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PloS One 2015Identification of specific cell death is of a great value for many scientists. Predominant types of cell death can be detected by flow-cytometry (FCM). Nevertheless, the...
Identification of specific cell death is of a great value for many scientists. Predominant types of cell death can be detected by flow-cytometry (FCM). Nevertheless, the absence of cellular morphology analysis leads to the misclassification of cell death type due to underestimated oncosis. However, the definition of the oncosis is important because of its potential reversibility. Therefore, FCM analysis of cell death using annexin V/propidium iodide assay was compared with holographic microscopy coupled with fluorescence detection - "Multimodal holographic microscopy (MHM)". The aim was to highlight FCM limitations and to point out MHM advantages. It was shown that the annexin V+/PI- phenotype is not specific of early apoptotic cells, as previously believed, and that morphological criteria have to be necessarily combined with annexin V/PI for the cell death type to be ascertained precisely. MHM makes it possible to distinguish oncosis clearly from apoptosis and to stratify the progression of oncosis.
Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Holography; Humans; Microscopy, Fluorescence; Multimodal Imaging; Necrosis; Phenotype; Time Factors
PubMed: 25803711
DOI: 10.1371/journal.pone.0121674 -
Journal of the American College of... Apr 2011The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients...
OBJECTIVES
The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities.
BACKGROUND
There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated.
METHODS
In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes.
RESULTS
CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality.
CONCLUSIONS
CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.
Topics: Adult; Cardiomyopathy, Dilated; Female; Fibrosis; Heart Failure; Humans; Male; Middle Aged; Myocytes, Cardiac; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Ventricular Remodeling
PubMed: 21453830
DOI: 10.1016/j.jacc.2010.09.080 -
Frontiers in Pharmacology 2020Artemisinin and its derivatives have shown broad-spectrum antitumor activities and . Furthermore, outcomes from a limited number of clinical trials provide encouraging... (Review)
Review
Artemisinin and its derivatives have shown broad-spectrum antitumor activities and . Furthermore, outcomes from a limited number of clinical trials provide encouraging evidence for their excellent antitumor activities. However, some problems such as poor solubility, toxicity and controversial mechanisms of action hamper their use as effective antitumor agents in the clinic. In order to accelerate the use of ARTs in the clinic, researchers have recently developed novel therapeutic approaches including developing novel derivatives, manufacturing novel nano-formulations, and combining ARTs with other drugs for cancer therapy. The related mechanisms of action were explored. This review describes ARTs used to induce non-apoptotic cell death containing oncosis, autophagy, and ferroptosis. Moreover, it highlights the ARTs-caused effects on cancer metabolism, immunosuppression and cancer stem cells and discusses clinical trials of ARTs used to treat cancer. The review provides additional insight into the molecular mechanism of action of ARTs and their considerable clinical potential.
PubMed: 33117153
DOI: 10.3389/fphar.2020.529881 -
Cellular and Molecular Life Sciences :... Sep 2022Oncosis (from Greek ónkos, meaning "swelling") is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of...
Oncosis (from Greek ónkos, meaning "swelling") is a non-apoptotic cell death process related to energy depletion. In contrast to apoptosis, which is the main form of cell death induced by anticancer drugs, oncosis has been relatively less explored but holds potential to overcome drug resistance phenomena. In this study, we report a novel rationally designed mitochondria-targeted iridium(III) complex (OncoIr3) with advantageous properties as a bioimaging agent. OncoIr3 exhibited potent anticancer activity in vitro against cancer cells and displayed low toxicity to normal dividing cells. Flow cytometry and fluorescence-based assays confirmed an apoptosis-independent mechanism involving energy depletion, mitochondrial dysfunction and cellular swelling that matched with the oncotic process. Furthermore, a Caenorhabditis elegans tumoral model was developed to test this compound in vivo, which allowed us to prove a strong oncosis-derived antitumor activity in animals (with a 41% reduction of tumor area). Indeed, OncoIr3 was non-toxic to the nematodes and extended their mean lifespan by 18%. Altogether, these findings might shed new light on the development of anticancer metallodrugs with non-conventional modes of action such as oncosis, which could be of particular interest for the treatment of apoptosis-resistant cancers.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Death; Cell Line, Tumor; Iridium; Necrosis; Neoplasms
PubMed: 36066676
DOI: 10.1007/s00018-022-04526-5 -
Cell Death and Differentiation Apr 2017Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory... (Review)
Review
Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections. Intriguingly, other gasdermin family members also share similar N-terminal domains, but they present different cell death programs. Herein, we summarize features and functions of the novel player proteins in cell death, including GSDMD triggering pyroptosis, Gsdma3/GSDMA initiating autophagy/apoptosis and DFNA5 inducing apoptosis/secondary necrosis. The gasdermin N terminus appears to be a novel pore-forming protein. This provides novel insight into the underlying roles and mechanisms of lytic or nonlytic forms of programmed cell death, as well as their potential applications in inflammation-associated diseases.
Topics: Autophagy; Caspases; Humans; Intracellular Signaling Peptides and Proteins; Neoplasm Proteins; Phosphate-Binding Proteins; Pyroptosis; Receptors, Estrogen; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Transforming Growth Factor beta
PubMed: 28362726
DOI: 10.1038/cdd.2017.24 -
Revista Espanola de Cardiologia Feb 2000Apoptosis consists of a distinct form of cell death that displays characteristic alterations in cell morphology and cell fate which are different than death due to... (Review)
Review
Apoptosis consists of a distinct form of cell death that displays characteristic alterations in cell morphology and cell fate which are different than death due to oncosis or necrosis. In terms of tissue kinetics, apoptosis may be considered a mechanism that counterbalances the effect of cell proliferation by mitotic division. In fact, deregulated apoptosis has been implicated in the development a wide variety of human diseases. Excessive apoptotic cell death may cause organ atrophy and organ failure. On the other hand, insufficient elimination of redundant cells may lead to organ and tissue structural remodeling. In recent years, apoptosis has become a highly fashionable and competitive area of research. Fortunately, it has not escaped the attention of the cardiovascular community. Sightings of apoptosis have been reported from every corner of cardiovascular medicine ranging from conduction system defects to congestive heart failure, and from atherosclerosis to aneurysms. There is no question that these sightings will eventually be converted into mechanistic etiopathogenic and physiopathological insights and will form the basis for designing new diagnostic modalities and novel therapies.
Topics: Apoptosis; Cardiovascular Diseases; Endothelium, Vascular; Humans; Muscle, Smooth, Vascular; Myocardium
PubMed: 10734757
DOI: 10.1016/s0300-8932(00)75089-5 -
Clinical and Experimental Immunology Apr 2012Death rules our lives. In this short paper, we summarize new insights into molecular mechanisms of neurodegeneration. Here we review the most important processes of cell... (Review)
Review
Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die--that is the question.
Death rules our lives. In this short paper, we summarize new insights into molecular mechanisms of neurodegeneration. Here we review the most important processes of cell death: apoptosis and oncosis. We focus on autophagy, which is pivotal for neuronal homeostasis, in the context of neurodegeneration, infection and immunity. Its dysfunction has been linked to several neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer's diseases. Our understanding is still incomplete, but may highlight attractive new avenues for the development of treatment strategies to combat neurodegenerative diseases.
Topics: Animals; Apoptosis; Autophagy; Central Nervous System; Central Nervous System Viral Diseases; Humans; Mice; Neurodegenerative Diseases; Neurons
PubMed: 22385237
DOI: 10.1111/j.1365-2249.2011.04544.x -
Theranostics 2023Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative... (Review)
Review
Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.
Topics: Humans; Nanomedicine; Hyperthermia, Induced; Neoplasms; Phototherapy; Combined Modality Therapy; Tumor Microenvironment; Cell Line, Tumor; Nanoparticles
PubMed: 37064867
DOI: 10.7150/thno.80887 -
Texas Heart Institute Journal 2013Ongoing investigation has provided new insights into the pathobiology of myocardial ischemic injury. These include an improved understanding of the roles of the major... (Review)
Review
Ongoing investigation has provided new insights into the pathobiology of myocardial ischemic injury. These include an improved understanding of the roles of the major modes of cell injury and death, including oncosis, apoptosis, and unregulated autophagy, as well as the central role of the mitochondria in the progression of myocardial ischemic injury, reperfusion injury, and myocardial conditioning. This understanding is providing insights for developing new pathophysiologic, pharmacologic, and cell-based therapies, alone or in combination with percutaneous coronary interventions, for better preservation of myocardium and reduction of morbidity and mortality rates from ischemic heart disease.
Topics: Acute Coronary Syndrome; Animals; Cell Death; Disease Progression; Humans; Mitochondria, Heart; Myocardium; Prognosis
PubMed: 23914009
DOI: No ID Found -
Journal of Healthcare Engineering 2021With the continuous popularization of smart medicine, the protective effect of silibinin in the liver has attracted much attention. This study mainly explores the liver...
With the continuous popularization of smart medicine, the protective effect of silibinin in the liver has attracted much attention. This study mainly explores the liver protection mechanism and absorption promotion technology of silybin based on intelligent medical analysis. Refining of silibinin: accurately weigh 1.0 g of silibinin in a three-necked flask; gradually add 50 mL of anhydrous methanol, reflux and filter the precipitated solid; and weigh it after drying. ICR male mice were taken as experimental subjects and randomly divided into groups of 10 each. The mice in the normal group and the model group were given intragastrically with 0.5% CMC-Na solution; the mice in the silibinin group were given intragastrically with SB/CMC-Na suspension; the mice in the remaining groups were given low, medium, and high-dose suspensions to their stomachs, and silibinin 23 acylate/CMC-Na suspension was administered at a dose of 10 mL/kg for 7 consecutive days. After that, the mice were fasted for 12 hours. After 6 hours of fasting (18 hours after modeling), the blood cells from their orbits were taken, placed in a 37°C water bath for 30 minutes, and centrifuged at 4000 rpm for 10 minutes, and then the serum was taken; the activity equivalent of AST and ALT in serum was measured; serum determination Medium AST and ALT vitality. The mice were killed by decapitation, fresh liver tissue was immediately collected, and part of it was frozen in liquid nitrogen for the RT-PCR test. The hepatocyte expansion and death were observed using a transmission electron microscope, and the oncosis index (OI) was calculated. Another part of the liver tissue was fixed in 4% paraformaldehyde solution, embedded in paraffin, dehydrated, and sliced at 4 m. Some sections were stained with conventional HE, and the pathological changes of liver cells were observed under light microscope; some sections were subjected to immunohistochemistry. Only one mouse died when 240 mg/kg of silibinin was given 10 minutes after the model was modeled. However, when 240 mg/kg silibinin was given to the mice 20 minutes after modeling, the mortality rate of the mice rose to 50%, and the therapeutic effect was significantly weakened. This research is helpful to advance the research of silybin in liver protection.
Topics: Animals; Humans; Liver; Male; Mice; Mice, Inbred ICR; Random Allocation; Silybin; Technology
PubMed: 34285784
DOI: 10.1155/2021/9968016