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Cork spot-like physiological disorder (CSPD) is a newly identified issue in 'Kurenainoyume' apples, yet its mechanism remains unclear. To investigate CSPD, we conducted morphological observations on 'Kurenainoyume' apples with and without pre-harvest fruit-bagging treatment using light-impermeable paper bags. Non-bagged fruit developed CSPD in mid-August, while no CSPD symptoms were observed in bagged fruit. The bagging treatment significantly reduced the proportion of opened lenticels, with only 17.9% in bagged fruit compared to 52.0% in non-bagged fruits. In non-bagged fruit, CSPD spots tended to increase from the lenticels, growing in size during fruit development. The cuticular thickness and cross-sectional area of fresh cells in CSPD spots were approximately 16 µm and 1600 µm², respectively. Healthy non-bagged fruit reached these values around 100 to 115 days after full bloom from mid- to late August. Microscopic and computerized tomography scanning observations revealed that many CSPD spots developed at the tips of vascular bundles. Therefore, CSPD initiation between opened lenticels and vascular bundle tips may be influenced by water stress, which is potentially caused by water loss, leading to cell death and the formation of CSPD spots. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies. Highlights: Colorectal cancer (CRC) is one of the leading causes of death among patients. CRC has been characterized with changes at the genetic and epigenetic factors. The molecular factors can be used as diagnostic and prognostic factors in CRC. The cell death mechanisms demonstrate dysregulation in CRC. Autophagy has aberrant activation in CRC and exerts dual function. [ABSTRACT FROM AUTHOR]

Background: Quercetin, a widespread polyphenolic flavonoid, is known for its extensive health benefits and is commonly found in the plant kingdom. The natural occurrence and extraction methods of quercetin are crucial due to its bioactive potential. Purpose: This review aims to comprehensively cover the natural sources of quercetin, its extraction methods, bioavailability, pharmacokinetics, and its role in various cell death pathways and liver fibrosis. Methods: A comprehensive literature search was performed across several electronic databases, including PubMed, Embase, CNKI, Wanfang database, and ClinicalTrials.gov, up to 10 February 2024. The search terms employedwere "quercetin", "natural sources of quercetin", "quercetin extraction methods", "bioavailability of quercetin", "pharmacokinetics of quercetin", "cell death pathways", "apoptosis", "autophagy", "pyroptosis", "necroptosis", "ferroptosis", "cuproptosis", "liver fibrosis", and "hepatic stellate cells". These keywords were interconnected using AND/OR as necessary. The search focused on studies that detailed the bioavailability and pharmacokinetics of quercetin, its role in different cell death pathways, and its effects on liver fibrosis. Results: This review details quercetin's involvement in various cell death pathways, including apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis, with particular attention to its regulatory influence on apoptosis and autophagy. It dissects the mechanisms through which quercetin affects these pathways across different cell types and dosages. Moreover, the paper delves into quercetin's effectson liver fibrosis, its interactions with hepatic stellate cells, and its modulation of pertinent signaling cascades. Additionally, it articulates from a physical organic chemistry standpoint the uniqueness of quercetin's structure and its potential for specific actions in the liver. Conclusion: The paper provides a detailed analysis of quercetin, suggesting its significant role in modulating cell death mechanisms and mitigating liver fibrosis, underscoring its therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a severe central nervous trauma that can cause serious consequences. Cell death is emerging as a common pathogenesis after SCI. In the last two decades, numerous studies have been published in the field of cell death after SCI. However, it is still rare to find relevant bibliometric analyses. This bibliometric study aims to visually represent global research trends in the field of cell death after SCI. Methods: Bibliometric data were sourced from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and R software ("bibliometrix" package) were used to analyze and visualize bibliometric data. Annual scientific production, countries/regions, institutions, authors, journals, highly cited papers, keywords, and literature co-citation were evaluated to determine research performance. Results: An analysis of 5,078 publications extracted from the WoSCC database revealed a fluctuating yet persistent growth in the field of cell death after SCI over the past 23 years. China and the United States, contributing 69% of the total publications, were the main driving force in this field. The Wenzhou Medical University from China contributed to the most papers. In terms of authors, Salvatore Cuzzocrea from the University of Messina had the highest number of publications. The "Journal of Neurotrauma" was the top journal in terms of the number of publications, however, the "Journal of Neuroscience" was the top journal in terms of the number of citations. The theme of the highly cited articles mainly focused on the mechanism of cell death after SCI. The keyword and literature co-citation analysis mainly focused on the mode of cell death, mechanism research of cell death, and functional recovery after SCI. Conclusion: This study analyzes the research hotspots, frontiers, and development trends in the field of cell death after SCI, which is important for future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Photodynamic therapy (PDT) is a cancer treatment that uses photogenerated reactive oxygen species (ROS) to damage target cells. The unique mechanism of action of PDT involves the systemic or local administration of a photosensitizing compound (photosensitizer), which is then activated by light of a specific energy. PDT induces a very strong local inflammatory response. A number of adaptive mechanisms are induced within the tumor, related to increased amino acid metabolism and damage to lymphatic vessels. In this review, we are describing the adaptive immune response induced by ROS and generated by PDT. Cancer is one of the most significant causes of death worldwide. Despite the rapid development of modern forms of therapy, results are still unsatisfactory. The prognosis is further worsened by the ability of cancer cells to metastasize. Thus, more effective forms of therapy, such as photodynamic therapy, are constantly being developed. The photodynamic therapeutic regimen involves administering a photosensitizer that selectively accumulates in tumor cells or is present in tumor vasculature prior to irradiation with light at a wavelength corresponding to the photosensitizer absorbance, leading to the generation of reactive oxygen species. Reactive oxygen species are responsible for the direct and indirect destruction of cancer cells. Photodynamically induced local inflammation has been shown to have the ability to activate an adaptive immune system response resulting in the destruction of tumor lesions and the creation of an immune memory. This paper focuses on presenting the latest scientific reports on the specific immune response activated by photodynamic therapy. We present newly discovered mechanisms for the induction of the adaptive response by analyzing its various stages, and the possible difficulties in generating it. We also present the results of research over the past 10 years that have focused on improving the immunological efficacy of photodynamic therapy for improved cancer therapy. [ABSTRACT FROM AUTHOR]

Cell death maintains cell morphology and homeostasis during development by removing damaged or obsolete cells. The concentration of metal ions whithin cells is regulated by various intracellular transporters and repositories to maintain dynamic balance. External or internal stimuli might increase the concentration of metal ions, which results in ions overloading. Abnormal accumulation of large amounts of metal ions can lead to disruption of various signaling in the cell, which in turn can produce toxic effects and lead to the occurrence of different types of cell deaths. In order to further study the occurrence and development of metal ions overloading induced cell death, this paper reviewed the regulation of Ca 2+ , Fe 3+ , Cu 2+ and Zn 2+ metal ions, and the internal mechanism of cell death induced by overloading. Furthermore, we found that different metal ions possess a synergistic and competitive relationship in the regulation of cell death. And the enhanced level of oxidative stress was present in all the processes of cell death due to metal ions overloading, which possibly due to the combination of factors. Therefore, this review offers a theoretical foundation for the investigation of the toxic effects of metal ions, and presents innovative insights for targeted regulation and therapeutic intervention. HIGHLIGHTS: • Metal ions overloading disrupts homeostasis, which in turn affects the regulation of cell death. • Metal ions overloading can cause cell death via reactive oxygen species (ROS). • Different metal ions have synergistic and competitive relationships for regulating cell death., (© 2024. The Author(s).)

Cetylpyridinium chloride (CPC) is a quaternary ammonium compound used widely in health and personal care products. Meanwhile, due to its increasing use, its potential adverse health effects are emerging as a topic of public concern. In this study, we first administered CPC by pharyngeal aspiration to determine the survival level (the maximum concentration at which no death is observed) and then administered CPC to mice repeatedly for 28 days using the survival level as the highest concentration. CPC increased the total number of pulmonary cells secreting pro- and anti-inflammatory cytokines and chemokines. Infiltration of inflammatory cells, production of foamy alveolar macrophages, and chronic inflammatory lesions were found in the lung tissue of male and female mice exposed to the highest dose of CPC. We also investigated the toxicity mechanism using BEAS-2B cells isolated from normal human bronchial epithelium. At 6 h after exposure to CPC, the cells underwent non-apoptotic cell death, especially at concentrations greater than 2 μg/mL. The expression of the transferrin receptor was remarkably enhanced, and the expression of proteins that contribute to intracellular iron storage was inhibited. The expression of both mitochondrial SOD and catalase increased with CPC concentration, and PARP protein was cleaved, suggesting possible DNA damage. In addition, the internal structure of mitochondria was disrupted, and fusion between damaged organelles was observed in the cytoplasm. Most importantly, lamellar body-like structures and autophagosome-like vacuoles were found in CPC-treated cells, with enhanced expression of ABCA3 protein, a marker for lamellar body, and a docking score between ABCA3 protein and CPC was considered to be approximately -6.8969 kcal/mol. From these results, we propose that mitochondrial damage and iron depletion may contribute to CPC-induced non-apoptotic cell death and that pulmonary accumulation of cell debris may be closely associated with the inflammatory response. Furthermore, we hypothesize that the formation of lamellar body-like structures may be a trigger for CPC-induced cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we designed an in vitro administration device based on compartment model theory and utilized it to construct an in vitro simulated one compartment extravascular administration model of copper chloride. Within the C max range of 3.91-1000.00 μM, the measured concentration-time curves of the simulated one compartment extravascular administration model almost coincide with the corresponding theoretical curves. The measured values of toxicokinetic parameters, including k e , T 1/2 , k a , T 1/2a , T max , C max , CL, and AUC 0-∞ are close to the corresponding theoretical values. The fitting coefficients are >0.9990. In simulated one compartment extravascular administration and classic in vitro administration, copper chloride dose-dependently induced HepG2 cell death. When C max /administration concentration is equal, classic in vitro administration induces a higher cell death rate than simulated one compartment extravascular administration. However, there is no significant difference in inducing cell death between the two administration models when area under the curve is equal. In conclusion, the device designed in this study can be used to in vitro simulate one compartment extravascular administration, making in vitro toxicity testing more similar to in vivo scenarios. There are differences in copper chloride induced HepG2 cell death between simulated one compartment extravascular administration and classic in vitro administration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Programmed cell death is intricately linked to various physiological phenomena such as growth, development, and metabolism, as well as the proper function of the pancreatic β cell and the migration and invasion of trophoblast cells in the placenta during pregnancy. Traditional and recently identified programmed cell death include apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition to cancer and degenerative diseases, abnormal activation of cell death has also been implicated in pregnancy related diseases like preeclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, fetal growth restriction, and recurrent miscarriage. Excessive or insufficient cell death and pregnancy related diseases may be mutually determined, ultimately resulting in adverse pregnancy outcomes. In this review, we systematically describe the characteristics and mechanisms underlying several types of cell death and their roles in pregnancy related diseases. Moreover, we discuss potential therapeutic strategies that target cell death signaling pathways for pregnancy related diseases, hoping that more meaningful treatments will be applied in clinical practice in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Innate immunity is not only the first line of host defense against microbial infections but is also crucial for the host responses against a variety of noxious stimuli. Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor that can induce inflammatory cell death in both immune and nonimmune cells upon sensing of incursive virus-derived Z-form nucleic acids and self-nucleic acids via its Zα domain. Mechanistically, aberrantly expressed or activated ZBP1 induced by pathogens or noxious stimuli enables recruitment of TANK binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 to drive type I interferon (IFN-I) responses and activation of nuclear factor kappa B (NF-κB) signaling. Meanwhile, ZBP1 promotes the assembly of ZBP1- and absent in melanoma 2 (AIM2)-PANoptosome, which ultimately triggers PANoptosis through caspase 3-mediated apoptosis, mixed lineage kinase domain like pseudokinase (MLKL)-mediated necroptosis, and gasdermin D (GSDMD)-mediated pyroptosis. In response to damaged mitochondrial DNA, ZBP1 can interact with cyclic GMP-AMP synthase to augment IFN-I responses but inhibits toll like receptor 9-mediated inflammatory responses. This review summarizes the structure and expression pattern of ZBP1, discusses its roles in human diseases through immune-dependent (e.g., the production of IFN-I and pro-inflammatory cytokines) and -independent (e.g., the activation of cell death) functions, and highlights the attractive prospect of manipulating ZBP1 as a promising therapeutic target in diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Patulin (PAT) is the most common mycotoxin found in moldy fruits and their derived products, and is reported to cause diverse toxic effects, including hepatotoxicity, nephrotoxicity, cardiotoxicity, neurotoxicity, immunotoxicity, gastrointestinal toxicity and dermal toxicity. The cell death induction by PAT is suggested to be a key cellular mechanism involved in PAT-induced toxicities. Accumulating evidence indicates that the multiple forms of cell death are induced in response to PAT exposure, including apoptosis, autophagic cell death, pyroptosis and ferroptosis. Mechanistically, the cell death induction by PAT is associated the oxidative stress induction via reducing the antioxidant capacity or inducing pro-oxidant NADPH oxidase, the activation of mitochondrial pathway via regulating BCL-2 family proteins, the disruption of iron metabolism through ferritinophagy-mediated ferritin degradation, and the induction of the NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome/caspase-1/gasdermin D (GSDMD) pathway. In this review article, we summarize the present understanding of the cell death induction by PAT, discuss the potential signaling pathways underlying PAT-induced cell death, and propose the issues that need to be addressed to promote the development of cell death-based approach to counteract PAT-induced toxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest. All the authors agree to the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cell death is one of the most important mechanisms of maintaining homeostasis in our body. Ferroptosis and pyroptosis are forms of necrosis-like cell death. These cell death modalities play key roles in the pathophysiology of cancer, cardiovascular, neurological diseases, and other pathologies. Transition metals are abundant group of elements in all living organisms. This paper presents a summary of ferroptosis and pyroptosis pathways and their connection to significant transition metals, namely zinc (Zn), copper (Cu), molybdenum (Mo), lead (Pb), cobalt (Co), iron (Fe), cadmium (Cd), nickel (Ni), mercury (Hg), uranium (U), platinum (Pt), and one crucial element, selenium (Se). Authors aim to summarize the up-to-date knowledge of this topic. In this review, there are categorized and highlighted the most common patterns in the alterations of ferroptosis and pyroptosis by transition metals. Special attention is given to zinc since collected data support its dual nature of action in both ferroptosis and pyroptosis. All findings are presented together with a brief description of major biochemical pathways involving mentioned metals and are visualized in attached comprehensive figures. This work concludes that the majority of disruptions in the studied metals' homeostasis impacts cell fate, influencing both death and survival of cells in the complex system of altered pathways. Therefore, this summary opens up the space for further research. [ABSTRACT FROM AUTHOR]

The non-natriuretic-dependent glutamate/cystine inverse transporter-system Xc- is composed of two protein subunits, SLC7A11 and SLC3A2, with SLC7A11 serving as the primary functional component responsible for cystine uptake and glutathione biosynthesis. SLC7A11 is implicated in tumor development through its regulation of redox homeostasis, amino acid metabolism, modulation of immune function, and induction of programmed cell death, among other processes relevant to tumorigenesis. In this paper, we summarize the structure and biological functions of SLC7A11, and discuss its potential role in tumor therapy, which provides a new direction for precision and personalized treatment of tumors. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Purpose: The vocal fold tissues undergo nearly continuous and repeated cycles of injury and repair throughout the course of an individual’s lifetime. It is well established that certain individuals are at greater risk of lesion development based on personality and behavioral classification. However, these characteristics alone do not wholly predict or explain lesion development or severity. In this review, we discuss current knowledge of mechanotransduction proteins and their potential relevance to tissue homeostasis in the vocal folds. Method: A review of literature surrounding mechanotransduction and tissue homeostasis as it relates to the vocal folds was conducted. Review of the literature included searches of PubMed, Google Scholar, and other various online peer-reviewed sources. Search terms pertained to mechanosensation, mechanotransduction, mechanically activated channels, mechanical cellular regulation, and other associated concepts and terms. Additional literature was identified through the reference lists of identified papers. Findings of this literature review were then applied to known physiology and pathophysiology of the vocal folds in order to speculate on the contribution of mechanically mediated mechanisms within the vocal fold. Discussion and Conclusion: Because the vocal folds are such mechanically active structures, withstanding nearly constant external forces, there is strong support for the idea that mechanically sensitive molecular pathways within the vocal fold tissue play a major role in tissue homeostasis in the presence of these considerable forces. As such, mechanotransduction within the vocal fold should be considered and targeted in future biological studies of vocal fold physiology. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis. However, the effectiveness of anti-PD-1/PDL1 treatment is limited when HCC becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in the negative regulation of PD-1 antibody targeted therapy in the tumor microenvironment (TME). Therefore, as an emerging direction in cancer immunotherapy research for the treatment of HCC, it is crucial to elucidate the correlations and mechanisms between TAMs and PD-1/PD-L1-mediated immune tolerance. This paper summarizes the effects of TAMs on the pathogenesis and progression of HCC and their impact on HCC anti-PD-1/PD-L1 immunotherapy, and further explores current potential therapeutic strategies that target TAMs in HCC, including eliminating TAMs in the TME, inhibiting TAMs recruitment to tumors and functionally repolarizing M2-TAMs (tumor-supportive) to M1-TAMs (antitumor type). [ABSTRACT FROM AUTHOR]

Cuproptosis, a recently discovered form of cell death, stems from an overabundance of copper ions infiltrating mitochondria. These ions directly engage lipoylated proteins, prompting their oligomerization and subsequent loss of iron-sulfur clusters. This sequence induces proteotoxic stress, ultimately culminating in cell death. Type 2 diabetes, a chronic metabolic disorder resulting from a complex interplay of genetic and environmental factors, has not yet been fully understood in terms of its etiology and pathogenesis. Intricately, it is linked to various modalities of cell death, including mitochondrial autophagy, apoptosis, pyroptosis, and ferroptosis. Studies have discovered impaired copper metabolism in individuals with Type 2 diabetes, hinting at a unique role for copper homeostasis in the progression of the disease. To this end, the present research aims to delineate the potential correlation between cuproptosis and Type 2 diabetes by exhaustively reviewing the existing literature. By synthesizing relevant research on cuproptosis, the paper intends to lay the groundwork for a thorough exploration of the pathogenesis of Type 2 diabetes and the development of targeted therapeutic interventions. The ultimate objective is to facilitate a deeper understanding of Type 2 diabetes and to identify novel therapeutic strategies associated with cuproptosis. [ABSTRACT FROM AUTHOR]

Background: Currently, no evidence exists on the expression of apoptosis (CASP3), autophagy (BECN1), and mitophagy (BNIP3) genes in the CA3 area after ischemia with long-term survival. Objective: The goal of the paper was to study changes in above genes expression in CA3 area after ischemia in the period of 6–24 months. Methods: In this study, using quantitative RT-PCR, we present the expression of genes associated with neuronal death in a rat ischemic model of Alzheimer's disease. Results: First time, we demonstrated overexpression of the CASP3 gene in CA3 area after ischemia with survival ranging from 0.5 to 2 years. Overexpression of the CASP3 gene was accompanied by a decrease in the activity level of the BECN1 and BNIP3 genes over a period of 0.5 year. Then, during 1-2 years, BNIP3 gene expression increased significantly and coincided with an increase in CASP3 gene expression. However, BECN1 gene expression was variable, increased significantly at 1 and 2 years and was below control values 1.5 years post-ischemia. Conclusions: Our observations suggest that ischemia with long-term survival induces neuronal death in CA3 through activation of caspase 3 in cooperation with the pro-apoptotic gene BNIP3. This study also suggests that the BNIP3 gene regulates caspase-independent pyramidal neuronal death post-ischemia. Thus, caspase-dependent and -independent death of neuronal cells occur post-ischemia in the CA3 area. Our data suggest new role of the BNIP3 gene in the regulation of post-ischemic neuronal death in CA3. This suggests the involvement of the BNIP3 together with the CASP3 in the CA3 in neuronal death post-ischemia. [ABSTRACT FROM AUTHOR]

Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1β and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis. [ABSTRACT FROM AUTHOR]

Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines how statins, which are drugs commonly used to lower cholesterol, affect the growth of liver cancer cells. Statins can be either lipophilic (lipid-soluble) or hydrophilic (water-soluble), and this characteristic influences how they enter cells. In our research, we compared the effects of lipophilic simvastatin and hydrophilic pravastatin. We found that simvastatin significantly reduces cancer cell growth and increases cell death depending on the dosage and duration of treatment. In contrast, pravastatin, due to its limited uptake, has a minimal impact on cancer cells. These findings suggest that the type of statin used could be crucial in cancer treatment, potentially offering better outcomes for patients with liver cancer. The HMG-CoA reductase inhibitors, statins, are drugs used globally for lowering the level of cholesterol in the blood. Different clinical studies of statins in cancer patients have indicated a decrease in cancer mortality, particularly in patients using lipophilic statins compared to those on hydrophilic statins. In this paper, we selected two structurally different statins (simvastatin and pravastatin) with different lipophilicities and investigated their effects on the proliferation and apoptosis of hepatocellular carcinoma cells. Lipophilic simvastatin highly influences cancer cell growth and survival in a time- and concentration-dependent manner, while pravastatin, due to its hydrophilic structure and limited cellular uptake, showed minimal cytotoxic effects. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-β (Aβ) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aβ oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aβ-mediated damage. [ABSTRACT FROM AUTHOR]

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Copyright of Tianjin Medical Journal is the property of Tianjin Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tumour immune microenvironment (TIME) plays an indispensable role in tumour progression, and tumour‐associated macrophages (TAMs) are the most abundant immune cells in TIME. Non‐apoptotic regulated cell death (RCD) can avoid the influence of tumour apoptosis resistance on anti‐tumour immune response. Specifically, autophagy, ferroptosis, pyroptosis and necroptosis mediate the crosstalk between TAMs and tumour cells in TIME, thus reprogram TIME and affect the progress of tumour. In addition, although some achievements have been made in immune checkpoint inhibitors (ICIs), there is still defect that ICIs are only effective for some people because non‐apoptotic RCD can bypass the apoptosis resistance of tumour. As a result, ICIs combined with targeting non‐apoptotic RCD may be a promising solution. In this paper, the basic molecular mechanism of non‐apoptotic RCD, the way in which non‐apoptotic RCD mediates crosstalk between TAMs and tumour cells to reprogram TIME, and the latest research progress in targeting non‐apoptotic RCD and ICIs are reviewed. [ABSTRACT FROM AUTHOR]

AbstractFerroptosis is a new type of cell death, which is mainly dependent on the formation and accumulation of reactive oxygen species and lipid peroxides mediated by iron. It is distinct from other forms of regulation of cell death in morphology, immunology, biochemistry, and molecular biology. Various cell death mechanisms have been observed in many viral infections, and virus-induced cell death has long been considered as a double-edged sword that can inhibit or aggravate viral infections. However, understanding of the role of ferroptosis in various viral infections is limited. Special attention will be paid to the mechanisms of ferroptosis in mediating viral infection and antiviral treatment associated with ferroptosis. In this paper, we outlined the mechanism of ferroptosis. Additionally, this paper also review research on ferroptosis from the perspective of the virus, discussed the research status of ferroptosis in virus infection and classified and summarized research on the interaction between viral infections and ferroptosis. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) is the most abundant chemical modification in eukaryotic cells. It is a post-transcriptional modification of mRNA, a dynamic reversible process catalyzed by methyltransferase, demethylase, and binding proteins. Ferroptosis, a unique iron-dependent cell death, is regulated by various cell metabolic events, including many disease-related signaling pathways. And different ferroptosis inducers or inhibitors have been identified that can induce or inhibit the onset of ferroptosis through various targets and mechanisms. They have potential clinical value in the treatment of diverse diseases. Until now, it has been shown that in several cancer diseases m6A can be involved in the regulation of ferroptosis, which can impact subsequent treatment. This paper focuses on the concept, function, and biological role of m6A methylation modification and the interaction between m6A and ferroptosis, to provide new therapeutic strategies for treating malignant diseases and protecting the organism by targeting m6A to regulate ferroptosis. [ABSTRACT FROM AUTHOR]

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and nonprogrammed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Hainan Medical University is the property of Journal of Hainan Medical College Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Kunming Medical University / Kunming Yike Daxue Xuebao is the property of Kunming Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Cuproptosis is a recently identified form of cell death induced by imbalanced copper levels. We aimed to explore the mechanism underlying copper-induced cell death. To achieve this, we surveyed the literature to understand the biochemical implications of cuproptosis in diseases, particularly in the context of cancer. The concept of copper ionophores, such as elesclomol and disulfiram, is highlighted as they elevate intracellular copper levels, triggering oxidative stress and ultimately leading to cell death–a potential avenue for cancer therapy. Furthermore, we will delve into the intricate relationship between copper, mitochondrial respiration, and protein lipoylation, shedding light on their connections in inducing cell death. Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper ionophores, such as elesclomol and disulfiram, increase intracellular copper levels. This elevation triggers oxidative stress and subsequent cell death, offering potential implications in cancer therapy. Additionally, copper ionophores disrupt mitochondrial respiration and protein lipoylation, further contributing to copper toxicity and cell death. Potential targets and biomarkers are identified, as copper can be targeted to those proteins to trigger cuproptosis. The role of copper in different cancers is discussed to understand targeted cancer therapies using copper nanomaterials, copper ionophores, and copper chelators. Furthermore, the role of copper is explored through diseases such as Wilson and Menkes disease to understand the physiological mechanisms of copper. Exploring cuproptosis presents an opportunity to improve treatments for copper-related disorders and various cancers, with the potential to bring significant advancements to modern medicine. [ABSTRACT FROM AUTHOR]

Efforts in researching the efficient anti-tumor properties of three novel arene ruthenium(II) complexes incorporating thiophene-based aroylhydrazone ligands have been undertaken. The complexes' elemental composition was [(η6-p-cymene)Ru(L)Cl]. They were comprehensively characterized through elemental and spectroscopic analyses (FT-IR, UV-vis, NMR, and HR-MS). Single crystal X-ray diffraction studies revealed a pseudo-octahedral geometry with bidentate coordination of the ligands in a representative complex. The in vitro assessment of the complexes' cancer cell growth inhibition was conducted using the MTT assay against A549 (human lung carcinoma), HeLa (human cervical carcinoma), HuH-7 (hepatocellular carcinoma), and NIH-3T3 (mouse fibroblast non-cancerous cell line). Results indicated significant cytotoxicity across all cancer cell lines, with IC50 concentrations of complex 2 being 6.8 μM for A549, 11.6 μM for HeLa, and 9.4 μM for HuH-7, compared to cisplatin with IC50 values of 18.9 μM, 17.68 μM, and 24 μM respectively. Notably, complex 2 demonstrated particularly promising cytotoxicity against all tested cancerous cell lines. Fluorescent staining analysis such as acridine orange/ethidium bromide (AO–EB) and HOECHST 33342 revealed cell death mechanisms involving membrane disintegration and nuclear condensation following treatment with complex 2. Further studies were conducted to measure reactive oxygen species (ROS) levels using the dichlorodihydrofluorescein diacetate (DCFH-DA) assay, and mitochondrial membrane potential (MMP) was assessed using the JC-1 dye assay. These studies demonstrated that complex 2 increased ROS levels, decreased membrane potential, and promoted mitochondrial dysfunction-mediated cell death pathways. Additionally, flow cytometry analysis, utilizing dual staining of Annexin V-FITC and propidium iodide (PI), was employed to quantitatively study apoptosis induction. [ABSTRACT FROM AUTHOR]

Here, we have synthesized and characterized three visible light responsive terpyridine based-Re(I)-tricarbonyl complexes; [Re(CO)3(ph-tpy)Cl] (Retp1), [Re(CO)3(an-tpy)Cl] (Retp2), and [Re(CO)3(py-tpy)Cl] (Retp3) where ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine; an-tpy = 4′-anthracenyl-2,2′:6′,2″-terpyridine, py-tpy = 4′-pyrenyl-2,2′:6′,2″-terpyridine. The structures of Retp1 and Retp2 were confirmed from the SC-XRD data, indicating distorted octahedral structures. Unlike traditional PDT agents, these complexes generated reactive oxygen species (ROS) via type I and type II pathways and oxidized redox crucial NADH (reduced nicotinamide adenine dinucleotide) upon visible light exposure. Retp3 showed significant mitochondrial localization and demonstrated photoactivated anticancer activity (IC50 ∼ 2 µM) by inducing ROS-mediated cell death in cancer cells selectively (photocytotoxicity Index, PI > 28) upon compromising mitochondrial function in A549 cells. Their diagnostic capabilities were ultimately assessed using clinically relevant 3D multicellular tumor spheroids (MCTs). [ABSTRACT FROM AUTHOR]

Ferroptotic cell death is significantly regulated by glutathione (GSH), an important antioxidant. This work describes the development of a novel, small fluorescent probe capable of detecting GSH levels and providing an understanding of the inhibitory effect of rutin, a naturally occurring flavonoid, during ferroptosis. The probe N-GSH exhibited outstanding sensitivity and selectivity towards GSH, as witnessed by the significant increase in fluorescence observed after GSH binding. Additionally, the probe N-GSH determined the possible inhibitory effect of rutin and the role of GSH in ferroptosis. Using fluorescence imaging, the probe N-GSH revealed that GSH levels reduced significantly during ferroptosis induction, demonstrating its vital role in the process. Furthermore, by significantly preserving GSH levels, rutin treatment prevented ferroptosis. Moreover, in comparison to additional typical ferroptosis inhibitors, such as dihydrolipoic acid (DHLA) and vitamin E (VE), it was hypothesized that rutin's inhibitory effect on ferroptosis was achieved through the synergistic effect of its antioxidant and chelate properties on Fe(II) ions. [ABSTRACT FROM AUTHOR]

Caspases are enzymes with protease activity. Despite being known for more than three decades, caspase investigation still yields surprising and fascinating information. Initially associated with cell death and inflammation, their functions have gradually been revealed to extend beyond, targeting pathways such as cell proliferation, migration, and differentiation. These processes are also associated with disease mechanisms, positioning caspases as potential targets for numerous pathologies including inflammatory, neurological, metabolic, or oncological conditions. While in vitro studies play a crucial role in elucidating molecular pathways, they lack the context of the body's complexity. Therefore, laboratory animals are an indispensable part of successfully understanding and applying caspase networks. This paper aims to summarize and discuss recent knowledge, understanding, and challenges in caspase knock-out mice. [ABSTRACT FROM AUTHOR]

A novel lysosome-targeted photosensitizer/photoredox catalyst based on cyclometalated Ir(III) complex IrL has been designed and synthesized, which exhibited excellent phosphorescence properties and the ability to generate single oxygen (1O2) and photocatalytically oxidize 1,4-dihydronicotinamide adenine dinucleotide (NADH) under light irradiation. Most importantly, the aforementioned activities are significantly enhanced due to protonation under acidic conditions, which makes them highly attractive in light-activated tumor therapy, especially for acidic lysosomes and tumor microenvironments. The photocytotoxicity of IrL and the mechanism of cell death have been investigated. Additionally, the tumor-killing ability of IrL under light irradiation was evaluated using a 4T1 tumor-bearing mouse model. This work provides a strategy for the development of lysosome-targeted photosensitizers/photoredox catalysts to overcome hypoxic tumors. [ABSTRACT FROM AUTHOR]

One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro‐inflammatory cell death type termed pyroptosis (also known as "Gasdermin‐mediated programmed cell death"). However, ever‐growing evidence showed that GSDMs can play multiple and complex roles in a context‐dependent manner. In this sense, Gasdermin‐B (GSDMB; the only GSDM gene absent in mice and rats) has been implicated in antibacterial defense, numerous inflammatory pathologies (e.g., asthma, ulcerative colitis), and cancer, but both cell death‐dependent and ‐independent functions have been reported in these diseases, fueling the debate on whether GSDMB has genuine pyroptotic capacity. Recently, a series of seminal papers cast light on the GSDMB multitasking capacity by showing that different GSDMB transcriptional isoforms have distinct biological activities. Nonetheless, there are still obscure areas to be clarified on the precise functional involvement of GSDMB translated variants in physiological and pathological conditions. In this viewpoint, we critically discuss the most recent and exciting data on this topic and propose a series of relevant challenges that need to be overcome before GSDMB‐driven biomedical applications (as a biomarker of disease risk/progression/outcome or as specific therapeutic target) become a reality in clinical settings. [ABSTRACT FROM AUTHOR]

Gasdermin D (GSDMD)-mediated pyroptotic cell death drives inflammatory cytokine release and downstream immune responses upon inflammasome activation, which play important roles in host defense and inflammatory disorders. Upon activation by proteases, the GSDMD N-terminal domain (NTD) undergoes oligomerization and membrane translocation in the presence of lipids to assemble pores. Despite intensive studies, the molecular events underlying the transition of GSDMD from an autoinhibited soluble form to an oligomeric pore form inserted into the membrane remain incompletely understood. Previous work characterized S-palmitoylation for gasdermins from bacteria, fungi, invertebrates, as well as mammalian gasdermin E (GSDME). Here, we report that a conserved residue Cys191 in human GSDMD was S-palmitoylated, which promoted GSDMD-mediated pyroptosis and cytokine release. Mutation of Cys191 or treatment with palmitoyltransferase inhibitors cyano-myracrylamide (CMA) or 2-bromopalmitate (2BP) suppressed GSDMD palmitoylation, its localization to the membrane and dampened pyroptosis or IL-1β secretion. Furthermore, Gsdmd-dependent inflammatory responses were alleviated by inhibition of palmitoylation in vivo. By contrast, coexpression of GSDMD with palmitoyltransferases enhanced pyroptotic cell death, while introduction of exogenous palmitoylation sequences fully restored pyroptotic activities to the C191A mutant, suggesting that palmitoylation-mediated membrane localization may be distinct from other molecular events such as GSDMD conformational change during pore assembly. Collectively, our study suggests that S-palmitoylation may be a shared regulatory mechanism for GSDMD and other gasdermins, which points to potential avenues for therapeutically targeting S-palmitoylation of gasdermins in inflammatory disorders. [ABSTRACT FROM AUTHOR]

In this paper, a mathematical ordinary differential tumor-immune model is proposed based on an immune checkpoint inhibitor, which is an innovative method for tumor immunotherapies. Two important factors in tumor-immune response are the programmed cell death protein 1 (PD-1) and its ligand PD-L1. The model consists of three populations: tumor cells, activated T cells and anti-PD-1. By analyzing the dynamics of the model, it is found that there is always a unique tumor-free equilibrium and at most two tumor interior equilibria. The nonexistence of nontrivial positive periodic orbits is established by using the new Dulac function, and then a global dynamics of the model is obtained. The conclusions of our analysis show that increasing the possibility of T cells killing tumor cells (p), early detection of tumor cells, or the use of PD-1 inhibitors to activate T cells are effective in eliminating tumor cells. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new type of iron-dependent cell death and is involved in many biological processes. Multiple ferroptosis signals affect enzymes and metabolites during glucose metabolism, altering the metabolic pathways of macrophages. In addition, macrophages with different polarization phenotypes have different resistance to ferroptosis, which affects the occurrence and signal transmission of ferroptosis. Therefore, the important process of glucose metabolism in macrophages is targeted to regulate the sensitivity of macrophages to ferroptosis through energy metabolism. In this paper, we review the recent research progress on the effect of ferroptosis signaling on the reprogramming of glucose metabo, lism in macrophages and the regulatory effects of various compounds. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under‐researched area through this comprehensive review. [ABSTRACT FROM AUTHOR]

For a special issue, we review studies on the pathogenesis of nigral cell death and the treatment of sporadic Parkinson's disease (sPD) over the past few decades, with a focus on the studies performed by Prof. Mizuno and our group. Prof. Mizuno proposed the initial concept that mitochondrial function may be impaired in sPD. When working at Jichi Medical School, he found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with Parkinson's disease (PD) and MPTP models. After moving to Juntendo University as a professor and chairman, he continued to study the mechanisms of cell death in the substantia nigra of patients with sPD. Under his supervision, I studied the relationships between PD and apoptosis, PD and iron involvement, mitochondrial dysfunction and apoptosis, and PD and neuroinflammation. Moving to Kitasato University, we focused on PD and the cytotoxicity of alpha synuclein (αSyn) as well as brain neuropathology. Eventually, I moved to Osaka University, where I continued working on PD and αSyn projects to promote therapeutic research. In this paper, we present the details of these studies in the following order: past, present, and future. [ABSTRACT FROM AUTHOR]