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The FEBS Journal Feb 2019Programmed cell death plays a central role in maintaining homeostasis. Various studies have demonstrated that programmed cell death is not a one-way street; cells can... (Review)
Review
Programmed cell death plays a central role in maintaining homeostasis. Various studies have demonstrated that programmed cell death is not a one-way street; cells can survive even when the core cell death processes are underway. Cell death initiation, prevention, and recovery function in a coordinated fashion to establish and maintain a homeostatic environment. In this review, we discuss how dying cells can be rescued from death's grip and the subsequent physiological consequences. We suggest a fundamental question to be answered-at least at the single cell level is, can we predict if a certain cell is more or less likely to survive or die? And importantly, what physiological and pathological consequences, as well as therapeutic approaches can we delineate from this ability to predict cell death versus survival.
Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Proteins; Cell Survival; Eukaryotic Cells; Gene Expression Regulation; Homeostasis; Humans; Mitochondria; Necrosis; Signal Transduction; Single-Cell Analysis
PubMed: 30506628
DOI: 10.1111/febs.14714 -
Current Neuropharmacology 2018Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be... (Review)
Review
BACKGROUND
Intracerebral hemorrhage (ICH) accounts for up to 15% of all strokes and is characterized by high rates of mortality and morbidity. The post-ICH brain injury can be distinguished in 1) primary, which are caused by disruption and mechanical deformation of brain tissue due to hematoma growth and 2) secondary, which are induced by microglia activation, mitochondrial dysfunction, neurotransmitter and inflammatory mediator release. Although these events typically lead to necrosis, the occurrence of programmed cell death has also been reported after ICH.
METHODS
We reviewed recent publications describing advance in pre- and clinic ICH research.
RESULTS
At present, treatment of ICH patients is based on oral anticoagulant reversal, management of blood pressure and other medical complications. Several pre-clinical studies showed promising results and demonstrated that anti-oxidative and anti-inflammatory treatments reduced neuronal cell death, however, to date, all of these attempts have failed in randomized controlled clinical trials. Yet, the time frame of administration may be crucial in translation from animal to clinical studies. Furthermore, the latest pre-clinical research points toward the existence of other, apoptosisunrelated forms kinds of programmed cell death.
CONCLUSION
Our review summarizes current knowledge of pathways leading to programmed cell death after ICH in addition to data from clinical trials. Some of the pre-clinical results have not yet demonstrated clinical confirmation, however they significantly contribute to our understanding of post-ICH pathology and can contribute to development of new therapeutic approaches, decreasing mortality and improving ICH patients' quality of life.
Topics: Animals; Cell Death; Cerebral Hemorrhage; Humans
PubMed: 28571544
DOI: 10.2174/1570159X15666170602112851 -
Advanced Healthcare Materials Oct 2023Ferroptosis as programmed cell death received considerable attention in cancer research. Recently, studies have associated ferroptosis with photodynamic therapy (PDT)...
Ferroptosis as programmed cell death received considerable attention in cancer research. Recently, studies have associated ferroptosis with photodynamic therapy (PDT) because PDT promotes glutathione (GSH) deletion, glutathione peroxidase 4 (GPX4) degradation, and lipid peroxide accumulation. However, PDT-induced ferroptosis may be potentially prevented by ferroptosis suppressor protein 1 (FSP1). To address this limitation, herein, a novel strategy is developed to trigger ferroptosis by PDT and FSP1 inhibition. For enhancement of this strategy, a photoresponsive nanocomplex, self-assembled by BODIPY-modified poly(amidoamine) (BMP), is utilized to stably encapsulate the inhibitor of FSP1 (iFSP1) and chlorin e6 (Ce6). The nanosystem promotes intracellular delivery, penetration, and accumulation of ferroptosis inducers in tumors with light irradiation. The nanosystem presents high-performance triggering of ferroptosis and immunogenic cell death (ICD) in vitro and in vivo. Importantly, the nanoparticles increase tumor infiltration of CD8 T cells and further enhance the efficacy of anti-PD-L1 immunotherapy. The study suggests the potential of photo-enhanced synergistic induction of ferroptosis by the photoresponsive nanocomplexes in cancer immunotherapy.
Topics: Photochemotherapy; Ferroptosis; Photosensitizing Agents; Cell Line, Tumor; CD8-Positive T-Lymphocytes; Immunotherapy
PubMed: 37432874
DOI: 10.1002/adhm.202300994 -
Seminars in Cell & Developmental Biology May 2021DNA replication is laden with obstacles that slow, stall, collapse, and break DNA replication forks. At each obstacle, there is a decision to be made whether to bypass... (Review)
Review
DNA replication is laden with obstacles that slow, stall, collapse, and break DNA replication forks. At each obstacle, there is a decision to be made whether to bypass the lesion, repair or restart the damaged fork, or to protect stalled forks from further demise. Each "decision" draws upon multitude of proteins participating in various mechanisms that allow repair and restart of replication forks. Specific functions for many of these proteins have been described and an understanding of how they come together in supporting replication forks is starting to emerge. Many questions, however, remain regarding selection of the mechanisms that enable faithful genome duplication and how "normal" intermediates in these mechanisms are sometimes funneled into "rogue" processes that destabilize the genome and lead to cancer, cell death, and emergence of chemotherapeutic resistance. In this review we will discuss molecular mechanisms of DNA damage bypass and replication fork protection and repair. We will specifically focus on the key players that define which mechanism is employed including: PCNA and its control by posttranslational modifications, translesion synthesis DNA polymerases, molecular motors that catalyze reversal of stalled replication forks, proteins that antagonize fork reversal and protect reversed forks from nucleolytic degradation, and the machinery of homologous recombination that helps to reestablish broken forks. We will also discuss risks to genome integrity inherent in each of these mechanisms.
Topics: DNA Damage; DNA Replication; Humans
PubMed: 33967572
DOI: 10.1016/j.semcdb.2020.10.001 -
Journal of Cellular and Molecular... Sep 2017Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific... (Review)
Review
Sepsis remains a leading cause of death worldwide, despite advances in critical care, and understanding of the pathophysiology and treatment strategies. No specific therapy or drugs are available for sepsis. Neutrophils play a critical role in controlling infection under normal conditions, and it is suggested that their migration and antimicrobial activity are impaired during sepsis which contribute to the dysregulation of immune responses. Recent studies further demonstrated that interruption or reversal of the impaired migration and antimicrobial function of neutrophils improves the outcome of sepsis in animal models. In this review, we provide an overview of the associated mediators and signal pathways involved which govern the survival, migration and antimicrobial function of neutrophils in sepsis, and discuss the potential of neutrophils as a target to specifically diagnose and/or predict the outcome of sepsis.
Topics: Animals; Biomarkers; Cell Movement; Humans; Models, Biological; Neutrophils; Sepsis; Signal Transduction
PubMed: 28244690
DOI: 10.1111/jcmm.13112 -
Journal of Medical Primatology Oct 2022One strategy to eliminate latently infected cells that persist in people with HIV on antiretroviral therapy is to activate virus transcription and virus production to... (Review)
Review
One strategy to eliminate latently infected cells that persist in people with HIV on antiretroviral therapy is to activate virus transcription and virus production to induce virus or immune-mediated cell death. This is called latency reversal. Despite clear activity of multiple latency reversal agents in vitro, clinical trials of latency-reversing agents have not shown significant reduction in latently infected cells. We review new insights into the biology of HIV latency and discuss novel approaches to enhance the efficacy of latency reversal agents.
Topics: Animals; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Virus Latency
PubMed: 36029233
DOI: 10.1111/jmp.12613 -
Plants (Basel, Switzerland) Jun 2015Senescence represents the final stage of leaf development but is often induced prematurely following exposure to biotic and abiotic stresses. Leaf senescence is... (Review)
Review
Senescence represents the final stage of leaf development but is often induced prematurely following exposure to biotic and abiotic stresses. Leaf senescence is manifested by color change from green to yellow (due to chlorophyll degradation) or to red (due to de novo synthesis of anthocyanins coupled with chlorophyll degradation) and frequently culminates in programmed death of leaves. However, the breakdown of chlorophyll and macromolecules such as proteins and RNAs that occurs during leaf senescence does not necessarily represent a one-way road to death but rather a reversible process whereby senescing leaves can, under certain conditions, re-green and regain their photosynthetic capacity. This phenomenon essentially distinguishes senescence from programmed cell death, leading researchers to hypothesize that changes occurring during senescence might represent a process of trans-differentiation, that is the conversion of one cell type to another. In this review, we highlight attributes common to senescence and dedifferentiation including chromatin structure and activation of transposable elements and provide further support to the notion that senescence is not merely a deterioration process leading to death but rather a unique developmental state resembling dedifferentiation.
PubMed: 27135333
DOI: 10.3390/plants4030356 -
Frontiers in Oncology 2022Defective silencing of tumor suppressor genes through epigenetic alterations contributes to oncogenesis by perturbing cell cycle regulation, DNA repair or cell death... (Review)
Review
Defective silencing of tumor suppressor genes through epigenetic alterations contributes to oncogenesis by perturbing cell cycle regulation, DNA repair or cell death mechanisms. Reversal of such epigenetic changes including DNA hypermethylation provides a promising anticancer strategy. Until now, the nucleoside derivatives 5-azacytidine and decitabine are the sole DNA methyltransferase (DNMT) inhibitors approved by the FDA for the treatment of specific hematological cancers. Nevertheless, due to their nucleoside structure, these inhibitors directly incorporate into DNA, which leads to severe side effects and compromises genomic stability. Much emphasis has been placed on the development of less toxic epigenetic modifiers. Recently, several preclinical studies demonstrated the potent epigenetic effects of local anesthetics, which are routinely used during primary tumor resection to relief surgical pain. These non-nucleoside molecules inhibit DNMT activity, affect the expression of micro-RNAs and repress histone acetylation, thus exerting cytotoxic effects on malignant cells. The in-depth mechanistic comprehension of these epigenetic effects might promote the use of local anesthetics as anticancer drugs.
PubMed: 36110954
DOI: 10.3389/fonc.2022.849895 -
Molecular Diagnosis & Therapy Jun 2024Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to... (Review)
Review
Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts.
PubMed: 38890247
DOI: 10.1007/s40291-024-00718-w -
Pakistan Journal of Biological Sciences... Jan 2023The DNA is constantly under attack from endogenous and exogenous damaging agents. The damaged DNA must be repaired quickly to avoid genomic instability and to prevent... (Review)
Review
The DNA is constantly under attack from endogenous and exogenous damaging agents. The damaged DNA must be repaired quickly to avoid genomic instability and to prevent the occurrence of a malignant transformation. Once a lesion is detected, the DNA repair mechanism initiates and replaces the structurally altered base or any other abnormality. The cell repair mechanisms include direct reversal, excision repair (base excision repair [BER] and nucleotide excision repair [NER]), mismatch repair (MMR), homologous recombination repair (HR) and non-homologous end joining (NHEJ). Unrepaired DNA could lead to mutation, cell death or cancer. This review will discuss how the defects in DNA repair play a vital role in cancer initiation, development and progression.
Topics: Humans; DNA Repair; DNA Damage; Neoplasms; DNA; DNA Repair-Deficiency Disorders
PubMed: 37129201
DOI: 10.3923/pjbs.2023.15.22