107,646 results on '"programmed cell death"'
Search Results
2. Insights into RNA N6-methyladenosine and programmed cell death in atherosclerosis.
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Long, Haijiao, Yu, Yulu, Ouyang, Jie, lu, Hongwei, and Zhao, Guojun
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APOPTOSIS , *RNA modification & restriction , *EUKARYOTIC cells , *ADENOSINES , *THERAPEUTICS - Abstract
N6-methyladenosine (m6A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m6A modification has gained increasing attention in the development of atherosclerosis and has become a research hotspot in recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, plays a pivotal role in atherosclerosis pathogenesis. In this review, we delve into the intricate interplay between m6A modification and diverse PCD pathways, shedding light on their complex association during the onset and progression of atherosclerosis. Clarifying the relationship between m6A and PCD in atherosclerosis is of great significance to provide novel strategies for cardiovascular disease treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Temperature change regulates pollen fertility of a PTGMS rice line PA64S by modulating the ROS homeostasis and PCD within the tapetum.
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Sun, Yujun, Ang, Yina, Fu, Ming, Bai, Yunxiu, Chen, Jiasheng, He, Ying, and Zeng, Hanlai
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HYBRID rice , *APOPTOSIS , *REACTIVE oxygen species , *TAPETUM , *MALE sterility in plants , *TEMPERATURE control - Abstract
SUMMARY Photoperiod and temperature‐sensitive male sterility rice is an important line for two‐line hybrid rice, and the changes in the cultivation temperature strictly control its pollen fertility. However, the mechanism by which temperature variation regulates pollen fertility is still unclear. This study obtained stable fertile PA64S(F) and sterile PA64S(S) rice from PA64S by controlling temperature changes. PA64S(F) shows a normal anther development and fertile pollen under low temperature (21°C), and PA64S(S) shows delayed degradation of the tapetum cells, leading to abnormal pollen wall formation and ubisch development under normal temperature (28°C). The accumulation of reactive oxygen species (ROS) positively correlates with the programmed cell death (PCD) process of tapetum cells. The delayed accumulation of ROS in the PA64S(S) tapetum at early stages leads to a delayed initiation of the PCD process. Importantly, we localized ascorbic acid (ASA) accumulation in the tapetum cells and determined that ASA is a major antioxidant for ROS homeostasis. ROS‐inhibited accumulation plants (PA64S‐ASA) demonstrated pollen sterility, higher ASA and lower ROS accumulation in the tapetum, and the absence of PCD processes in the tapetum cell. Abnormal changes in the tapetum of PA64S(S) rice disrupted metabolic pathways such as lipid metabolism, cutin and wax synthesis, sugar accumulation, and phenylpropane, affecting pollen wall formation and substance accumulation, suggesting that the timely accumulation of ROS is critical for male fertility. This study highlights the central role of ROS homeostasis in fertility alteration and also provides an avenue to address the effect of environmental temperature changes on pollen fertility in rice. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.
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Lin Miao, Haowei Wang, Yi Li, Jian Huang, Chan Wang, Hanxin Teng, Lisha Xu, Xue Yang, Yunqing Tian, Genmeng Yang, Xiaofeng Zeng, and Juan Li
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SIGMA-1 receptor ,UNSAFE sex ,HIV ,CARRIER proteins ,VIRAL load - Abstract
Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1- infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Identification and validation of an immune-derived multiple programmed cell death index for predicting clinical outcomes, molecular subtyping, and drug sensitivity in lung adenocarcinoma.
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Li, Chunhong, Hu, Jiahua, Jiang, Xiling, Tan, Haiyin, and Mao, Yiming
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Objectives: Comprehensive cross-interaction of multiple programmed cell death (PCD) patterns in the patients with lung adenocarcinoma (LUAD) have not yet been thoroughly investigated. Methods: Here, we collected 19 different PCD patterns, including 1911 PCD-related genes, and developed an immune-derived multiple programmed cell death index (MPCDI) based on machine learning methods. Results: Using the median MPCDI scores, we categorized the LUAD patients into two groups: low-MPCDI and high-MPCDI. Our analysis of the TCGA-LUAD training cohort and three external GEO cohorts (GSE37745, GSE30219, and GSE68465) revealed that patients with high-MPCDI experienced a more unfavorable prognosis, whereas those with low-MPCDI had a better prognosis. Furthermore, the results of both univariate and multivariate Cox regression analyses further confirmed that MPCDI serves as a novel independent risk factor. By combining clinical characteristics with the MPCDI, we constructed a nomogram that provides an accurate and reliable quantitative tool for personalized clinical management of LUAD patients. The findings obtained from the analysis of C-index and the decision curve revealed that the nomogram outperformed various clinical variables in terms of net clinical benefit. Encouragingly, the low-MPCDI patients are more sensitive to commonly used chemotherapy drugs, which suggests that MPCDI scores have a guiding role in chemotherapy for LUAD patients. Conclusion: Therefore, MPCDI can be used as a novel clinical diagnostic classifier, providing valuable insights into the clinical management and clinical decision-making for LUAD patients. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Screening of genes related to programmed cell death in esophageal squamous cell carcinoma and construction of prognostic model based on transcriptome analysis.
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Chen, Min, Qi, Yijun, Zhang, Shenghua, Du, Yubo, Cheng, Haodong, and Gao, Shegan
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APOPTOSIS ,PROGNOSTIC models ,SQUAMOUS cell carcinoma ,REGULATORY T cells ,ESOPHAGEAL cancer - Abstract
To screen programmed cell death (PCD)-related genes in esophageal squamous cell carcinoma (ESCC) based on transcriptomic data and to explore its clinical value. Differentially expressed PCD genes (DEPCDGs) were screened from ESCC transcriptome and clinical data in TCGA database. Univariate COX and LASSO COX were performed on prognostically DEPCDGs in ESCC to develop prognostic model. Differences in immune cell infiltration in different RiskScore groups were determined by ssGSEA and CIBERSORT. The role of RiskScore in immunotherapy response was explored using Tumor Immune Dysfunction and Exclusion (TIDE) and IMvigor210 cohorts. Fourteen DEPCDGs associated with prognosis were tapped in ESCC. These DEPCDGs form a RiskScore with good predictive performance for prognosis. RiskScore demonstrated excellent prediction accuracy in three data sets. The abundance of M2 macrophages and Tregs was higher in the high RiskScore group, and the abundance of M1 macrophages was higher in the low RiskScore group. The RiskScore also showed good immunotherapy sensitivity. RT-qPCR analysis showed that AUP1, BCAP31, DYRK2, TAF9 and UBQLN2 were higher expression in KYSE-150 cells. Knockdown BCAP31 inhibited migration and invasion. A prognostic risk model can predict prognosis of ESCC and may be a useful biomarker for risk stratification and immunotherapy assessment. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Solid-state electron-mediated z-scheme heterostructured semiconductor nanomaterials induce dual programmed cell death for melanoma therapy.
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Ren, Yiping, Wang, Yun, Chen, Cheng, Yan, Xiang, Chao, Minghao, Li, Yuting, Yu, Dehong, Huang, Yuqi, Hou, Xiaoyang, Gao, Fenglei, Jiang, Guan, and Guan, Ming
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APOPTOSIS , *CELL death , *REACTIVE oxygen species , *TREATMENT effectiveness , *PYROPTOSIS - Abstract
The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e–h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e–h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Prognostic and immunological implications of heterogeneous cell death patterns in prostate cancer.
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Wang, Ming, Dai, Bangshun, Liu, Qiushi, and Zhang, Xiansheng
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APOPTOSIS , *GENE expression , *PROGNOSIS , *KILLER cells , *CELL anatomy , *PROSTATE cancer - Abstract
Background: Prostate cancer is one of the most common cancers in men with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. Programmed cell death (PCD) mechanisms are known to play critical roles in tumor progression and can potentially serve as prognostic and therapeutic biomarkers in PCa. This study aimed to develop a prognostic signature for BCR in PCa using PCD-related genes. Materials and methods: We conducted an analysis of 19 different modes of PCD to develop a comprehensive model. Bulk transcriptomic, single-cell transcriptomic, genomic, and clinical data were collected from multiple cohorts, including TCGA-PRAD, GSE58812, METABRIC, GSE21653, and GSE193337. We analyzed the expression and mutations of the 19 PCD modes and constructed, evaluated, and validated the model. Results: Ten PCD modes were found to be associated with BCR in PCa, with specific PCD patterns exhibited by various cell components within the tumor microenvironment. Through Lasso Cox regression analysis, we established a Programmed Cell Death Index (PCDI) utilizing an 11-gene signature. High PCDI values were validated in five independent datasets and were found to be associated with an increased risk of BCR in PCa patients. Notably, older age and advanced T and N staging were associated with higher PCDI values. By combining PCDI with T staging, we constructed a nomogram with enhanced predictive performance. Additionally, high PCDI values were significantly correlated with decreased drug sensitivity, including drugs such as Docetaxel and Methotrexate. Patients with lower PCDI values demonstrated higher immunophenoscores (IPS), suggesting a potentially higher response rate to immune therapy. Furthermore, PCDI was associated with immune checkpoint genes and key components of the tumor microenvironment, including macrophages, T cells, and NK cells. Finally, clinical specimens validated the differential expression of PCDI-related PCDRGs at both the gene and protein levels. Conclusion: In conclusion, we developed a novel PCD-based prognostic feature that successfully predicted BCR in PCa patients and provided insights into drug sensitivity and potential response to immune therapy. These findings have significant clinical implications for the treatment of PCa. [ABSTRACT FROM AUTHOR]
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- 2024
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9. 6-Methyl-5-hepten-2-one promotes programmed cell death during superficial scald development in pear.
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Niu, Junpeng, Xu, Mingzhen, Zhang, Xu, Li, Luqi, Luo, Weiqi, Ma, Meng, Zhu, Lin, Tian, Decai, Zhang, Shaoling, Xie, Bing, Wang, Guodong, Wang, Libin, and Hui, Wei
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APOPTOSIS , *PEARS , *COLD storage , *GENETIC transcription , *DIPHENYLAMINE - Abstract
Plants possess the ability to induce programmed cell death (PCD) in response to abiotic and biotic stresses; nevertheless, the evidence on PCD initiation during pear scald development and the involvement of the scald trigger 6-methyl-5-hepten-2-one (MHO) in this process is rudimentary. Pyrus bretschneideri Rehd. cv. 'Dangshansuli' pear was used to validate such hypothesis. The results showed that superficial scald occurred after 120-d chilling exposure, which accompanied by typical PCD-associated morphological alterations, such as plasmolysis, cell shrinkage, cytosolic and nuclear condensation, vacuolar collapse, tonoplast disruption, subcellular organelle swelling, and DNA fragmentation. These symptoms were aggravated after MHO fumigation but alleviated by diphenylamine (DPA) dipping. Through transcriptome assay, 24 out of 146 PCD-related genes, which were transcribed during cold storage, were identified as the key candidate members responsible for these cellular biological alternations upon scald development. Among these, PbrCNGC1, PbrGnai1, PbrACD6, and PbrSOBIR1 were implicated in the MHO signaling pathway. Additionally, PbrWRKY2, 34 and 39 could bind to the W-box element in the promoter of PbrGnai1 or PbrSOBIR1 and activate their transcription, as confirmed by dual-luciferase, yeast one-hybrid, and transient overexpression assays. Hence, our study confirms the PCD initiation during scald development and explores the critical role of MHO in this process. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Multidimensional role of adapalene in regulating cell death in multiple myeloma.
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Xinya Cao, Jie Xiang, Qi Zhang, Jinwen Liu, Dongming Zhou, Yong Xu, Peipei Xu, Bing Chen, and Hua Bai
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APOPTOSIS ,CELL death ,MOLECULAR dynamics ,MULTIPLE myeloma ,TRYPAN blue - Abstract
Aims: Multiple myeloma (MM) remains a challenging condition to cure, with persistent drug resistance negating the benefits of treatment advancements. The unraveling complexities in programmed cell death (PCD), inclusive of apoptosis, autophagy, and ferroptosis, have highlighted novel therapeutic avenues. Our study focuses on deciphering how adapalene (ADA), a small molecule compound, accelerates the demise of MM cells via targeting their compensatory survival mechanisms. Methods: To assess the impact of ADA on MM, we employed flow cytometry and trypan blue exclusion assays to determine cell viabilities across MM cell lines and primary patient samples post-treatment. To delineate ADA's therapeutic targets and mechanisms, we conducted RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), molecular docking, and molecular dynamics simulations. We further designed pre-clinical trials emphasizing MM, exploring the efficacy of ADA as a standalone and in combination with bortezomib (BTZ). Results: ADA elicited a dose-responsive induction of MM cell death. Building upon ADA's anti-MM capabilities as a single agent, we proposed that ADA-BTZ co-treatment might amplify this lethality. Indeed, ADA and BTZ together greatly potentiated MM cell death. ADA proved beneficial in restoring BTZ susceptibility in BTZ-resistant relapsed or refractory MM (RRMM) patient cells. Molecular simulations highlighted ADA's high affinity (-9.17 kcal/mol) for CD138, with MM-GBSA revealing a binding free energy of -27.39 kcal/mol. Detailed interaction analyses indicated hydrogen-bonding of ADA with CD138 at the Asp35 and Gln34 residues. Additionally, ADA emerged as a versatile instigator of both ferroptosis and apoptosis in MM cells. Furthermore, ADA disrupted activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway triggered by BTZ, fostering cell death in BTZ-resistant MM subsets. Conclusion: ADA demonstrates a comprehensive capability to orchestrate MM cell death, exerting pronounced anti-MM activity while disrupting NF-κB-related drug resistance. ADA sensitization of MM cells to BTZ unravels its potential as a novel therapeutic drug for MM management. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.
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Yuan, Meng‐nan, Liu, Ting, Cai, An‐qi, Zhan, Zibo, Cheng, Yi‐li, Wang, Qi‐yue, Xia, Yu‐xuan, Shen, Nong‐er, Huang, Ping, and Zou, Xiao‐zhou
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VASCULAR remodeling ,APOPTOSIS ,VASCULAR resistance ,PULMONARY hypertension ,PULMONARY artery - Abstract
Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD‐associated drug targets for PH. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Identification of programmed cell death-related genes and diagnostic biomarkers in endometriosis using a machine learning and Mendelian randomization approach.
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Zi-Wei Xie, Yue He, Yu-Xin Feng, and Xiao-Hong Wang
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APOPTOSIS ,GENE expression ,DELAYED diagnosis ,MOLECULAR docking ,BIOMARKERS - Abstract
Background: Endometriosis (EM) is a prevalent gynecological disorder frequently associated with irregular menstruation and infertility. Programmed cell death (PCD) is pivotal in the pathophysiological mechanisms underlying EM. Despite this, the precise pathogenesis of EM remains poorly understood, leading to diagnostic delays. Consequently, identifying biomarkers associated with PCD is critical for advancing the diagnosis and treatment of EM. Methods: This study used datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) following preprocessing. By crossreferencing these DEGs with genes associated with PCD, differentially expressed PCD-related genes (DPGs) were identified. Enrichment analyses for KEGG and GO pathways were conducted on these DPGs. Additionally, Mendelian randomization and machine learning techniques were applied to identify biomarkers strongly associated with EM. Results: The study identified three pivotal biomarkers: TNFSF12, AP3M1, and PDK2, and established a diagnostic model for EM based on these genes. The results revealed a marked upregulation of TNFSF12 and PDK2 in EM samples, coupled with a significant downregulation of AP3M1. Single-cell analysis further underscored the potential of TNFSF12, AP3M1, and PDK2 as biomarkers for EM. Additionally, molecular docking studies demonstrated that these genes exhibit significant binding affinities with drugs currently utilized in clinical practice. Conclusion: This study systematically elucidated the molecular characteristics of PCD in EM and identified TNFSF12, AP3M1, and PDK2 as key biomarkers. These findings provide new directions for the early diagnosis and personalized treatment of EM. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Programmed cell death in Helicobacter pylori infection and related gastric cancer.
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Yukun Lin, Kunjing Liu, Fang Lu, Changming Zhai, and Fafeng Cheng
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HELICOBACTER pylori infections ,APOPTOSIS ,HELICOBACTER pylori ,GASTRIC mucosa ,STOMACH cancer ,ALIMENTARY canal - Abstract
Programmed cell death (PCD) plays a crucial role in maintaining the normal structure and function of the digestive tract in the body. Infection with Helicobacter pylori (H. pylori) is an important factor leading to gastric damage, promoting the Correa cascade and accelerating the transition from gastritis to gastric cancer. Recent research has shown that several PCD signaling pathways are abnormally activated during H. pylori infection, and the dysfunction of PCD is thought to contribute to the development of gastric cancer and interfere with treatment. With the deepening of studies on H. pylori infection in terms of PCD, exploring the interaction mechanisms between H. pylori and the body in different PCD pathways may become an important research direction for the future treatment of H. pylori infection and H. pylori-related gastric cancer. In addition, biologically active compounds that can inhibit or induce PCD may serve as key elements for the treatment of this disease. In this review, we briefly describe the process of PCD, discuss the interaction between different PCD signaling pathways and the mechanisms of H. pylori infection or H. pylori-related gastric cancer, and summarize the active molecules that may play a therapeutic role in each PCD pathway during this process, with the expectation of providing a more comprehensive understanding of the role of PCD in H. pylori infection. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment.
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Xiu Yang, Zheng-Chao Zhang, Yun-Nan Lu, Han-Lin Chen, Hong-Shen Wang, Tao Lin, Qing-Quan Chen, Jin-Shui Chen, and Wu-Bing He
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KILLER cells ,APOPTOSIS ,GENE expression ,VALPROIC acid ,IMMUNOLOGIC memory ,T cells - Abstract
Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP. Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses. Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4
+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers. Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings. [ABSTRACT FROM AUTHOR]- Published
- 2024
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15. Predicting prognosis and drug sensitivity in bladder cancer: an insight into Pan-programmed cell death patterns regulated by M6A modifications.
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Wang, Rongjiang, Li, Zhaojun, and Shen, Junwen
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The team aimed to explore the possible functional significance of M6A regulation in Pan-programmed cell death (PCD) among patients with bladder cancer (BLCA). In BLCA patients, the analysis was conducted on the13 patterns of programmed cell death (PCD) and the regulation of M6A. Transcriptome, genomics, and clinical data were collected from TCGA-BLCA, GEO32548, and IMvigor210. Consensus clustering analysis, functional enrichment analysis, and other prognostic tools were used to validate the Pan-PCD. Finally, in vitro experiments and transcription sequencing were performed to understand the potential influence of the PI3K pathway on Pan-PCD in BLCA patients. Diverse PCD patterns were simultaneously activated, and M6A regulators exhibited significant variability in bladder malignant tissues. The machine learning algorithm established an 8-gene M6A-related Pan-PCD signature. This signature was validated in three independent datasets, and BLCA patients with higher risk scores had worse prognosis. An unsupervised clustering approach identified activated and suppressed Pan-PCD subgroups of BLCA patients, with distinct responses to immunotherapy and drug sensitivity. In addition, the PI3K pathway was identified as a key mechanism for various forms of programmed cell death, encompassing apoptosis, pyroptosis, autophagy, and cell death dependent on lysosomes. This research revealed that the Pan-PCD model was a more promising approach for BLCA patients under M6A regulation. A new signature from M6A-related Pan-PCD was proposed, with prognostic value for survival or drug sensitivity. The PI3K pathway was a key mechanism for multiple PCDs in BLCA patients. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Global Trends in Research of Programmed Cell Death in Osteoporosis: A Bibliometric and Visualized Analysis (2000–2023).
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Rong, Yi‐fa, Liang, Xue‐Zhen, Jiang, Kai, Jia, Hai‐Feng, Li, Han‐Zheng, Lu, Bo‐Wen, and Li, Gang
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APOPTOSIS , *BIBLIOMETRICS , *METABOLIC bone disorders , *BONE density ,CHINA-United States relations - Abstract
Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co‐cited journal. These publications come from 14,801 authors, with Liu Zong‐Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong‐Yan having published the most papers. Ronald S. Weinstein was co‐cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound.
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Favaron, Cristina, Gaiaschi, Ludovica, Casali, Claudio, De Luca, Fabrizio, Gola, Federica, Cavallo, Margherita, Ramundo, Valeria, Aldieri, Elisabetta, Milanesi, Gloria, Visonà, Silvia Damiana, Ravera, Mauro, and Bottone, Maria Grazia
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MEDICAL sciences , *APOPTOSIS , *IRON overload , *IRON metabolism , *COMBINATION drug therapy - Abstract
Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Nanomedicine-induced programmed cell death enhances tumor immunotherapy.
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Lu, Jiaye, Tai, Zongguang, Wu, Junchao, Li, Lisha, Zhang, Tingrui, Liu, Jun, Zhu, Quangang, and Chen, Zhongjian
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APOPTOSIS , *NANOMEDICINE , *IMMUNOTHERAPY , *TUMOR treatment , *CANCER treatment , *CANCER-related mortality - Abstract
[Display omitted] • This article focuses on immunotherapy, a new treatment for tumors with low side effects, and suggests the direction of improvement. • Programmed cell death (apoptosis, necroptosis, ferroptosis, pyroptosis and autophagy) induced by nanomedicine was reviewed in this paper. • This paper focuses on the role of nanomedicine-induced programmed cell death in cancer therapy. • This article reviews the improvement of the limitations of immunotherapy with nanomedicine-induced PCD. • In this paper, the development prospect of tumor therapy and immunotherapy of PCD mediated by nanomedical drugs is prospected. There has been widespread concern about the high cancer mortality rate and the shortcomings of conventional cancer treatments. Immunotherapy is a novel oncology therapy with high efficiency and low side effects, which is a revolutionary direction for clinical oncology treatment. However, its clinical effectiveness is uneven. Based on the redefinition and reclassification of programmed cell death (PCD) (divided into necroptosis, ferroptosis, pyroptosis, and autophagy), the role of nanomedicine-induced PCD in cancer therapy has also received significant attention. Clinical and preclinical studies have begun to combine PCD with immunotherapy. In this article, we present recent research in tumor immunotherapy, provide an overview of how nanomedicine-induced PCD is involved in tumor therapy, and review how nanomedicine-induced PCD can improve the limitations of immunotherapy to enhance tumor immunotherapy. The future development of nanomedicine-mediated PCD tumor therapy and tumor immunotherapy is also proposed Key scientific concepts of overview Nanomedicine-induced PCD is a prospective method of tumor immunotherapy. Nanomedicines increase tumor site penetration and targeting ability, and nanomedicine-mediated PCD activation can stimulate powerful anti-tumor immune effects, which has a good contribution to immunotherapy of tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Creation of signatures and identification of molecular subtypes of glioblastoma based on disulfidptosis-related genes for predicting patient prognosis and immunological activity.
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Li, Dongjun, Li, Xiaodong, Lv, Jianfeng, and Li, Shaoyi
- Abstract
In recent times, disulfidptosis, an intricate form of cellular demise, has garnered attention due to its impact on prognosis, tumor progression and treatment response. Nevertheless, the exact significance of disulfidptosis-related genes (DisRGs) in glioblastoma (GBM) remains enigmatic. The GEO and TCGA databases provided transcriptional and clinically relevant data on tumor samples, while the GTEx database provided data on healthy tissues. Disulfidptosis-related genes (DisRGs) were procured from previous scholarly investigations. The expression profile of DisRGs was initially scrutinized among patients diagnosed with GBM, subsequent to which their prognostic value was explored. Through consensus clustering, we constructed DisRGs-related clusters and gene subtypes. Our results established that the DisRG-related clusters had differentially expressed genes, resulting in a DisulfidptosisScore model, which had a positive prognostic value. The differential expression profile of 24 DisRGs between GBM samples and healthy samples was acquired. Through consensus cluster analysis, two distinct disulfidptosis subtypes, namely DisRGcluster A and DisRGcluster B, were identified. Then, the DisulfidptosisScore model including 4 characteristic genes was constructed.Notably, patients with GBM assigned with lower score demonstrated a considerably longer overall survival (OS) compared to those with higher score. We have effectively devised a prognostic model associated with disulfidptosis, presenting autonomous prognostic predictions for patients with GBM. These findings serve as a valuable addition to the current comprehension of disulfidptosis and offer fresh theoretical substantiation for the development of enhanced treatment strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Bombyx mori voltage‐dependent anion‐selective channel induces programmed cell death to defend against Bombyx mori nucleopolyhedrovirus infection.
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Lv, Jun‐li, Lai, Wen‐qing, Gong, Yu‐quan, Zheng, Kai‐yi, Zhang, Xiao‐ying, Lu, Zhan‐peng, Li, Mu‐wang, Wang, Xue‐yang, and Dai, Li‐shang
- Subjects
APOPTOSIS ,SILKWORMS ,NUCLEOPOLYHEDROVIRUSES ,RNA interference ,BEET armyworm ,CHLORIDE channels ,SODIUM channels - Abstract
BACKGROUND: Voltage‐dependent anion‐selective channels (VDACs) serve as pore proteins within the mitochondrial membrane, aiding in the regulation of cell life and cell death. Although the occurrence of cell death is crucial for defense against virus infection, the function played by VDAC in Bombyx mori, in response to the influence of Bombyx mori nucleopolyhedrovirus (BmNPV), remains unclear. RESULTS: BmVDAC was found to be relatively highly expressed both during embryonic development, and in the Malpighian tubule and midgut. Additionally, the expression levels of BmVDAC were found to be different among silkworm strains with varying levels of resistance to BmNPV, strongly suggesting a connection between BmVDAC and virus infection. To gain further insight into the function of BmVDAC in BmNPV, we employed RNA interference (RNAi) to silence and overexpress it by pIZT/V5‐His‐mCherry. The results revealed that BmVDAC is instrumental in developing the resistance of host cells to BmNPV infection in BmN cell‐line cells, which was further validated as likely to be associated with initiating programmed cell death (PCD). Furthermore, we evaluated the function of BmVDAC in another insect, Spodoptera exigua. Knockdown of the BmVDAC homolog in S. exigua, SeVDAC, made the larvae more sensitive to BmNPV. CONCLUSION: We have substantiated the pivotal role of BmVDAC in conferring resistance against BmNPV infection, primarily associated with the initiation of PCD. The findings of this study shine new light on the molecular mechanisms governing the silkworm's response to BmNPV infection, thereby supporting innovative approaches for pest biocontrol. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]
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- 2024
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21. TLR4 signalling in ischemia/reperfusion injury: a promising target for linking inflammation, oxidative stress and programmed cell death to improve organ transplantation outcomes.
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Sutian Wang, Kunli Zhang, Qiuyan Huang, Fanming Meng, and Shoulong Deng
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APOPTOSIS ,TRANSPLANTATION of organs, tissues, etc. ,TOLL-like receptors ,OXIDATIVE stress ,DEATH receptors ,REPERFUSION injury - Abstract
Transplantations represent the principal therapeutic interventions for terminal organ failure, a procedure that has salvaged myriad lives annually. Ischemia/reperfusion injury (IRI) is frequently correlated with an unfavourable prognosis and is relevant for early graft dysfunction and graft survival. IRI constitutes a complex pathological state influenced by a series of factors such as oxidative stress, metabolic stress, leukocytic infiltration, programmed cell death pathways, and inflammatory immune responses. Reducing ischemia/reperfusion injury is one of the main directions of transplantation research. Toll-like receptors (TLRs) are important pattern-recognition receptors expressed on various organs that orchestrate the immune responses upon recognising PAMPs and DAMPs. Targeting the TLR4 signalling has recently been suggested as a promising approach for alleviating IRI by affecting inflammation, oxidative stress and programmed cell death (PCD). In this minireview, we summarise the role of TLR4 signalling in regulating inflammation, oxidative stress and PCD in organ transplantation and discuss their interactions during IRI. A detailed understanding of the multiple functions of TLR4 in IRI provides novel insights into developing therapies to improve organ transplantation outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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22. A disulfidptosis-related glucose metabolism and immune response prognostic model revealing the immune microenvironment in lung adenocarcinoma.
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Kai Zhang, Gang Li, Qin Wang, Xin Liu, Hong Chen, Fuqiang Li, Shuangyan Li, Xinmao Song, and Yi Li
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NON-small-cell lung carcinoma ,APOPTOSIS ,IMMUNE checkpoint proteins ,TREATMENT effectiveness ,PROGNOSTIC models - Abstract
Background: Lung adenocarcinoma accounts for the majority of lung cancer cases and impact survival rate of patients severely. Immunotherapy is an effective treatment for lung adenocarcinoma but is restricted by many factors including immune checkpoint expression and the inhibitory immune microenvironment. This study aimed to explore the immune microenvironment in lung adenocarcinoma via disulfidptosis. Methods: Public datasets of lung adenocarcinoma from the TCGA and GEO was adopted as the training and validation cohort. Based on the differences in the expression of disulfidptosis -related genes, a glucose metabolism and immune response prognostic model was constructed. The prognostic value and clinical relationship of the model were further explored. Immune-related analyses were performed according to CIBERSORT, ssGSEA, TIDE, IPS. Results: We verified that the model could accurately predict the survival expectancy of lung adenocarcinoma patients. Patients with lung adenocarcinoma and a low-risk score had better survival outcomes according to the model. Moreover, the high-risk group tended to have an immunosuppressive effect, as reflected by the immune cell components, phenotypes and functions. We also found that the clinically relevant immune checkpoint CTLA-4 was significantly higher in low-risk group (P<0.05), indicating that the high-risk group may suffer worse tumor immunotherapy efficacy. Finally, we found that this model has accurate predictive value for the efficacy of immune checkpoint blockade in non-small cell lung cancer (P<0.05). Conclusion: The prognostic model demonstrated the feasibility of predicting survival and immunotherapy efficacy via disulfidptosis-related genes and will facilitate the development of personalized anticancer therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.
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Sun, Haiyan, Yisi Shan, Cao, Liyan, Wu, Xiping, Chen, Jiangdong, Yuan, Rong, and Qian, Min
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APOPTOSIS ,SCIENTIFIC knowledge ,NEURONS ,CELL death ,PYROPTOSIS - Abstract
Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Oxidative Stress-Mediated Programmed Cell Death: a Potential Therapy Target for Atherosclerosis.
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Chen, Yuwu, Luo, Xing, Xu, Biyi, Bao, Xiaoyi, Jia, Haibo, and Yu, Bo
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Nowadays, as a type of orderly and active death determined by genes, programmed cell death (PCD), including apoptosis, pyroptosis, ferroptosis, and necroptosis, has attracted much attention owing to its participation in numerous chronic cardiovascular diseases, especially atherosclerosis (AS), a canonical chronic inflammatory disease featured by lipid metabolism disturbance. Abundant researches have reported that PCD under distinct internal conditions fulfills different roles of atherosclerotic pathological processes, including lipid core expansion, leukocyte adhesion, and infiltration. Noteworthy, emerging evidence recently has also suggested that oxidative stress (OS), an imbalance of antioxidants and oxygen free radicals, has the potential to mediate PCD occurrence via multiple ways, including oxidization and deubiquitination. Interestingly, more recently, several studies have proposed that the mediating mechanisms could effect on the atherosclerotic initiation and progression significantly from variable aspects, so it is of great clinical importance to clarify how OS-mediated PCD and AS interact. Herein, with the aim of summarizing potential and sufficient atherosclerotic therapy targets, we seek to provide extensive analysis of the specific regulatory mechanisms of PCD mediated by OS and their multifaceted effects on the entire pathological atherosclerotic progression. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Iris setosa Pall. ex Link Extract Reveals Amoebicidal Activity against Acanthamoeba castellanii and Acanthamoeba polyphaga with Low Toxicity to Human Corneal Cells.
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Lê, Hương Giang, Hwang, Buyng Su, Choi, Ji-Su, Jeong, Yong Tae, Kang, Jung-Mi, Võ, Tuấn Cường, Oh, Young Taek, and Na, Byoung-Kuk
- Subjects
ACANTHAMOEBA castellanii ,APOPTOSIS ,ACANTHAMOEBA keratitis ,IRIS (Eye) ,ACANTHAMOEBA - Abstract
Acanthamoeba keratitis (AK) is a sight-threatening and difficult-to-treat ocular infection. The significant side effects of current AK treatments highlight the urgent need to develop a safe and effective AK medication. In this study, the amoebicidal activity of Iris setosa Pall. ex Link extract (ISE) against Acanthamoeba was examined and its specific amoebicidal mechanism was explored. ISE induced significant morphological changes in Acanthamoeba trophozoites and exhibited amoebicidal activity against A. castellanii and A. polyphaga. ISE was further fractionated into five subfractions by sequential extraction with n-hexane, chloroform, ethyl acetate, n-butanol, and water, and their amoebicidal activities and underlying amoebicidal mechanisms were investigated. The n-butanol subfraction of ISE (ISE-BuOH) displayed selective amoebicidal activity against the Acanthamoeba species with minimal cytotoxicity in human corneal cells (HCE-2). ISE-BuOH triggered apoptosis-like programmed cell death (PCD) in amoebae, characterized by DNA fragmentation, increased ROS production, and caspase-3 activity elevation. ISE-BuOH also demonstrated a partial cysticidal effect against the amoeba species. ISE-BuOH could be a promising candidate in the development of therapeutic drugs for AK. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Temperature and immune challenges modulate the transcription of genes of the ubiquitin and apoptosis pathways in two high-latitude Notothenioid fish across the Antarctic Polar Front.
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Saravia, Julia, Nualart, Daniela, Paschke, Kurt, Pontigo, Juan Pablo, Navarro, Jorge M., and Vargas-Chacoff, Luis
- Abstract
Thermal variations due to global climate change are expected to modify the distributions of marine ectotherms, with potential pathogen translocations. This is of particular concern at high latitudes where cold-adapted stenothermal fish such as the Notothenioids occur. However, little is known about the combined effects of thermal fluctuations and immune challenges on the balance between cell damage and repair processes in these fish. The aim of this study was to determine the effect of thermal variation on specific genes involved in the ubiquitination and apoptosis pathways in two congeneric Notothenioid species, subjected to simulated bacterial and viral infections. Adult fish of Harpagifer bispinis and Harpagifer antarcticus were collected from Punta Arenas (Chile) and King George Island (Antarctica), respectively, and distributed as follows: injected with PBS (control), LPS (2.5 mg/kg) or Poly I:C (2 mg/kg) and then submitted to 2, 5 and 8 °C. After 1 week, samples of gills, liver and spleen were taken to evaluate the expression by real-time PCR of specific genes involved in ubiquitination (E3-ligase enzyme) and apoptosis (BAX and SMAC/DIABLO). Gene expression was tissue-dependent and increased with increasing temperature in the gills and liver while showing an opposite pattern in the spleen. Studying a pair of sister species that occur across the Antarctic Polar Front can help us understand the particular pressures of intertidal lifestyles and the effect of temperature in combination with biological stressors on cell damage and repair capacity in a changing environment. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Exploring a specialized programmed-cell death patterns to predict the prognosis and sensitivity of immunotherapy in cutaneous melanoma via machine learning.
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Xiao, Leyang, He, Ruifeng, Hu, Kaibo, Song, Gelin, Han, Shengye, Lin, Jitao, Chen, Yixuan, Zhang, Deju, Wang, Wuming, Peng, Yating, Zhang, Jing, and Yu, Peng
- Subjects
MACHINE learning ,TREATMENT effectiveness ,APOPTOSIS ,PROGNOSIS ,IMMUNOTHERAPY ,MELANOMA - Abstract
The mortality and therapeutic failure in cutaneous melanoma (CM) are mainly caused by wide metastasis and chemotherapy resistance. Meanwhile, immunotherapy is considered a crucial therapy strategy for CM patients. However, the efficiency of currently available methods and biomarkers in predicting the response of immunotherapy and prognosis of CM is limited. Programmed cell death (PCD) plays a significant role in the occurrence, development, and therapy of various malignant tumors. In this research, we integrated fourteen types of PCD, multi-omics data from TCGA-SKCM and other cohorts in GEO, and clinical CM patients to develop our analysis. Based on significant PCD patterns, two PCD-related CM clusters with different prognosis, tumor microenvironment (TME), and response to immunotherapy were identified. Subsequently, seven PCD-related features, especially CD28, CYP1B1, JAK3, LAMP3, SFN, STAT4, and TRAF1, were utilized to establish the prognostic signature, namely cell death index (CDI). CDI accurately predicted the response to immunotherapy in both CM and other cancers. A nomogram with potential superior predictive ability was constructed, and potential drugs targeting CM patients with specific CDI have also been identified. Given all the above, a novel CDI gene signature was indicated to predict the prognosis and exploit precision therapeutic strategies of CM patients, providing unique opportunities for clinical intelligence and new management methods for the therapy of CM. [ABSTRACT FROM AUTHOR]
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- 2024
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28. 假体周围骨溶解中的新型细胞程序性死亡.
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梁晓龙, 郑 恺, 耿德春, and 徐耀增
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BACKGROUND: In addition to apoptosis, recent studies have discovered novel forms of programmed cell death in periprosthetic osteolysis, which is involved in regulating local chronic inflammation and the outcome of osteoblast and osteoclast under pathological conditions. This has an important value for the treatment and prognosis of periprosthetic osteolysis. OBJECTIVE: To provide new ideas and strategies for the prevention and treatment of periprosthetic osteolysis by summarizing studies on the novel forms of programmed cell death. METHODS: The first author used the computer to search the articles published from 2005 to 2022. Chinese search terms “wear particles, periprosthetic osteolysis, programmed cell death, apoptosis, autophagy, pyroptosis, necrotizing apoptosis, iron death” were used to search the databases of CNKI, WanFang and VIP. English search terms “osteolysis, wear debris, wear particles, peri*prosthetic osteolysis, PPOL, aseptic loosening, autophagy, regulated cell death, programmed cell death, apoptosis, pyroptosis, autophagic cell death, autophagy, necroptosis, ferroptosis” were used for search in PubMed and Web of Science databases. A total of 68 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION: (1) Inadequate or excessive activation of autophagy can cause cell death, inhibit bone formation, and promote bone resorption, leading to bone metabolism disorders and osteolysis. (2) Recent studies have paid close attention to pyroptosis in periprosthetic osteolysis, where the Nod-like receptor, pyrin containing 3 inflammasome plays an important role in local inflammation. Inhibiting pyroptosis can effectively alleviate osteolysis. (3) In vitro studies have shown that necroptosis can inhibit the formation and function of osteoblasts and osteoclasts, affecting the process of osteolysis and destruction. (4) Ferroptosis is the newest form of programmed cell death, which is regulated by complex signaling pathways and mechanisms, but is not yet fully understood. (5) Autophagy, pyroptosis, necroptosis, and ferroptosis play important roles in the development of periprosthetic osteolysis, and their associated signaling pathways and genes require further investigation. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis.
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Zilu Cheng, Huikuan Chu, Ekihiro Seki, Rong Lin, and Ling Yang
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CELL death ,FATTY liver ,FIBROSIS ,METABOLIC disorders ,INFLAMMATION ,TREATMENT effectiveness ,APOPTOSIS - Abstract
By replacing and removing defective or infected cells, programmed cell death (PCD) contributes to homeostasis maintenance and body development, which is ubiquitously present in mammals and can occur at any time. Besides apoptosis, more novel modalities of PCD have been described recently, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. PCD not only regulates multiple physiological processes, but also participates in the pathogenesis of diverse disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is mainly classified into metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction associated steatohepatitis (MASH), and the latter putatively progresses to cirrhosis and hepatocellular carcinoma. Owing to increased incidence and obscure etiology of MASH, its management still remains a tremendous challenge. Recently, hepatocyte PCD has been attracted much attention as a potent driver of the pathological progression from MASL to MASH, and some pharmacological agents have been proved to exert their salutary effects on MASH partly via the regulation of the activity of hepatocyte PCD. The current review recapitulates the pathogenesis of different modalities of PCD, clarifies the mechanisms underlying how metabolic disorders in MASLD induce hepatocyte PCD and how hepatocyte PCD contributes to inflammatory and fibrotic progression of MASH, discusses several signaling pathways in hepatocytes governing the execution of PCD, and summarizes some potential pharmacological agents for MASH treatment which exert their therapeutic effects partly via the regulation of hepatocyte PCD. These findings indicate that hepatocyte PCD putatively represents a new therapeutic point of intervention for MASH. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Endosperm cell death: roles and regulation in angiosperms.
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Doll, Nicolas M and Nowack, Moritz K
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CELL death , *ENDOSPERM , *APOPTOSIS , *SEEDS , *SEED development , *ANGIOSPERMS , *CASTOR beans , *GERMINATION - Abstract
Double fertilization in angiosperms results in the formation of a second zygote, the fertilized endosperm. Unlike its embryo sibling, the endosperm is a transient structure that eventually undergoes developmentally controlled programmed cell death (PCD) at specific time points of seed development or germination. The nature of endosperm PCD exhibits a considerable diversity, both across different angiosperm taxa and within distinct endosperm tissues. In endosperm-less species, PCD might cause central cell degeneration as a mechanism preventing the formation of a fertilized endosperm. In most other angiosperms, embryo growth necessitates the elimination of surrounding endosperm cells. Nevertheless, complete elimination of the endosperm is rare and, in most cases, specific endosperm tissues persist. In mature seeds, these persisting cells may be dead, such as the starchy endosperm in cereals, or remain alive to die only during germination, like the cereal aleurone or the endosperm of castor beans. In this review, we explore current knowledge surrounding the cellular, molecular, and genetic aspects of endosperm PCD, and the influence environmental stresses have on PCD processes. Overall, this review provides an exhaustive overview of endosperm PCD processes in angiosperms, shedding light on its diverse mechanisms and its significance in seed development and seedling establishment. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Understanding Water Utilization Mechanisms in Degrading Bamboo Shoots: A Cytological and Physiological Study.
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Hu, Tianyi, Wu, Zhengchun, Deng, Meng, Liu, Haiwen, Xiao, Jiao, Wei, Qiang, and Yu, Fen
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WATER use ,BAMBOO shoots ,CYTOLOGICAL techniques ,STUNTED growth ,WATER pressure - Abstract
Degradation of shoots, characterized by stunted growth and signs of water deficit, is common in bamboo stands. However, the specific mechanisms underlying water utilization in degrading shoots remain unclear. This study sought to address this gap by harvesting bamboo shoots and culms of Phyllostachys edulis 'Pachyloen', employing cytological and physiological techniques to compare water utilization mechanisms between healthy and degrading shoots, and investigating the water supply to bamboo shoots by the parent bamboo. The water pressure in the degrading shoots was markedly lower compared to that of the healthy shoots, and it declined as the degradation progressed, resulting in reduced water content and the cessation of guttation in the degrading shoots. In conditions of water deficit, the percentage of free water in bamboo shoots decreased while the percentages of bound and semi-bound water increased, with the proportion of semi-bound water reaching as high as 88.13% in the late stages of degradation. The water potential of parent bamboo culms of different ages varied at different times of the day and during different growth stages of bamboo shoots, showing a strong association with the development of bamboo shoots. Conversely, the correlation between changes in the water potential of bamboo shoots and their degradation patterns was found to be comparatively minimal. The weakening of the connection between the bamboo shoots and the parent bamboo culms may play a significant role in the degradation of the bamboo shoots. This is evidenced by a decrease in the fluorescence intensity of the nucleus in bamboo shoots and the degradation of genetic material. This study lays the foundation for future research into the mechanisms of bamboo shoot degradation. [ABSTRACT FROM AUTHOR]
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- 2024
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32. A novel prognostic signature related to programmed cell death in osteosarcoma.
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Yu-Chen Jiang, Qi-Tong Xu, Hong-Bin Wang, Si-Yuan Ren, and Yao Zhang
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APOPTOSIS ,OSTEOSARCOMA ,GENE expression ,PROGNOSIS ,LITERARY sources - Abstract
Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, andmanually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessedmRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes--CLTCL1, EDIL3, and SQLE--resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model--CLTCL1, MTM1, MLH1, EDIL3, and SQLE--were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma. [ABSTRACT FROM AUTHOR]
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- 2024
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33. The Emerging Role of Ferroptosis in EBV-Associated Cancer: Implications for Cancer Therapy.
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He, Shan, Luo, Cheng, Shi, Feng, Zhou, Jianhua, and Shang, Li
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APOPTOSIS , *CELLULAR signal transduction , *ONCOGENIC viruses , *EPSTEIN-Barr virus , *CELL death , *CANCER treatment - Abstract
Simple Summary: This review will discuss the connection between ferroptosis and Epstein–Barr Virus as well as its associated cancers. It delves into both known and potential ways in which EBV regulates the ferroptosis signaling pathways and focuses on the potential and prospects of targeting the ferroptosis pathway for the treatment of EBV-related tumors. The review may offer new perspectives for future research directions and clinical therapies. Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors. This review will firstly describe the mechanism of ferroptosis, then summarize EBV infection and EBV-associated tumors, as well as the crosstalk between EBV infection and the ferroptosis signaling pathway, and finally discuss the role and potential application of ferroptosis-related reagents in EBV-associated tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation.
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Zhu, Yihao, Chen, Yuxi, and Zu, Yao
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MYOCARDIAL infarction , *APOPTOSIS , *GENE expression , *MATRIX decomposition , *NONNEGATIVE matrices - Abstract
Background: Programmed cell death (PCD) has recently been implicated in modulating the removal of neutrophils recruited in acute myocardial infarction (AMI). Nonetheless, the clinical significance and biological mechanism of neutrophil-related PCD remain unexplored. Methods: We employed an integrative machine learning-based computational framework to generate a predictive neutrophil-derived PCD signature (NPCDS) within five independent microarray cohorts from the peripheral blood of AMI patients. Non-negative matrix factorization was leveraged to develop an NPCDS-based AMI subtype. To elucidate the biological mechanism underlying NPCDS, we implemented single-cell transcriptomics on Cd45+ cells isolated from the murine heart of experimental AMI. We finally conducted a Mendelian randomization (MR) study and molecular docking to investigate the therapeutic value of NPCDS on AMI. Results: We reported the robust and superior performance of NPCDS in AMI prediction, which contributed to an optimal combination of random forest and stepwise regression fitted on nine neutrophil-related PCD genes (MDM2, PTK2B, MYH9, IVNS1ABP, MAPK14, GNS, MYD88, TLR2, CFLAR). Two divergent NPCDS-based subtypes of AMI were revealed, in which subtype 1 was characterized as inflammation-activated with more vibrant neutrophil activities, whereas subtype 2 demonstrated the opposite. Mechanically, we unveiled the expression dynamics of NPCDS to regulate neutrophil transformation from a pro-inflammatory phase to an anti-inflammatory phase in AMI. We uncovered a significant causal association between genetic predisposition towards MDM2 expression and the risk of AMI. We also found that lidoflazine, isotetrandrine, and cepharanthine could stably target MDM2. Conclusion: Altogether, NPCDS offers significant implications for prediction, stratification, and therapeutic management for AMI. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Non-Apoptotic Programmed Cell Death as Targets for Diabetic Retinal Neurodegeneration.
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Lin, Yingjia, Ke, Shuping, Ye, Weiqing, Xie, Biyao, and Huang, Zijing
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APOPTOSIS , *CELL death , *DIABETIC retinopathy , *PYROPTOSIS , *DISEASE management - Abstract
Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in neurotrophic factors are the key determinants in the pathophysiology of DRN. Non-apoptotic programmed cell death (PCD) plays a crucial role in regulating stress response, inflammation, and disease management. Therapeutic modalities targeting PCD have shown promising potential for mitigating DRN. In this review, we highlight recent advances in identifying the role of various PCD types in DRN, with specific emphasis on necroptosis, pyroptosis, ferroptosis, parthanatos, and the more recently characterized PANoptosis. In addition, the therapeutic agents aimed at the regulation of PCD for addressing DRN are discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Significance of genotypes and resistance status of Mycobacterium tuberculosis strains in gene expression of apoptosis cell death and inflammatory pathways in A549 lung epithelial cell line.
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Abdolhamidi, Rouhollah, Haghighat, Setareh, Moshiri, Arfa, Fateh, Abolfazl, and Siadat, Seyed Davar
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GENE expression , *MYCOBACTERIUM tuberculosis , *CELL death , *EPITHELIAL cells , *GENOTYPES , *MYCOBACTERIA - Abstract
Objective(s):Tuberculosis (TB) has been a major health issue throughout history. As part of TB infection, host-Mycobacterium tuberculosis (Mtb) interactions are important. Through immune pathology and cell death control processes, Mtb infection facilitates intracellular growth. The relationship between apoptosis and inflammation in Mtb infection remains unclear. In this study, the levels of related apoptosis and inflammatory genes were assessed in A549 cells infected with a variety of Mtb strains. Materials and Methods: Mtb isolates with different phenotypes (sensitive, INHR, RifR, MDR, and XDR) were collected from the Pasteur Institute of Iran, during this study. Whole genome sequencing was previously performed on all strains, and the Beijing genotype was selected as sensitive. Also, for other resistant strains, the New-1 genotype was available and isolated for genotype comparison. A549 lung carcinoma cells were also grown and infected with selected Mtb strains. Genes involved in inflammation and apoptosis were detected using reverse transcription-PCR (RT-PCR). Results: All sensitive strains and resistant strains were found to significantly up-regulate anti-apoptotic (bcl2 and rb1), chemokine (IL-8 and MCP-1), and pro-inflammatory cytokine (TNF-α and IFN-γ) expression, while significant down-regulation was observed after 24 and 48 hr of infection in antiinflammatory genes (IL-10) and pro-apoptotic genes (bad and bax). Besides resistance strains, Mtb genotypes also affected gene expression. The Beijing genotype (sensitive isolate) influences inflammatory and apoptotic genes more sharply than the New-1 genotype (INHR, RifR, MDR, and XDR). Conclusion: Gene expression differences related to apoptosis and inflammation examined in the current study may be attributed to genotypes rather than resistance status since the expression of most genes has been observed to be lower in n resistant strains (INHR, RifR, MDR, and XDR belonging to the New-1 genotype) compared to sensitive strains (Beijing genotype). [ABSTRACT FROM AUTHOR]
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- 2024
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37. Molecular insights into programmed cell death in esophageal squamous cell carcinoma.
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Chen, Min, Qi, Yijun, Zhang, Shenghua, Du, Yubo, Cheng, Haodong, and Gao, Shegan
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APOPTOSIS ,RECEIVER operating characteristic curves ,SQUAMOUS cell carcinoma ,SUPPORT vector machines ,RANDOM forest algorithms - Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is a deadly type of esophageal cancer. Programmed cell death (PCD) is an important pathway of cellular self-extermination and is closely involved in cancer progression. A detailed study of its mechanism may contribute to ESCC treatment. Methods: We obtained expression profiling data of ESCC patients from public databases and genes related to 12 types of PCD from previous studies. Hub genes in ESCC were screened from PCD-related genes applying differential expression analysis, machine learning analysis, linear support vector machine (SVM), random forest and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. In addition, based on the HTFtarget and TargetScan databases, transcription factors (TFs) and miRNAs interacting with the hub genes were selected. The relationship between hub genes and immune cells were analyzed using the CIBERSORT algorithm. Finally, to verify the potential impact of the screened hub genes on ESCC occurrence and development, a series of in vitro cell experiments were conducted. Results: We screened 149 PCD-related DEGs, of which five DEGs (INHBA, LRRK2, HSP90AA1, HSPB8, and EIF2AK2) were identified as the hub genes of ESCC. The area under the curve (AUC) of receiver operating characteristic (ROC) curve of the integrated model developed using the hub genes reached 0.997, showing a noticeably high diagnostic accuracy. The number of TFs and miRNAs regulating hub genes was 105 and 22, respectively. INHBA, HSP90AA1 and EIF2AK2 were overexpressed in cancer tissues and cells of ESCC. Notably, INHBA knockdown suppressed ECSS cell migration and invasion and altered the expression of important apoptotic and survival proteins. Conclusion: This study identified significant molecules with promising accuracy for the diagnosis of ESCC, which may provide a new perspective and experimental basis for ESCC research. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Exploring Aluminum Tolerance Mechanisms in Plants with Reference to Rice and Arabidopsis : A Comprehensive Review of Genetic, Metabolic, and Physiological Adaptations in Acidic Soils.
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Chakraborty, Nilakshi, Das, Abir, Pal, Sayan, Roy, Soumita, Sil, Sudipta Kumar, Adak, Malay Kumar, and Hassanzamman, Mirza
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BIOLOGICAL transport ,APOPTOSIS ,MITOCHONDRIAL proteins ,NUCLEIC acids ,ORGANIC acids - Abstract
Aluminum (Al) makes up a third of the Earth's crust and is a widespread toxic contaminant, particularly in acidic soils. It impacts crops at multiple levels, from cellular to whole plant systems. This review delves into Al's reactivity, including its cellular transport, involvement in oxidative redox reactions, and development of specific metabolites, as well as the influence of genes on the production of membrane channels and transporters, alongside its role in triggering senescence. It discusses the involvement of channel proteins in calcium influx, vacuolar proton pumping, the suppression of mitochondrial respiration, and the initiation of programmed cell death. At the cellular nucleus level, the effects of Al on gene regulation through alterations in nucleic acid modifications, such as methylation and histone acetylation, are examined. In addition, this review outlines the pathways of Al-induced metabolic disruption, specifically citric acid metabolism, the regulation of proton excretion, the induction of specific transcription factors, the modulation of Al-responsive proteins, changes in citrate and nucleotide glucose transporters, and overall metal detoxification pathways in tolerant genotypes. It also considers the expression of phenolic oxidases in response to oxidative stress, their regulatory feedback on mitochondrial cytochrome proteins, and their consequences on root development. Ultimately, this review focuses on the selective metabolic pathways that facilitate Al exclusion and tolerance, emphasizing compartmentalization, antioxidative defense mechanisms, and the control of programmed cell death to manage metal toxicity. [ABSTRACT FROM AUTHOR]
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- 2024
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39. Development and Holocrine Secretion of Resin Ducts in Kielmeyera appariciana (Calophyllaceae).
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Costa, Ellenhise Ribeiro and Demarco, Diego
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APOPTOSIS ,HYDROLASES ,REACTIVE oxygen species ,ENDOPLASMIC reticulum ,CELL death - Abstract
The modes of formation and release of secretion are complex processes that occur in secretory ducts and their description has great divergence in some species. The use of modern techniques to detect hydrolytic enzymes, cytoskeleton arrangement and indicators of programmed cell death may help clarify the processes involved during the ontogeny of that gland. The goal of our study was to analyze subcellular changes during schizogenous formation and secretion production and release into the lumen in resin ducts of Kielmeyera appariciana. Our results demonstrate the participation of pectinase through the loosening of the central cells of the rosette, which subsequently split from each other through polarized growth mediated by a rearrangement of the microtubules. The resin is mainly synthesized in plastids and endoplasmic reticulum and is observed inside vesicles and small vacuoles. The secretion release is holocrine and occurs through programmed cell death related to the release of reactive oxygen species, causing cytoplasm darkening, chromatin condensation, vacuole rupture and plastid and mitochondria degeneration. Cellulase activity was identified prior to the rupture of the cell wall, causing the release of secretion into the lumen of the duct. The participation of the cytoskeleton was observed for the first time during schizogeny of ducts as well as programmed cell death as part of the process of the release of holocrine secretion. This type of secretion release may be a key innovation in Kielmeyera since it has not been observed in ducts of any other plant thus far. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma.
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Zhao, Yubao, Wang, Liang, Li, Xiaoyan, Jiang, Junzhi, Ma, Yan, Guo, Shuxia, Zhou, Jinming, and Li, Yingjun
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Background: Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, and prognosis. There is still no research on the relationship between PCD-related genes and UVM. A novel PCD-associated prognostic model is urgently needed to improve treatment strategies. Objective: We aim to screen PCD-related prognostic signature and investigate its proliferation ability and apoptosis in UVM cells. Methods: The clinical information and RNA-seq data of the UVM patients were collected from the TCGA cohort. All the patients were classified using consensus clustering by the selected PCD-related genes. After univariate Cox regression and PPI network analysis, the prognostic PCD-related genes were then submitted to the LASSO regression analysis to build a prognostic model. The level of immune infiltration of 8-PCD signature in high- and low-risk patients was analyzed using xCell. The prediction on chemotherapy and immunotherapy response in UVM patients was assessed by GDSC and TIDE algorithm. CCK-8, western blot and Annexin V-FITC/PI staining were used to explore the roles of HMOX1 in UVM cells. Results: A total of 8-PCD signature was constructed and the risk score of the PCD signature was negatively correlated with the overall survival, indicating strong predictive ability and independent prognostic value. The risk score was positively correlated with CD8 Tcm, CD8 Tem and Th2 cells. Immune cells in high-risk group had poorer overall survival. The drug sensitivity demonstrated that cisplatin might impact the progression of UVM and better immunotherapy responsiveness in the high-risk group. Finally, Overespression HMOX1 (OE-HMOX1) decreased the cell viability and induced apoptosis in UVM cells. Recuse experiment results showed that ferrostatin-1 (fer-1) protected MP65 cells from apoptosis and necrosis caused by OE-HMOX1. Conclusion: The PCD signature may have a significant role in the tumor microenvironment, clinicopathological characteristics, prognosis and drug sensitivity. More importantly, HMOX1 depletion greatly induced tumor cell growth and inhibited cell apoptosis and fer-1 protected UVM cells from apoptosis and necrosis induced by OE-HMOX1. This work provides a foundation for effective therapeutic strategy in tumour treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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41. ZBP1 promotes hepatocyte pyroptosis in acute liver injury by regulating the PGAM5/ROS pathway.
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Shengguang Yan, Lina Yu, Ziren Chen, Dan Xie, Zuli Huang, and Shi Ouyang
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PYROPTOSIS ,WESTERN immunoblotting ,LIVER injuries ,CELL death ,APOPTOSIS ,REPERFUSION injury - Abstract
Introduction and Objectives: Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria and release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) is a sensor that induces cell death. Here, we investigated whether ZBP1 participates in hepatocyte pyroptosis and explored the possible pathogenesis of ALI. Materials and Methods: Hepatocyte pyrotosis was induced with lipopolysaccharide (LPS) and nigericin (Nig), and the expression of Zbp1 (ZBP1) was examined by western blot analysis and RT-qPCR. Further, we transfected AML-12 (LO2 and HepG2) cell lines with Zbp1 (ZBP1) siRNA. After ZBP1 was silenced, LDH release and flow cytometry were used to measure the cell death; Western blot analysis and RT-qPCR were used to detect the marker of NLRP3 inflammasome activation and pyroptosis. We also detected the expression of mitochondrial linear rupture marker phosphoglycerate mutase family member 5 (PGAM5) using western blot analysis and reactive oxygen species (ROS) using the DCFH-DA method. Results: The expression of ZBP1 was up-regulated in LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited NLRP3 inflammasome activation and pyroptosis in LPS/Nig-induced hepatocytes. Moreover, ZBP1 silencing inhibited the expression of PGAM5 by reducing ROS production. Conclusions: ZBP1 promotes hepatocellular pyroptosis by modulating mitochondrial damage, which facilitates the extracellular release of ROS. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Deciphering the tumour microenvironment of clear cell renal cell carcinoma: Prognostic insights from programmed death genes using machine learning.
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Tu, Hongtao, Hu, Qingwen, Ma, Yuying, Huang, Jinbang, Luo, Honghao, Jiang, Lai, Zhang, Shengke, Jiang, Chenglu, Lai, Haotian, Liu, Jie, Chen, Jianyou, Guo, Liwei, Yang, Guanhu, Xu, Ke, Chi, Hao, and Chen, Haiqing
- Subjects
RENAL cell carcinoma ,CELL communication ,TUMOR microenvironment ,MACHINE learning ,APOPTOSIS ,RENAL cancer ,GIANT cell arteritis - Abstract
Clear cell renal cell carcinoma (ccRCC), a prevalent kidney cancer form characterised by its invasiveness and heterogeneity, presents challenges in late‐stage prognosis and treatment outcomes. Programmed cell death mechanisms, crucial in eliminating cancer cells, offer substantial insights into malignant tumour diagnosis, treatment and prognosis. This study aims to provide a model based on 15 types of Programmed Cell Death‐Related Genes (PCDRGs) for evaluating immune microenvironment and prognosis in ccRCC patients. ccRCC patients from the TCGA and arrayexpress cohorts were grouped based on PCDRGs. A combination model using Lasso and SuperPC was constructed to identify prognostic gene features. The arrayexpress cohort validated the model, confirming its robustness. Immune microenvironment analysis, facilitated by PCDRGs, employed various methods, including CIBERSORT. Drug sensitivity analysis guided clinical treatment decisions. Single‐cell data enabled Programmed Cell Death‐Related scoring, subsequent pseudo‐temporal and cell–cell communication analyses. A PCDRGs signature was established using TCGA‐KIRC data. External validation in the arrayexpress cohort underscored the model's superiority over traditional clinical features. Furthermore, our single‐cell analysis unveiled the roles of PCDRG‐based single‐cell subgroups in ccRCC, both in pseudo‐temporal progression and intercellular communication. Finally, we performed CCK‐8 assay and other experiments to investigate csf2. In conclusion, these findings reveal that csf2 inhibit the growth, infiltration and movement of cells associated with renal clear cell carcinoma. This study introduces a PCDRGs prognostic model benefiting ccRCC patients while shedding light on the pivotal role of programmed cell death genes in shaping the immune microenvironment of ccRCC patients. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Research Progress on Micro(nano)plastic-Induced Programmed Cell Death Associated with Disease Risks.
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Liu, Huanpeng, Li, Huiqi, Chen, Ting, Yu, Fan, Lin, Qizhuan, Zhao, Haiyang, Jin, Libo, and Peng, Renyi
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APOPTOSIS ,CELL death ,POLLUTANTS ,FOOD chains ,CELL aggregation - Abstract
Due to their robust migration capabilities, slow degradation, and propensity for adsorbing environmental pollutants, micro(nano)plastics (MNPs) are pervasive across diverse ecosystems. They infiltrate various organisms within different food chains through multiple pathways including inhalation and dermal contact, and pose a significant environmental challenge in the 21st century. Research indicates that MNPs pose health threats to a broad range of organisms, including humans. Currently, extensive detection data and studies using experimental animals and in vitro cell culture indicate that MNPs can trigger various forms of programmed cell death (PCD) and can induce various diseases. This review provides a comprehensive and systematic analysis of different MNP-induced PCD processes, including pyroptosis, ferroptosis, autophagy, necroptosis, and apoptosis, based on recent research findings and focuses on elucidating the links between PCD and diseases. Additionally, targeted therapeutic interventions for these diseases are described. This review provides original insights into the opportunities and challenges posed by current research findings. This review evaluates ways to mitigate various diseases resulting from cell death patterns. Moreover, this paper enhances the understanding of the biohazards associated with MNPs by providing a systematic reference for subsequent toxicological research and health risk mitigation efforts. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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44. The study of the mechanism of non-coding RNA regulation of programmed cell death in diabetic cardiomyopathy.
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Zhang, Bingrui, Wu, Hua, Zhang, Jingwen, Cong, Cong, and Zhang, Lin
- Abstract
Diabetic cardiomyopathy (DCM) represents a distinct myocardial disorder elicited by diabetes mellitus, characterized by aberrations in myocardial function and structural integrity. This pathological condition predominantly manifests in individuals with diabetes who do not have concurrent coronary artery disease or hypertension. An escalating body of scientific evidence substantiates the pivotal role of programmed cell death (PCD)—encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis—in the pathogenic progression of DCM, thereby emerging as a prospective therapeutic target. Additionally, numerous non-coding RNAs (ncRNAs) have been empirically verified to modulate the biological processes underlying programmed cell death, consequently influencing the evolution of DCM. This review systematically encapsulates prevalent types of PCD manifest in DCM as well as nascent discoveries regarding the regulatory influence of ncRNAs on programmed cell death in the pathogenesis of DCM, with the aim of furnishing novel insights for the furtherance of research in PCD-associated disorders relevant to DCM. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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45. Forms of Non-Apoptotic Cell Death and Their Role in Gliomas—Presentation of the Current State of Knowledge.
- Author
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Nafe, Reinhold and Hattingen, Elke
- Subjects
APOPTOSIS ,CELL physiology ,CELL death ,CELL anatomy ,TUMOR microenvironment ,NECROSIS - Abstract
In addition to necrosis and apoptosis, the two forms of cell death that have been known for many decades, other non-apoptotic forms of cell death have been discovered, many of which also play a role in tumors. Starting with the description of autophagy more than 60 years ago, newer forms of cell death have become important for the biology of tumors, such as ferroptosis, pyroptosis, necroptosis, and paraptosis. In this review, all non-apoptotic and oncologically relevant forms of programmed cell death are presented, starting with their first descriptions, their molecular characteristics, and their role and their interactions in cell physiology and pathophysiology. Based on these descriptions, the current state of knowledge about their alterations and their role in gliomas will be presented. In addition, current efforts to therapeutically influence the molecular components of these forms of cell death will be discussed. Although research into their exact role in gliomas is still at a rather early stage, our review clarifies that all these non-apoptotic forms of cell death show significant alterations in gliomas and that important insight into understanding them has already been gained. [ABSTRACT FROM AUTHOR]
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- 2024
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46. The Role of Programmed Cell Death 1/Programmed Death Ligand 1 (PD-1/PD-L1) Axis in Sepsis-Induced Apoptosis.
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Coman, Oana, Grigorescu, Bianca-Liana, Huțanu, Adina, Bacârea, Anca, Văsieșiu, Anca Meda, Fodor, Raluca Ștefania, Stoica, Florin, and Azamfirei, Leonard
- Subjects
PROGRAMMED death-ligand 1 ,PROGRAMMED cell death 1 receptors ,APACHE (Disease classification system) ,SEPTIC shock ,APOPTOSIS - Abstract
Background and Objectives: Sepsis involves a dysregulated host response, characterized by simultaneous immunosuppression and hyperinflammation. Initially, there is the release of pro-inflammatory factors and immune system dysfunction, followed by persistent immune paralysis leading to apoptosis. This study investigates sepsis-induced apoptosis and its pathways, by assessing changes in PD-1 and PD-L1 serum levels, CD4+ and CD8+ T cells, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) severity scores. Materials and Methods: This prospective, observational, single-centre study enrolled 87 sepsis patients admitted to the intensive care unit at the County Emergency Clinical Hospital in Târgu Mureș, Romania. We monitored the parameters on day 1 (the day sepsis or septic shock was diagnosed as per the Sepsis-3 Consensus) and day 5. Results: Our study found a statistically significant variation in the SOFA score for the entirety of the patients between the studied days (p = 0.001), as well as for the studied patient groups: sepsis, septic shock, survivors, and non-survivors (p = 0.001, p = 0.003, p = 0.01, p = 0.03). On day 1, we found statistically significant correlations between CD8+ cells and PD-1 (p = 0.02) and PD-L1 (p = 0.04), CD4+ and CD8+ cells (p < 0.0001), SOFA and APACHE II scores (p < 0.0001), and SOFA and APACHE II scores and PD-L1 (p = 0.001 and p = 0.01). On day 5, we found statistically significant correlations between CD4+ and CD8+ cells and PD-L1 (p = 0.03 and p = 0.0099), CD4+ and CD8+ cells (p < 0.0001), and SOFA and APACHE II scores (p < 0.0001). Conclusions: The reduction in Th CD4+ and Tc CD8+ lymphocyte subpopulations were evident from day 1, indicating that apoptosis is a crucial factor in the progression of sepsis and septic shock. The increased expression of the PD-1/PD-L1 axis impairs costimulatory signalling, leading to diminished T cell responses and lymphopenia, thereby increasing the susceptibility to nosocomial infections. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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47. Regulation of defective mitochondrial DNA accumulation and transmission in C. elegans by the programmed cell death and aging pathways.
- Author
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Flowers, Sagen, Kothari, Rushali, Torres Cleuren, Yamila, Alcorn, Melissa, Ewe, Chee, Alok, Geneva, Fiallo, Samantha, Joshi, Pradeep, and Rothman, Joel
- Subjects
C. elegans ,aging ,cell biology ,genetics ,genomics ,heteroplasmy ,insulin signaling ,programmed cell death ,purifying selection ,uaDf5 ,Animals ,Caenorhabditis elegans ,DNA ,Mitochondrial ,Apoptosis ,Caspases ,Caenorhabditis elegans Proteins ,Aging - Abstract
The heteroplasmic state of eukaryotic cells allows for cryptic accumulation of defective mitochondrial genomes (mtDNA). Purifying selection mechanisms operate to remove such dysfunctional mtDNAs. We found that activators of programmed cell death (PCD), including the CED-3 and CSP-1 caspases, the BH3-only protein CED-13, and PCD corpse engulfment factors, are required in C. elegans to attenuate germline abundance of a 3.1-kb mtDNA deletion mutation, uaDf5, which is normally stably maintained in heteroplasmy with wildtype mtDNA. In contrast, removal of CED-4/Apaf1 or a mutation in the CED-4-interacting prodomain of CED-3, do not increase accumulation of the defective mtDNA, suggesting induction of a non-canonical germline PCD mechanism or non-apoptotic action of the CED-13/caspase axis. We also found that the abundance of germline mtDNAuaDf5 reproducibly increases with age of the mothers. This effect is transmitted to the offspring of mothers, with only partial intergenerational removal of the defective mtDNA. In mutants with elevated mtDNAuaDf5 levels, this removal is enhanced in older mothers, suggesting an age-dependent mechanism of mtDNA quality control. Indeed, we found that both steady-state and age-dependent accumulation rates of uaDf5 are markedly decreased in long-lived, and increased in short-lived, mutants. These findings reveal that regulators of both PCD and the aging program are required for germline mtDNA quality control and its intergenerational transmission.
- Published
- 2023
48. Insights into RNA N6-methyladenosine and programmed cell death in atherosclerosis
- Author
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Haijiao Long, Yulu Yu, Jie Ouyang, Hongwei lu, and Guojun Zhao
- Subjects
Atherosclerosis ,N6-methyladenosine ,Programmed cell death ,Diagnosis ,Treatment ,Therapeutics. Pharmacology ,RM1-950 ,Biochemistry ,QD415-436 - Abstract
Abstract N6-methyladenosine (m6A) modification stands out among various RNA modifications as the predominant form within eukaryotic cells, influencing numerous cellular processes implicated in disease development. m6A modification has gained increasing attention in the development of atherosclerosis and has become a research hotspot in recent years. Programmed cell death (PCD), encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, plays a pivotal role in atherosclerosis pathogenesis. In this review, we delve into the intricate interplay between m6A modification and diverse PCD pathways, shedding light on their complex association during the onset and progression of atherosclerosis. Clarifying the relationship between m6A and PCD in atherosclerosis is of great significance to provide novel strategies for cardiovascular disease treatment.
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- 2024
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49. Advances in the role of programmed cell death in retinal ganglion cells in glaucoma
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Song Shiyi and Liang Liang
- Subjects
programmed cell death ,glaucoma ,retinal ganglion cells ,apoptosis ,ferroptosis ,pyroptosis ,autophagy ,parthanatos ,Ophthalmology ,RE1-994 - Abstract
Programmed cell death(PCD)is a unique cell death involving effector molecules, including various forms such as apoptosis, autophagy, and pyroptosis. PCD is involved in many aspects of normal physiological activities in humans, and is closely related to the development of many diseases. Glaucoma is the leading cause of irreversible blindness worldwide. Relevant studies have shown that the development of glaucoma is associated with the abnormal expression of a variety of PCD-related proteins. The mechanism and interplay of apoptosis, autophagy, pyroptosis, ferroptosis and parthanatos of retinal ganglion cells in the course of glaucoma were reviewed, to provide a new direction for the prevention treatment of glaucoma.
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- 2024
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50. Solid-state electron-mediated z-scheme heterostructured semiconductor nanomaterials induce dual programmed cell death for melanoma therapy
- Author
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Yiping Ren, Yun Wang, Cheng Chen, Xiang Yan, Minghao Chao, Yuting Li, Dehong Yu, Yuqi Huang, Xiaoyang Hou, Fenglei Gao, Guan Jiang, and Ming Guan
- Subjects
Heterostructured ,Programmed cell death ,Immunogenic cell death ,Pyroptosis ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e–h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e–h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors. Graphical abstract
- Published
- 2024
- Full Text
- View/download PDF
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