The mechanisms of ferroptosis and its role in atherosclerosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112

Published: Jan. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Language: Английский

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Regulated cell death‐amplified sonodynamic anti‐tumor immune nanotherapeutics

BMEMat, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Nanomedicine‐assisted sonodynamic therapy (SDT) has emerged as one of the most promising cancer therapies due to its unique advantages high penetration, non‐radiation, and excellent oxidative stress effect, but always suffered from self‐protection mechanism apoptosis resistance characteristics evolutionarily mutated cells. Regulated cell death (RCD) received increasing attention in precision treatments because significant role synergistically sensitizing reversing immunosuppressive microenvironment during SDT nanomedicine‐triggered immunogenic death. Herein, paradigmatic research RCD‐augmented tumor immunotherapeutics are typically introduced, such autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, PANoptosis trigger, coordinated anti‐tumor mechanisms discussed detail. Multiple analysis focusing on currently unsolved problems future development prospects RCD‐based nano‐oncology medicine also prospected further strengthen expand scope therapeutic applications.

Language: Английский

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Membrane-anchoring clickable Iridium(III) nanosonosensitizer in situ evokes PANoptosis for augmented tumor sono-immunotherapy

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102270 - 102270

Published: April 15, 2024

Language: Английский

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Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: May 14, 2024

As the global population ages, incidence of elderly patients with dementia, represented by Alzheimer's disease (AD), will continue to increase. Previous studies have suggested that β-amyloid protein (Aβ) deposition is a key factor leading AD. However, clinical efficacy treating AD anti-Aβ antibodies not satisfactory, suggesting Aβ amyloidosis may be pathological change rather than Identification causes and development corresponding prevention treatment strategies an important goal current research. Following discovery soluble oligomeric forms (AβO) in 1998, scientists began focus on neurotoxicity AβOs. endogenous neurotoxin, active growth AβOs can lead neuronal death, which believed occur before plaque formation, are factors PANoptosis, newly proposed concept cell death includes known modes pyroptosis, apoptosis, necroptosis, form regulated PANoptosome complex. Neuronal survival depends proper mitochondrial function. Under conditions AβO interference, dysfunction occurs, releasing lethal contents as potential upstream effectors PANoptosome. Considering critical role neurons cognitive function well regulatory survival, investigation mechanisms PANoptosis crucial. This review describes disruption elucidates how activate causing during AD, providing guidance for targeted strategies.

Language: Английский

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Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 54(9)

Published: April 17, 2024

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes heavy economic burden on people and society. Although it well established IVDD associated with genetic susceptibility, ageing obesity, its pathogenesis remains incompletely understood. Previously, was thought to occur because of excessive mechanical loading leading destruction nucleus pulposus cells (NPCs), but studies have shown much more complex process inflammation, metabolic factors NPCs death can involve all parts the disc, characterized by causing extracellular matrix (ECM) degradation. The damage pattern like some programmed cell death, suggesting death. apoptosis pyroptosis been studied IVDD, intervertebral still not be fully elucidated using only traditional modalities. With increasing research, new modes PANoptosis, ferroptosis senescence found closely related degeneration. Among these, PANoptosis combines essential elements pyroptosis, necroptosis form highly coordinated dynamically balanced inflammatory process. Furthermore, we believe may also crosstalk senescence. Therefore, review progress research multiple deaths provide guidance for clinical treatment.

Language: Английский

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The necroptosis cell death pathway drives neurodegeneration in Alzheimer’s disease

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: June 1, 2024

Abstract Although apoptosis, pyroptosis, and ferroptosis have been implicated in AD, none fully explains the extensive neuronal loss observed AD brains. Recent evidence shows that necroptosis is abundant closely linked to appearance of Tau pathology, markers accumulate granulovacuolar neurodegeneration vesicles (GVD). We review here neuron-specific activation mediated neuronal-necroptosis pathway, potential AD-relevant triggers upstream this interaction necrosome with endo-lysosomal possibly providing links pathology. In addition, we underscore therapeutic inhibiting neurodegenerative diseases such as presents a novel avenue for drug development targeting preserve cognitive abilities. Such an approach seems particularly relevant when combined amyloid-lowering drugs.

Language: Английский

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Ultrasmall Enzyodynamic PANoptosis Nano‐Inducers for Ultrasound‐Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(45)

Published: Sept. 3, 2024

Abstract Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form inflammatory programmed cell death, presents dependable strategy combating cancer by engaging multiple death pathways (apoptosis, pyroptosis, necroptosis). In this study, ultrasmall Bi 2 Sn O 7 nanozyme with ultrasound‐magnified multienzyme‐mimicking properties designed engineered as PANoptosis inducer through destroying mitochondrial function tumor cells enhancing intracellular accumulation toxic reactive oxygen species, finally triggering activation process. The role has been verified expression related proteins, including cleaved Caspase 3, NLRP3, N‐GSDMD, 1, p‐MLKL, RIPK3. inclusion external ultrasonic irradiation significantly augments enzyodynamic efficiency. vitro in vivo antineoplastic efficacy, along inhibition lung metastasis, validate benefits ‐mediated pathway. This study not only elucidates intricate mechanisms underlying inducer, but also offers novel perspective treatment carcinoma.

Language: Английский

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Identification of PANoptosis-related subtypes, construction of a prognosis signature, and tumor microenvironment landscape of hepatocellular carcinoma using bioinformatic analysis and experimental verification

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

Published: April 29, 2024

Background Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. PANoptosis a recently unveiled programmed cell death pathway, Nonetheless, precise implications within context HCC remain incompletely elucidated. Methods We conducted comprehensive bioinformatics analysis to evaluate both expression and mutation patterns PANoptosis-related genes (PRGs). categorized into two clusters identified differentially expressed (DEPRGs). Next, risk model was constructed using LASSO multivariate Cox regression analyses. The relationship between PRGs, genes, model, immune microenvironment studies. In addition, drug sensitivity high- low-risk groups examined. profiles these four were elucidate by qRT-PCR or immunohistochemical (IHC). Furthermore, effect CTSC knock down on behavior verified in vitro experiments. Results prognostic signature DEPRGs (CTSC, CDCA8, G6PD, CXCL9). Receiver operating characteristic curve analyses underscored superior capacity this assessing outcomes patients. Subsequently, patients stratified based their scores, which revealed that group had better prognosis than those high-risk group. High-risk displayed lower Stromal Score, Immune ESTIMATE score, higher cancer stem content, tumor burden (TMB) values. correlation noted 56 chemotherapeutic agents, as well immunotherapy efficacy, patient with. These findings provide valuable guidance for personalized clinical treatment strategies. qRT−PCR upregulated CTSC, whereas downregulated CXCL9 compared with adjacent tissue normal liver lines. knockdown significantly reduced proliferation migration. Conclusion Our study underscores promise PANoptosis-based molecular clustering signatures predicting survival discerning intricacies HCC. insights hold potential advance our comprehension therapeutic contribution plays pave way generating more efficacious

Language: Английский

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PANoptosis in Bacterial Infections: A Double-Edged Sword Balancing Host Immunity and Pathogenesis

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 43 - 43

Published: Jan. 8, 2025

PANoptosis is a newly identified programmed cell death pathway that integrates characteristics of apoptosis, pyroptosis, and necroptosis. It plays dual role in the host immune response to bacterial infections. On one hand, acts as protective mechanism by inducing infected cells eliminate pathogens releasing pro-inflammatory cytokines amplify response. other bacteria can exploit evade defenses. This nature underscores potential target for developing novel therapies against review summarizes molecular mechanisms PANoptosis, along with crosstalk integration different pathways various pathogens. We also discuss roles infectious diseases, including sepsis, pulmonary infections, intestinal Elucidating underlying how manipulate this offers critical insights into host-pathogen interactions. These provide foundation designing targeted antibacterial strategies, modulating inflammation, advancing precision medicine improve clinical outcomes.

Language: Английский

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Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities

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

Published: Jan. 20, 2025

Language: Английский

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