Biomineralization-Tuned Nanounits Reprogram the Signal Transducer and Activator of Transcription 3 Signaling for Ferroptosis-Immunotherapy in Cancer Stem Cells DOI
Youbo Zhao, Yang Fei, Yang Zhao

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(32), P. 21268 - 21287

Published: July 31, 2024

Cancer stem cells (CSCs) are promising targets for improving anticancer treatment outcomes while eliminating recurrence, but their remains a major challenge. Here, we report nanointegrative strategy to realize CSC-targeted ferroptosis-immunotherapy through spatiotemporally controlled reprogramming of STAT3-regulated signaling circuits. Specifically, STAT3 inhibitor niclosamide (Ni) and an experimental ferroptosis drug (1S, 3R)-RSL3 (RSL3) integrated into hyaluronic acid-modified amorphous calcium phosphate (ACP) nanounits biomineralization (CaP-PEG-HA@Ni/RSL3), which could be recognized by CD44-overexpressing CSCs released in synchronized manner. Ni inhibits the CSC-intrinsic STAT3-PD-L1 axis stimulate adaptive immunity enhance interferon gamma (IFNγ) secretion CD8+ T downregulate SLC7A11 SLC3A2 blocking glutathione biosynthesis. Meanwhile, Ni-dependent inhibition also upregulates ACSL4 downstream IFNγ feedback. These effects cooperate with RSL3-mediated GPX4 deactivation induce pronounced ferroptosis. Furthermore, CaP-PEG-HA@Ni/RSL3 impairs immunosuppressive M2-like tumor-associated macrophages, Ca2+ ions from degraded ACP chelate lipid peroxides ferroptotic avoid T-cell inhibition, thus boosting effector function activated cells. This study offers cooperative ferroptosis-immunotherapeutic approach refractory cancer.

Language: Английский

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations DOI Creative Commons
Nan Zhou, Xiaoqing Yuan, Qingsong Du

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 51(D1), P. D571 - D582

Published: Oct. 28, 2022

Abstract Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation lipid peroxidation. It closely linked to the pathophysiological processes in many diseases. Since our publication first ferroptosis database 2020 (FerrDb V1), new findings have been published. To keep up with rapid progress research and provide timely high-quality data, here we present successor, FerrDb V2. contains 1001 regulators 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, which 264 drivers, 238 suppressors, 9 markers, 110 unclassified genes; 380 substance 201 inducers 179 inhibitors. Compared V1, articles increase >300%, 175%, 50.5%. Circular RNA pseudogene novel V2, percentage non-coding increases 7.3% 13.6%. External gene-related data were integrated, enabling thought-provoking gene-oriented analysis In conclusion, V2 will help acquire deeper insights into ferroptosis. freely accessible at http://www.zhounan.org/ferrdb/.

Language: Английский

Citations

244
Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism DOI Creative Commons
Zhifu Cui, Xingtao Zhao, Felix Kwame Amevor

et al.

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

Published: July 22, 2022

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in treatment of aging-related diseases. Sirtuin 1 (SIRT1), member NAD+-dependent deacetylase enzyme family, is extensively explored as potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against diseases such Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) reperfusion (MI/R), Atherosclerosis (AS), Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, regulates cellular senescence multiple processes, including SIRT1/Keap1/Nrf2/HO-1 SIRTI/PI3K/Akt/GSK-3β mediated oxidative stress, SIRT1/NF-κB SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mitochondrial damage, SIRT1/FoxO autophagy, SIRT1/FoxG1/CREB/BDNF/Trkβ-catenin neuroprotective effects. In this review, we summarized improvement attenuation effect quercetin on relationship between relevant signaling pathways by SIRT1. Moreover, functional regulation markers function, autophagy apoptosis through was discussed. Finally, prospects extracellular vesicles (EVs) loading delivery, SIRT1-mediated EVs signal carriers treating diseases, well discussed ferroptosis alleviation to protect via activating Generally, may serve promising inhibiting reducing responses, restoring dysfunction.

Language: Английский

Citations

213
Signaling pathways in Parkinson’s disease: molecular mechanisms and therapeutic interventions DOI Creative Commons

Dong-Chen Xu,

Yong Chen, Yang Xu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 21, 2023

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative worldwide, and its treatment remains a big challenge. The pathogenesis of PD may be related to environmental genetic factors, exposure toxins gene mutations beginning brain lesions. identified mechanisms include α-synuclein aggregation, oxidative stress, ferroptosis, mitochondrial dysfunction, neuroinflammation, gut dysbiosis. interactions among these molecular complicate pose great challenges drug development. At same time, diagnosis detection are also one obstacles due long latency complex mechanism. Most conventional therapeutic interventions for possess limited effects have serious side effects, heightening need develop novel treatments this disease. In review, we systematically summarized pathogenesis, especially PD, classical research models, clinical diagnostic criteria, reported therapy strategies, as well newly candidates in trials. We shed light on components derived from medicinal plants that their treatment, with expectation provide summary outlook developing next generation drugs preparations therapy.

Language: Английский

Citations

207
Hyper-sausage coverage function neuron model and learning algorithm for image classification DOI Creative Commons
Xin Ning, Weijuan Tian,

He Feng

et al.

Pattern Recognition, Journal Year: 2022, Volume and Issue: 136, P. 109216 - 109216

Published: Dec. 8, 2022

Recently, deep neural networks (DNNs) promote mainly by network architectures and loss functions; however, the development of neuron models has been quite limited. In this study, inspired mechanism human cognition, a hyper-sausage coverage function (HSCF) model possessing high flexible plasticity. Then, novel cross-entropy volume-coverage (CE_VC) is defined, which compresses volume to hilt, helps alleviate confusion among different classes, thus ensuring intra-class compactness samples. Finally, divisive iteration method introduced, considers each as weak classifier, iteratively increases number classifiers. Thus, optimal HSCF adaptively determined an end-to-end learning framework constructed. particular, improve classification performance, can be applied classical DNNs. Comprehensive experiments on eight datasets in several domains demonstrate effectiveness proposed method. The exhibits feasibility boosting DNNs with plasticity provides perspective for further developments source code available at https://github.com/Tough2011/HSCFNet.git .

Language: Английский

Citations

116
Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease DOI Creative Commons

Manlian Zhu,

Xia Liu, Yiru Ye

et al.

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

Published: June 24, 2022

Parkinson’s disease (PD) is the second most common neurodegenerative characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis involved in occurrence, development and progression of PD. Numerous clinical trials have identified characteristics changed microbiota profiles, preclinical studies PD animal models indicated can influence onset via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels α-synuclein fibrils, oxidative stress, decreasing neurotransmitter production. The be considered promising diagnostic therapeutic targets for PD, which regulated probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal transplantation, diet modifications, Chinese medicine. This review summarizes recent PD-associated profiles functions, potential roles, mechanisms microbiota-targeted interventions Deciphering underlying roles will help interpret pathogenesis from new perspectives elucidate novel strategies

Language: Английский

Citations

111
Ferroptosis in Parkinson's disease: Molecular mechanisms and therapeutic potential DOI

Xv-shen Ding,

Li Gao, Han Zheng

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102077 - 102077

Published: Sept. 24, 2023

Language: Английский

Citations

71
Metabolic reprogramming and polarization of microglia in Parkinson’s disease: Role of inflammasome and iron DOI
Haiyang Yu, Qing Chang,

Tong Sun

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 90, P. 102032 - 102032

Published: Aug. 10, 2023

Language: Английский

Citations

61
Research on ferroptosis as a therapeutic target for the treatment of neurodegenerative diseases DOI Creative Commons
Yi Wang,

Meng-nan Lv,

Weijiang Zhao

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 91, P. 102035 - 102035

Published: Aug. 23, 2023

Ferroptosis is an iron- and lipid peroxidation (LPO)-mediated programmed cell death type. Recently, mounting evidence has indicated the involvement of ferroptosis in neurodegenerative diseases, especially Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), Huntington's (HD), so on. Treating presents opportunities as well challenges for diseases. This review provides a comprehensive overview underlying mechanisms that contribute to occurrence ferroptosis, their implications pathogenesis advancement major disorders. Meanwhile, we summarize interaction between other types diseases contribution corresponding drug development. In addition, specifically recent advances developing therapeutic means targeting these which may guide future approaches effective management devastating medical conditions.

Language: Английский

Citations

51
Mechanisms of ferroptosis in Alzheimer's disease and therapeutic effects of natural plant products: A review DOI Open Access
Zhao Da, Kailin Yang, Hua Guo

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114312 - 114312

Published: May 19, 2023

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its pathogenesis limitations clinical treatment strategies, it poses serious medical challenge burden worldwide. The AD not clear, potential biological mechanisms include aggregation soluble amyloid form insoluble plaques, abnormal phosphorylation tau protein formation intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress metal ion disorders. Among them, ferroptosis newly discovered programmed cell death induced iron-dependent lipid peroxidation reactive oxygen species. Recent studies have shown that closely related AD, but the mechanism remains unclear. may be iron metabolism, amino acid metabolism affecting accumulation ions. Some chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine derivatives, antioxidants (vitamin E, lipoic acid, selenium), derivatives Fer-1, tet, etc. been in animal effective exert neuroprotective effects. This review summarizes regulation natural plant products on order provide reference information for future research development inhibitors.

Language: Английский

Citations

48
Iron homeostasis imbalance and ferroptosis in brain diseases DOI Creative Commons
Haining Long,

Wangshu Zhu,

Liming Wei

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: June 26, 2023

Brain iron homeostasis is maintained through the normal function of blood-brain barrier and regulation at systemic cellular levels, which fundamental to brain function. Excess can catalyze generation free radicals Fenton reactions due its dual redox state, thus causing oxidative stress. Numerous evidence has indicated diseases, especially stroke neurodegenerative are closely related mechanism imbalance in brain. For one thing, diseases promote accumulation. another, accumulation amplifies damage nervous system exacerbates patients' outcomes. In addition, triggers ferroptosis, a newly discovered iron-dependent type programmed cell death, neurodegeneration received wide attention recent years. this context, we outline metabolism focus on current stroke, Alzheimer's disease, Parkinson's disease. Meanwhile, also discuss ferroptosis simultaneously enumerate drugs for chelators inhibitors.

Language: Английский

Citations

47