulation of Galectin-1 and selenoproteins, shedding lights upon molecular biology of selenium and novel therapeutic for obesity and relevant metabolic disorders.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123259"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decrease of K_ATP channel expression through D3 receptor-mediated GSK3β signaling alleviates levodopa-induced dyskinesia (LID) in Parkinson's disease mouse model.","authors":"Yi-Ying Kuo, Sih-Yu Pen, Chia-Hui Cheng, Wan-Chen Ho, Ching-Yi Chen, Wen-Chung Wu, Ho-Hsuan Chou, Jung-Yao Chen, Ching-Han Lin, Jen-Feng Lin, Shi-Bing Yang, Pei-Chun Chen","doi":"10.1016/j.lfs.2024.123255","DOIUrl":"10.1016/j.lfs.2024.123255","url":null,"abstract":"<p><strong>Aims: </strong>The standard Parkinson's disease (PD) treatment is L-3,4-dihydroxyphenylalanine (L-DOPA); however, its long-term use may cause L-DOPA-induced dyskinesia (LID). Aberrant activation of medium spiny neurons (MSNs) contributes to LID, and MSN excitability is regulated by dopamine D3 receptor (D3R) and ATP-sensitive potassium (K_ATP) channel activity. Nevertheless, it remains unclear if D3R and K_ATP channels may be linked in the context of LID.</p><p><strong>Methods: </strong>Wild-type and tyrosine hydroxylase (TH)-specific Kir6.2 knockout mice were injected with 6-hydroxydopamine (6-OHDA) to generate a PD mouse model, then chronically treated with L-DOPA to induce LID. Analyses included immunohistochemical staining, biochemical endpoints, and behavior tests. The mechanisms by which D3R/K_ATP channels regulate LID in the PD/LID mouse model were probed by treatment with a D3R antagonist, K_ATP channel opener and glycogen synthase kinase 3β (GSK3β) inhibitor, followed by evaluation of abnormal involuntary movements (AIMs).</p><p><strong>Key findings: </strong>The D3R antagonist FAUC365 alleviated LID, reducing AIMs and protecting against degeneration of the nigrostriatal pathway, which occurred through a direct interaction between D3Rs and K_ATP channels. In line with this mechanism, activation of D3R/GSK3β signaling increased K_ATP channel expression in the striatum of PD/LID mice. Additionally, the K_ATP channel opener Diz slowed LID progression and preserved nigrostriatal projections. Consistently, mice with TH-specific knockout of Kir6.2 exhibited reduced PD-like symptoms and less severe LID.</p><p><strong>Significance: </strong>D3Rs act through GSK3β signaling to regulate expression of K_ATP channels, which may subsequently modulate LID. Inhibition of K_ATP channels in TH-positive cells is sufficient to reduce AIMs in a mouse model of PD/LID.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123255"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothyroidism modulates mitochondrial dynamics and mitophagy in the heart of rats under fed and fasting conditions.","authors":"Juliana Santos Romão, Jessika Geisebel Oliveira Neto, Cherley Borba Vieira Andrade, Jorge José Carvalho, Carmen Cabanelas Pazos-Moura, Karen Jesus Oliveira","doi":"10.1016/j.lfs.2024.123254","DOIUrl":"10.1016/j.lfs.2024.123254","url":null,"abstract":"<p><strong>Aims: </strong>Investigate the impact of hypothyroidism on mitochondrial dynamics and mitophagy in the heart under fed and fasting conditions.</p><p><strong>Methods: </strong>Hypothyroidism was induced in male Wistar rats with methimazole (0.03 %) for 21 days. Half of the euthyroid and hypothyroid groups underwent a 48-h fasting. Mitochondrial number and ultrastructure were evaluated by transmission electron microscopy. Fusion, fission, mitophagy, oxidative stress, and mitochondrial oxidative phosphorylation system (OXPHOS) components were analyzed by Western Blot and qPCR.</p><p><strong>Results: </strong>Hypothyroidism increased DRP1 activation and the p-DRP1/OPA1 ratio, indicating a shift toward mitochondrial fission over fusion. Under fasting, hypothyroidism prevented the increases in mitochondrial size, elongation, OPA1, and OXPHOS seen in euthyroid fasted rats. Hypothyroidism also raised 4-HNE content, an oxidative stress product, increased mitochondrial injury, and exacerbated fasting-related mitochondrial damage. This was accompanied by elevated Parkin levels in both fed and fasted hypothyroid groups, but without changes in PINK1 levels or Parkin activation. While fasting upregulated Bnip3l and Map1lc3b expression in euthyroid rats, hypothyroidism suppressed this response, though it did not prevent fasting-induced Bnip3 increases.</p><p><strong>Conclusions: </strong>Hypothyroidism increases the activation of mitochondrial fission machinery and oxidative stress, and induces mitochondrial damage without activation of mitophagy proteins, suggesting disrupted mitophagy signaling. It also interferes with fasting-induced mitochondrial dynamics adaptations, highlighting the essential role of thyroid hormones in metabolic adaptation to fasting.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123254"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contributions of the gut microbiota to Gulf War Illness susceptibility: Findings from a mouse model.","authors":"Diptaraj S Chaudhari, Dina M Francescutti, Andrew D Winters, Orena Koka, David J Kracht, Jonathan M Greenberg, Kevin R Theis, Mariana Angoa-Perez","doi":"10.1016/j.lfs.2024.123244","DOIUrl":"10.1016/j.lfs.2024.123244","url":null,"abstract":"<p><strong>Aims: </strong>In light of the evidence supporting a significant role of the gut microbiome in Gulf War Illness (GWI) pathology, we sought to examine its contribution to GWI susceptibility in a mouse model. We also aimed to identify bacterial taxa and microbially-derived metabolites associated with disease susceptibility.</p><p><strong>Main methods: </strong>Male mice receiving pyridostigmine bromide (PB) orally, and controls were evaluated for symptoms of GWI at 8 weeks post-treatment. The Kansas criteria were adapted to assess behaviors associated with the following domains: gastrointestinal alterations, pain, mood, cognitive function, skin and respiratory disturbances. PB-treated subjects were classified into susceptible (GWI-S) or resilient (GWI-R). The status of the gut microbiome was assessed via analyses of the 16S rRNA gene and microbial-derived metabolites were evaluated with metabolomics tools.</p><p><strong>Key findings: </strong>Our results indicate that application of the Kansas criteria to behavioral outcomes in PB-treated mice resulted in a GWI susceptibility rate of ~35 %, similar to the one reported in humans. The composition and structure of the gut microbiome was different in GWI-S subjects compared to both control and GWI-R mice at 8 weeks but differences in microbial community structure were observed prior to PB treatment between GWI-R and GWI-S mice. GWI-S subjects exhibited a pattern of differentially abundant bacterial taxa and microbial metabolites.</p><p><strong>Significance: </strong>To our knowledge, this is the first preclinical report in which a stratification by susceptibility to GWI and its association with the gut microbiome is described. In light of the research conundrum that vulnerability to GWI represents, the use of tools that could provide further insight into this complex factor should be considered.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123244"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manual dexterity, tactile perception and inflammatory profile in HCWs affected by long Covid: A case - control study.","authors":"Mauro Marcella, Bestiaco Nicoletta, Zulian Elisa, Markežič Maria Margherita, Bignolin Ilaria, Larese Filon Francesca","doi":"10.1016/j.lfs.2024.123234","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123234","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123234"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes-induced alteration of metal ion levels declines the activity of MMPs to decrease aortic aneurysm risk.","authors":"Han Nie, Zi-Sheng Huang, Geng Liu, Tao-Sheng Li","doi":"10.1016/j.lfs.2024.123243","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123243","url":null,"abstract":"<p><strong>Aims: </strong>Diabetes mellitus (DM) links the risk of cardiovascular diseases. Inverse to the enhanced expression of matrix metalloproteinases (MMPs), the development of aortic aneurysm is lower in diabetic population. We examined the hypothesis that DM-induced alteration of metal ion levels declines the activity of MMPs to decrease aortic aneurysm risk.</p><p><strong>Methods & results: </strong>By culturing vascular smooth muscle cells (VSMCs) or macrophages with different concentrations of glucose in the medium, we confirmed that high glucose significantly increased the expression of fibronectin and CTGF in VSMCs, and induced MMP2 expression and MMP9 secretion in macrophages. We also established an abdominal aortic aneurysm model in streptozotocin-induced diabetic mice and evaluated aneurysm development six weeks later. Compared to the healthy controls, diabetic mice had significantly lower levels of Zn²⁺ and Mg²⁺ in serum and developed significantly smaller sizes of aneurysms with higher expression of fibronectin and CTGF; but dietary zinc supplementation to diabetic mice effectively neutralized these differences. Gelatin zymography assay indicated that the enzymatic digestion activity of MMP2 was changed under different concentrations of ZnSO₄ and MgSO₄. Clinical data analysis also confirmed that DM, serum Zn²⁺ level, and aortic aneurysm risk closely correlated with each other.</p><p><strong>Conclusion: </strong>It seems that DM-induced alteration of metal ion levels declines the activity of MMPs to negate aortic aneurysm development. Our data provide novel mechanistical insight and therapeutic strategy for aortic aneurysms.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123243"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PANoptosis: A new era for anti-cancer strategies.","authors":"Ziheng Cui, Yuan Li, Yao Bi, Wenjing Li, Junjie Piao, Xiangshan Ren","doi":"10.1016/j.lfs.2024.123241","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123241","url":null,"abstract":"<p><p>Cancer cells possess an extraordinary ability to dodge cell death through various pathways, granting them a form of immortality-a key obstacle in oncotherapy. Thus, it's vital to unravel the intricate mechanisms behind newly discovered types of cell death that drive tumor suppression, going beyond apoptosis alone. The emergence of PANoptosis, a form of cell death intertwining necroptosis, pyroptosis, and apoptosis, offers a fresh perspective, integrating these pathways into one cohesive process. When cells detect damage signals, they assemble PANoptosome complexes that disrupt their balance, trigger immune responses, and lead to their eventual collapse. PANoptosis has been associated with multiple cellular pathways, including ferroptosis. Mitochondrial dysfunction also plays a critical role in sparking and advancing PANoptosis. In this review, we map out the molecular machinery and regulatory web controlling PANoptosis. We explore cutting-edge research and future trends in PANoptosis-centered tumor therapies, spotlighting promising innovations that could amplify cancer treatment effectiveness through harnessing this multifaceted cell death pathway. The development of nanomedicines and nanomaterials provides solutions to the therapeutic challenges of clinical drugs. Developing novel tumor nano-PANoptosis inducers by leveraging the advantages of nanomedicine is of research value. Traditional Chinese medicine (TCM) treatment is characterized by multiple targets, and it has distinct advantages in triggering PANoptosis through multiple pathways. Additionally, photodynamic Therapy (PDT) may offer new insights into promoting PANoptosis in tumor cells by increasing oxidative stress and reactive oxygen species levels. These will establish a solid theoretical groundwork for the development of integrated treatment methodologies.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123241"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}