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Biochimica Et Biophysica Acta. Reviews... Nov 2023For decades, common chemotherapeutic drugs have been established to trigger apoptosis, the preferred immunologically "silent" form of cell death. The primary objective... (Review)
Review
For decades, common chemotherapeutic drugs have been established to trigger apoptosis, the preferred immunologically "silent" form of cell death. The primary objective of this review was to show that various FDA-approved chemotherapeutic drugs, including cisplatin, cyclosporine, doxorubicin, etoposide, 5-fluorouracil, gemcitabine, paclitaxel, or vinblastine can trigger necroptosis and pyroptosis. We aimed to provide the advantages and disadvantages of the induction of the given type of cell death by chemotherapeutical agents. Moreover, we give a short overview of the molecular mechanism of each type of cell death and indicate the existing crosstalks between cell death types. Finally, we provide a comparison of cell death types to facilitate the exploration of cell death types induced by other chemotherapeutical agents. Understanding the cell death pathway induced by a drug can lessen side effects and assist the discovery of new combinations with synergistic effects and low systemic toxicity.
Topics: Humans; Pyroptosis; Necroptosis; Apoptosis; Cell Death; Paclitaxel
PubMed: 37980943
DOI: 10.1016/j.bbcan.2023.189024 -
Biomedicine & Pharmacotherapy =... Dec 2023Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy... (Review)
Review
Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy plays a major role because of its condition of absolute increase in ventricular mass under various stresses. Ferroptosis, it could be defined as regulatory mechanisms that regulate cell death in the absence of apoptosis in iron-dependent cells. This paper introduces various new research findings on the use of different regulatory mechanisms of cellular ferroptosis for the treatment of heart failure and cardiac hypertrophy, providing new therapeutic targets and research directions for clinical treatment. The role and mechanism of ferroptosis in the field of heart failure has been increasingly demonstrated, and the relationship between cardiac hypertrophy, which is one of the causes of heart failure, is also an area of research that we should focus on. In addition, the latest applications and progress of inducers and inhibitors of ferroptosis are reported in this paper, updating the breakthroughs in their fields.
Topics: Humans; Ferroptosis; Heart Failure; Apoptosis; Cell Death; Cardiomegaly
PubMed: 37879210
DOI: 10.1016/j.biopha.2023.115765 -
CNS Neuroscience & Therapeutics Dec 2023We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for...
AIM
We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI).
METHODS
Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests.
RESULTS
Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment.
CONCLUSION
Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.
Topics: Animals; Mice; Apoptosis; Blood-Brain Barrier; Brain Injuries, Traumatic; Disease Models, Animal; Glucagon-Like Peptide-1 Receptor; Glymphatic System
PubMed: 37353947
DOI: 10.1111/cns.14308 -
Frontiers in Immunology 2023Cell death is an important aspect of atherosclerotic plaque development. Insufficient efferocytosis of death cells by phagocytic macrophages leads to the buildup of a... (Review)
Review
Cell death is an important aspect of atherosclerotic plaque development. Insufficient efferocytosis of death cells by phagocytic macrophages leads to the buildup of a necrotic core that impacts stability of the plaque. Furthermore, in the presence of calcium and phosphate, apoptotic bodies resulting from death cells can act as nucleation sites for the formation of calcium phosphate crystals, mostly in the form of hydroxyapatite, which leads to calcification of the atherosclerotic plaque, further impacting plaque stability. Excessive uptake of cholesterol-loaded oxidized LDL particles by macrophages present in atherosclerotic plaques leads to foam cell formation, which not only reduces their efferocytosis capacity, but also can induce apoptosis in these cells. The resulting apoptotic bodies can contribute to calcification of the atherosclerotic plaque. Moreover, other forms of macrophage cell death, such as pyroptosis, necroptosis, parthanatos, and ferroptosis can also contribute by similar mechanisms to plaque calcification. This review focuses on macrophage death in atherosclerosis, and its potential role in calcification. Reducing macrophage cell death and/or increasing their efferocytosis capacity could be a novel therapeutic strategy to reduce the formation of a necrotic core and calcification and thereby improving atherosclerotic plaque stability.
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Macrophages; Apoptosis; Necrosis; Calcinosis
PubMed: 37469518
DOI: 10.3389/fimmu.2023.1215612 -
Frontiers in Immunology 2023Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by cell swelling, cytomembrane perforation and lysis,... (Review)
Review
Pyroptosis, a novel form of programmed cell death (PCD) discovered after apoptosis and necrosis, is characterized by cell swelling, cytomembrane perforation and lysis, chromatin DNA fragmentation, and the release of intracellular proinflammatory contents, such as Interleukin (IL) 8, IL-1β, ATP, IL-1α, and high mobility group box 1 (HMGB1). Our understanding of pyroptosis has increased over time with an increase in research on the subject: gasdermin-mediated lytic PCD usually, but not always, requires cleavage by caspases. Moreover, new evidence suggests that pyroptosis induction in tumor cells results in a strong inflammatory response and significant cancer regression, which has stimulated great interest among scientists for its potential application in clinical cancer therapy. It's worth noting that the side effects of chemotherapy and radiotherapy can be triggered by pyroptosis. Thus, the intelligent use of pyroptosis, the double-edged sword for tumors, will enable us to understand the genesis and development of cancers and provide potential methods to develop novel anticancer drugs based on pyroptosis. Hence, in this review, we systematically summarize the molecular mechanisms of pyroptosis and provide the latest available evidence supporting the antitumor properties of pyroptosis, and provide a summary of the various antitumor medicines targeting pyroptosis signaling pathways.
Topics: Humans; Pyroptosis; Apoptosis; Caspases; Apoptosis Regulatory Proteins; Neoplasms
PubMed: 38016064
DOI: 10.3389/fimmu.2023.1290885 -
Frontiers in Immunology 2023Cell migration-inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the... (Review)
Review
Cell migration-inducing protein (CEMIP), also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family that degrades hyaluronic acid (HA) and remodels the extracellular matrix. In recent years, some studies have reported that CEMIP can promote the proliferation, invasion, and adhesion of various tumor cells and can play an important role in bacterial infection and arthritis. This review focuses on the pathological mechanism of CEMIP in a variety of diseases and expounds the function of CEMIP from the aspects of inhibiting cell apoptosis, promoting HA degradation, inducing inflammatory responses and related phosphorylation, adjusting cellular microenvironment, and regulating tissue fibrosis. The diagnosis and treatment strategies targeting CEMIP are also summarized. The various functions of CEMIP show its great potential application value.
Topics: Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Apoptosis; Arthritis; Cell Movement
PubMed: 37662915
DOI: 10.3389/fimmu.2023.1222425 -
Frontiers in Immunology 2023Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS),... (Review)
Review
Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment.
Topics: Humans; Reactive Oxygen Species; Immunotherapy; Oxidative Stress; Apoptosis; Autophagy; Neoplasms
PubMed: 37600785
DOI: 10.3389/fimmu.2023.1247268 -
Journal of Translational Medicine Jul 2023Programmed cell death (PCD) plays an important role in many aspects of individual development, maintenance of body homeostasis and pathological processes. Ferroptosis is... (Review)
Review
Programmed cell death (PCD) plays an important role in many aspects of individual development, maintenance of body homeostasis and pathological processes. Ferroptosis is a novel form of PCD characterized by the accumulation of iron-dependent lipid peroxides resulting in lethal cell damage. It contributes to tumor progression in an apoptosis-independent manner. In recent years, an increasing number of non-coding RNAs (ncRNAs) have been demonstrated to mediate the biological process of ferroptosis, hence impacting carcinogenesis, progression, drug resistance, and prognosis. However, the clear regulatory mechanism for this phenomenon remains poorly understood. Moreover, ferroptosis does not usually exist independently. Its interaction with PCD, like apoptosis, necroptosis, autophagy, pyroptosis, and cuproptosis, to destroy cells appears to exist. Furthermore, ncRNA seems to be involved. Here, we review the mechanisms by which ferroptosis occurs, dissect its relationship with other forms of death, summarize the key regulatory roles played by ncRNAs, raise relevant questions and predict possible barriers to its application in the clinic, offering new ideas for targeted tumour therapy.
Topics: Humans; Ferroptosis; Apoptosis; Neoplasms; Carcinogenesis; Pyroptosis; RNA, Untranslated
PubMed: 37516888
DOI: 10.1186/s12967-023-04370-6 -
Nature Immunology Sep 2023Cytotoxic T lymphocytes (CTLs) fight intracellular pathogens and cancer by identifying and destroying infected or transformed target cells. To kill, CTLs form a...
Cytotoxic T lymphocytes (CTLs) fight intracellular pathogens and cancer by identifying and destroying infected or transformed target cells. To kill, CTLs form a specialized cytotoxic immune synapse (IS) with a target of interest and then release toxic perforin and granzymes into the interface to elicit programmed cell death. The IS then dissolves, enabling CTLs to search for additional prey and professional phagocytes to clear the corpse. While the mechanisms governing IS assembly have been studied extensively, far less is known about target cell release. Here, we applied time-lapse imaging to explore the basis for IS dissolution and found that it occurred concomitantly with the cytoskeletal contraction of apoptotic targets. Genetic and pharmacological perturbation of this contraction response indicated that it was both necessary and sufficient for CTL dissociation. We also found that mechanical amplification of apoptotic contractility promoted faster CTL detachment and serial killing. Collectively, these results establish a biophysical basis for IS dissolution and highlight the importance of mechanosensory feedback in the regulation of cell-cell interactions.
Topics: T-Lymphocytes, Cytotoxic; Apoptosis; Perforin; Granzymes
PubMed: 37500886
DOI: 10.1038/s41590-023-01572-4 -
Biomedicine & Pharmacotherapy =... Sep 2023α-Hederin is a natural bioactive molecule very abundant in aromatic and medicinal plants (AMP). It was identified, characterized, and isolated using different... (Review)
Review
α-Hederin is a natural bioactive molecule very abundant in aromatic and medicinal plants (AMP). It was identified, characterized, and isolated using different extraction and characterization technologies, such as HPLC, LC-MS and NMR. Biological tests have revealed that this natural molecule possesses different biological properties, particularly anticancer activity. Indeed, this activity has been investigated against several cancers (e.g., esophageal, hepatic, breast, colon, colorectal, lung, ovarian, and gastric). The underlying mechanisms are varied and include induction of apoptosis and cell cycle arrest, reduction of ATP generation, as well as inhibition of autophagy, cell proliferation, invasion, and metastasis. In fact, these anticancer mechanisms are considered the most targeted for new chemotherapeutic agents' development. In the light of all these data, α-hederin could be a very interesting candidate as an anticancer drug for chemotherapy, as well as it could be used in combination with other molecules already validated or possibly investigated as an agent sensitizing tumor cells to chemotherapeutic treatments.
Topics: Cell Line, Tumor; Cell Cycle Checkpoints; Apoptosis; Cell Proliferation
PubMed: 37499451
DOI: 10.1016/j.biopha.2023.115205