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Cytokine Delivery Systems
Cytokines are polypeptides or glycoproteins that help immune cells communicate to each other to induce proliferation, activation, differentiation, and inflammatory or anti-inflammatory signals in various cell types.Gonçalves, A., Machado, R., Gomes, A. C., & Costa, A. da. (2020). Nanotechnology Solutions for Controlled Cytokine Delivery: An Applied Perspective. ''NATO Advanced Science Institutes Series E: Applied Sciences'', ''10''(20), 7098.Razeghian, E., Margiana, R., Chupradit, S., Bokov, D. O., Abdelbasset, W. K., Marofi, F., Shariatzadeh, S., Tosan, F., & Jarahian, M. (2021). Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy. ''Frontiers of Medicine'', ''8'', 721174. Studies utilizing cytokines for antitumor therapies has increased significantly since 2000, and different cytokines provide unique antitumor activities.Nash, A. M., Jarvis, M. I., Aghlara-Fotovat, S., Mukherjee, S., Hernandez, A., Hecht, A. D., Rios, P. ...
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Cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes and mast cells, as well as Endothelium, endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptor, cytokine receptors on the target cell surface. Cytokines are especially important in the immune system; cytokines modulate the balance between humoral immunity, humoral and cell-mediated immunity, cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex way ...
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Carcinoembryonic Antigen
Carcinoembryonic antigen (CEA) describes a set of highly-related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is usually present at very low levels in the blood of healthy adults (about 2–4 ng/mL). However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smoking, smokers. CEA are Glycosylphosphatidylinositol, glycosyl phosphatidyl inositol (GPI) cell-surface-anchored glycoproteins whose specialized Sialyl-Lewis X, sialo Fucosylation, fucosylated glycoforms serve as functional colon carcinoma L-selectin and E-selectin ligands, which may be critical to the metastatic dissemination of colon carcinoma cells. Immunologically they are characterized as members of the CD66 cluster of differentiation. The proteins include CD66a, CD66b, CD6 ...
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TRAIL
A trail, also known as a path or track, is an unpaved lane or a small paved road (though it can also be a route along a navigable waterways) generally not intended for usage by motorized vehicles, usually passing through a natural area. However, it is sometimes applied to highways in North America. In the United Kingdom and Ireland, a path or footpath is the preferred term for a pedestrian or hiking trail. In the US, the term was historically used for a route into or through wild territory used by explorers and migrants (e.g. the Oregon Trail). In the United States, "trace" is a synonym for trail, as in Natchez Trace. Some trails are restricted to use by only walkers, or cyclists, or equestrians, or for snowshoeing, or cross-country skiing, others, for example bridleways in the UK, are shared, and can be used by walkers, cyclists and equestrians. Although most ban motorized use, there are unpaved trails used by dirt bikes, quad bikes and other off-road vehicles, u ...
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Phospholipase A2
The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyses the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid "tail" and the glycerol molecule: :phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate This particular phospholipase specifically recognizes the ''sn''2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidyl choline, a precursor of lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases, arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes, which are categorized as anti-inflammatory and inflammatory mediators. PLA2 enzymes are commonly found in mammalian tissues as well as arachnid, insect, and snake venom. Venom from bees is largely composed of melittin, which is a stimulan ...
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Polyethylenimine
Polyethylenimine (PEI) or polyaziridine is a polymer with repeating units composed of the amine group and two carbon Aliphatic_compound, aliphatic ''CHCH'' spacers. Linear polyethyleneimines contain all Amines#Classification_of_amines, secondary amines, in contrast to branched PEIs which contain primary, secondary and tertiary amino groups. Totally branched, dendrimeric forms were also reported. PEI is produced on an industrial scale and finds many applications usually derived from its polyelectrolyte, polycationic character. Properties The linear PEI is a semi-crystalline solid at room temperature while branched PEI is a fully amorphous polymer existing as a liquid at all molecular weights. Linear polyethyleneimine is soluble in hot water, at low pH, in methanol, ethanol, or chloroform. It is insoluble in cold water, benzene, Diethyl ether, ethyl ether, and acetone. Linear polyethylenimine has a melting point of around 67 °C. Both linear and branched polyethylneimine c ...
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Vectors In Gene Therapy
Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses (sometimes called biological nanoparticles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods). Viruses All viruses bind to their hosts and introduce their genetic material into the host cell as part of their replication cycle. This genetic material contains basic 'instructions' of how to produce more copies of these viruses, hacking the body's normal production machinery to serve the needs of the virus. The host cell will carry out these instructions and produce additional copies of the virus, leading to more and more cells becoming infected. Some types of viruses insert their genome into the host's cytoplasm, but do not actually enter the cell. Others penetrate the cell membrane disguised as protein molecules and enter the cell. There are two main types of vir ...
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Electroporation
Electroporation, also known as electropermeabilization, is a microbiological and biotechnological technique in which an electric field is applied to cells to briefly increase the permeability of the cell membrane. The application of a high-voltage electric field induces a temporary destabilization of the lipid bilayer, resulting in the formation of nanoscale pores that permit the entry or exit of macromolecules. This method is widely employed to introduce molecules—including small molecules, DNA, RNA, and proteins—into cells. Electroporation can be performed on cells in suspension using electroporation cuvettes, or directly on adherent cells ''in situ'' within their culture vessels. In microbiology, electroporation is frequently utilized for the transformation of bacteria or yeast cells, often with plasmid DNA. It is also used in the transfection of plant protoplasts and mammalian cells. Notably, electroporation plays a critical role in the '' ex vivo'' manipulation ...
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Nucleic Acid
Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). If the sugar is ribose, the polymer is RNA; if the sugar is deoxyribose, a variant of ribose, the polymer is DNA. Nucleic acids are chemical compounds that are found in nature. They carry information in cells and make up genetic material. These acids are very common in all living things, where they create, encode, and store information in every living cell of every outline of life forms, life-form on Earth. In turn, they send and express that information inside and outside the cell nucleus. From the inner workings of the cell to the young of a living thing, they contain and provide information via the nucleic acid sequence. This gives the RNA and DNA their unmistakable 'la ...
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Tumor Necrosis Factor
Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors on other cells. It is a member of the tumor necrosis factor superfamily, a family of transmembrane proteins that are cytokines, chemical messengers of the immune system. Excessive production of TNF plays a critical role in several inflammatory diseases, and TNF-blocking drugs are often employed to treat these diseases. TNF is produced primarily by macrophages but is also produced in several other cell types, such as T cells, B cells, dendritic cells, and mast cells. It is produced rapidly in response to pathogens, cytokines, and environmental stressors. TNF is initially produced as a type II transmembrane protein (tmTNF), which is then cleaved by TNF alpha converting enzyme (TACE) into a soluble form (sTNF) and secreted from the cell ...
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Gold Nanoparticles In Chemotherapy
Gold nanoparticles in chemotherapy and radiotherapy is the use of colloidal gold in therapeutic treatments, often for cancer or arthritis. Gold nanoparticle technology shows promise in the advancement of cancer treatments. Some of the properties that gold nanoparticles possess, such as small size, non-toxicity and non-immunogenicity make these molecules useful candidates for targeted drug delivery systems. With tumor-targeting delivery vectors becoming smaller, the ability to by-pass the natural barriers and obstacles of the body becomes more probable. To increase specificity and likelihood of drug delivery, tumor specific ligands may be grafted onto the particles along with the chemotherapeutic drug molecules, to allow these molecules to circulate throughout the tumor without being redistributed into the body. Physical properties Size Gold nanoparticles range in size depending on which therapy they are being used for. In photothermal cancer therapy, many gold nanoparticle mol ...
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Liposome
A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes (such as by sonication). Liposomes are most often composed of phospholipids, especially phosphatidylcholine, and cholesterol, but may also include other lipids, such as those found in egg and phosphatidylethanolamine, as long as they are compatible with lipid bilayer structure. A liposome design may employ surface ligands for attaching to desired cells or tissues. Based on vesicle structure, there are seven main categories for liposomes: multilamellar large (MLV), oligolamellar (OLV), small unilamellar (SUV), medium-sized unilamellar (MUV), larg ...
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Interleukin 10
Interleukin 10 (IL-10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti- inflammatory cytokine. In humans, interleukin 10 is encoded by the ''IL10'' gene. IL-10 signals through a receptor complex consisting of two IL-10 receptor-1 and two IL-10 receptor-2 proteins. Consequently, the functional receptor consists of four IL-10 receptor molecules. IL-10 binding induces STAT3 signalling via the phosphorylation of the cytoplasmic tails of IL-10 receptor 1 + IL-10 receptor 2 by JAK1 and TYK2 respectively. Gene and protein structure The IL-10 protein is a homodimer; each of its subunits is 178- amino-acid long. IL-10 is classified as a class-2 cytokine, a set of cytokines including IL-19, IL-20, IL-22, IL-24 (Mda-7), IL-26 and interferons type-I ( IFN-alpha, -beta, -epsilon, -kappa, -omega), type-II (IFN-gamma) and type-III (IFN-lambda, including IL-28A, IL-28B, IL-29, and IFNL4). Expression and synthesis In humans, IL-10 is encoded by ...
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