CD73 alleviates GSDMD‐mediated microglia pyroptosis in spinal cord injury through PI3K/AKT/Foxo1 signaling DOI Creative Commons
Shun Xu, Jin Wang, Junjie Zhong

et al.

Clinical and Translational Medicine, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 31, 2020

Abstract Background Neuroinflammation‐induced secondary injury is an important cause of sustained progression spinal cord injury. Inflammatory programmed cell death pyroptosis executed by the pore‐forming protein gasdermin D (GSDMD) essential step neuroinflammation. However, it unclear whether CD73, a widely accepted immunosuppressive molecule, can inhibit via mediating GSDMD. Methods C57BL/6J CD73 deficient mice and wild‐type mice, Lipopolysaccharide (LPS)‐induced primary microglia BV2 cells were respectively used to illustrate effect on in vivo vitro. A combination molecular histological methods was performed assess explore mechanism both Results We have shown evidence for suppresses activation NLRP3 inflammasome complexes reduce maturation GSDMD, leading decreased microglia. Further analysis reveals that adenosine‐A 2B adenosine receptor‐PI3K‐AKT‐Foxo1 cascade possible regulation. Importantly, we determine inhibits expression GSDMD at transcriptional level through Foxo1. What's more, confirm accumulation HIF‐1α promotes overexpression after (SCI), increased turn upregulates HIF‐1α, eventually forming positive feedback regulatory loop. Conclusion Our data reveal novel function pyroptosis, suggesting unique therapeutic opportunity mitigating disease process SCI.

Language: Английский

Inflammation-related pyroptosis, a novel programmed cell death pathway, and its crosstalk with immune therapy in cancer treatment DOI Creative Commons

Sheng‐Kai Hsu,

Chia‐Yang Li, I‐Ling Lin

et al.

Theranostics, Journal Year: 2021, Volume and Issue: 11(18), P. 8813 - 8835

Published: Jan. 1, 2021

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed death, such as ferroptosis, necroptosis, pyroptosis, recently been reported to play significant roles in the modulation cancer progression are considered a promising strategy for treatment. Thus, switch between pyroptosis also discussed. Cancer immunotherapy gained increasing attention due breakthroughs immune checkpoint inhibitors; moreover, highly correlated with immunity tumor microenvironment. Compared necroptosis primary mechanism host defense crucial bridging innate adaptive immunity. Furthermore, exerts benefits on immunotherapies, including inhibitors (ICIs) chimeric antigen receptor T-cell therapy (CAR-T). Hence, this review, we elucidate role We summarize potential small molecules nanomaterials target pyroptotic death mechanisms their therapeutic effects cancer.

Language: Английский

Citations

315
Apoptosis, Pyroptosis, and Necroptosis—Oh My! The Many Ways a Cell Can Die DOI
Natália Ketelut-Carneiro, Katherine A. Fitzgerald

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 434(4), P. 167378 - 167378

Published: Nov. 25, 2021

Language: Английский

Citations

287
Cell death in the gut epithelium and implications for chronic inflammation DOI
Jay V. Patankar, Christoph Becker

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(9), P. 543 - 556

Published: July 10, 2020

Language: Английский

Citations

280
Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate DOI Creative Commons
Lei Hu, Meng Chen, Xueran Chen

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(4)

Published: April 24, 2020

Many chemotherapy treatments induce apoptosis or pyroptosis through BAK/BAX-dependent mitochondrial pathway. BAK/BAX activation causes the outer membrane permeabilization (MOMP), which induces of pro-apoptotic caspase cascade. GSDME cleavage by caspases determines whether drug pyroptosis, however, its regulation mechanisms are not clear. In this study, we showed that TNFα+CHX and navitoclax-induced cancer cell a BAK/BAX-caspase-3-GSDME signaling knockdown inhibited suggesting essential role in process. Interestingly, was found to be palmitoylated on C-terminal (GSDME-C) during chemotherapy-induced while 2-bromopalmitate (2-BP) could inhibit GSDME-C palmitoylation pyroptosis. Mutation sites also diminished induced drugs. Moreover, 2-BP treatment increased interaction between GSDME-N, providing potential mechanism function. Further studies indicated several ZDHHC proteins including ZDHHC-2,7,11,15 interact with palmitoylate GSDME. Our findings offered new targets achieve transformation apoptosis.

Language: Английский

Citations

233
ROS from Physical Plasmas: Redox Chemistry for Biomedical Therapy DOI Creative Commons
Angela Privat‐Maldonado, Anke Schmidt, Abraham Lin

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2019, Volume and Issue: 2019, P. 1 - 29

Published: Oct. 8, 2019

Physical plasmas generate unique mixes of reactive oxygen and nitrogen species (RONS or ROS). Only a bit more than decade ago, these plasmas, operating at body temperature, started to be considered for medical therapy with considerably little mechanistic redox chemistry biomedical research existing on that topic time. Today, vast evidence is available physical plasma-derived ROS, from their spatiotemporal resolution in the plasma gas phase sophisticated chemical biochemical analysis once dissolved liquids. Data silico dissected potential reaction pathways biological membranes, vitro vivo experiments cell animal disease models identified molecular mechanisms therapeutic benefits plasmas. In 2013, first systems entered European market as class IIa devices have proven valuable resource dermatology, especially supporting healing chronic wounds. The results cancer patients treated are promising, too. Due many potentials this blooming new field ahead, there need highlight main concepts distilled biology serve link between physics (how which ROS produced) (what benefit). This inevitably puts cellular membranes focus, natural interphase produced by translation reactivity into distinct responses.

Language: Английский

Citations

232
Immunogenic cell death in anticancer chemotherapy and its impact on clinical studies DOI
Qiang Wang,

Xiaoli Ju,

Jiayou Wang

et al.

Cancer Letters, Journal Year: 2018, Volume and Issue: 438, P. 17 - 23

Published: Sept. 11, 2018

Language: Английский

Citations

230
Activation of Pyroptosis by Membrane‐Anchoring AIE Photosensitizer Design: New Prospect for Photodynamic Cancer Cell Ablation DOI
Min Wu, Xingang Liu, Huan Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(16), P. 9093 - 9098

Published: Feb. 6, 2021

Pyroptosis as a lytic and inflammatory form of cell death is powerful tool to fight against cancer. However, pyroptosis usually activated by chemotherapeutic drugs, which limits its anti-tumor applications due drug resistance severe side effects. Herein, we demonstrate that membrane targeting photosensitizers can induce for cancer ablation with noninvasiveness low A series anchoring (TBD-R PSs) aggregation-induced emission (AIE) characteristics were prepared through conjugation TBD phenyl ring cationic chains. Upon light irradiation, cytotoxic ROS produced in situ, resulting direct damage superior ablation. Detailed study revealed gradually became the dominant pathway along increase TBD-R PSs capability. This offers photo-activated pyroptosis-based intervention strategy

Language: Английский

Citations

227
Epigenetics-Based Tumor Cells Pyroptosis for Enhancing the Immunological Effect of Chemotherapeutic Nanocarriers DOI
Jin‐Xuan Fan, Ronghui Deng, He Wang

et al.

Nano Letters, Journal Year: 2019, Volume and Issue: 19(11), P. 8049 - 8058

Published: Sept. 27, 2019

Pyroptosis is a lytic and inflammatory form of programmed cell death could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated DFNA5 gene) during caspase-3-mediated pyroptosis process absent in most tumor cells because hypermethylation (deafness autosomal dominant 5) gene. Here, we develop strategy combining decitabine (DAC) with nanodrugs to trigger epigenetics, further enhancing immunological effect chemotherapy. DAC pre-performed specific tumor-bearing mice for demethylation gene cells. Subsequently, commonly used tumor-targeting nanoliposome loaded cisplatin (LipoDDP) administrate activating pathway pyroptosis. Experiments demonstrate that reversal GSDME silencing achieved facilitates occurrence According anti-tumor activities, anti-metastasis results, inhibition recurrence, this pyroptosis-based enhances effects also provides an important insight into immunotherapy.

Language: Английский

Citations

217
Programmed Cell Death Tunes Tumor Immunity DOI Creative Commons
Jing Liu,

Minjing Hong,

Yijia Li

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 30, 2022

The demise of cells in various ways enables the body to clear unwanted cells. Studies over years revealed distinctive molecular mechanisms and functional consequences several key cell death pathways. Currently, most intensively investigated programmed (PCD) includes apoptosis, necroptosis, pyroptosis, ferroptosis, PANoptosis, autophagy, which has been discovered play crucial roles modulating immunosuppressive tumor microenvironment (TME) determining clinical outcomes cancer therapeutic approaches. PCD can dual roles, either pro-tumor or anti-tumor, partly depending on intracellular contents released during process. also regulates enrichment effector regulatory immune cells, thus participating fine-tuning anti-tumor immunity TME. In this review, we focused primarily discussed messengers regulating their intricate crosstalk with response TME, explored immunological consequence its implications future therapy developments.

Language: Английский

Citations

213
Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy DOI
Rui Wang, Xingshu Li, Juyoung Yoon

et al.

ACS Applied Materials & Interfaces, Journal Year: 2021, Volume and Issue: 13(17), P. 19543 - 19571

Published: April 26, 2021

Subcellular organelles are the cornerstones of cells, and destroying them will cause cell dysfunction even death. Therefore, realizing precise organelle targeting photosensitizers (PSs) can help reduce PS dosage, minimize side effects, avoid drug resistance, enhance therapeutic efficacy in photodynamic therapy (PDT). Organelle-targeted PSs provide a new paradigm for construction next generation may implementable strategies future precision medicine. In this Review, recent different corresponding design principles molecular nanostructured summarized discussed. The current challenges opportunities organelle-targeted PDT also presented.

Language: Английский

Citations

212