16,882 results
Search Results
2. Unraveling the Mechanism of Cork Spot-like Physiological Disorders in 'Kurenainoyume' Apples Based on Occurrence Location.
- Author
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Imura, Eichi, Nakagomi, Mitsuho, Hayashida, Taishi, Fujita, Tomomichi, Sato, Saki, and Matsumoto, Kazuhiro
- Subjects
CORK ,COMPUTED tomography ,APPLES ,FRUIT development ,PAPER bags ,CELL death - Abstract
Cork spot-like physiological disorder (CSPD) is a newly identified issue in 'Kurenainoyume' apples, yet its mechanism remains unclear. To investigate CSPD, we conducted morphological observations on 'Kurenainoyume' apples with and without pre-harvest fruit-bagging treatment using light-impermeable paper bags. Non-bagged fruit developed CSPD in mid-August, while no CSPD symptoms were observed in bagged fruit. The bagging treatment significantly reduced the proportion of opened lenticels, with only 17.9% in bagged fruit compared to 52.0% in non-bagged fruits. In non-bagged fruit, CSPD spots tended to increase from the lenticels, growing in size during fruit development. The cuticular thickness and cross-sectional area of fresh cells in CSPD spots were approximately 16 µm and 1600 µm², respectively. Healthy non-bagged fruit reached these values around 100 to 115 days after full bloom from mid- to late August. Microscopic and computerized tomography scanning observations revealed that many CSPD spots developed at the tips of vascular bundles. Therefore, CSPD initiation between opened lenticels and vascular bundle tips may be influenced by water stress, which is potentially caused by water loss, leading to cell death and the formation of CSPD spots. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Human SHARPIN deficiency is linked to inborn errors of cell death.
- Subjects
- Humans, Mutation, Cell Death
- Published
- 2024
- Full Text
- View/download PDF
4. A white paper on Phospholipid Hydroperoxide Glutathione Peroxidase (GPx4) forty years later.
- Author
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Ursini, Fulvio, Bosello Travain, Valentina, Cozza, Giorgio, Miotto, Giovanni, Roveri, Antonella, Toppo, Stefano, and Maiorino, Matilde
- Subjects
- *
MEMBRANE lipids , *GLUTATHIONE peroxidase , *REVERSE genetics , *PEROXIDASE , *CELL death , *ANTINEOPLASTIC agents , *DEGENERATION (Pathology) - Abstract
The purification of a protein inhibiting lipid peroxidation led to the discovery of the selenoperoxidase GPx4 forty years ago. Thus, the evidence of the enzymatic activity was reached after identifying the biological effect and unambiguously defined the relationship between the biological function and the enzymatic activity. In the syllogism where GPx4 inhibits lipid peroxidation and its inhibition is lethal, cell death is operated by lipid peroxidation. Based on this rationale, this form of cell death emerged as regulated iron-enforced oxygen toxicity and was named ferroptosis in 2012. In the last decades, we learned that reduction of lipid hydroperoxides is indispensable and, in cooperation with prooxidant systems, controls the critical steady state of lipid peroxidation. This concept defined the GPx4 reaction as both the target for possible anti-cancer therapy and if insufficient, as cause of degenerative diseases. We know the reaction mechanism, but the details of the interaction at the membrane cytosol interface are still poorly defined. We know the gene structure, but the knowledge about expression control is still limited. The same holds true for post-transcriptional modifications. Reverse genetics indicate that GPx4 has a role in inflammation, immunity, and differentiation, but the observations emerging from these studies need a more specifically addressed biochemical evidence. Finally, the role of GPx4 in spermatogenesis disclosed an area unconnected to lipid peroxidation. In its mitochondrial and nuclear form, the peroxidase catalyzes the oxidation of protein thiols in two specific aspects of sperm maturation: stabilization of the mid-piece and chromatin compaction. Thus, although available evidence converges to the notion that GPx4 activity is vital due to the inhibition of lipid peroxidation, it is reasonable to foresee other unknown aspects of the GPx4 reaction to be disclosed. [Display omitted] • GPx4 is the vital selenoperoxidase active on membrane lipid hydroperoxides. • The redox center is flanked by a site for binding the phospholipid polar head. • GPx4 prevents regulated cell death routines operated by peroxidation. • Survival controlled by GPx4 impacts on immunity inflammation and differentiation. • Protein oxidation by distinct GPx4 isoforms is indispensable to sperm maturation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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5. The boundary-spanning mechanisms of Nobel Prize winning papers
- Author
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Chaomei Chen and Yakub Sebastian
- Subjects
FOS: Computer and information sciences ,Computer and Information Sciences ,Cell Physiology ,Entropy ,Autophagic Cell Death ,Science ,Boundary spanning ,Space (commercial competition) ,Bibliometrics ,Research and Analysis Methods ,Betweenness centrality ,Citation analysis ,Medicine and Health Sciences ,Centrality ,Digital Libraries (cs.DL) ,Sociology ,Multidisciplinary ,Cell Death ,Physics ,Publications ,Biology and Life Sciences ,Computer Science - Digital Libraries ,Cell Biology ,Research Assessment ,Nobel Prize ,Databases as Topic ,Cell Processes ,Citation Analysis ,Physical Sciences ,Thermodynamics ,Medicine ,Bibliographies as Topic ,Mathematical economics ,Network Analysis ,Research Article - Abstract
The breakthrough potentials of research papers can be explained by their boundary-spanning qualities. Here, for the first time, we apply the structural variation analysis (SVA) model and its affiliated metrics to investigate the extent to which such qualities characterize a group of Nobel Prize winning papers. We find that these papers share remarkable boundary-spanning traits, marked by exceptional abilities to connect disparate and topically-diverse clusters of research papers. Further, their publications exert structural variations on the scale that significantly alters the betweenness centrality distributions of existing intellectual space. Overall, SVA not only provides a set of leading indicators for describing future Nobel Prize winning papers, but also broadens our understanding of the similar prize-winning properties that may have been overlooked among other regular publications., 27 pages, 8 figures, 9 tables. Submitted to Frontiers in Research Metrics and Analytics
- Published
- 2021
6. HSP27 role in cardioprotection by modulating chemotherapeutic doxorubicin-induced cell death.
- Author
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Ramani S and Park S
- Subjects
- Animals, Antibiotics, Antineoplastic therapeutic use, Apoptosis drug effects, Apoptosis genetics, Cardiomyopathies etiology, Cardiomyopathies metabolism, Cardiotoxicity etiology, Cardiotoxicity metabolism, Cell Survival drug effects, Cell Survival genetics, Disease Susceptibility, Doxorubicin therapeutic use, HSP27 Heat-Shock Proteins metabolism, Heart Failure etiology, Heart Failure metabolism, Humans, Oxidative Stress drug effects, Antibiotics, Antineoplastic adverse effects, Cell Death drug effects, Cell Death genetics, Doxorubicin adverse effects, HSP27 Heat-Shock Proteins genetics
- Abstract
The common phenomenon expected from any anti-cancer drug in use is to kill the cancer cells without any side effects to non-malignant cells. Doxorubicin is an anthracycline derivative anti-cancer drug active over different types of cancers with anti-cancer activity but attributed to unintended cytotoxicity and genotoxicity triggering mitogenic signals inducing apoptosis. Administration of doxorubicin tends to both acute and chronic toxicity resulting in cardiomyopathy (left ventricular dysfunction) and congestive heart failure (CHF). Cardiotoxicity is prevented through administration of different cardioprotectants along with the drug. This review elaborates on mechanism of drug-mediated cardiotoxicity and attenuation principle by different cardioprotectants, with a focus on Hsp27 as cardioprotectant by prevention of drug-induced oxidative stress, cell survival pathways with suppression of intrinsic cell death. In conclusion, Hsp27 may offer an exciting/alternating cardioprotectant, with a wider study being need of the hour, specifically on primary cell line and animal models in conforming its cardioprotectant behaviour.
- Published
- 2021
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7. Determining the effector response to cell death.
- Author
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Rothlin CV, Hille TD, and Ghosh S
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- Animals, Cellular Microenvironment immunology, Cytokines immunology, Homeostasis immunology, Host-Pathogen Interactions immunology, Humans, Immunity, Innate, Mathematical Concepts, Models, Immunological, Phagocytes classification, Phagocytes immunology, Phagocytosis immunology, Signal Transduction immunology, Cell Death immunology
- Abstract
Cell death occurs when a pathogen invades a host organism or the organism is subjected to sterile injury. Thus, cell death is often closely associated with the induction of an immune response. Furthermore, cell death can occur as a consequence of the immune response and precedes the tissue renewal and repair responses that are initiated by innate immune cells during resolution of an immune response. Beyond immunity, cell death is required for development, morphogenesis and homeostasis. How can such a ubiquitous event as cell death trigger such a wide range of context-specific effector responses? Dying cells are sensed by innate immune cells using specialized receptors and phagocytosed through a process termed efferocytosis. Here, we outline a general principle whereby signals within the dead cell as well as the environment are integrated by specific efferocytes to define the appropriate effector response.
- Published
- 2021
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8. Consensus Paper. Cerebellar Reserve: From Cerebellar Physiology to Cerebellar Disorders.
- Author
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Mitoma, H., Buffo, A., Gelfo, F., Guell, X., Fucà, E., Kakei, S., Lee, J., Manto, M., Petrosini, L., Shaikh, A.G., and Schmahmann, J.D.
- Subjects
- *
PHYSIOLOGY , *EYE movements , *CEREBRAL hemispheres , *DISEASES , *SPINOCEREBELLAR ataxia , *CELL death - Abstract
Cerebellar reserve refers to the capacity of the cerebellum to compensate for tissue damage or loss of function resulting from many different etiologies. When the inciting event produces acute focal damage (e.g., stroke, trauma), impaired cerebellar function may be compensated for by other cerebellar areas or by extracerebellar structures (i.e., structural cerebellar reserve). In contrast, when pathological changes compromise cerebellar neuronal integrity gradually leading to cell death (e.g., metabolic and immune-mediated cerebellar ataxias, neurodegenerative ataxias), it is possible that the affected area itself can compensate for the slowly evolving cerebellar lesion (i.e., functional cerebellar reserve). Here, we examine cerebellar reserve from the perspective of the three cornerstones of clinical ataxiology: control of ocular movements, coordination of voluntary axial and appendicular movements, and cognitive functions. Current evidence indicates that cerebellar reserve is potentiated by environmental enrichment through the mechanisms of autophagy and synaptogenesis, suggesting that cerebellar reserve is not rigid or fixed, but exhibits plasticity potentiated by experience. These conclusions have therapeutic implications. During the period when cerebellar reserve is preserved, treatments should be directed at stopping disease progression and/or limiting the pathological process. Simultaneously, cerebellar reserve may be potentiated using multiple approaches. Potentiation of cerebellar reserve may lead to compensation and restoration of function in the setting of cerebellar diseases, and also in disorders primarily of the cerebral hemispheres by enhancing cerebellar mechanisms of action. It therefore appears that cerebellar reserve, and the underlying plasticity of cerebellar microcircuitry that enables it, may be of critical neurobiological importance to a wide range of neurological/neuropsychiatric conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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9. Simultaneous saccharification and co-fermentation of paper sludge to ethanol bySaccharomyces cerevisiaeRWB222-Part I: Kinetic modeling and parameters
- Author
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Oliver V. Townsend, Xiongjun Shao, Lee R. Lynd, and Jiayi Zhang
- Subjects
Paper ,Bioengineering ,Saccharomyces cerevisiae ,Cellulase ,Xylose ,Applied Microbiology and Biotechnology ,chemistry.chemical_compound ,Hydrolysis ,Enzymatic hydrolysis ,Ethanol fuel ,Cellulose ,Glucans ,Microbial Viability ,Models, Statistical ,Chromatography ,Cell Death ,Ethanol ,Sewage ,biology ,Xylan ,Kinetics ,chemistry ,Biochemistry ,Fermentation ,biology.protein ,Biotechnology - Abstract
A kinetic model was developed to predict batch simultaneous saccharification and co-fermentation (SSCF) of paper sludge by the xylose-utilizing yeast Saccharomyces cerevisiae RWB222 and the commercial cellulase preparation Spezyme CP. The model accounts for cellulose and xylan enzymatic hydrolysis and competitive uptake of glucose and xylose. Experimental results show that glucan and xylan enzymatic hydrolysis are highly correlated, and that the low concentrations of xylose encountered during SSCF do not have a significant inhibitory effect on enzymatic hydrolysis. Ethanol is found to not only inhibit the specific growth rate, but also to accelerate cell death. Glucose and xylose uptake rates were found to be competitively inhibitory, but this did not have a large impact during SSCF because the sugar concentrations are low. The model was used to evaluate which constants had the greatest impact on ethanol titer for a fixed substrate loading, enzyme loading, and fermentation time. The cellulose adsorption capacity and cellulose hydrolysis rate constants were found to have the greatest impact among enzymatic hydrolysis related constants, and ethanol yield and maximum ethanol tolerance had the greatest impact among fermentation related constants.
- Published
- 2009
10. Toxicity testing and chemical analyses of recycled fibre-based paper for food contact
- Author
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Anne Marie Vinggaard, Hanne Rosenquist, Tommy Licht Cederberg, Gitte Alsing Pedersen, Eva Rasmussen, and Mona-Lise Binderup
- Subjects
Paper ,Aerobic bacteria ,Health, Toxicology and Mutagenesis ,Bacillus cereus ,Food Contamination ,Pilot Projects ,engineering.material ,Toxicology ,Gas Chromatography-Mass Spectrometry ,Ames test ,chemistry.chemical_compound ,Toxicity Tests ,Equipment Reuse ,Humans ,Bioassay ,Food science ,Cell Death ,Ethanol ,biology ,Mutagenicity Tests ,Pulp (paper) ,Food Packaging ,Public Health, Environmental and Occupational Health ,Estrogens ,Resazurin ,General Chemistry ,biology.organism_classification ,Yeast ,Receptors, Aryl Hydrocarbon ,chemistry ,Chemistry (miscellaneous) ,Toxicity ,engineering ,Biological Assay ,Food Science - Abstract
Food-contact materials, including paper, have to comply with a basic set of criteria concerning safety. This means that paper for food contact should not give rise to migration of components, which can endanger human health. The objectives of this pilot study were, first, to compare paper of different qualities as food-contact materials and to perform a preliminary evaluation of their suitability, from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B-D) and a raw material produced from virgin fibres (A) were obtained from industry, and extracts were examined by chemical analyses and diverse in vitro toxicity test systems. The products tested were either based on different raw materials or different treatments were applied. Paper category B was made from 40% virgin fibres, 40% unprinted cuttings from newspapers, and 20% de-inked newspapers and magazines. Paper categories C and D were based on newspapers and magazines. However, paper D was de-inked, whereas C was not. To identify constituents of the papers with a potential to migrate into foodstuff, samples of the paper products were extracted with either 99% ethanol or water. Potential migrants in the extracts were identified and semiquantified by GC-IR-MS or GC-HRMS. In parallel to the chemical analyses, a battery of four different in vitro toxicity tests with different endpoints were applied to the same extracts. (1) a cytotoxicity test using normal human skin fibroblasts. The test was based on measurements of the reduction of resazurin to resorufin by cellular redox processes and used as a screening test for acute or general toxicity; (2) a Salmonella/microsome assay (Ames test) as a screening test for mutagenic and potentially carcinogenic compounds; (3) a recombinant yeast cell bioassay as a screening test for compounds with oestrogenic activity; (4) an aryl hydrocarbon (Ah)-receptor assay (CALUX assay) as a screening test for compounds with dioxin-like activity. In addition, the papers were testedfor microbial content and, in general, the microbiological load was quite low. The following microorganisms were counted and identified on both surface and homogenized pulp samples: the total number of aerobic bacteria, the number of aerobic and anaerobic spore formers, the number of Bacillus cereus/thuringiensis, and the number of yeast and moulds. The chemical analyses showed a significantly higher amount and different composition pattern of chemicals extracted with ethanol compared with water. Analyses of the ethanol extracts showed a distinctly smaller number and lower concentrations of chemicals in extracts prepared from sample A compared with extracts of samples B-D. The compounds identified in B-D were similar, but the amounts were lower in B compared with C and D. In accordance with the chemical analyses, the water extracts were less cytotoxic than the ethanol extracts. The extract prepared from virgin fibres was less cytotoxic than the extracts prepared from paper made from recycled fibres, and extracts prepared from C was the most cytotoxic. None of the extracts showed mutagenic activity. No conclusion about the oestrogenic activity could be made, because all extracts were cytotoxic to the test organism (yeast cells). Ethanol extracts of A and B showed a negligible positive response in the Ah-receptor assay at the highest nontoxic concentration, whereas C and D showed a more pronounced effect with C being the most potent. A comparable weak effect of water extracts of samples B-D was observed, too. However, the active compound(s) was not identified by chemical analyses.
- Published
- 2002
11. The gasdermins, a protein family executing cell death and inflammation.
- Author
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Broz P, Pelegrín P, and Shao F
- Subjects
- Cell Membrane metabolism, Cell Membrane Permeability physiology, Humans, Pyroptosis physiology, Cell Death physiology, Inflammation metabolism, Neoplasm Proteins metabolism
- Abstract
The gasdermins are a family of recently identified pore-forming effector proteins that cause membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. Gasdermins contain a cytotoxic N-terminal domain and a C-terminal repressor domain connected by a flexible linker. Proteolytic cleavage between these two domains releases the intramolecular inhibition on the cytotoxic domain, allowing it to insert into cell membranes and form large oligomeric pores, which disrupts ion homeostasis and induces cell death. Gasdermin-induced pyroptosis plays a prominent role in many hereditary diseases and (auto)inflammatory disorders as well as in cancer. In this Review, we discuss recent developments in gasdermin research with a focus on mechanisms that control gasdermin activation, pore formation and functional consequences of gasdermin-induced membrane permeabilization.
- Published
- 2020
- Full Text
- View/download PDF
12. Neighborhood size effects on mortality, growth and crown morphology of paper birch.
- Author
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Simard, Suzanne W. and Zimonick, Barbara J.
- Subjects
BIRCH ,BETULACEAE ,DEATH (Biology) ,CELL death - Abstract
Abstract: Neighborhood removal treatments are commonly used to increase forest tree productivity, but it is unknown if they correspond with target zone of perception or if they differentially affect mortality, growth and crown morphology. In 12–13-year-old stands, naturally regenerated paper birch (Betula papyrifera Marsh.) was removed in neighborhoods 1m, 2m, 3m, and 4m in radius using three methods (single cutting, double cutting, or triclopyr). Zone of neighbor perception for target birch ranged between 0.9 and 4m, depending on the response variable. The birch-free radius where neighbors started to reduce target performance was 3–4m for diameter increment and 2–3m for crown size. Crown diameter was reduced in 1m smaller radii than where height-to-live crown was increased. Self-thinning occurred in 0.9–1.3m spaced controls, but target mortality was not reduced with increased birch-free radius. Triclopyr killed most treated birch in all radii within 1 year, and also many target trees because of inter-tree chemical transfer through roots and soil. Most cut birch sprouted, but sprout mortality increased and height decreased with decreasing radius. A critical radius of 2–3m resulted in increased target diameter growth while still restricting crown expansion and suppressing neighbor sprouting. These results highlight the need to recognize variation in zone of perception for different response variables when evaluating competitive effects or designing removal treatments. [Copyright &y& Elsevier]
- Published
- 2005
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13. Separation and purification of dolichol and dolichyl phosphate by anion-exchange paper chromatography: application to cultured cells
- Author
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M.L. Tomassoni, A. Kupferberg, and M. Mersel
- Subjects
Chromatography, Paper ,Ion chromatography ,Biophysics ,Acetates ,Biochemistry ,chemistry.chemical_compound ,Dolichol ,Glycolipid ,Biosynthesis ,Dolichols ,Glycerol ,Animals ,Molecular Biology ,Ketocholesterols ,Cells, Cultured ,Cell Line, Transformed ,Brain Chemistry ,Dolichol Phosphates ,Chromatography ,biology ,Cell Death ,Chemistry ,Acid phosphatase ,Brain ,Cell Biology ,Chromatography, Ion Exchange ,Thin-layer chromatography ,Hydroxycholesterols ,Rats ,Paper chromatography ,Animals, Newborn ,Astrocytes ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Chromatography, Thin Layer - Abstract
Dolichyl phosphate, dolichol C80–105 (dolichol 17:dihydroheptadecaprenol-dolichol 21:dihydrohexeicosaprenol), and dolichol C55 (dolichol 11:dihydroundecaprenol) were separated by anion-exchange paper chromatography. Squalene, sterols, phospholipids, anionic glycolipids, and glycerol did not migrate as dolichyl phosphate, dolichol C80–105, and dolichol C55 under our elution conditions. However, since the R f of triglycerides was similar to that of dolichol C80–105, saponification, prior to chromatography, removed traces of triglycerides. Silica gel thin-layer chromatography (TLC) allowed the separation of dolichol C80–105 from dolichol C55, whereas dolichyl phosphate was eluted with other lipids. Incubation of spontaneously transformed cells derived from rat astrocytes primary cultures with [2- 14 C]acetate, saponification of the extracted lipids, and anion-exchange paper chromatography revealed the presence of radioactive dolichyl phosphate and dolichol C80–105 (15 pmol/mg protein). Extraction of labeled dolichyl phosphate followed by acid phosphatase treatment and subsequent analysis on TLC confirmed the identity of dolichyl phosphate since all the radioactivity was associated with dolichol C55. Treatment of the transformed cells with 30 μ m 7-ketocholesterol or 7β-hydroxycholesterol stimulated markedly (two- to threefold) the incorporation of [2- 14 C]acetate in both dolichol C80–105 and dolichyl phosphate. These data demonstrate that anion-exchange paper chromatography is technically suitable for the separation and analysis of dolichol C55, dolichol C80–105, and dolichyl phosphate in cultured cells prelabeled with radioactive precursors.
- Published
- 1992
14. Call for Special Issue Papers: Virus-Induced Programmed Cell Death: Deadline for Manuscript Submission: January 15, 2022.
- Author
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Russell, Rodney S.
- Subjects
- *
ACQUISITION of manuscripts , *CELL death , *APOPTOSIS , *CELL death inhibition - Abstract
We have known for decades that many viruses kill their host cells, and the discovery of programmed cell death, such as apoptosis, provided distinction from regular necrotic cell death. To highlight the various types of virus-induced cell death, and to frame these in the context of how they affect the immune response against various viruses, Viral Immunology is organizing a Special Issue on Virus-Induced Programmed Cell Death. [Extracted from the article]
- Published
- 2022
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15. Call for Special Issue Papers: Virus-Induced Programmed Cell Death: Deadline for Manuscript Submission: January 15, 2022.
- Author
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Russell, Rodney S.
- Subjects
- *
ACQUISITION of manuscripts , *CELL death , *APOPTOSIS , *CELL death inhibition - Abstract
We have known for decades that many viruses kill their host cells, and the discovery of programmed cell death, such as apoptosis, provided distinction from regular necrotic cell death. To highlight the various types of virus-induced cell death, and to frame these in the context of how they affect the immune response against various viruses, Viral Immunology is organizing a Special Issue on Virus-Induced Programmed Cell Death. [Extracted from the article]
- Published
- 2021
- Full Text
- View/download PDF
16. Research Trends and Most Influential Clinical Studies on Anti-PD1/PDL1 Immunotherapy for Cancers: A Bibliometric Analysis.
- Author
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Liu, Yanhao, Xu, Yan, Cheng, Xi, Lin, Yaru, Jiang, Shu, Yu, Haiming, Zhang, Zhen, Lu, Linlin, and Zhang, Xiaotao
- Subjects
NON-small-cell lung carcinoma ,BIBLIOMETRICS ,IMMUNOTHERAPY ,CELL death - Abstract
In this study, a bibliometric analysis was carried out to identify the most influential clinical studies and research trends on anti-programmed cell death 1/programmed cell death 1 ligand 1 (anti-PD1/PDL1) immunotherapy. On January 1, 2022, we used Web of Science to identify the 100 most frequently cited papers on clinical studies investigating anti-PD1/PDL1 immunotherapy, and extracted the following data: publication year, source title, country/region, institution, and the total number of citations. The research design and area were classified independently by the authors. Subsequently, we carried out a bibliometric analysis to determine the trends and identify the major journals on anti-PD1/PDL1 immunotherapy. The authors analyzed the current research hotspots based on papers published in major journals from 2020 to 2021. These 100 papers were cited a total of 138,840 times, and the median number of citations was 899.5 (range: 341–7,983). "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" by Topalian et al. had the highest number of citations (7,983 times). New England Journal of Medicine had the highest number of top-cited papers (40 papers), average citations per paper (1,558.3 citations), and rate of top-cited papers (65.6%). Authors from the USA contributed most of the papers (76 papers). Lung cancer (30 papers, 46,422 citations) and melanoma (20 papers, 30,881 citations) were the most cited research areas. In summary, anti-PD1/PDL1 has become standard treatment for various cancer, while adjuvant anti-PD1/PDL1 therapy is currently a research hotspot. New England Journal of Medicine was identified as the most influential journal in this area. Non-small cell lung cancer and melanoma are the most well-studied cancers, while nivolumab and pembrolizumab are the most commonly investigated anti-PD1/PDL1 antibodies. Further studies are warranted to identify effective predictive biomarkers or models, clarify the molecular mechanism of combined therapy, and establish optimal therapeutic strategies. This study may assist researchers in obtaining a comprehensive impression of the landscape and current trends in anti-PD1/PDL1 immunotherapy and gain inspiration to conduct further studies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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17. Eckpunktepapier zur notfallmedizinischen Versorgung der Bevölkerung in der Prä- und Hospitalphase.
- Author
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Scherer, G. and Luiz, T.
- Subjects
- *
MEDICAL emergencies , *MEDICAL societies , *CELL death , *PSYCHOLOGY of the sick , *TOTAL quality management , *EMERGENCY medical services - Abstract
Up-to-date management of medical emergencies implies primarily that definitive diagnoses and treatment are performed in a timely manner. These claims have been reconfirmed in 2007 by the leading German language medical associations in their 'White Paper on Emergency Treatment'. To actually realize the demands described in this paper a timely, transsectoral and close collaboration of all involved organizations is mandatory. To illustrate this race against cell death the phrase relay of survival is proposed and launched to replace the hitherto used but rigid concept of chain of survival. The tasks of each member of this relay of survival are critically scrutinized one after the other from a patient perspective. The paper presents tangible recommendations for improving the respective individual performance as well as, in particular, the cooperation and coordination between the team members which is comparable to handing over the baton in a relay race. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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18. Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.
- Author
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Deng, Huimin, Wei, Juan, Min, Keting, Yang, Hao, Wang, Sheng, Xiao, Zhuoran, Liu, Meiyun, Zheng, Li, Zhou, Huanping, Chen, Yuanli, Zhu, Wanli, Li, Quanfu, and Lv, Xin
- Subjects
BIBLIOMETRICS ,TRANSLATIONAL research ,RESEARCH teams ,MEDICAL research ,TUMOR microenvironment ,CELL death - Abstract
Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell‐death', 'iron', 'expression', and 'lipid‐peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. I think autophagy controls the death of my cells: What do I do to get my paper published?
- Author
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Andrew Thorburn
- Subjects
Publishing ,Programmed cell death ,Cell Death ,Mechanism (biology) ,Research ,Publications ,Autophagy ,Cell Biology ,Biology ,Cell biology ,Apoptosis ,Humans ,Molecular Biology ,Neuroscience - Abstract
Many people are studying how autophagy intersects with cell death. While most of those studies relate to autophagy acting as a protective mechanism (e.g., to block apoptosis), many papers conclude that autophagy is a death mechanism, and there is a widespread belief that autophagy (in most, but not all cases, we are talking about macroautophagy) can both kill and protect cells depending on the circumstances. Not surprisingly therefore, many of the papers submitted to Autophagy study the relationship between autophagy and cell death.
- Published
- 2011
20. TWO RECENT PAPERS SHED LIGHT ON HOW BREAST CANCER CELLS AVOID CELL DEATH
- Subjects
Cancer cells ,Cell death ,Biochemistry ,Breast cancer ,News, opinion and commentary ,University of Notre Dame - Abstract
NOTRE DAME, Ind. -- The following information was released by the University of Notre Dame: Two new papers from the lab of Zach Schafer, Coleman Assistant Professor of Cancer Biology [...]
- Published
- 2015
21. RESEARCH PAPER: miR-19 is a key oncogenic component of mir-17-92.
- Author
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Olive, Virginie, Bennett, Margaux J., Walker, James C., Cong Ma, Jiang, Iris, Cordon-Cardo, Carlos, Qi-Jing Li, Lowe, Scott W., Hannon, Gregory J., and Lin He
- Subjects
- *
LYMPHOMAS , *CANCER genetics , *TUMOR suppressor genes , *LABORATORY mice , *CELL death - Abstract
Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the Eμ1/4-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt?"mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
22. Morphological features and occurrence of degenerative characteristics in the hypopharyngeal glands of the paper wasp Polistes versicolor (Olivier) (Hymenoptera: Vespidae)
- Author
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Britto, Fábio Barros and Caetano, Flávio Henrique
- Subjects
- *
CELLS , *PHYSIOLOGY , *BIOLOGICAL transport , *BIOLOGY - Abstract
Abstract: Different histochemical techniques were applied to examine the morphological features of the secretory cells of hypopharyngeal glands in the wasp Polistes versicolor. The results showed that most analyzed individuals present active glands with secretion stored in the cytoplasm. In some glands, morphological analyses revealed the presence of degenerative characteristics. Analyses of cellular integrity, however, did not detect dead cells. The results showed that, in P. versicolor, the development and regression of the hypopharyngeal glands were not age related, unlike glands of social bees. [Copyright &y& Elsevier]
- Published
- 2006
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23. research paper Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase signalling pathway.
- Author
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Di Lu, Xiao-chun Bai, Li Gui, Yong-Chun Su, Fan Deng, Bin Liu, Xiu-Mei Li, Wei-Sen Zeng, Bao-Luan Cheng, and Shen-Qiu Luo
- Subjects
- *
HYDROGEN peroxide , *LYMPHOMAS , *RETICULOENDOTHELIAL granulomas , *APOPTOSIS , *CELL death , *CELL culture - Abstract
Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H2O2) on arsenic trioxide (As2O3)-induced cell killing. Low concentrations of H2O2 (200 μmol/l) inhibited the ability of As2O3 to induce apoptosis in the Burkitt's lymphoma cell line Raji. H2O2 altered the form of cell death from apoptosis to pyknosis/ necrosis and also lowered the degree of cell killing by As2O3. H2O2 was capable of preventing caspase-3 activation induced by As2O3 in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H2O2 on As2O2-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H2O2 on up-regulation of Bcl-2 and Bcl-X1. protein expression, down-regulation of Bax protein expression, and phosphorylation of Bcl-2 and IκBα. This investigation demonstrated for the first time that low concentrations of H2O2 provide protection against the in vivo of As2O3- induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H2O2, inhibiting As2O3-induced apoptosis in the Burkitt's lymphoma cells. As2O3-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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24. research paper Expression of cyclin E in resting and activated B-chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target.
- Author
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Decker, Thomas, Hipp, Susanne, Hahntow, Ines, Schneller, Folker, and Peschel, Christian
- Subjects
- *
LYMPHOCYTIC leukemia , *CYCLIN-dependent kinases , *B cells , *LEUKEMIA , *CELL proliferation , *CELL death - Abstract
Disease progression in B-cell chronic lymphocytic leukaemia (B-CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B-CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B-CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin-dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B-CLL cells. Cyclin E and cdk2 expression was increased in B-CLL cells stimulated with a CpG-oligodeoxynucleotide and interleukin-2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine-inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B-CLL. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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25. research paper Impairment of death-inducing signalling complex formation in CD95-resistant human primary lymphoma B cells.
- Author
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Lajmanovich, Alicia, Irisarri, Magdalena, Molens, Jean-Paul, Pasquier, Marie-Anne, Sotto, Jean-Jacques, Bensa, Jean-Claude, Leroux, Dominique, and Plumas, Joël
- Subjects
- *
CELLULAR signal transduction , *LYMPHOMAS , *CELL death , *B cells , *INTERLEUKIN-1 , *LYMPHOCYTES - Abstract
Multiple mechanisms exist by which tumour cells can escape CD95-mediated apoptosis. Previous studies by our laboratory have shown that primary B cells from non-Hodgkin's Lymphoma (B-NHL) were resistant to CD95-induced cell death. In the current study, we have analysed the mechanisms underlying CD95 resistance in primary human lymphoma B cells. We report that FADD (FAS-associated death domain protein) and caspase-8 were constitutively expressed in lymphoma B cells and that the CD95 pathway was blocked upstream to caspase-8 activation. However, caspase-8 was processed and functional after treatment with staurosporine (STS). We found that the expression levels of FLICE (FADD-like interleukin-1 beta-converting enzyme)-Inhibitory Protein (c-FLIP) and Bcl-2-related proteins were heterogeneous in B-NHL cells and were not related to CD95 resistance. Finally, we report the absence of a CD95-induced signalling complex [death-inducing signalling complex (DISC)] in lymphoma B cells, with no FADD and caspase-8 recruitment to CD95 receptor. In contrast, DISC formation was observed in CD95-resistant non-tumoural (NT) B cells. Therefore, we propose that the absence of DISC formation in primary lymphoma B cells may contribute to protect these cells from CD95-induced apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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- View/download PDF
26. research paper Apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive human leukaemia cells by enhancing the activation of mitochondria-dependent caspase cascades.
- Author
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Jin Seok Kim, Finbarr E., Hoi Kyung Jeung, Finbarr E., June-Won Cheong, Finbarr E., Hoyoung Maeng, Finbarr E., Seung Tae Lee, Finbarr E., Jee Sook Hahn, Finbarr E., Yun Woong Ko, Finbarr E., and Yoo Hong Min, Finbarr E.
- Subjects
- *
IMATINIB , *ANTINEOPLASTIC agents , *LEUKEMIA , *APOPTOSIS , *PROTEIN-tyrosine kinase inhibitors , *CELL death - Abstract
Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with potent antiproliferative activity against various cancer cells. We examined whether apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive human leukaemia cells. In K562 cells, the co-administration of minimally toxic concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a marked increase in mitochondrial damage, processing of caspase cascades and apoptosis. Similar results were observed in leukaemic blasts obtained from patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product. Both the degradation of XIAP and increased release of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a prominent decrease in Bcr–Abl protein levels in a caspase-dependent manner. In summary, these data indicate that apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive leukaemia cells through the enhanced activation of the mitochondria-dependent caspase cascades, accompanied by caspase-dependent downregulation of Bcr–Abl and XIAP. These findings generate a rationale for further investigation of apicidin and imatinib as a potential therapeutic strategy in Bcr–Abl-positive leukaemias. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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27. The labile iron pool: characterization, measurement, and participation in cellular processes1 <FN ID="FN1"><NO>1</NO>This article is part of a series of reviews on “Iron and Cellular Redox Status.” The full list of papers may be found on the homepage of the journal.</FN>
- Author
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Kakhlon, Or and Cabantchik, Z. Ioav
- Subjects
- *
IRON metabolism , *CELL death - Abstract
The cellular labile iron pool (LIP) is a pool of chelatable and redox-active iron, which is transitory and serves as a crossroad of cell iron metabolism. Various attempts have been made to analyze the levels of LIP following cell disruption. The chemical identity of this pool has remained poorly characterized due to the multiplicity of iron ligands present in cells. However, the levels of LIP recently have been assessed with novel nondisruptive techniques that rely on the application of fluorescent metalosensors. Methodologically, a fluorescent chelator loaded into living cells binds to components of the LIP and undergoes stoichiometric fluorescence quenching. The latter is revealed and quantified in situ by addition of strong permeating iron chelators. Depending on the intracellular distribution of the sensing and chelating probes, LIP can be differentially traced in subcellular structures, allowing the dynamic assessment of its levels and roles in specific cell compartments. The labile nature of LIP was also revealed by its capacity to promote formation of reactive oxygen species (ROS), whether from endogenous or exogenous redox-active sources. LIP and ROS levels were shown to follow similar “rise and fall” patterns as a result of changes in iron import vs. iron chelation or ferritin (FT) degradation vs. ferritin synthesis. Those patterns conform with the accepted role of LIP as a self-regulatory pool that is sensed by cytosolic iron regulatory proteins (IRPs) and feedback regulated by IRP-dependent expression of iron import and storage machineries. However, LIP can also be modulated by biochemical mechanisms that override the IRP regulatory loops and, thereby, contribute to basic cellular functions. This review deals with novel methodologies for assessing cellular LIP and with recent studies in which changes in LIP and ROS levels played a determining role in cellular processes. [Copyright &y& Elsevier]
- Published
- 2002
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28. Exploring the Role of Different Cell-Death-Related Genes in Sepsis Diagnosis Using a Machine Learning Algorithm.
- Author
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Wang, Xuesong, Wang, Ziyi, Guo, Zhe, Wang, Ziwen, Chen, Feng, and Wang, Zhong
- Subjects
MACHINE learning ,SEPSIS ,APOPTOSIS ,GENES ,CELL death - Abstract
Sepsis, a disease caused by severe infection, has a high mortality rate. At present, there is a lack of reliable algorithmic models for biomarker mining and diagnostic model construction for sepsis. Programmed cell death (PCD) has been shown to play a vital role in disease occurrence and progression, and different PCD-related genes have the potential to be targeted for the treatment of sepsis. In this paper, we analyzed PCD-related genes in sepsis. Implicated PCD processes include apoptosis, necroptosis, ferroptosis, pyroptosis, netotic cell death, entotic cell death, lysosome-dependent cell death, parthanatos, autophagy-dependent cell death, oxeiptosis, and alkaliptosis. We screened for diagnostic-related genes and constructed models for diagnosing sepsis using multiple machine-learning models. In addition, the immune landscape of sepsis was analyzed based on the diagnosis-related genes that were obtained. In this paper, 10 diagnosis-related genes were screened for using machine learning algorithms, and diagnostic models were constructed. The diagnostic model was validated in the internal and external test sets, and the Area Under Curve (AUC) reached 0.7951 in the internal test set and 0.9627 in the external test set. Furthermore, we verified the diagnostic gene via a qPCR experiment. The diagnostic-related genes and diagnostic genes obtained in this paper can be utilized as a reference for clinical sepsis diagnosis. The results of this study can act as a reference for the clinical diagnosis of sepsis and for target discovery for potential therapeutic drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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29. Ferroptosis as a New Type of Cell Death and its Role in Cancer Treatment.
- Author
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Skoupilová H, Michalová E, and Hrstka R
- Subjects
- Humans, Neoplasms drug therapy, Cell Death, Iron metabolism, Neoplasms metabolism, Reactive Oxygen Species metabolism
- Abstract
Background: Ferroptosis is a recently discovered type of cell death. It is genetically, morphologically, and biochemically distinct from other types of programmed cell death, such as necrosis, apoptosis, and autophagy. The level of intracellular free iron and reactive oxygen species formation are important for ferroptosis activation, which can occur through either of two key inhibitory processes. The first one involves inhibition of cystine transfer into cells by the cystine/glutamate antiporter system (Xc-). Cystine serves as a precursor for the synthesis of glutathione, a major cellular antioxidant. The second one involves the inhibition of glutathione peroxidase 4, which protects cells from lipid peroxidation. Ferroptosis is associated with many metabolic disorders, including neurological diseases and cancer. Molecules involved in the activation of ferroptotic pathways are involved in protecting cells against stress conditions, and in the maintenance of nicotinamide adenine dinucleotide phosphate and glutathione levels, as well as iron homeostasis. Also important is the connection with autophagy, so called ferritinophagy, in which iron is released from lysosomes into the cytosol. Cascade reactions of free unstable iron atoms with other molecules result in the production of reactive oxygen species that initiate the cellular stress that triggers ferroptosis. In diseases such as cancer where cell death inducing mechanisms, including apoptosis, are usually suppressed by genetic changes, the induction of alternative pathways leading to cell death could provide an attractive treatment strategy., Conclusion: In recent years, research into new antimetastatic drugs has focused on the activation of alternative cell death pathways that might overcome disturbed metabolic processes inside cancer cells or the chemotherapy resistance acquired in the course of routine treatment. A number of molecules have been found to induce ferroptosis in tumor cells, suggesting that they may offer new alternatives for anticancer treatment. Key words: cell death - cancer - autophagy - ferroptosis - ferritinophagy - cellular stress - ROS This work was supported by the projects GAČR 17-05838S, MEYS - NPS I - LO1413 and MH CZ- -DRO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 31. 8. 2018.
- Published
- 2018
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30. In response to the comments to the paper 'Modelling of cell killing due to sparsely ionizing radiation in normoxic and hypoxic conditions and an extension to high LET radiation' by T. Friedrich et al.
- Author
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Mairani, A., Böhlen, T. T., Dokic, I., Cabal, G., Brons, S., and Haberer, T.
- Subjects
- *
CELL death , *PHYSIOLOGICAL effects of ionizing radiation - Abstract
A response from A. Mairani and colleagues to a letter to the editor about their article "Modelling of Cell Killing Due to Sparsely Ionizing Radiation in Normoxic and Hypoxic Conditions and an Extension to High LET Radiation" in a 2013 issue is presented.
- Published
- 2015
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31. Cellular and molecular events in colorectal cancer: biological mechanisms, cell death pathways, drug resistance and signalling network interactions.
- Author
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Yan, Lei, Shi, Jia, and Zhu, Jiazuo
- Subjects
COLORECTAL cancer ,EPIGENOMICS ,CELL death ,DRUG resistance ,CARCINOGENS ,CELL analysis ,GENETIC mutation - Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies. Highlights: Colorectal cancer (CRC) is one of the leading causes of death among patients. CRC has been characterized with changes at the genetic and epigenetic factors. The molecular factors can be used as diagnostic and prognostic factors in CRC. The cell death mechanisms demonstrate dysregulation in CRC. Autophagy has aberrant activation in CRC and exerts dual function. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
32. A detailed overview of quercetin: implications for cell death and liver fibrosis mechanisms.
- Author
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Fei Xiong, Yichen Zhang, Ting Li, Yiping Tang, Si-Yuan Song, Qiao Zhou, and Yi Wang
- Subjects
HEPATIC fibrosis ,CELL death ,CARBON tetrachloride ,QUERCETIN ,LIVER cells ,PHYSICAL organic chemistry ,FLAVONOIDS - Abstract
Background: Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential. Purpose: This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis. Methods: A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employedwere "quercetin", "natural sources of quercetin", "quercetin extraction methods", "bioavailability of quercetin", "pharmacokinetics of quercetin", "cell death pathways", "apoptosis", "autophagy", "pyroptosis", "necroptosis", "ferroptosis", "cuproptosis", "liver fibrosis", and "hepatic stellate cells". These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis. Results: This review details quercetin's involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin's effectson liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin's structure and its potential for specific actions in the liver. Conclusion: The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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33. A bibliometric analysis of the research hotspots and frontiers related to cell death in spinal cord injury.
- Author
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Kelin He, Han Yu, Jieqi Zhang, Lei Wu, Dexiong Han, and Ruijie Ma
- Subjects
BIBLIOMETRICS ,CELL death ,SPINAL cord injuries ,CHINA-United States relations ,DATABASES - Abstract
Background: Spinal cord injury (SCI) is a severe central nervous trauma that can cause serious consequences. Cell death is emerging as a common pathogenesis after SCI. In the last two decades, numerous studies have been published in the field of cell death after SCI. However, it is still rare to find relevant bibliometric analyses. This bibliometric study aims to visually represent global research trends in the field of cell death after SCI. Methods: Bibliometric data were sourced from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and R software ("bibliometrix" package) were used to analyze and visualize bibliometric data. Annual scientific production, countries/regions, institutions, authors, journals, highly cited papers, keywords, and literature co-citation were evaluated to determine research performance. Results: An analysis of 5,078 publications extracted from the WoSCC database revealed a fluctuating yet persistent growth in the field of cell death after SCI over the past 23 years. China and the United States, contributing 69% of the total publications, were the main driving force in this field. The Wenzhou Medical University from China contributed to the most papers. In terms of authors, Salvatore Cuzzocrea from the University of Messina had the highest number of publications. The "Journal of Neurotrauma" was the top journal in terms of the number of publications, however, the "Journal of Neuroscience" was the top journal in terms of the number of citations. The theme of the highly cited articles mainly focused on the mechanism of cell death after SCI. The keyword and literature co-citation analysis mainly focused on the mode of cell death, mechanism research of cell death, and functional recovery after SCI. Conclusion: This study analyzes the research hotspots, frontiers, and development trends in the field of cell death after SCI, which is important for future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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34. New Notre Dame paper offers insights into how cancer cells avoid cell death
- Subjects
Biochemistry ,Cell death ,Cancer ,Cancer cells ,General interest ,University of Notre Dame - Abstract
India, June 23 -- A new study by a team of researchers from the University of Notre Dame provides an important new insight into how cancer cells are able to [...]
- Published
- 2013
35. NEW PAPER OFFERS INSIGHTS INTO HOW CANCER CELLS AVOID CELL DEATH
- Subjects
Biochemistry ,Cell death ,Cancer ,Cancer cells ,News, opinion and commentary ,University of Notre Dame - Abstract
NOTRE DAME, Ind. -- The following information was released by the University of Notre Dame: Author: William G. Gilroy Published: June 18, 2013 A new study by a team of [...]
- Published
- 2013
36. NEW PAPER DESCRIBES IMPORTANT ADVANCE IN IMAGING OF CELL DEATH
- Subjects
Biochemistry ,Cell death ,Medical research ,Medicine, Experimental ,Company legal issue ,News, opinion and commentary ,University of Notre Dame -- Investigations - Abstract
NOTRE DAME, Ind. -- The following information was released by the University of Notre Dame: For quite some time, the 'Holy Grail' in medical imaging has been the development of [...]
- Published
- 2010
37. Photodynamic Therapy and Adaptive Immunity Induced by Reactive Oxygen Species: Recent Reports.
- Author
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Aebisher, David, Woźnicki, Paweł, and Bartusik-Aebisher, Dorota
- Subjects
TUMOR treatment ,MYELOID-derived suppressor cells ,REACTIVE oxygen species ,SYSTEMATIC reviews ,MEDLINE ,METABOLITES ,CELL death ,PHOTODYNAMIC therapy ,INFLAMMATION ,ONLINE information services ,CYTOKINES ,EXTRACELLULAR matrix ,IMMUNITY - Abstract
Simple Summary: Photodynamic therapy (PDT) is a cancer treatment that uses photogenerated reactive oxygen species (ROS) to damage target cells. The unique mechanism of action of PDT involves the systemic or local administration of a photosensitizing compound (photosensitizer), which is then activated by light of a specific energy. PDT induces a very strong local inflammatory response. A number of adaptive mechanisms are induced within the tumor, related to increased amino acid metabolism and damage to lymphatic vessels. In this review, we are describing the adaptive immune response induced by ROS and generated by PDT. Cancer is one of the most significant causes of death worldwide. Despite the rapid development of modern forms of therapy, results are still unsatisfactory. The prognosis is further worsened by the ability of cancer cells to metastasize. Thus, more effective forms of therapy, such as photodynamic therapy, are constantly being developed. The photodynamic therapeutic regimen involves administering a photosensitizer that selectively accumulates in tumor cells or is present in tumor vasculature prior to irradiation with light at a wavelength corresponding to the photosensitizer absorbance, leading to the generation of reactive oxygen species. Reactive oxygen species are responsible for the direct and indirect destruction of cancer cells. Photodynamically induced local inflammation has been shown to have the ability to activate an adaptive immune system response resulting in the destruction of tumor lesions and the creation of an immune memory. This paper focuses on presenting the latest scientific reports on the specific immune response activated by photodynamic therapy. We present newly discovered mechanisms for the induction of the adaptive response by analyzing its various stages, and the possible difficulties in generating it. We also present the results of research over the past 10 years that have focused on improving the immunological efficacy of photodynamic therapy for improved cancer therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Metal ions overloading and cell death.
- Author
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Lai Y, Gao FF, Ge RT, Liu R, Ma S, and Liu X
- Subjects
- Humans, Animals, Oxidative Stress drug effects, Ions metabolism, Homeostasis drug effects, Apoptosis drug effects, Cell Death drug effects, Metals toxicity, Metals metabolism, Reactive Oxygen Species metabolism
- Abstract
Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca
2+ , Fe3+ , Cu2+ and Zn2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. HIGHLIGHTS: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death., (© 2024. The Author(s).)- Published
- 2024
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39. The formation of lamellar body-like structures may be a trigger of cetylpyridinium chloride-induced cell death and inflammatory response.
- Author
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Jung W, Yang MJ, Kang MS, Pyo G, Choi H, Li K, and Park EJ
- Subjects
- Animals, Humans, Female, Male, Mice, Cell Line, Lung drug effects, Lung pathology, Lung metabolism, Mitochondria drug effects, Mitochondria pathology, Mitochondria metabolism, Inflammation chemically induced, Inflammation pathology, Inflammation metabolism, Dose-Response Relationship, Drug, Cytokines metabolism, Cetylpyridinium toxicity, Cell Death drug effects
- Abstract
Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 μg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately -6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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- View/download PDF
40. Construction of an in vitro simulated one compartment extravascular administration model and its comparison with classic in vitro administration model in copper chloride induced HepG2 cell death.
- Author
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Yan L, Fu D, Chen J, Hao M, Fu J, Yao B, Hao W, and Zhao P
- Subjects
- Humans, Hep G2 Cells, Cell Survival drug effects, Toxicity Tests methods, Copper toxicity, Cell Death drug effects, Models, Biological
- Abstract
In this study, we designed an in vitro administration device based on compartment model theory and utilized it to construct an in vitro simulated one compartment extravascular administration model of copper chloride. Within the C
max range of 3.91-1000.00 μM, the measured concentration-time curves of the simulated one compartment extravascular administration model almost coincide with the corresponding theoretical curves. The measured values of toxicokinetic parameters, including ke , T1/2 , ka , T1/2a , Tmax , Cmax , CL, and AUC0-∞ are close to the corresponding theoretical values. The fitting coefficients are >0.9990. In simulated one compartment extravascular administration and classic in vitro administration, copper chloride dose-dependently induced HepG2 cell death. When Cmax /administration concentration is equal, classic in vitro administration induces a higher cell death rate than simulated one compartment extravascular administration. However, there is no significant difference in inducing cell death between the two administration models when area under the curve is equal. In conclusion, the device designed in this study can be used to in vitro simulate one compartment extravascular administration, making in vitro toxicity testing more similar to in vivo scenarios. There are differences in copper chloride induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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- View/download PDF
41. The autoimmune response induced by α-synuclein peptides drives neuronal cell death and glial cell activation.
- Author
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Choe YH, Jo MG, Kim BG, Lee S, Lee B, Kim SH, Seong H, Yoo WS, Kim M, Lee DK, Kim SJ, Yun SP, and Kim M
- Subjects
- Animals, Mice, Neuroglia immunology, Neuroglia metabolism, Neuroglia drug effects, Parkinson Disease immunology, Parkinson Disease pathology, Parkinson Disease metabolism, Mice, Inbred C57BL, Humans, Lymphocyte Activation immunology, Lymphocyte Activation drug effects, Peptides immunology, Cells, Cultured, Female, T-Lymphocytes, Regulatory immunology, alpha-Synuclein immunology, alpha-Synuclein metabolism, Autoimmunity, Cell Death drug effects, Neurons immunology, Neurons metabolism, Neurons pathology
- Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
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42. The crosstalk between cell death and pregnancy related diseases: A narrative review.
- Author
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Xie X, Liu J, Gao J, Shang C, Jiang Y, Chen L, Qian Z, Liu L, Wu D, Zhang Y, Ru Z, and Zhang Y
- Subjects
- Humans, Pregnancy, Female, Animals, Signal Transduction, Apoptosis physiology, Autophagy physiology, Cell Death physiology, Pregnancy Complications metabolism, Pregnancy Complications pathology
- Abstract
Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic β cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
43. Z-DNA binding protein 1 orchestrates innate immunity and inflammatory cell death.
- Author
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Song Q, Fan Y, Zhang H, and Wang N
- Subjects
- Humans, Animals, Signal Transduction immunology, Receptor-Interacting Protein Serine-Threonine Kinases immunology, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, Necroptosis immunology, Interferon Type I immunology, Interferon Type I metabolism, NF-kappa B metabolism, NF-kappa B immunology, Interferon Regulatory Factor-3 metabolism, Interferon Regulatory Factor-3 immunology, Apoptosis, Immunity, Innate, Inflammation immunology, Cell Death immunology, RNA-Binding Proteins immunology, RNA-Binding Proteins metabolism
- Abstract
Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
44. Involvement of multiple forms of cell death in patulin-induced toxicities.
- Author
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Fan L and Hu H
- Subjects
- Humans, Animals, Oxidative Stress drug effects, Signal Transduction drug effects, Apoptosis drug effects, Inflammasomes metabolism, Patulin toxicity, Cell Death drug effects
- Abstract
Patulin (PAT) is the most common mycotoxin found in moldy fruits and their derived products, and is reported to cause diverse toxic effects, including hepatotoxicity, nephrotoxicity, cardiotoxicity, neurotoxicity, immunotoxicity, gastrointestinal toxicity and dermal toxicity. The cell death induction by PAT is suggested to be a key cellular mechanism involved in PAT-induced toxicities. Accumulating evidence indicates that the multiple forms of cell death are induced in response to PAT exposure, including apoptosis, autophagic cell death, pyroptosis and ferroptosis. Mechanistically, the cell death induction by PAT is associated the oxidative stress induction via reducing the antioxidant capacity or inducing pro-oxidant NADPH oxidase, the activation of mitochondrial pathway via regulating BCL-2 family proteins, the disruption of iron metabolism through ferritinophagy-mediated ferritin degradation, and the induction of the NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome/caspase-1/gasdermin D (GSDMD) pathway. In this review article, we summarize the present understanding of the cell death induction by PAT, discuss the potential signaling pathways underlying PAT-induced cell death, and propose the issues that need to be addressed to promote the development of cell death-based approach to counteract PAT-induced toxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
45. New Notre Dame paper offers insights into how cancer cells avoid cell death
- Subjects
Biochemistry ,Cell death ,Antioxidants ,Cancer ,Cancer cells ,Business ,Health ,Health care industry ,University of Notre Dame - Abstract
By a News Reporter-Staff News Editor at Cancer Weekly -- A new study by a team of researchers from the University of Notre Dame provides an important new insight into [...]
- Published
- 2013
46. Enhanced Intracellular Reactive Oxygen Species by Photodynamic Therapy Effectively Promotes Chemoresistant Cell Death
- Author
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Xiaolin Xu, Chenglong Wang, Peipei Zhang, Xuzhu Gao, Wencai Guan, Fanchen Wang, Xin Li, Jia Yuan, Hongjing Dou, and Guoxiong Xu
- Subjects
Mice, Inbred BALB C ,Cell Death ,malignant tumor ,oxidative phosphorylation ,ROS ,Cell Biology ,glycolysis ,Xenograft Model Antitumor Assays ,Applied Microbiology and Biotechnology ,Mice ,Photochemotherapy ,photodynamic therapy ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Animals ,Humans ,Female ,Reactive Oxygen Species ,Molecular Biology ,Chemoresistance ,Ecology, Evolution, Behavior and Systematics ,Research Paper ,Developmental Biology - Abstract
Anti-cancer chemo-drugs can cause a rapid elevation of intracellular reactive oxygen species (ROS) levels. An imbalance in ROS production and elimination systems leads to cancer cell resistance to chemotherapy. This study aimed to evaluate the mechanism and effect of ROS on multidrug resistance in various human chemoresistant cancer cells by detecting the changes in the amount of ROS, the expression of ROS-related and glycolysis-related genes, and cell death. We found that ROS was decreased while oxidative phosphorylation was increased in chemoresistant cells. We verified that the chemoresistance of cancer cells was achieved in two ways. First, chemoresistant cells preferred oxidative phosphorylation instead of anaerobic glycolysis for energy generation, which increased ATPase activity and produced much more ATP to provide energy. Second, ROS-scavenging systems were enhanced in chemoresistant cancer cells, which in turn decreased ROS amount and thus inhibited chemo-induced cell death. Our in vitro and in vivo photodynamic therapy further demonstrated that elevated ROS production efficiently inhibited chemo-drug resistance and promoted chemoresistant cell death. Taken together, targeting ROS systems has a great potential to treat cancer patients with chemoresistance.
- Published
- 2022
47. Phyto‐fabricated silver nanoparticles inducing microbial cell death via reactive oxygen species‐mediated membrane damage
- Author
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Ch. V. Ramana Devi and L. Srinivas Naik
- Subjects
Silver ,Biocompatibility ,Metal Nanoparticles ,Microbial Sensitivity Tests ,Bacillus subtilis ,Silver nanoparticle ,Enterobacteriaceae ,Momordica dioica ,Electrical and Electronic Engineering ,Cell Death ,biology ,Plant Extracts ,Chemistry ,Biofilm ,Antimicrobial ,biology.organism_classification ,Anti-Bacterial Agents ,Electronic, Optical and Magnetic Materials ,Original Research Paper ,Membrane ,Nucleic acid ,Reactive Oxygen Species ,Original Research Papers ,TP248.13-248.65 ,Biotechnology ,Nuclear chemistry - Abstract
Eco‐friendly synthesis of the silver nanoparticles (AgNPs) has a number of advantages like simplicity, biocompatibility, low toxicity in nature over their physical and chemical methods. In the present study, the authors report biosynthesized AgNPs using the root extract of the perennial plant ‘Spiny gourd’ (Momordica dioica) and investigated their anti‐bacterial application with mechanistic approaches. Different biophysical techniques such as UV‐Vis spectroscopy, FTIR, XRD, TEM, SAED, and DLS were employed for AgNPs characterization. The synthesized AgNPs were polydispersed, crystalline in nature, with anionic surface (−22.3 mV), spherical in shape with an average size of 13.2 nm. In addition, the AgNPs were stable in room temperature and in different biological buffers. The anti‐bacterial activities of AgNPs were studied with respect to the pathogens such as Bacillus subtilis, Staphylococcus aureus (Gram‐positive), Pseudomonas aeruginosa, Escherichia coli, Klebsiella planticola (Gram‐negative), and Candida albicans. Also, mechanistic studies of AgNPs such as protein leakage assay, nucleic acid leakage assay, ATP leakage assay, ROS accumulation, determination of biofilm degrading activity, measurement of potassium, showing that the synthesized AgNPs are capable of containing a potential application in the antimicrobial therapeutic agents and the pharmaceutical industry.
- Published
- 2021
48. Celecoxib prevents tumor necrosis factor-α (TNF-α)-induced cellular senescence in human chondrocytes
- Author
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Qunli Wang, Qi Chen, Jie Sui, Yuanyuan Tu, Xiang Guo, and Feng Li
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,chondrocytes ,Bioengineering ,Ataxia Telangiectasia Mutated Proteins ,Resting Phase, Cell Cycle ,Applied Microbiology and Biotechnology ,Cell Line ,Humans ,Phosphorylation ,Telomerase ,Cellular Senescence ,Cell Death ,Tumor Necrosis Factor-alpha ,G1 Phase ,Cell Cycle Checkpoints ,General Medicine ,Checkpoint Kinase 2 ,osteoarthritis ,Celecoxib ,cell senescence ,Tumor Suppressor Protein p53 ,Reactive Oxygen Species ,TP248.13-248.65 ,Research Article ,Research Paper ,Biotechnology - Abstract
Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the elderly population and significantly impacts the normal life of OA patients. It has been reported that the development of pathological cell senescence in chondrocytes is involved in the pathogenesis of OA. Celecoxib is a common non-steroidal anti-inflammatory drug, and it has been recently reported to exert therapeutic effects on OA. However, its underlying mechanism is still unclear. The present study intends to explore its mechanism and provide fundamental evidence for the application of Celecoxib in the treatment of clinical OA. Tumor necrosis factor-α (TNF-α) was utilized to establish an in vitro model of chondrocytes senescence. The elevated reactive oxygen species (ROS) generation, increased cell cycle arrest in G0/G1 phase, reduced telomerase activity, and upregulated senescence-associatedβ-galactosidase (SA-β-Gal) staining were all observed in TNF-α-treated chondrocytes, which were then dramatically reversed by 10 and 20 μM Celecoxib. In addition, the upregulated DNA damage biomarkers, p-ATM, and p-CHK2, observed in TNF-α-treated chondrocytes were significantly downregulated by 10 and 20 μM Celecoxib. Lastly, the expression level of p21 and p53 was greatly elevated in chondrocytes by stimulation with TNF-α which was then pronouncedly repressed by treatment with Celecoxib. Taken together, our data reveal that Celecoxib ameliorated TNF-α-induced cellular senescence in human chondrocytes.
- Published
- 2021
49. Rotigotine protects against oxidized low-density lipoprotein(ox-LDL)-induced damages in human umbilical vein endothelial cells(HUVECs)
- Author
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Ge Cao, Hui Kang, Hui Yu, and Jingxiu Fan
- Subjects
huvecs ,Tetrahydronaphthalenes ,Bioengineering ,Thiophenes ,Pharmacology ,Protective Agents ,Applied Microbiology and Biotechnology ,Umbilical vein ,Monocytes ,chemistry.chemical_compound ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Cell adhesion ,nf-κb ,chemistry.chemical_classification ,Reactive oxygen species ,NADPH oxidase ,biology ,Cell Death ,Chemistry ,Cholesterol ,NF-kappa B ,rotigotine ,Rotigotine ,NF-κB ,General Medicine ,ox-ldl ,cardiovascular diseases ,Lipoproteins, LDL ,Oxidative Stress ,Receptors, LDL ,biology.protein ,Cytokines ,Inflammation Mediators ,Proprotein Convertase 9 ,Cell Adhesion Molecules ,TP248.13-248.65 ,medicine.drug ,Lipoprotein ,Research Article ,Research Paper ,Sterol Regulatory Element Binding Protein 2 ,Biotechnology - Abstract
Rotigotine is a non-ergoline dopamine agonist that has been licensed for the treatment of Parkinson’s disease. Cardiovascular diseases are the world’s leading cause of death. Ox-LDL- induced endothelial damages are involved in the initiation and progression of cardiovascular diseases. In this study, we assessed the beneficial properties of Rotigotine on ox-LDL-induced insults to HUVECs to highlight its potential use in the treatment of cardiovascular diseases. Our findings show that Rotigotine suppresses the expressions of low-density lipoprotein receptor (LDL-R), proprotein convertase subtilisin/kexin type 9 (PCSK-9), and sterol regulatory element-binding protein (SREBP-2). It also inhibits ox-LDL-induced cholesterol accumulation in endothelial cells (ECs), improves U937 monocytes adhesion, and decreases the representation of NADPH oxidase (NOX-4) and generation of reactive oxygen species (ROS) in endothelial cells (ECs). Furthermore, Rotigotine inhibited the expressions of both vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs and had anti-inflammatory efficacy in ox-LDL-induced cells by inhibiting the expressions of pro-inflammatory cytokines. Notably, Rotigotine inhibits the activation of nuclear factor-kappaB (NF-κB) by preventing nuclear translocation of NF-κB p65 and reducing the luciferase activity of NF-κB reporter. We, therefore, conclude that these effects of Rotigotine on HUVECs suggest that it may play a therapeutic role in cardiovascular diseases.
- Published
- 2021
50. Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology, molecular docking and experimental verification
- Author
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Rui Dong, Renxuan Huang, Xiaohua Shi, Zhongxin Xu, and Jing Mang
- Subjects
Cell Survival ,Bioengineering ,target prediction ,Network Pharmacology ,Applied Microbiology and Biotechnology ,PC12 Cells ,enrichment analysis ,ischemic stroke ,Animals ,Humans ,Protein Interaction Maps ,Luteolin ,Cell Death ,Reproducibility of Results ,General Medicine ,Rats ,Molecular Docking Simulation ,Oxygen ,Gene Ontology ,Glucose ,Gene Expression Regulation ,Caco-2 Cells ,TP248.13-248.65 ,Biotechnology ,Research Article ,Research Paper - Abstract
Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive research. Recently, traditional Chinese medicine has attracted attention because of potential benefits for stroke treatment. Among these, luteolin, a natural plant flavonoid compound, offers neuroprotection following against ischemic stroke, although the specific mechanisms are unknown. Here we used network pharmacology, molecular docking, and experimental verification to explore the mechanisms whereby luteolin can benefit stroke recovery. The pharmacological and molecular properties of luteolin were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The potential targets of luteolin and ischemic stroke were collected from interrogating public databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed by Funrich and Database for Annotation, Visualization and Integrated Discovery respectively, a luteolin-target-pathway network constructed using Cytoscape, Autodock vina was used for molecular docking simulation with Discovery Studio was used to visualize and analyze the docked conformations. Lastly, we employed an in vitro model of stroke injury to evaluate the effects of luteolin on cell survival and expression of the putative targets. From 95 candidate luteolin target genes, our analysis identified six core targets . KEGG analysis of the candidate targets identified that luteolin provides therapeutic effects on stroke through TNF signaling and other pathways. Our experimental analyses confirmed the conclusions analyzed above. In summary, the molecular and pharmacological mechanisms of luteolin against stroke are indicated in our study from a systematic perspective.
- Published
- 2021
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