作者：
Fleisher, TAImmunology Service
Warren G. Magnuson Clinical Center National Institutes of Health Bethesda MD United States
Learning objectives: Reading this article will introduce the reader to the basic concept of physiologic cell death referred to as apoptosis. In addition, the role of apoptosis in immune function as well as its contrib...
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Learning objectives: Reading this article will introduce the reader to the basic concept of physiologic cell death referred to as apoptosis. In addition, the role of apoptosis in immune function as well as its contribution to various clinical disorders will be developed. Data Source: The author's experience with recently described patients who have a unique autoimmune syndrome associated with a defect in apoptosis. In addition, recent reviews on the subject of apoptosis in health and disease served as informational outlines. Study Selection: Data source included pertinent reviews and articles meeting the educational objectives and these were critically reviewed. Results: apoptosis is a critical process in cellular homeostasis that only recently has been appreciated. Its role in both immune development and the control of immune responses as well as in T cell cytotoxic effector function has been established. Information is accumulating that diseases such as cancer can be linked to underlying defects in the apoptosis pathway allowing cells that normally would have been eliminated to live. The role of alterations in apoptosis in other chronic diseases, including autoimmune and neurodegenerative disorders, is beginning to emerge. Conclusions: apoptosis plays a central part in normal tissue homeostasis as well as having a role in a variety of clinical diseases that are characterized by either increased or decreased cell survival.
apoptosis is a process of cell suicide, the mechanisms of which are encoded in the genomes of all higher eukaryotes. The mechanisms involved in apoptosis suggest that the process is based on a viral defense originally...
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apoptosis is a process of cell suicide, the mechanisms of which are encoded in the genomes of all higher eukaryotes. The mechanisms involved in apoptosis suggest that the process is based on a viral defense originally developed in primitive multicelled eukaryotes and that the fundamental execution platform of the process involves 1) inhibition of protein synthesis at the level of translation initiation, 2) proteolysis specifically involving degradation of DNA repair mechanisms, and 3) polynucleotide degradation. In mammals this execution platform is regulated by a complex molecular signaling system that includes feedback mechanisms tending toward activation of all elements of the execution platform if only one element is initially engaged. Tissue ischemia and reperfusion activate elements of the apoptosis system, which thus represents a therapeutic target for emerging treatment approaches to preserve cellular integrity in critical organs such as the heart and brain.
MECHANISMS IN HEMATOLOGY is a book with an accompanying interactive CD-ROM;I designed to assemble basic concepts that underlie clinical understanding and progress. It is presented as a concise text with a series of di...
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MECHANISMS IN HEMATOLOGY is a book with an accompanying interactive CD-ROM;I designed to assemble basic concepts that underlie clinical understanding and progress. It is presented as a concise text with a series of diagrams that distill diffuse information into a compact form. The interactive CD, in particular, brings many of the processes "to life" as details of the more complex pathways are conveyed in clear visual images. The text begins with the basic molecular biology that underlies hematological and oncological physiology/pathology-cell signaling, adhesion molecules, and apoptosis. This is followed by sections, among others, on hematopoiesis, iron, B-12, and folate metabolism, neutrophil function, immunoproteins, chemotherapy, and coagulation, With the permission of the authors and publisher, STEM CELLS has reproduced the section on apoptosis, which we think our readers will enjoy.
Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge...
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Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge is the scarcity of chloride transporters that can selectively induce toxicity in cancer cells while minimizing harm to normal healthy cells. This work reports a series of 2-hydroxyphenyl benzamide-based small molecules 1 a-1 c, which self-assemble to form barrel rosette-type artificial ion channels that adequately transport chloride ions across membranes. The formation of these ion channels primarily relies on intermolecular hydrogen bonding and pi-pi stacking interactions, as supported by the analysis of single-crystal X-ray diffraction and molecular dynamics (MD) simulations. Importantly, chloride ion transport by these compounds specifically triggers apoptosis in cancer cells while demonstrating relatively low toxicity toward non-cancerous cell lines.
This research introduces a new hybrid material for potential cancer treatment. It combines carbon nanotubes decorated with copper nanodots and Arabic gum through an electroless reduction deposition technique. The resu...
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This research introduces a new hybrid material for potential cancer treatment. It combines carbon nanotubes decorated with copper nanodots and Arabic gum through an electroless reduction deposition technique. The resulting nanocomposite was thoroughly characterized confirming the successful decoration of carbon nanotubes with copper nanodots ranging in size from 1.55 to 7.77 nm. The hybrid material exhibits a high zeta-potential of - 20.3 mV, indicating excellent stability due to surface charge. The nanocomposite demonstrated cytotoxicity against MCF-7 breast cancer cells and A549 lung cancer cells in a dose-dependent manner. Notably, MCF-7 cells showed higher sensitivity to the hybrid material with (IC50) of 30.8 mu g/ml compared to A549 cells with an IC50 of 48.23 mu g/ml. Furthermore, the hybrid induced apoptosis in treated cells, as confirmed by apoptotic-related markers. This novel hybrid material holds promising potential for cancer therapy due to its high stability, targeted cytotoxicity, and induce apoptosis in cancer cells.
Muscle atrophy occurs during natural aging and under disease conditions. Muscle cell apoptosis is considered one of the main causes of muscle atrophy, while several recent studies argued that muscle cells do not die d...
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Muscle atrophy occurs during natural aging and under disease conditions. Muscle cell apoptosis is considered one of the main causes of muscle atrophy, while several recent studies argued that muscle cells do not die during muscle atrophy. Here, sensor zebrafish are generated to visualize muscle cell apoptosis and the engulfment of dead muscle cells by macrophages. Using these sensor zebrafish, starvation, and natural aging-induced muscle atrophy models are established. The data showed that the diameters of muscle cells decreased in both models;however, muscle cell apoptosis is not found in the process of muscle atrophy. In starvation-induced muscle atrophy, it also showed that the number of nuclei in muscle cells remained constant, and there is no increase in the number of macrophages in muscle tissues, both of which further confirmed that muscle cells do not die. In both models, transcriptional analysis showed that the apoptosis pathway is down-regulated, and autophagy and protein degradation pathways are up-regulated. All these data indicated that although there is a great reduction of muscle mass during starvation or aging-induced muscle atrophy, muscle cells do not die by apoptosis. These findings provide new insights into muscle atrophy and can benefit the treatments for muscle atrophy-related diseases.
Background: Deoxynivalenol is one of the common fungal toxins in processed grain foods. It has the characteristic of high temperature resistance. Dietary intake of DON contaminated food can cause adverse symptoms. Its...
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Background: Deoxynivalenol is one of the common fungal toxins in processed grain foods. It has the characteristic of high temperature resistance. Dietary intake of DON contaminated food can cause adverse symptoms. Its cytotoxicity is mainly associated with the expression of apoptosis and interfering with protein synthesis. Among which, caspase family proteases play a crucial role in different types of apoptosis signaling pathways. Thus, it is important to develop a platform for real-time and in situ monitoring of caspase in living cells. Results: In this paper, a polypeptide functionalized gold nanoprobe was designed for real-time and in situ detection of caspase-9 in living cells during DON induced apoptosis. Highly anisotropic gold nanostars (AuNSs) with good LSPR effect were synthesized. It could either serve as the surface enhanced Raman scattering (SERS) substrate or quench fluorescence through fluorescence resonance energy transfer (FRET). Polypeptide containing the LEHD (Leu-Glu-His-Asp) sequence was connected to AuNSs through Au-S bonds. During DON induced cell apoptosis, caspase-9 was activated, which could specifically cleave the recognition site LEHD, causing the polypeptide chain modified with Rhodamine B (Rb) signal group to fall off and move away from AuNSs, ultimately reducing the SERS signal and enhancing the fluorescence signal in the system. The experimental results showed that the nanoprobe had high sensitivity, with a linear range of 5 ng/mL to 400 ng/mL and a minimum detection limit of 0.38 ng/mL. Significance: This method achieved dual signal quantification and visualization imaging of fluorescence and SERS for caspase-9 in living cells. The application of nanomaterials has been broadened and the assay was well versatile in different human cell lines. It provided a new platform in studying the relationship between food safety and cellular homeostasis mechanisms.
Medicinal plants have been used in the treatment of diseases for centuries due to their pharmaceutical activities. It is known that a significant majority of medicinal plants have antimicrobial, antiplasmodial and ant...
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Medicinal plants have been used in the treatment of diseases for centuries due to their pharmaceutical activities. It is known that a significant majority of medicinal plants have antimicrobial, antiplasmodial and antitrypanosomal activities and are also effective in the treatment of infections. Medicinal plants also make significant contributions to cancer treatment. Medicinal plants of the Rumex genus are widely used in the treatment of skin, liver inflammation-related diseases as well as cancer. Rumex crispus, a sub-class of the Rumex genus, is a perennial plant known for its wavy and curly leaves and is used as a useful alternative in traditional medicine. In this study, cytotoxicity of Rumex crispus plant extracts was determined by MTT method. Extract contents of the plant were determined by GC-MS, antioxidant capacity by kit and relationship with apoptosis genes by RT-PCR. Finally, the molecular interactions between Rumex crispus leaf extracts and certain proteins associated with colon cancer (PDB ID: 3DTC and 4UYA) and lung cancer (PDB ID: 4ZXT and 5ZMA) were investigated and their respective activity were compared. The binding free energy of the molecule with the highest docking score is computed using MM/GBSA techniques.
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