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Topic Review
Mast Cells as a Therapeutic Target
Anaphylaxis is one of the most life-threatening and intensive allergic reactions. Unlike anaphylactoid reaction, it is an immunoglobulin E-mediated response. Its symptoms can occur in multiple organ systems, such as cutaneous, respiratory, cardiovascular, and others. Mast cells together with basophils are the first cells that are responding to IgE-mediated anaphylaxis. Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation. It can be triggered by immunological factors, such as immunoglobulins, lymphocytes, or antigen–antibody complexes, and non-immune factors, such as radiation and pathogens. An intensive reaction of mast cells can even lead to anaphylaxis, one of the most life-threatening allergic reactions. What is more, mast cells play a role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. 
  • 432
  • 04 May 2023
Topic Review
Extracellular Vesicles of MSCs
Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. These cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Soon thereafter, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation.
  • 432
  • 26 Jul 2021
Topic Review
Endospore Appendages
The endospores (spores) of many Bacillus cereus sensu lato species are decorated with multiple hair/pilus-like appendages. Although they have been observed for more than 50 years, all efforts to characterize these fibers in detail have failed until now, largely due to their extraordinary resilience to proteolytic digestion and chemical solubilization. A recent structural analysis of B. cereus endospore appendages (Enas) using cryo-electron microscopy has revealed the structure of two distinct fiber morphologies: the longer and more abundant “Staggered-type” (S-Ena) and the shorter “Ladder-like” type (L-Ena), which further enabled the identification of the genes encoding the S-Ena. Ena homologs are widely and uniquely distributed among B. cereus sensu lato species, suggesting that appendages play important functional roles in these species. The discovery of ena genes is expected to facilitate functional studies involving Ena-depleted mutant spores to explore the role of Enas in the interaction between spores and their environment. 
  • 432
  • 09 Dec 2021
Topic Review
Chaperone-Mediated Autophagy in Peritumoral Pericyte during Glioblastoma Multiforme
Glioblastoma multiforme (GB) is an aggressive cancer with poor prognosis as it is one of the most difficult cancers to treat. Glioblastoma (GB) cells physically interact with peritumoral pericytes (PCs) present in the brain microvasculature. These interactions facilitate tumor cells to aberrantly increase and benefit from chaperone-mediated autophagy (CMA) in the PC. GB-induced CMA leads to major changes in PC immunomodulatory phenotypes, which, in turn, support cancer progression. 
  • 432
  • 18 Sep 2023
Topic Review Peer Reviewed
Techniques for Theoretical Prediction of Immunogenic Peptides
Small peptides are an important component of the vertebrate immune system. They are important molecules for distinguishing proteins that originate in the host from proteins derived from a pathogenic organism, such as a virus or bacterium. Consequently, these peptides are central for the vertebrate host response to intracellular and extracellular pathogens. Computational models for prediction of these peptides have been based on a narrow sample of data with an emphasis on the position and chemical properties of the amino acids. In past literature, this approach has resulted in higher predictability than models that rely on the geometrical arrangement of atoms. However, protein structure data from experiment and theory are a source for building models at scale, and, therefore, knowledge on the role of small peptides and their immunogenicity in the vertebrate immune system. The following sections introduce procedures that contribute to theoretical prediction of peptides and their role in immunogenicity. Lastly, deep learning is discussed as it applies to immunogenetics and the acceleration of knowledge by a capability for modeling the complexity of natural phenomena.
  • 434
  • 20 Mar 2024
Topic Review
Unexpected Role of MPO-Oxidized LDLs in Atherosclerosis
Inflammation and its resolution are the result of the balance between pro-inflammatory and pro-resolving factors, such as specialized pro-resolving mediators (SPMs). This balance is crucial for plaque evolution in atherosclerosis, a chronic inflammatory disease. Myeloperoxidase (MPO) has been related to oxidative stress and atherosclerosis, and MPO-oxidized low-density lipoproteins (Mox-LDLs) have specific characteristics and effects. They participate in foam cell formation and cause specific reactions when interacting with macrophages and endothelial cells. They also increase the production of intracellular reactive oxygen species (ROS) in macrophages and the resulting antioxidant response. Mox-LDLs also drive macrophage polarization. Mox-LDLs are known to be pro-inflammatory particles. However, in the presence of Mox-LDLs, endothelial cells produce resolvin D1 (RvD1), a SPM. SPMs are involved in the resolution of inflammation by stimulating efferocytosis and by reducing the adhesion and recruitment of neutrophils and monocytes. RvD1 also induces the synthesis of other SPMs. In vitro, Mox-LDLs have a dual effect by promoting RvD1 release and inducing a more anti-inflammatory phenotype macrophage, thereby having a mixed effect on inflammation.
  • 431
  • 23 Jun 2022
Topic Review
Mitochondrial Unfolded Protein Response for Therapy
The mitochondrial unfolded protein response (UPRmt) is a mechanism aimed to preserve or repair damaged mitochondria. UPRmt is responsible for maintaining mitochondrial proteostasis via mitochondrial activation of a transcriptional program in the nuclear DNA. This compensation system can be divided into three main pathways: activation of (1) chaperones, which boost refolding of misfolded proteins to restore them to their functional conformation and assist the folding of newly synthesized proteins; (2) proteases that are able to degrade aberrant proteins or aggregates; and (3) an antioxidant system that palliates ROS overproduction. Although human UPRmt is not fully understood, it is gaining relevance in a variety of physiological processes on top of its canonical function, such as ageing, oxidative stress resistance, hematopoietic stem cell maintenance, glycolysis, antibacterial immunity, coenzyme Q biosynthesis, and mitochondrial fission. Loss of mitochondrial proteostasis is the main UPRmt inducer. Accumulation of damaged proteins exceeding the protein-processing capacity of the chaperones and proteases in mitochondria would activate UPRmt, for instance. Additionally, factors interfering with mitochondrial function promote UPRmt induction. Examples of these are the inhibition of complex I by rotenone, bacterial toxins, knockdown of quality control proteins, or generation of excess ROS by paraquat.
  • 431
  • 22 Jul 2022
Topic Review
Mitochondria in Health and Disease
Mitochondrial alterations have been implicated in a wide range of diseases, such as neurodegenerative disorders, metabolic disorders, and cancer. 
  • 432
  • 29 May 2023
Topic Review
ABCA1 and Atherogenesis
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs.
  • 430
  • 06 Jan 2022
Topic Review
Regulatory Role of Snc1 in Endocytosis and Exocytosis
Fungi are an important group of microorganisms that play crucial roles in a variety of ecological and biotechnological processes. Fungi depend on intracellular protein trafficking, which involves moving proteins from their site of synthesis to the final destination within or outside the cell. The soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins are vital components of vesicle trafficking and membrane fusion, ultimately leading to the release of cargos to the target destination. The v-SNARE (vesicle-associated SNARE) Snc1 is responsible for anterograde and retrograde vesicle trafficking between the plasma membrane (PM) and Golgi. It allows for the fusion of exocytic vesicles to the PM and the subsequent recycling of Golgi-localized proteins back to the Golgi via three distinct and parallel recycling pathways. This recycling process requires several components, including a phospholipid flippase (Drs2-Cdc50), an F-box protein (Rcy1), a sorting nexin (Snx4-Atg20), a retromer submit, and the COPI coat complex. Snc1 interacts with exocytic SNAREs (Sso1/2, Sec9) and the exocytic complex to complete the process of exocytosis. It also interacts with endocytic SNAREs (Tlg1 and Tlg2) during endocytic trafficking. Snc1 has been extensively investigated in fungi and has been found to play crucial roles in various aspects of intracellular protein trafficking.
  • 432
  • 16 Jun 2023
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