Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

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Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Autophagy is a mechanism by which cellular material is delivered to lysosomes for degradation, leading to the basal turnover of cell components and providing energy and macromolecular precursors. Autophagy has opposing, context-dependent roles in cancer, and interventions to both stimulate and inhibit autophagy have been proposed as cancer therapies. This has led to the therapeutic targeting of autophagy in cancer to be sometimes viewed as controversial. In this Review, we suggest a way forwards for the effective targeting of autophagy by understanding the context-dependent roles of autophagy and by capitalizing on modern approaches to clinical trial design.

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Targeting autophagy in cancer

Macroautophagy/autophagy is a conserved transport pathway where targeted structures are sequestered by phagophores, which mature into autophagosomes, and then delivered into lysosomes for degradati...

/pdf/chloroquine-inhibits-autophagic-flux-by-decreasing-29tresuftu.pdf

Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (β = −14.43, p = 0.008; β = −0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control.

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Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography

Purpose To develop a zebrafish cataract model for screening potential anti-cataract compounds. Methods Living zebrafish were anesthetized and exposed to ultraviolet-C (UV-C) irradiation at a dosage of 3250 mJ/cm2/d until they developed severe cataracts. These cataracts were graded based on photographs analyzed with ImageQuant TL version 7.0. Fish with severe cataracts were used to evaluate a range of compounds for cataract treatment, including the previously demonstrated hit compound lanosterol. For the initial evaluation, fish were divided into four groups: no treatment, balanced salt solution, β-cyclodextrin (β-CD), and lanosterol dissolved in β-CD. The treatments were performed for 10 days, and the clarity of lenses was evaluated. To assess the persistence of treatment, fish were treated with β-CD and lanosterol dissolved in β-CD for seven consecutive days followed by monitoring for three days without treatment. Results The average time for zebrafish to develop severe cataracts using the present UV-C irradiation protocol was 7.8 days (range 4–15 days). Both study designs required only another 10 days to determine the effect of hit compounds. The total experimental period could be completed within one month, and the entire experiment was economical. Conclusions We could assay a large number of hit compounds at a reasonable cost and within a short time using this newly developed zebrafish cataract model. These assays may allow development of an efficient platform for screening potential anti-cataract compounds. Translational Relevance The results may facilitate the development of ani-cataract medication for humans after further experiments and investigations.

Zebrafish (Danio rerio) Is an Economical and Efficient Animal Model for Screening Potential Anti-cataract Compounds

Coumarin was first discovered in Tonka bean and then widely in other plants. Coumarin has an anticoagulant effect, and its derivative, warfarin, is a vitamin K analogue that inhibits the synthesis of clotting factors and is more widely used in the clinical treatment of endovascular embolism. At present, many artificial chemical synthesis methods can be used to modify the structure of coumarin to develop many effective drugs with low toxicity. In this study, we investigated the effects of six coumarin derivatives on the platelet aggregation induced by adenosine diphosphate (ADP). We found that the six coumarin derivatives inhibited the active form of GPIIb/IIIa on platelets and hence inhibit platelet aggregation. We found that 7-hydroxy-3-phenyl 4H-chromen-4-one (7-hydroxyflavone) had the most severe effect. In addition, we further analyzed the downstream signal transduction of the ADP receptor, including the release of calcium ions and the regulation of cAMP, which were inhibited by the six coumarin derivatives selected in this study. These results suggest that coumarin derivatives inhibit coagulation by inhibiting the synthesis of coagulation factors and they may also inhibit platelet aggregation.

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Yau Hung Chen

Papers

Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography

Zebrafish (Danio rerio) Is an Economical and Efficient Animal Model for Screening Potential Anti-cataract Compounds

Coumarin Derivatives Inhibit ADP-Induced Platelet Activation and Aggregation