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SUMMARY Lesion‐mimic mutants (LMMs) serve as valuable resources for uncovering the molecular mechanisms that govern programmed cell death (PCD) in plants. Despite extensive research, the regulatory mechanisms of PCD and lesion formation in various LMMs remain to be fully elucidated. In this study, we identified a rice LMM named early leaf lesion and senescence 1 (els1), cloned the causal gene through map‐based cloning, and confirmed its function through complementation. ELS1 encodes an anthranilate synthase α‐subunit involved in anthranilate biosynthesis. It is predominantly localized in chloroplasts and is primarily expressed in light‐exposed tissues. Mutation of ELS1 triggers upregulation of its homologous gene, ASA1, via a genetic compensation response, leading to the activation of the tryptophan (Trp) synthesis pathway and amino acid metabolism. The accumulation of abnormal Trp‐derived intermediate metabolites results in reactive oxygen species (ROS) production and abnormal PCD in the els1 mutant, ultimately causing the leaf lesion phenotype. The els1 mutant also exhibits reduced chlorophyll content, upregulation of genes related to chloroplast degradation and leaf senescence, and decreased activity of photosynthetic proteins, indicating that ELS1 plays a role in chloroplast development. These factors collectively contribute to the premature leaf senescence observed in the els1 mutant. Our findings shed light on the role of ELS1 in regulating ROS accumulation and PCD in rice, providing further genetic insights into the molecular mechanisms governing leaf lesions and senescence. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) serves as the underlying pathology for various spinal degenerative conditions and is a primary contributor to low back pain (LBP). Recent studies have revealed a strong correlation between IDD and biological processes such as Programmed Cell Death (PCD), cellular senescence, inflammation, cell proliferation, extracellular matrix (ECM) degradation, and oxidative stress (OS). Of particular interest is the emerging evidence highlighting the significant involvement of the JNK signaling pathway in these fundamental biological processes of IDD. This paper explores the potential mechanisms through the JNK signaling pathway influences IDD in diverse ways. The objective of this article is to offer a fresh perspective and methodology for in-depth investigation into the pathogenesis of IDD by thoroughly examining the interplay between the JNK signaling pathway and IDD. Moreover, this paper summarizes the drugs and natural compounds that alleviate the progression of IDD by regulating the JNK signaling pathway. This paper aims to identify potential therapeutic targets and strategies for IDD treatment, providing valuable insights for clinical application. [ABSTRACT FROM AUTHOR]

PANoptosis, a burgeoning area of research, is a unique type of programmed cell death typified by pyroptosis, apoptosis, and necroptosis, yet it defies singular classification by any one mode of death. The assembly and activation of PANoptosomes are pivotal processes in PANoptosis, with several PANoptosomes already identified. Linkages between PANoptosis and the pathophysiology of various systemic illnesses are established, with increasing recognition of its association with oral ailments. This paper aims to deepen understanding by conducting a comprehensive analysis of the molecular pathways driving PANoptosis and exploring its potential implications in oral diseases. [ABSTRACT FROM AUTHOR]

Introduction: Programmed cell death (PCD) is a fundamental biological process crucial for plant development. Despite recent advancements in our understanding of PCD's molecular mechanisms, the intricate orchestration of this process within plant cells remains enigmatic. To address this knowledge gap, the present study focuses on Decaisnea insignis, a plant species renowned for its unique fruit anatomy, including laticiferous canals that secrete latex. While extensive anatomical studies have elucidated the structural features of these canals,molecular insights into their developmental regulation, particularly the involvement of PCD, are lacking. Methods: In this study, we sequenced the single-cell transcriptomes at two developmental stage of Decaisnea insignis fruit using the technology known as 10x Genomics (S1, S2). Using sequencing technology combining full- length RNA sequencing and single-nucleus RNA sequencing (snRNA-seq) in combination with ultrastructural analyses, our study revealed a cellular map of Decaisnea insignis fruit at the single-cell level and identified different cell types. Results: In particular, we identified a possible PCD-mediated cluster of Decaisnea insignis fruit lactiferous canals in epidermal cells and clarified the expression patterns of DiRD21A (a hydrolase) and DiLSD1 (a transcription factor), which may be closely related to the development of laticiferous canals in Decaisnea insignis fruits. Discussion: By integrating high-resolution gene expression profiling with visual insights into cellular transformations, we sought to more precisely characterize the regulatory role of PCD during the developmental formation of lactiferous canals in Decaisnea insignis fruit. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are formed in plant cells continuously. When ROS production exceeds the antioxidant capacity of the cells, oxidative stress develops which causes damage of cell components and may even lead to the induction of programmed cell death (PCD). The levels of ROS production increase upon abiotic stress, but also during pathogen attack in response to elicitors, and upon application of toxic compounds such as synthetic herbicides or natural phytotoxins. The commercial value of many synthetic herbicides is based on weed death as result of oxidative stress, and for a number of them, the site and the mechanism of ROS production have been characterized. This review summarizes the current knowledge on ROS production in plants subjected to different groups of synthetic herbicides and natural phytotoxins. We suggest that the use of ROS-specific fluorescent probes and of ROS-specific marker genes can provide important information on the mechanism of action of these toxins. Furthermore, we propose that, apart from oxidative damage, elicitation of ROS-induced PCD is emerging as one of the important processes underlying the action of herbicides and phytotoxins. [Display omitted] • The main reactive oxygen species (ROS) formed immediately after application of a phytotoxin indicate its mode of action. • ROS-specific marker genes and fluorescent probes can help to identify the major ROS induced in weeds by phytotoxins. • ROS induced in plants by natural phytotoxins can initiate programmed cell death (PCD). • Future herbicides with reduced toxicity for humans and animals should be based on induction of plant-specific PCD. [ABSTRACT FROM AUTHOR]

SUMMARY: Living organisms possess mechanisms to safeguard genome integrity. To avoid spreading mutations, DNA lesions are detected and cell division is temporarily arrested to allow repair mechanisms. Afterward, cells either resume division or respond to unsuccessful repair by undergoing programmed cell death (PCD). How the success rate of DNA repair connects to later cell fate decisions remains incompletely known, particularly in plants. The Arabidopsis thaliana RETINOBLASTOMA‐RELATED1 (RBR) protein and its partner E2FA, play both structural and transcriptional functions in the DNA damage response (DDR). Here we provide evidence that distinct RBR protein interactions with LXCXE motif‐containing proteins guide these processes. Using the N849F substitution in the RBR B‐pocket domain, which specifically disrupts binding to the LXCXE motif, we show that these interactions are dispensable in unchallenging conditions. However, N849F substitution abolishes RBR nuclear foci and promotes PCD and growth arrest upon genotoxic stress. NAC044, which promotes growth arrest and PCD, accumulates after the initial recruitment of RBR to foci and can bind non‐focalized RBR through the LXCXE motif in a phosphorylation‐independent manner, allowing interaction at different cell cycle phases. Disrupting NAC044‐RBR interaction impairs PCD, but their genetic interaction points to opposite independent roles in the regulation of PCD. The LXCXE‐binding dependency of the roles of RBR in the DDR suggests a coordinating mechanism to translate DNA repair success to cell survival. We propose that RBR and NAC044 act in two distinct DDR pathways, but interact to integrate input from both DDR pathways to decide upon an irreversible cell fate decision. Significance Statement: RBR has recently emerged as a DNA damage response regulator in parallel to SOG1, which promotes growth arrest and Programmed Cell Death (PCD) upon genotoxic stress. We report that the ability to interact with the LXCXE motif is essential for RBR to form repair foci and to bind NAC044, the closest homolog, and target of SOG1, to regulate DNA damage‐induced PCD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the systematic review is to verify the presence of PANoptosis in periodontitis based on the published literatures studying cell death in periodontitis. Materials and Methods: We conducted a comprehensive review of literature studying the types of cell death in vitro cellular experiments, in vivo rodent studies and clinical studies from three major databases: PubMed, Scopus, and Web of Science. The present systematic review was recorded in the PROSPERO database, under registration number CRD42022383456. Results: In total, 51 articles were included in this study. Our analysis of in vitro cell models revealed that pyroptosis, necroptosis, and apoptosis could be induced by periodontal pathogens in macrophages, fibroblasts, stem cells, and periodontal ligament cells. Furthermore, three types of cell death were detected in in vivo rodent periodontitis models. Clinical studies on human periodontitis tissue specimens and gingival crevicular fluid (GCF) showed that some key proteins related to pyroptosis, necroptosis, and apoptosis were elevated in periodontitis. Conclusions: Various studies have established similar in vivo and in vitro models with three modes of death detected under the same conditions, revealing complex interactions between different types of cell death pathways in periodontitis and the potential for PANoptosis to occur in periodontitis. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) presents a significant global health burden, characterized by a heterogeneous molecular landscape and various genetic and epigenetic alterations. Programmed cell death (PCD) plays a critical role in CRC, offering potential targets for therapy by regulating cell elimination processes that can suppress tumor growth or trigger cancer cell resistance. Understanding the complex interplay between PCD mechanisms and CRC pathogenesis is crucial. This study aims to construct a PCD‐related prognostic signature in CRC using machine learning integration, enhancing the precision of CRC prognosis prediction. Method: We retrieved expression data and clinical information from the Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Fifteen forms of PCD were identified, and corresponding gene sets were compiled. Machine learning algorithms, including Lasso, Ridge, Enet, StepCox, survivalSVM, CoxBoost, SuperPC, plsRcox, random survival forest (RSF), and gradient boosting machine, were integrated for model construction. The models were validated using six GEO datasets, and the programmed cell death score (PCDS) was established. Further, the model's effectiveness was compared with 109 transcriptome‐based CRC prognostic models. Result: Our integrated model successfully identified differentially expressed PCD‐related genes and stratified CRC samples into four subtypes with distinct prognostic implications. The optimal combination of machine learning models, RSF + Ridge, showed superior performance compared with traditional methods. The PCDS effectively stratified patients into high‐risk and low‐risk groups, with significant survival differences. Further analysis revealed the prognostic relevance of immune cell types and pathways associated with CRC subtypes. The model also identified hub genes and drug sensitivities relevant to CRC prognosis. Conclusion: The current study highlights the potential of integrating machine learning models to enhance the prediction of CRC prognosis. The developed prognostic signature, which is related to PCD, holds promise for personalized and effective therapeutic interventions in CRC. [ABSTRACT FROM AUTHOR]

Breast cancer is a prevalent and severe form of cancer that affects women all over the world. The incidence and mortality of breast cancer continue to rise due to factors such as population growth and the aging of the population. There is a growing area of research focused on a cell death mechanism known as PANoptosis. This mechanism is primarily regulated by the PANoptosome complex and displays important characteristics of cell death, including pyroptosis, apoptosis, and/or necroptosis, without being strictly defined by the cell death pathway. PANoptosis acts as a defensive response to external stimuli and pathogens, contributing to the maintenance of cellular homeostasis and overall stability. Increasing evidence suggests that programmed cell death (PCD) plays an important role in the development of breast cancer, and PANoptosis, as a novel form of PCD, may be a crucial factor in the development of breast cancer, potentially leading to the identification of new therapeutic strategies. Therefore, the concept of PANoptosis not only deepens our understanding of PCD, but also opens up new avenues for treating malignant diseases, including breast cancer. This review aims to provide an overview of the definition of PANoptosis, systematically explore the interplay between PANoptosis and various forms of PCD, and discuss its implications for breast cancer. Additionally, it delves into the current progress and future directions of PANoptosis research in the context of breast cancer, establishing a theoretical foundation for the development of molecular targets within critical signaling pathways related to PANoptosis, as well as multi-target combination therapy approaches, with the goal of inducing PANoptosis as part of breast cancer treatment. [ABSTRACT FROM AUTHOR]

Key message: Cathepsin B plays an important role that degrades the Rubisco large subunit RbcL in freezing stress. Programmed cell death (PCD) has been well documented in both development and in response to environmental stresses in plants, however, PCD induced by freezing stress and its molecular mechanisms remain poorly understood. In the present study, we characterized freezing-induced PCD and explored its mechanisms in Arabidopsis. PCD induced by freezing stress was similar to that induced by other stresses and senescence in Arabidopsis plants with cold acclimation. Inhibitor treatment assays and immunoblotting indicated that cathepsin B mainly contributed to increased caspase-3-like activity during freezing-induced PCD. Cathepsin B was involved in freezing-induced PCD and degraded the large subunit, RbcL, of Rubisco. Our results demonstrate an essential regulatory mechanism of cathepsin B for Rubisco degradation in freezing-induced PCD, improving our understanding of freezing-induced cell death and nitrogen and carbohydrate remobilisation in plants. [ABSTRACT FROM AUTHOR]

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte’s programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI. [ABSTRACT FROM AUTHOR]

Abstract Background The aleurone layer is a part of many plant seeds, and during seed germination, aleurone cells undergo PCD, which is promoted by GA from the embryo. However, the numerous components of the GA signaling pathway that mediate PCD of the aleurone layers remain to be identified. Few genes and transcriptomes have been studied thus far in aleurone layers to improve our understanding of how PCD occurs and how the regulatory mechanism functions during PCD. Our previous studies have shown that histone deacetylases (HDACs) are required in GA-induced PCD of aleurone layer. To further explore the molecular mechanisms by which epigenetic modifications regulate aleurone PCD, we performed a global comparative transcriptome analysis of embryoless aleurones treated with GA or histone acetylase (HAT) inhibitors. Results In this study, a total of 7,919 differentially expressed genes (DEGs) were analyzed, 2,554 DEGs of which were found to be common under two treatments. These identified DEGs were involved in various biological processes, including DNA methylation, lipid metabolism and ROS signaling. Further investigations revealed that inhibition of DNA methyltransferases prevented aleurone PCD, suggesting that active DNA methylation plays a role in regulating aleurone PCD. GA or HAT inhibitor induced lipoxygenase gene expression, leading to lipid degradation, but this process was not affected by DNA methylation. However, DNA methylation inhibitor could regulate ROS-related gene expression and inhibit GA-induced production of hydrogen peroxide (H2O2). Conclusion Overall, linking of lipoxygenase, DNA methylation, and H2O2 may indicate that GA-induced higher HDAC activity in aleurones causes breakdown of lipids via regulating lipoxygenase gene expression, and increased DNA methylation positively mediates H2O2 production; thus, DNA methylation and lipid metabolism pathways may represent an important and complex signaling network in maize aleurone PCD.

Background: Uncontrolled cellular proliferation may result in the progression of diseases such as cancer that promote organism death. Programmed cell death (PCD) is an important mechanism that ensures the quality and quantity of cells, which could be developed as a potential biomarker for disease diagnosis and treatment. Methods: RNA-seq data and clinical information of nasopharyngeal carcinoma (NPC) patients were downloaded from the Gene Expression Omnibus (GEO), and 1548 PCD-related genes were collected. We used the “limma” package to analyze differentially expressed genes (DEGs). The STRING database was used for protein interaction analysis, and the least absolute shrinkage and selection operator (Lasso) and support vector machines (SVMs) regression analyses were used to identify biomarkers. Then, the timeROC package was used for classifier efficiency assessment, and the “CIBERSORT” package was used for immune infiltration analysis. Wound healing and transwell migration assay were performed to evaluate migration and invasion. Results: We identified 800 DEGs between our control and NPC patient groups, in which 59 genes appeared to be PCD-related DEGs, with their function closely associated with NPC progression, including activation of the PI3K–Akt, TGF-β, and IL-17 signaling pathways. Furthermore, based on the STRING database, Cytoscape and six algorithms were employed to screen 16 important genes (GAPDH, FN1, IFNG, PTGS2, CXCL1, MYC, MUC1, LTF, S100A8, CAV1, CDK4, EZH2, AURKA, IL33, S100A9, and MIF). Subsequently, two reliably characterized biomarkers, FN1 and MUC1, were obtained from the Lasso and SVM analyses. The Receiver operating characteristic (ROC) curves showed that both biomarkers had area under the curve (AUC) values higher than 0.9. Meanwhile, the enrichment analysis showed that in NPC patients, the FN1 and MUC1 expression levels correlated with programmed cell death-related pathways. The enrichment analysis and cellular experimental results indicated that FN1 and MUC1 were overexpressed in NPC cells and associated with programmed cell death-related pathways. Importantly, FN1 and MUC1 severely affected the ability of NPC cells to migrate, invade, and undergo apoptosis. Finally, medroxyprogesterone acetate and 8-Bromo-cAMP acted as drug molecules for the docking of FN1 and MUC1 molecules, respectively, and had binding capacities of –9.17 and –7.27 kcal/mol, respectively. Conclusion: We examined the PCD-related phenotypes and screened FN1 and MUC1 as reliable biomarkers of NPC; our findings may promote the development of NPC treatment strategy.

Background: The aleurone layer is a part of many plant seeds, and during seed germination, aleurone cells undergo PCD, which is promoted by GA from the embryo. However, the numerous components of the GA signaling pathway that mediate PCD of the aleurone layers remain to be identified. Few genes and transcriptomes have been studied thus far in aleurone layers to improve our understanding of how PCD occurs and how the regulatory mechanism functions during PCD. Our previous studies have shown that histone deacetylases (HDACs) are required in GA-induced PCD of aleurone layer. To further explore the molecular mechanisms by which epigenetic modifications regulate aleurone PCD, we performed a global comparative transcriptome analysis of embryoless aleurones treated with GA or histone acetylase (HAT) inhibitors. Results: In this study, a total of 7,919 differentially expressed genes (DEGs) were analyzed, 2,554 DEGs of which were found to be common under two treatments. These identified DEGs were involved in various biological processes, including DNA methylation, lipid metabolism and ROS signaling. Further investigations revealed that inhibition of DNA methyltransferases prevented aleurone PCD, suggesting that active DNA methylation plays a role in regulating aleurone PCD. GA or HAT inhibitor induced lipoxygenase gene expression, leading to lipid degradation, but this process was not affected by DNA methylation. However, DNA methylation inhibitor could regulate ROS-related gene expression and inhibit GA-induced production of hydrogen peroxide (H2O2). Conclusion: Overall, linking of lipoxygenase, DNA methylation, and H2O2 may indicate that GA-induced higher HDAC activity in aleurones causes breakdown of lipids via regulating lipoxygenase gene expression, and increased DNA methylation positively mediates H2O2 production; thus, DNA methylation and lipid metabolism pathways may represent an important and complex signaling network in maize aleurone PCD. [ABSTRACT FROM AUTHOR]

Seed aging, a common physiological phenomenon during forage seed storage, is a crucial factor contributing to a loss of vigor, resulting in delayed seed germination and seedling growth, as well as limiting the production of hay. Extensive bodies of research are dedicated to the study of seed aging, with a particular focus on the role of the production and accumulation of reactive oxygen species (ROS) and the ensuing oxidative damage during storage as a primary cause of decreases in seed vigor. To preserve optimal seed vigor, ROS levels must be regulated. The excessive accumulation of ROS can trigger programmed cell death (PCD), which causes the seed to lose vigor permanently. LESION SIMULATING DISEASE (LSD) is one of the proteins that regulate PCD, encodes a small C2C2 zinc finger protein, and plays a molecular function as a transcriptional regulator and scaffold protein. However, genome-wide analysis of LSD genes has not been performed for alfalfa (Medicago sativa), as one of the most important crop species, and, presently, the molecular regulation mechanism of seed aging is not clear enough. Numerous studies have also been unable to explain the essence of seed aging for LSD gene regulating PCD and affecting seed vigor. In this study, we obtained six MsLSD genes in total from the alfalfa (cultivar Zhongmu No. 1) genome. Phylogenetic analysis demonstrated that the MsLSD genes could be classified into three subgroups. In addition, six MsLSD genes were unevenly mapped on three chromosomes in alfalfa. Gene duplication analysis demonstrated that segmental duplication was the key driving force for the expansion of this gene family during evolution. Expression analysis of six MsLSD genes in various tissues and germinating seeds presented their different expressions. RT-qPCR analysis revealed that the expression of three MsLSD genes, including MsLSD2, MsLSD5, and MsLSD6, was significantly induced by seed aging treatment, suggesting that they might play an important role in maintaining seed vigor. Although this finding will provide valuable insights into unveiling the molecular mechanism involved in losing vigor and new strategies to improve alfalfa seed germinability, additional research must comprehensively elucidate the precise pathways through which the MsLSD genes regulate seed vigor. [ABSTRACT FROM AUTHOR]

Flower senescence is a fundamental aspect of the developmental trajectory in flowers, occurring after the differentiation of tissues and maturation of petals, and preceding the growth and development of seeds. It is accompanied by various alterations at the cytological, physiological, and molecular levels, similar to other forms of programmed cell death (PCD). It involves an intricate interplay of various plant growth regulators, with ethylene being the key orchestrator in ethylene-dependent petal senescence. Petal senescence mediated by ethylene is marked by various changes such as petal wilting, amplified oxidative stress, degradation of proteins and nucleic acids, and autophagy. Ethylene crosstalks with other growth regulators and triggers genetic and/or epigenetic reprogramming of genes during senescence in flowers. While our understanding of the mechanism and regulation of petal senescence in ethylene-sensitive species has advanced, significant knowledge gaps still exist, which demand critical reappraisal of the available literature on the topic. A deeper understanding of the various mechanisms and regulatory pathways involved in ethylene-dependent senescence has the capacity to facilitate a more precise regulation of the timing and site of senescence, thus leading to optimized crop yields, enhanced product quality, and extended longevity. [ABSTRACT FROM AUTHOR]

The chemical diversity of sphingolipids in plants allows the assignment of specific roles to special molecular species. These roles include NaCl receptors for glycosylinositolphosphoceramides or second messengers for long-chain bases (LCBs), free or in their acylated forms. Such signaling function has been associated with plant immunity, with an apparent connection to mitogen-activated protein kinase 6 (MPK6) and reactive oxygen species (ROS). This work used in planta assays with mutants and fumonisin B1 (FB1) to generate varying levels of endogenous sphingolipids. This was complemented with in planta pathogenicity tests using virulent and avirulent Pseudomonas syringae strains. Our results indicate that the surge of specific free LCBs and ceramides induced by FB1 or an avirulent strain trigger a biphasic ROS production. The first transient phase is partially produced by NADPH oxidase, and the second is sustained and is related to programmed cell death. MPK6 acts downstream of LCB buildup and upstream of late ROS and is required to selectively inhibit the growth of the avirulent but not the virulent strain. Altogether, these results provide evidence that a LCB– MPK6– ROS signaling pathway contributes differentially to the two forms of immunity described in plants, upregulating the defense scheme of a non-compatible interaction. [ABSTRACT FROM AUTHOR]

A lung illness with the longest English word (45 letters) pneumono ultramicroscopic silicovolcanoconiosis Inhaling sand and silica dust can lead to the lung irritation that results in silicosis. The earth's crust has the most silica minerals. Affected individuals are those who breathe in the fine silica dust while working in the mining or construction industries. Silicosis is a degenerative condition that has no known treatment. Infections like mycobacterial infection, fungal infection, and TB are caused by it. This article outlines the several types of silicosis, as well as it historical context, epidemiology, diagnosis and therapy. The progression of silicosis is thought to be intimately related to programmed cell death (PCD), which includes autophagy, apoptosis and pyro ptosis, according to our hypothesis in this review and additionally, proteins plays a significant role in formation and development of silicosis. In conclusion, more in depth study on these mechanism and impact may be anticipated to become interesting candidates for silica therapy or intervention in future[1]. [ABSTRACT FROM AUTHOR]

Plant glandular trichomes have received much attention due to their commercial and biological value. Recent studies have focused on the development of various glands in plants, suggesting that programmed cell death (PCD) may play an important role during the development of plant secretory structures. However, the development processes and cytological characteristics in different types of plant secretory structures differed significantly. This study aims to provide new data on the developmental PCD of the capitate glandular hairs in Dictamnus dasycarpus. Light, scanning, immunofluorescence labeling, and transmission electron microscopy were used to determine the different developmental processes of the capitate glandular hairs from a cytological perspective. Morphologically, the capitate glandular hair originates from one initial epidermal cell and differentiates into a multicellular trichome characterized by two basal cells, two lines of stalk cells, and a multicellular head. It is also histochemically detected by essential oils. TUNEL-positive reactions identified nuclei with diffused fluorescence or an irregular figure by DAPI, and Evans blue staining showed that the head and stalk cells lost their viability. Ultrastructural evidence revealed the developmental process by two possible modes of PCD. Non-autolytic PCD was characterized by buckling cell walls and degenerated nuclei, mitochondria, plastids, multivesicular body (MVB), and end-expanded endoplasmic reticulum in the condensed cytoplasm, which were mainly observed in the head cells. The MVB was detected in the degraded vacuole, a degraded nucleus with condensed chromatin and diffused membrane, and eventual loss of the vacuole membrane integrity exhibited typical evidence of vacuole-mediated autolytic PCD in the stalk cells. Furthermore, protoplasm degeneration coupled with dark oil droplets and numerous micro-dark osmiophilic substances was observed during late stages. The secretion mode of essential oils is also described in this paper. [ABSTRACT FROM AUTHOR]

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This article is a Commentary on Wang et al. (2022), 236: 1691–1707. [ABSTRACT FROM AUTHOR]

The beneficial effects of γ-aminobutyric acid (GABA) on oxidative damage and programmed cell death (PCD) in fresh-cut pumpkins were preliminarily demonstrated in our previous research. However, the mechanism by which GABA alleviates PCD in fresh-cut pumpkins remains unclear. In this study, we discovered that GABA treatment effectively reduced mitochondrial structural damage and membrane permeability while increasing the mitochondrial membrane potential (ΔΨm) in fresh-cut pumpkins compared to the control. Additionally, GABA-treated pumpkins exhibited higher adenosine triphosphate (ATP) content and energy charge, consistent with increased activity of H+-ATPase, succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and cytochrome c oxidase (COX). Conversely, the activity of alternative oxidase (AOX), Ca2+-ATPase, and K+-ATPase was reduced in GABA-treated pumpkins compared to the control. Moreover, key factors in apoptosis, such as the activity of six caspases and the gene expression of apoptosis-inducing factors (CmAIFs) and metacaspases (CmMCAs), were significantly decreased following GABA treatment. In conclusion, GABA effectively suppressed PCD in postharvest fresh-cut pumpkins by improving mitochondrial physiological properties and energy metabolism while inhibiting apoptosis-related factors. [Display omitted] ● GABA maintained normal ΔΨm, MPTP and ultrastructure of mitochondria. ● GABA increased energy charge by enhancing TCA cycle and electron transport chain. ● GABA decreased the activity and gene expression of apoptosis factors to inhibit PCD. [ABSTRACT FROM AUTHOR]

Seed aging, a common physiological phenomenon during forage seed storage, is a crucial factor contributing to a loss of vigor, resulting in delayed seed germination and seedling growth, as well as limiting the production of hay. Extensive bodies of research are dedicated to the study of seed aging, with a particular focus on the role of the production and accumulation of reactive oxygen species (ROS) and the ensuing oxidative damage during storage as a primary cause of decreases in seed vigor. To preserve optimal seed vigor, ROS levels must be regulated. The excessive accumulation of ROS can trigger programmed cell death (PCD), which causes the seed to lose vigor permanently. LESION SIMULATING DISEASE (LSD) is one of the proteins that regulate PCD, encodes a small C2C2 zinc finger protein, and plays a molecular function as a transcriptional regulator and scaffold protein. However, genome-wide analysis of LSD genes has not been performed for alfalfa (Medicago sativa), as one of the most important crop species, and, presently, the molecular regulation mechanism of seed aging is not clear enough. Numerous studies have also been unable to explain the essence of seed aging for LSD gene regulating PCD and affecting seed vigor. In this study, we obtained six MsLSD genes in total from the alfalfa (cultivar Zhongmu No. 1) genome. Phylogenetic analysis demonstrated that the MsLSD genes could be classified into three subgroups. In addition, six MsLSD genes were unevenly mapped on three chromosomes in alfalfa. Gene duplication analysis demonstrated that segmental duplication was the key driving force for the expansion of this gene family during evolution. Expression analysis of six MsLSD genes in various tissues and germinating seeds presented their different expressions. RT-qPCR analysis revealed that the expression of three MsLSD genes, including MsLSD2, MsLSD5, and MsLSD6, was significantly induced by seed aging treatment, suggesting that they might play an important role in maintaining seed vigor. Although this finding will provide valuable insights into unveiling the molecular mechanism involved in losing vigor and new strategies to improve alfalfa seed germinability, additional research must comprehensively elucidate the precise pathways through which the MsLSD genes regulate seed vigor.

We review the relationship between miRNAs associated with ferroptosis and the evolution of AS. Even though, more evidence is asked to determine the role of miRNAs associated with ferroptosis in the AS, this review will help us understand the role of miRNAs in ferroptosis and AS and may provide new insights for probing new biomarkers for the diagnosis and treatment of AS for the time to come. This is a narrative essay. Using PubMed as the main source, a literature search strategy was randomly implemented to index Scopus articles. No specific terminology is used. Studies have shown that ferroptosis plays a crucial role in the development of AS, and a large amount of ferroptosis in cells can lead to the progression of AS. MicroRNAs (MiRNAs) have been proved to be taken part in the biological course of ferroptosis and thus the process of AS is affected. The exact regulatory mechanism behind this appearance remains unclear. In order to clarify this, a growing number of studies have concentrated the regulatory role of miRNAs in the process of generation and development of ferroptosis, as well as the function of ferroptosis in the progression of AS. MiRNAs play a significant role in the process of ferroptosis and are incredibly significant in the occurrence, development, clinical diagnosis, treatment and prognosis evaluation of AS. [ABSTRACT FROM AUTHOR]

Main conclusion: CgVPE1 is important in the differentiation of TE cells in C. grandis ‘Tomentosa’ fruits as it may directly affects secondary cell wall construction while participating in PCD. The vacuolar processing enzyme (VPE) plays an important role in both developmental and environmentally inducible programmed cell death (PCD); it was originally identified as a cysteine protease localized in the vacuole to activate and mature vacuolar proteins in plants. Interestingly, we found a VPE called CgVPE1 to be associated with deposition of the secondary cell wall in tracheary element (TE) cells in the pericarp of Citrus grandis ‘Tomentosa’ fruits. We then used ultrathin sections and the TUNEL assay to verify that PCD is involved in TE development. Furthermore, CgVPE1 was found to be mainly expressed in secretory cavities and TEs in the pericarp of Citrus grandis ‘Tomentosa’ fruits. Immunolocalization of CgVPE1 in the pericarp indicated that CgVPE1 is mainly distributed in the central large vacuole, endoplasmic reticulum, Golgi vesicles, cytosol, and secondary wall before TE maturation. CgVPE1 appeared earlier in the endoplasmic reticulum and Golgi vesicles of TEs cells. The vesicles containing CgVPE1 near the large central vacuole and secondary wall were observed, respectively. CgVPE1 proteins content in the cytoplasm decreased sharply, while the CgVPE1 content in the secondary cell wall did not change significantly after vacuole rupture. CgVPE1 protein contents in the secondary cell wall were significantly reduced until the TE cells developed into hollow thick-walled cells. Furthermore, labeling of VPE homologues in Arabidopsis thaliana using immunoelectron microscopy with anti-CgVPE1 antibody revealed that VPE homologues were specifically distributed in the secondary cell wall of stem TEs. Overall, these results suggested that CgVPE1 is not only involved PCD during TE cell development; furthermore, it may directly participate in the construction of plant secondary cell walls. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) serves as the underlying pathology for various spinal degenerative conditions and is a primary contributor to low back pain (LBP). Recent studies have revealed a strong correlation between IDD and biological processes such as Programmed Cell Death (PCD), cellular senescence, inflammation, cell proliferation, extracellular matrix (ECM) degradation, and oxidative stress (OS). Of particular interest is the emerging evidence highlighting the significant involvement of the JNK signaling pathway in these fundamental biological processes of IDD. This paper explores the potential mechanisms through the JNK signaling pathway influences IDD in diverse ways. The objective of this article is to offer a fresh perspective and methodology for in-depth investigation into the pathogenesis of IDD by thoroughly examining the interplay between the JNK signaling pathway and IDD. Moreover, this paper summarizes the drugs and natural compounds that alleviate the progression of IDD by regulating the JNK signaling pathway. This paper aims to identify potential therapeutic targets and strategies for IDD treatment, providing valuable insights for clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Gao, Wang, Xie, Gao and Wu.)

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes' transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition. [ABSTRACT FROM AUTHOR]

Phytopathogenic bacteria inject effector proteins into plant host cells to promote disease. Plant resistance (R) genes encoding nucleotide-binding leucine-rich repeat (NLR) proteins mediate the recognition of functionally and structurally diverse microbial effectors, including transcription-activator like effectors (TALEs) from the bacterial genus Xanthomonas. TALEs bind to plant promoters and transcriptionally activate either disease-promoting host susceptibility (S) genes or cell death-inducing executor-type R genes. It is perplexing that plants contain TALE-perceiving executor-type R genes in addition to NLRs that also mediate the recognition of TALE-containing xanthomonads. We present recent findings on the evolvability of TALEs, which suggest that the native function of executors is not in plant immunity, but possibly in the regulation of developmentally controlled programmed cell death (PCD) processes. Xanthomonads inject transcription-activator like effectors (TALEs) into plant cells, where TALEs bind to effector binding elements (EBE s) in plant promoters and transcriptionally activate downstream host susceptibility genes to promote disease. Some plant genotypes contain transcriptionally activatable cell death-inducing genes, termed executors, that are preceded by TALE-compatible EBE s. Such EBE -equipped executor alleles are, by definition, resistance (R) genes, since their presence provides protection against TALE-containing xanthomonads. Recent studies uncovered that TALEs can rapidly change their sequence specificity by rearranging their modular DNA domain to circumvent detection by matching executor-type R genes. Evolutionary evidence suggests that the native function of executors is likely to be not in plant immunity, but rather in the regulation of programmed cell death, possibly in the context of plant developmental processes. [ABSTRACT FROM AUTHOR]

Eucalyptus is widely planted in China for wood industries, and there are increasing concerns about its ecotoxicity in the environment. This study explored the in-vitro toxicity of Eucalyptus extracts by assessing the impacts of water-soluble and dimethylsulfoxide (DMSO)-soluble fractions via a whole-cell bioreporter, Acinetobacter baylyi ADPWH_recA. Compounds identified in Eucalyptus extracts included one tannin, two phenolic acids, four terpenoids, four glycosides, and five flavonoids. The leaf extracts contained more biological-active components than barks and roots. Genotoxicity induced by Eucalyptus extracts was mainly associated with water extracts (e.g., flavonoids, phenolic acids) instead of DMSO extracts. The significant cytotoxicity was explained by programmed cell death (PCD), suggested by the results of propidium iodide (PI) and 2′,7′-dichlorofluorescein-diacetate (DCFH-DA) assays. Generally, water-soluble fractions contributed more toxicities than DMSO-soluble fractions, particularly at high concentrations. A robust linear regression was built between the compromised toxicity and PCD index (Compromised toxicity = −2.192 × PCD index + 2.219; R2 = 0.8886), suggesting a PCD-dependent compromised toxicity which was greatly underestimated. Our results implied non-neglectable ecotoxicological risks of Eucalyptus extracts, hinting at the possible magnified ecological impacts of its large-scale plantation and the potential adverse outcomes to the surrounding ecosystems.

The secretory ducts of Ferula ferulaeoides (Steud.) Korov. are the main tissue of synthesis, secretion, and accumulation of resin. The formation of secretory ducts is closely related to the harvest and quality of resin, but the lumen formation mode and corresponding mechanism have not been thoroughly studied. This study of F. ferulaeoides investigated the microstructure and ultrastructure of the secretory ducts from a developmental point of view. Stem samples were analyzed by light microscopy, transmission electron microscopy, and fluorescence microscopy. The data results showed (1) the walls of secretory cells were intact during the development of secretory ducts in F. ferulaeoides; (2) the plastids and endoplasmic reticulum of secretory cells participated in the synthesis of resin; (3) pectinase was involved in the degradation of the middle lamella; and (4) no features of programmed cell death during the formation of secretory ducts. The results suggested that the formation of F. ferulaeoides' secretory ducts was schizogenous, and pectinase was involved in its formation. These data may be beneficial to further explore the formation of secretory duct in other species of Ferula L. and the formation mechanism of schizogenous secretory structures. [ABSTRACT FROM AUTHOR]

In monocarpic plants, stem cells are fated to die. However, the potential mechanism of stem cell death has remained elusive. Here, we reveal that the levels of two forms of reactive oxygen species (ROS), superoxide anion free radical ( O 2 · − ) and hydrogen peroxide (H2O2), show dynamic changes in the shoot apex during the plant life cycle of Arabidopsis thaliana. We found that the level of O 2 · − decreased and disappeared at four weeks after bolting (WAB), while H2O2 appeared at 3 WAB and showed a burst at 5 WAB. The timing of dynamic changes in O 2 · − and H2O2 was delayed for approximately three weeks in clv3-2, which has a longer lifespan. Moreover, exogenous application of H2O2 inhibited the expression of the stem cell determinant WUSCHEL (WUS) and promoted the expression of the developmentally programmed cell death (dPCD) marker gene ORESARA 1 (ORE1). These results indicate that H2O2 triggers an important signal inducing dPCD in stem cells. Given that O 2 · − plays roles in maintaining WUS expression and stem cell activity, we speculate that the dynamic shift from O 2 · − to H2O2 in the shoot apex results in stem cell death. Our findings provide novel insights for understanding ROS-mediated regulation during plant stem cell death. [ABSTRACT FROM AUTHOR]

Synergids are metabolically dynamic cells of the egg apparatus and represent an important component of the female gametophyte. Besides directing the growth of the pollen tube towards the micropylar end of the embryo sac, these ephemeral structures make room for the pollen tube cytoplasm. Research carried out on model systems such as Arabidopsis, Brassica, Capsella, Triticum and Torenia has expanded our understanding of the molecular regulation of the pollen tube journey, its guidance and navigation in the pistil. Recently, the critical role of the central cell in fertilization and prevention of polytubey has also been thoroughly investigated. Sophisticated confocal microscopy, live cell imaging, and molecular tools have helped in furthering our knowledge of the functioning of synergids. Research using high throughput techniques has deciphered the role of various genes that regulate and govern the release of chemotropic substances, cell-to-cell interaction and synergid cell degeneration. Moreover, with the diversity displayed in form and function of organs in the angiosperms, and the switching of roles of the cells of egg apparatus, new insights have been provided into the involvement of synergids both pre- and post-fertilization. The present review provides a comprehensive account of synergids, their role in fertilization and the post fertilization events that have emerged using interdisciplinary approaches in recent years. We also discuss the variations observed in degeneration of synergids and the molecular mechanisms that govern the degeneration. Since environmental factors such as light and temperature have a significant impact on synergids and fertilization, it would be rewarding to study the role of chemo-attractants and other factors in elucidating the functional roles of synergids. Further studies into developing adequate protocols for manipulating synergid functions is certainly required. This research has enormous potential in the advancement of basic science and has potential applications in agriculture, horticulture, and bioprospecting. [ABSTRACT FROM AUTHOR]

Cyanobacteria can form nitrogen-fixing symbioses with a broad range of plant species. Unlike other plant-bacteria symbioses, little is understood about the immunological responses induced by plant cyanobionts (symbiotic cyanobacteria). Here, we demonstrated that the model plant-symbiotic cyanobacteria, Nostoc punctiforme is capable of protecting against programmed cell death (PCD) when induced in Arabidopsis thaliana suspension cell cultures. We also profiled the early transcriptomic changes that were induced in response to conditioned medium (CM) from N. punctiforme cell cultures. Interestingly, the reduction in PCD was preceded by the induction of genes associated with defence and immunity, the most striking of which were a number of WRKY-family transcription factors. Down-regulated genes included those involved in the regulation of cell growth and differentiation. This work is the first to show that a cyanobiont can affect plant PCD and provides a useful transcriptome resource for studying early plant cell responses to symbiotic cyanobacteria.

Regenerative medicine and surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival, and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting the effectiveness and outcome of the therapeutic choices. Thus, the authors developed a novel 360° regenerative strategy based on the synergic action of several new components called the bioactive composite therapies (BACTs) to improve grafted cells intake, and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Bioactive composite mixtures (BACMs) are tailor-made bioactive mixtures containing several bioactive components that support cells' survival and induce a regenerative response in vivo by stimulating the recipient site to act as an in situ real bioreactor. Many different tissues have been used in the past for the isolation of cells, molecules, and growth factors, but the adipose tissue and its stromal vascular fraction (SVF) remains the most valuable, abundant, safe, and reliable source of regenerative components and particularly of adipose-derived stems cells (ADSCs). The role of plastic surgeons as the historical experts in all the most advanced techniques for harvesting, manipulating, and grafting adipose tissue is fundamental in this constant process of expansion of regenerative procedures. In this article, we analyze the main causes of cell death and the strategies for preventing it, and we present all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions. The second section of this work is dedicated to the logical and sequential evolution from simple bioactive composite grafts (BACGs) that distinguished our initial approach to regenerative medicine, to BACTs where many other fundamental technical steps are analyzed and integrated for supporting and enhancing the most efficient regenerative activity. Level of Evidence: Not gradable [ABSTRACT FROM AUTHOR]

Cyanobacteria can form nitrogen-fixing symbioses with a broad range of plant species. Unlike other plant-bacteria symbioses, little is understood about the immunological responses induced by plant cyanobionts (symbiotic cyanobacteria). Here, we demonstrated that the model plant-symbiotic cyanobacteria, Nostoc punctiforme is capable of protecting against programmed cell death (PCD) when induced in Arabidopsis thaliana suspension cell cultures. We also profiled the early transcriptomic changes that were induced in response to conditioned medium (CM) from N. punctiforme cell cultures. Interestingly, the reduction in PCD was preceded by the induction of genes associated with defence and immunity, the most striking of which were a number of WRKY-family transcription factors. Down-regulated genes included those involved in the regulation of cell growth and differentiation. This work is the first to show that a cyanobiont can affect plant PCD and provides a useful transcriptome resource for studying early plant cell responses to symbiotic cyanobacteria. [ABSTRACT FROM AUTHOR]

Abstract Background Vacuolar processing enzymes (VPEs) have been identified as the enzymes that regulate vacuole-mediated programmed cell death (PCD) in plants. The mechanism that VPE regulates the PCD in rice aleurone layers remains unknown. Results The aleurone layers treated with distilled water exerted caspase-1 and VPE activity, both of which were inhibited by the caspase-1 specific inhibitor Ac-YVAD-CMK but not by the caspase-3 specific inhibitor Ac-DEVD-CHO. However, the caspase-1 and caspase-3 inhibitors weakened the activity of caspase-3. Combined with the effects of endogenous gibberellin (GA) on the induction of OsVPEs, we suggest that the OsVPE3 in the aleurone layers, which exhibits caspase-1-like activity, is a key molecule in GA-induced PCD via regulating the protease with caspase-3-like activity. Many studies have confirmed that vacuolar fusion is an important feature of vacuole-mediated PCD in plants. In this experiment, the process of vacuole fusion was accompanied by changes in the structure of actin filaments (AFs), specifically, their depolymerization and polymerization. The process of vacuolar fusion was accelerated or delayed by the promotion or inhibition of the depolymerization of AFs, respectively. Here, the inhibition of OsVPE3 blocked the depolymerization of AFs and delayed the fusion of vacuoles, indicating that OsVPE3 can regulate the fusion of vacuoles in rice aleurone layers via mediating AFs. Furthermore, the depolymerization of AFs contributed to the up-regulation of OsVPE3 gene expression and VPE activity, resulting in accelerated PCD in rice aleurone layers. However, the inhibitor of VPE reversed the effects of AF depolymerization on the activity of VPE, then postponing the process of PCD, implying that AF can involve in GA-induced PCD of rice aleurone layers by mediating OsVPE3. Conclusions Together, activation of OsVPE3 and depolymerization of AFs shortened the process of vacuolation and PCD in rice aleurone layers, and OsVPE3 interacted with AFs during regulation.

Plant glandular trichomes have received much attention due to their commercial and biological value. Recent studies have focused on the development of various glands in plants, suggesting that programmed cell death (PCD) may play an important role during the development of plant secretory structures. However, the development processes and cytological characteristics in different types of plant secretory structures differed significantly. This study aims to provide new data on the developmental PCD of the capitate glandular hairs in Dictamnus dasycarpus. Light, scanning, immunofluorescence labeling, and transmission electron microscopy were used to determine the different developmental processes of the capitate glandular hairs from a cytological perspective. Morphologically, the capitate glandular hair originates from one initial epidermal cell and differentiates into a multicellular trichome characterized by two basal cells, two lines of stalk cells, and a multicellular head. It is also histochemically detected by essential oils. TUNEL-positive reactions identified nuclei with diffused fluorescence or an irregular figure by DAPI, and Evans blue staining showed that the head and stalk cells lost their viability. Ultrastructural evidence revealed the developmental process by two possible modes of PCD. Non-autolytic PCD was characterized by buckling cell walls and degenerated nuclei, mitochondria, plastids, multivesicular body (MVB), and end-expanded endoplasmic reticulum in the condensed cytoplasm, which were mainly observed in the head cells. The MVB was detected in the degraded vacuole, a degraded nucleus with condensed chromatin and diffused membrane, and eventual loss of the vacuole membrane integrity exhibited typical evidence of vacuole-mediated autolytic PCD in the stalk cells. Furthermore, protoplasm degeneration coupled with dark oil droplets and numerous micro-dark osmiophilic substances was observed during late stages. The secretion mode of essential oils is also described in this paper.

Introduction: Programmed cell death (PCD) is a fundamental biological process crucial for plant development. Despite recent advancements in our understanding of PCD's molecular mechanisms, the intricate orchestration of this process within plant cells remains enigmatic. To address this knowledge gap, the present study focuses on Decaisnea insignis , a plant species renowned for its unique fruit anatomy, including laticiferous canals that secrete latex. While extensive anatomical studies have elucidated the structural features of these canals,molecular insights into their developmental regulation, particularly the involvement of PCD, are lacking., Methods: In this study, we sequenced the single-cell transcriptomes at two developmental stage of Decaisnea insignis fruit using the technology known as 10x Genomics (S1, S2). Using sequencing technology combining full- length RNA sequencing and single-nucleus RNA sequencing (snRNA-seq) in combination with ultrastructural analyses, our study revealed a cellular map of Decaisnea insignis fruit at the single-cell level and identified different cell types., Results: In particular, we identified a possible PCD-mediated cluster of Decaisnea insignis fruit lactiferous canals in epidermal cells and clarified the expression patterns of DiRD21A (a hydrolase) and DiLSD1 (a transcription factor), which may be closely related to the development of laticiferous canals in Decaisnea insignis fruits., Discussion: By integrating high-resolution gene expression profiling with visual insights into cellular transformations, we sought to more precisely characterize the regulatory role of PCD during the developmental formation of lactiferous canals in Decaisnea insignis fruit., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhao, Shi, Li, Yang, Wang and Zhou.)

Background: Uncontrolled cellular proliferation may result in the progression of diseases such as cancer that promote organism death. Programmed cell death (PCD) is an important mechanism that ensures the quality and quantity of cells, which could be developed as a potential biomarker for disease diagnosis and treatment., Methods: RNA-seq data and clinical information of nasopharyngeal carcinoma (NPC) patients were downloaded from the Gene Expression Omnibus (GEO), and 1548 PCD-related genes were collected. We used the "limma" package to analyze differentially expressed genes (DEGs). The STRING database was used for protein interaction analysis, and the least absolute shrinkage and selection operator (Lasso) and support vector machines (SVMs) regression analyses were used to identify biomarkers. Then, the timeROC package was used for classifier efficiency assessment, and the "CIBERSORT" package was used for immune infiltration analysis. Wound healing and transwell migration assay were performed to evaluate migration and invasion., Results: We identified 800 DEGs between our control and NPC patient groups, in which 59 genes appeared to be PCD-related DEGs, with their function closely associated with NPC progression, including activation of the PI3K-Akt, TGF-β, and IL-17 signaling pathways. Furthermore, based on the STRING database, Cytoscape and six algorithms were employed to screen 16 important genes ( GAPDH , FN1 , IFNG , PTGS2 , CXCL1 , MYC , MUC1 , LTF , S100A8 , CAV1 , CDK4 , EZH2 , AURKA , IL33 , S100A9 , and MIF ). Subsequently, two reliably characterized biomarkers, FN1 and MUC1 , were obtained from the Lasso and SVM analyses. The Receiver operating characteristic (ROC) curves showed that both biomarkers had area under the curve (AUC) values higher than 0.9. Meanwhile, the enrichment analysis showed that in NPC patients, the FN1 and MUC1 expression levels correlated with programmed cell death-related pathways. The enrichment analysis and cellular experimental results indicated that FN1 and MUC1 were overexpressed in NPC cells and associated with programmed cell death-related pathways. Importantly, FN1 and MUC1 severely affected the ability of NPC cells to migrate, invade, and undergo apoptosis. Finally, medroxyprogesterone acetate and 8-Bromo-cAMP acted as drug molecules for the docking of FN1 and MUC1 molecules, respectively, and had binding capacities of -9.17 and -7.27 kcal/mol, respectively., Conclusion: We examined the PCD-related phenotypes and screened FN1 and MUC1 as reliable biomarkers of NPC; our findings may promote the development of NPC treatment strategy., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by muscle inflammation and extramuscular involvements. Present literatures have revealed that dysregulated cell death in combination with impaired elimination of dead cells contribute to the release of autoantigens, damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and result in immune responses and tissue damages in autoimmune diseases, including IIMs. This review summarizes the roles of various forms of programmed cell death pathways in the pathogenesis of IIMs and provides evidence for potential therapeutic targets. [ABSTRACT FROM AUTHOR]

N6‐methyladenosine (m6A) modification affects the post‐transcriptional regulation of eukaryotic gene expression, but the underlying mechanisms and their effects in plants remain largely unknown. Here, we report that the N6‐adenine methyltransferase‐like domain‐containing protein ENHANCED DOWNY MILDEW 2‐LIKE (OsEDM2L) is essential for rice (Oryza sativa L.) anther development. The osedm2l knockout mutant showed delayed tapetal programmed cell death (PCD) and defective pollen development. OsEDM2L interacts with the transcription factors basic helix‐loop‐helix 142 and TAPETUM DEGENERATION RETARDATION to regulate the expression of ETERNAL TAPETUM 1 (EAT1), a positive regulator of tapetal PCD. Mutation of OsEDM2L altered the transcriptomic m6A landscape, and caused a distinct m6A modification of the EAT1 transcript leading to dysregulation of its alternative splicing and polyadenylation, followed by suppression of the EAT1 target genes OsAP25 and OsAP37 for tapetal PCD. Therefore, OsEDM2L is indispensable for proper messenger RNA m6A modification in rice anther development. [ABSTRACT FROM AUTHOR]

In plants, programmed cell death (PCD) is involved in both the development and the response to biotic and abiotic aggressions. In early stages of PCD, mitochondrial membranes are made permeable by the formation of permeability transition pores, whose protein composition is debated. Cytochrome c (cyt c) is then released from mitochondria, inducing the degradation of chromatin characteristic of PCD. Since flooding stress can produce PCD in several plant species, the first goal of this study was to know if flooding stress could be used to induce PCD in Beta vulgaris roots. To do this, 2-month-old beet plants were flood-stressed from 1 to 5 days, and the alterations indicating PCD in stressed beetroot cells were observed with a confocal fluorescence microscope. As expected, nuclei were deformed, and chromatin was condensed and fragmented in flooded beetroots. In addition, cyt c was released from mitochondria. After assessing that flood stress induced PCD in beetroots, the composition of mitochondrial protein complexes was observed in control and flood-stressed beetroots. Protein complexes from isolated mitochondria were separated by native gel electrophoresis, and their proteins were identified by mass spectrometry. The spectra count of three isoforms of voltage-dependent anion-selective channels (VDACs) increased after 1 day of flooding. In addition, the size of the complexes formed by VDAC was higher in flood-stressed beetroots for 1 day (∼200 kDa) compared with non-stressed ones (∼100 kDa). Other proteins, such as chaperonin CPN60-2, also formed complexes with different masses in control and flood-stressed beetroots. Finally, possible interactions of VDAC with other proteins were found performing a cluster analysis. These results indicate that mitochondrial protein complexes formed by VDAC could be involved in the process of PCD in flood-stressed beetroots. Data are available via ProteomeXchange with identifier PXD027781. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by muscle inflammation and extramuscular involvements. Present literatures have revealed that dysregulated cell death in combination with impaired elimination of dead cells contribute to the release of autoantigens, damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and result in immune responses and tissue damages in autoimmune diseases, including IIMs. This review summarizes the roles of various forms of programmed cell death pathways in the pathogenesis of IIMs and provides evidence for potential therapeutic targets.

In plants, programmed cell death (PCD) is involved in both the development and the response to biotic and abiotic aggressions. In early stages of PCD, mitochondrial membranes are made permeable by the formation of permeability transition pores, whose protein composition is debated. Cytochrome c (cyt c) is then released from mitochondria, inducing the degradation of chromatin characteristic of PCD. Since flooding stress can produce PCD in several plant species, the first goal of this study was to know if flooding stress could be used to induce PCD in Beta vulgaris roots. To do this, 2-month-old beet plants were flood-stressed from 1 to 5 days, and the alterations indicating PCD in stressed beetroot cells were observed with a confocal fluorescence microscope. As expected, nuclei were deformed, and chromatin was condensed and fragmented in flooded beetroots. In addition, cyt c was released from mitochondria. After assessing that flood stress induced PCD in beetroots, the composition of mitochondrial protein complexes was observed in control and flood-stressed beetroots. Protein complexes from isolated mitochondria were separated by native gel electrophoresis, and their proteins were identified by mass spectrometry. The spectra count of three isoforms of voltage-dependent anion-selective channels (VDACs) increased after 1 day of flooding. In addition, the size of the complexes formed by VDAC was higher in flood-stressed beetroots for 1 day (∼200 kDa) compared with non-stressed ones (∼100 kDa). Other proteins, such as chaperonin CPN60-2, also formed complexes with different masses in control and flood-stressed beetroots. Finally, possible interactions of VDAC with other proteins were found performing a cluster analysis. These results indicate that mitochondrial protein complexes formed by VDAC could be involved in the process of PCD in flood-stressed beetroots. Data are available via ProteomeXchange with identifier PXD027781.

Abstract Background Previously, we demonstrated that pollen chamber formation (PCF) in G. biloba ovules was a process of programmed cell death (PCD) within the nucellar cells at the micropylar end. However, the signal triggering the cascades of the programmed events in these nucellar cells remains unexplored. Results A transcriptomic strategy was employed to unravel the mechanism underlying the nucellar PCD via the comparative profiles of RNA-seq between pre-PCF and post-PCF ovules. A total of 5599 differentially expressed genes (DEGs) with significance was identified from G. biloba ovules and classified into three main categories of GO annotation, including 17 biological processes, 15 cellular components and 17 molecular functions. KEGG analysis showed that 72 DEGs were enriched in “Plant hormone signal transduction”. Furthermore, 99 DEGs were found to be associated with the PCD process, including the genes involved in ethylene signaling pathway, PCD initiation, and PCD execution. Moreover, calcium-cytochemical localization indicated that calcium could play a role in regulating PCD events within the nucellar cells during pollen chamber formation in G. biloba ovules. Conclusions A putative working model, consisting of three overlapping processes, is proposed for the nucellar PCD: at the stage of PCD preparation, ethylene signaling pathway is activated for transcriptional regulation of the downstream targets; subsequently, at the stage of PCD initiation, the upregulated expression of several transcription factors, i.e., NAC, bHLH, MADS-box, and MYB, further promotes the corresponding transcript levels of CYTOCHROME C and CALMODULINs, thereby, leads to the PCD initiation via the calcium-dependent signaling cascade; finally, at the stage of PCD execution, some proteases like metacaspases and vacuolar processing enzyme for hydrolysis, together with the process of autophagy, play roles in the clearance of cellular components. Afterwards, a pollen chamber is generated from the removal of specific nucellar cells in the developing ovule.

Programmed cell death (PCD) is the result of an intracellular program and is accomplished by a regulated process in both prokaryotic and eukaryotic organisms. Here, we report a programed cell death process in Mycobacterium smegmatis, an Actinobacteria species which involves a transcription factor and a DNase of the HNH family. We found that over-expression of an ArsR family member of the transcription factor, MSMEG_6762, leads to cell death. Transcriptome analysis revealed an increase in the genes’ transcripts involved in DNA repair and homologous recombination, and in three members of HNH family DNases. Knockout of one of the DNase genes, MSMEG_1275, alleviated cell death and its over-expression of programmed cell death. Purified MSMEG_1275 cleaved the M. smegmatis DNA at multiple sites. Overall, our results indicate that the MSMEG_6762 affects cell death and is mediated, at least partially, by activation of the HNH nuclease expression under a stress condition.

Key message: Endogenous hydrogen peroxide (H2O2) is involved in regulating the gibberellic acid-induced programmed cell death (PCD) of the aleurone layers by cooperating with OsVPE3 during rice seed germination. Preliminary experiments revealed that H2O2 produced by the NOX pathway is the key factor affecting rice germination. Histochemical analysis indicated that H2O2 is located in the aleurone layer. Both the H2O2 scavenger DMTU and the NOX inhibitor DPI decreased H2O2 content and significantly slowed down vacuolation in a dose-dependent manner. Interestingly, DMTU down-regulated the OsNOX8 transcript or DMTU and DPI decreased the intracellular H2O2 level, resulting in a delay of PCD. In contrast, GA and H2O2 up-regulated the OsNOX8 transcript and intracellular H2O2 level, leading to premature PCD, and the effects of GA and H2O2 were reversed by DMTU and DPI, respectively. These results showed that the imbalance of intracellular H2O2 levels leads to the delayed or premature PCD. Further experiments indicated that GA up-regulated the OsVPE3 transcript and VPE activity, and the effect was reversed by DPI. Furthermore, Ac-YVAD-CMK significantly blocked H2O2 accumulation, and DPI + Ac-YVAD-CMK had a more significant inhibitory effect compared with DPI alone, resulting in the delayed PCD, suggesting that OsVPE3 regulates PCD by promoting H2O2 generation. Meanwhile, DPI significantly inhibited the OsVPE3 transcript and VPE activity, and in turn delayed PCD occurrence, suggesting that the H2O2 produced by the NOX pathway may regulate PCD by up-regulating the OsVPE3 transcript. Thus, the endogenous H2O2 produced by the NOX pathway mediates the GA-induced PCD of rice aleurone layers by interacting with OsVPE3. [ABSTRACT FROM AUTHOR]

Nitrogen-fixing heterocystous cyanobacteria are used as biofertilizer inoculants for stimulating plant growth but can also alleviate plant stress by exometabolite secretion. However, only a small number of studies have focused on elucidating the identity of said bioactives because of the wide array of exuded compounds. Here, we used the root hair assay (RHA) as a rapid programmed cell death (PCD) screening tool for characterizing the bioactivity of cyanobacteria Nostoc muscorum conditioned medium (CM) on Arabidopsis thaliana root hair stress tolerance. We found that heat-stressed A. thaliana pre-treated with N. muscorum CM fractions exhibited significantly lower root hair PCD levels compared to untreated seedlings. Treatment with CM increased stress tolerance by suppressing PCD in root hairs but not necrosis, indicating the bioactive compound was specifically modulating the PCD pathway and not a general stress response. Based on documented N. muscorum exometabolites, we identified the stress-responsive proline as a compound of interest and strong evidence from the ninhydrin assay and HPLC indicate that proline is present in N. muscorum CM. To establish whether proline was capable of suppressing PCD, we conducted proline supplementation experiments. Our results showed that exogenous proline had a similar effect on root hairs as N. muscorum CM treatment, with comparable PCD suppression levels and insignificant necrosis changes. To verify proline as one of the biologically active compounds in N. muscorum CM, we used three mutant A. thaliana lines with proline transporter mutations (lht1, aap1 and atprot1-1::atprot2-3::atprot3-2). Compared with the wild-type seedlings, PCD-suppression in lht1and aap1 mutants was significantly reduced when supplied with low proline (1–5 μM) levels. Similarly, pre-treatment with N. muscorum CM resulted in elevated PCD levels in all three mutant lines compared to wild-type seedlings. Our results show that plant uptake of cyanobacteria-derived proline alters their root hair PCD sensitivity threshold. This offers evidence of a novel biofertilizer mechanism for reducing stress-induced PCD levels, independent of the existing mechanisms documented in the literature.