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Frontiers in Immunology 2022Extracellular vesicles are mediators of cell-cell communication playing a key role in both steady-state and disease conditions. Extracellular vesicles carry diverse... (Review)
Review
Extracellular vesicles are mediators of cell-cell communication playing a key role in both steady-state and disease conditions. Extracellular vesicles carry diverse donor-derived cargos, including DNA, RNA, proteins, and lipids that induce a complex network of signals in recipient cells. Due to their ability to capture particulate matter and/or capacity to polarize and orchestrate tissue responses, myeloid immune cells (e.g., dendritic cells, macrophages, etc.) rapidly respond to extracellular vesicles, driving local and systemic effects. In cancer, myeloid-extracellular vesicle communication contributes to chronic inflammation, self-tolerance, and therapeutic resistance while in autoimmune disease, extracellular vesicles support inflammation and tissue destruction. Here, we review cellular mechanisms by which extracellular vesicles modulate myeloid immunity in cancer and autoimmune disease, highlighting some contradictory results and outstanding questions. We will also summarize how understanding of extracellular vesicle biology is being utilized for novel therapeutic and diagnostic applications.
Topics: Autoimmune Diseases; Cell Communication; Extracellular Vesicles; Humans; Inflammation; Neoplasms
PubMed: 35320943
DOI: 10.3389/fimmu.2022.818538 -
Environmental Science & Technology Jun 2022Recent discovery of vesicle-cloaked virus clusters (i.e., viral vesicles) has greatly challenged the central paradigm of viral transmission and infection as a single...
Recent discovery of vesicle-cloaked virus clusters (i.e., viral vesicles) has greatly challenged the central paradigm of viral transmission and infection as a single virion. To understand the environmental transmission of viral vesicles, we used an in vivo model to investigate their environmental persistence and engineering control by disinfection. Murine rotavirus vesicles maintained both their integrity and infectivity after incubation in filtered freshwater and wastewater for at least 7 days, with 24.5-27.5% of the vesicles still intact at 16 weeks after exposure to both waters. Free chlorine disinfection at a dosage of 13.3 mg min L did not decompose murine rotavirus vesicles, and it was much less effective in inactivating rotaviruses inside vesicles than free rotaviruses based on the quantification of rotavirus shedding in mouse stool and rotavirus replication in small intestines. Rotavirus vesicles may be more environmentally transmissible than free rotaviruses regardless of disinfection. Vesicle-mediated transmission could be responsible for vesicles' resistance to disinfection due to an increased multiplicity of infection and/or genetic recombination or reassortment to promote infection. Our work highlights the environmental, biological, and public health significance of viral vesicles, and the findings call for urgent action in advancing disinfection for pathogen control.
Topics: Animals; Chlorine; Disinfection; Feces; Mice; Rotavirus; Wastewater
PubMed: 35653550
DOI: 10.1021/acs.est.2c00732 -
Journal of Molecular Biology Jan 2023Neuronal communication depends on exquisitely regulated membrane fusion between synaptic vesicles and presynaptic neurons, which results in neurotransmitter release in... (Review)
Review
Neuronal communication depends on exquisitely regulated membrane fusion between synaptic vesicles and presynaptic neurons, which results in neurotransmitter release in precisely timed patterns. Presynaptic dysfunctions are known to occur prior to the onset of neurodegenerative diseases, including Parkinson's disease. Synaptic accumulation of α-synuclein (α-Syn) oligomers has been implicated in the pathway leading to such outcomes. α-Syn oligomers exert aberrant effects on presynaptic fusion machinery through their interactions with synaptic vesicles and proteins. Here, we summarize in vitro bulk and single-vesicle assays for investigating the functions of α-Syn monomers and oligomers in synaptic vesicle fusion and then discuss the current understanding of the roles of α-Syn monomers and oligomers in synaptic vesicle fusion. Finally, we suggest a new therapeutic avenue specifically targeting the mechanisms of α-Syn oligomer toxicity rather than the oligomer itself.
Topics: alpha-Synuclein; Membrane Fusion; SNARE Proteins; Synaptic Transmission; Synaptic Vesicles
PubMed: 35931109
DOI: 10.1016/j.jmb.2022.167775 -
Advanced Pharmaceutical Bulletin Jan 2022Transdermal delivery over the past decade has become the field of interest for drug delivery due to its various advantages such as no first-pass metabolism, increased... (Review)
Review
Transdermal delivery over the past decade has become the field of interest for drug delivery due to its various advantages such as no first-pass metabolism, increased drug bioavailability, and easy administration. Different vesicle systems like ethosomes, liposomes, niosomes, and transferosomes along with particle systems like lipid nanoparticles, polymeric nanoparticles, carbon nanotubes, and fullerenes have been developed. These vesicles and particle systems have been developed using various easy and effective methods like cold injection method, rotary film evaporation, thin film hydration, high shear homogenization, solvent extraction method, and many more. These drug delivery systems are a very effective and feasible option for transdermal drug delivery and further developments can be made to increase their use. This article explains in detail the preparation methods and applications for these drug delivery systems.
PubMed: 35517881
DOI: 10.34172/apb.2022.006 -
Current Opinion in Cell Biology Jun 2024Vesicle transport at the Golgi apparatus is a well-described process, and the major protein components involved have been identified. This includes the coat proteins... (Review)
Review
Vesicle transport at the Golgi apparatus is a well-described process, and the major protein components involved have been identified. This includes the coat proteins that function in cargo sorting and vesicle formation, and the proteins that mediate the downstream events of vesicle tethering and membrane fusion. However, despite this knowledge, there remain significant gaps in our mechanistic understanding of these processes which includes how they are coordinated in space and time. In this review we discuss recent advances that have provided new insights into the mechanisms of Golgi trafficking, focussing on vesicle formation and cargo sorting, and vesicle tethering and fusion. These studies point to a high degree of spatial organisation of trafficking components at the Golgi and indicate an inherent plasticity of trafficking. Going forward, further advancements in technology and more sophisticated functional assays are expected to yield greater understanding of the mechanisms that govern Golgi trafficking events.
Topics: Golgi Apparatus; Humans; Animals; Protein Transport; Biological Transport; Transport Vesicles; Membrane Fusion
PubMed: 38705050
DOI: 10.1016/j.ceb.2024.102365 -
Cell Reports Methods Apr 2022Vesicle exo- and endocytosis mediate important biological functions, including synaptic transmission. In this issue of , Seong J. An et al. found that the fluorescently...
Vesicle exo- and endocytosis mediate important biological functions, including synaptic transmission. In this issue of , Seong J. An et al. found that the fluorescently tagged C2 domain of phospholipase A binds to membrane phosphatidylcholine and thus labels vesicle membrane, allowing for super-resolution and electron microscopic visualization of vesicle trafficking.
Topics: Synaptic Vesicles; Phospholipases A2; Endocytosis; Synaptic Transmission; Multimodal Imaging
PubMed: 35497501
DOI: 10.1016/j.crmeth.2022.100206 -
Proceedings of the National Academy of... Aug 2023Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic...
Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca. Using this setup, we identify new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca-triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca-dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of docked, release-ready vesicles. Dynamic single-molecule imaging of Complexin binding to release-ready vesicles directly establishes that DAG accelerates the rate of SNAREpin assembly mediated by chaperones, Munc13 and Munc18. The selective effects of physiologically validated mutations confirmed that the Munc18-Syntaxin-VAMP2 "template" complex is a functional intermediate in the production of primed, release-ready vesicles, which requires the coordinated action of Munc13 and Munc18.
Topics: Humans; Diglycerides; Synaptic Vesicles; Exocytosis; Synaptic Transmission; Synaptotagmins; Blister
PubMed: 37590407
DOI: 10.1073/pnas.2309516120 -
Frontiers in Immunology 2022As nano-sized materials prepared by isolating, disrupting and extruding cell membranes, cellular vesicles are emerging as a novel vehicle for immunotherapeutic drugs to... (Review)
Review
As nano-sized materials prepared by isolating, disrupting and extruding cell membranes, cellular vesicles are emerging as a novel vehicle for immunotherapeutic drugs to activate antitumor immunity. Cell membrane-derived vesicles inherit the surface characteristics and functional properties of parental cells, thus having superior biocompatibility, low immunogenicity and long circulation. Moreover, the potent antitumor effect of cellular vesicles can be achieved through surface modification, genetic engineering, hybridization, drug encapsulation, and exogenous stimulation. The capacity of cellular vesicles to combine drugs of different compositions and functions in physical space provides a promising vehicle for combinational immunotherapy of cancer. In this review, the latest advances in cellular vesicles as vehicles for combinational cancer immunotherapy are systematically summarized with focuses on manufacturing processes, cell sources, therapeutic strategies and applications, providing an insight into the potential and existing challenges of using cellular vesicles for cancer immunotherapy.
Topics: Cell Membrane; Drug Delivery Systems; Humans; Immunity, Cellular; Immunotherapy; Neoplasms
PubMed: 35874757
DOI: 10.3389/fimmu.2022.923598 -
Frontiers in Immunology 2021Archaea are prokaryotic organisms that were classified as a new domain in 1990. Archaeal cellular components and metabolites have found various applications in the... (Review)
Review
Archaea are prokaryotic organisms that were classified as a new domain in 1990. Archaeal cellular components and metabolites have found various applications in the pharmaceutical industry. Some archaeal lipids can be used to produce archaeosomes, a new family of liposomes that exhibit high stability to temperatures, pH and oxidative conditions. Additionally, archaeosomes can be efficient antigen carriers and adjuvants promoting humoral and cellular immune responses. Some archaea produce gas vesicles, which are nanoparticles released by the archaea that increase the buoyancy of the cells and facilitate an upward flotation in water columns. Purified gas vesicles display a great potential for bioengineering, due to their high stability, immunostimulatory properties and uptake across cell membranes. Both archaeosomes and archaeal gas vesicles are attractive tools for the development of novel drug and vaccine carriers to control various diseases. In this review we discuss the current knowledge on production, preparation methods and potential applications of archaeosomes and gas vesicles as carriers for vaccines. We give an overview of the traditional structures of these carriers and their modifications. A comparative analysis of both vaccine delivery systems, including their advantages and limitations of their use, is provided. Gas vesicle- and archaeosome-based vaccines may be powerful next-generation tools for the prevention and treatment of a wide variety of infectious and non-infectious diseases.
Topics: Adjuvants, Immunologic; Animals; Archaea; Cytoplasmic Vesicles; Drug Carriers; Humans; Liposomes; Nanoparticles; Vaccine Development
PubMed: 34567012
DOI: 10.3389/fimmu.2021.746235 -
Journal of Controlled Release :... Mar 2023Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the... (Review)
Review
Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the ideal vesicle, since their properties and features are related, as changes in one affect the others. Here, we review the main components, preparation and characterization methods commonly used, and the key properties that lead to highly efficient vesicles for transdermal drug delivery purposes. We stand by size, deformability degree and drug loading, as the most important vesicle features that determine the further transdermal drug absorption. The interest in this technology is increasing, as demonstrated by the exponential growth of publications on the topic. Although long-term preservation and scalability issues have limited the commercialization of lipid vesicle products, freeze-drying and modern escalation methods overcome these difficulties, thus predicting a higher use of these technologies in the market and clinical practice.
Topics: Humans; Liposomes; Drug Carriers; Skin; Drug Delivery Systems; Administration, Cutaneous; Blister; Lipids
PubMed: 36775245
DOI: 10.1016/j.jconrel.2023.02.006