1,721,055 research outputs found
Polarization and repolarization of macrophages
Full text linkMacrophages can acquire distinct phenotypes and biological functions depending on the microenvironment and
the metabolic state. Macrophages classically activated by IFN-γ and/or microbial products display an M1 phenotype
characterized by high expression of interleukin (IL)-12, inducible nitric oxide synthase (iNOS) and TNF-α. They
trigger a Th1 immune response and are generally considered potent effector cells which kill microorganisms and
tumor cells. Alternatively activated or M2 macrophages are stimulated by IL-4, IL-10, IL-13, immune complexes, or
glucocorticoids. M2 phenotype is characterized by low iNOS and IL-12 production and triggers Th2 response. M2
macrophages are involved in tissue repair and angiogenesis. M1 and M2 macrophages display differences in
metabolism and reduced glutathione (GSH) concentration. This review describes the main macrophage phenotypes
with a major focus on the differences in protein, glucose and lipid metabolism. Moreover, repolarization of
macrophages as potential therapeutic approach and the critical role of GSH in regulating repolarization are
discussed
Glutathione and glutathione derivatives in immunotherapy
No full textReduced glutathione (GSH) is the most prevalent non-protein thiol in animal cells. Its de novo and salvage synthesis serves to maintain a reduced cellular environment, which is important for several cellular functions. Altered intracellular GSH levels are observed in a wide range of pathologies, including several viral infections, as well as in aging, all of which are also characterized by an unbalanced Th1/Th2 immune response. A central role in influencing the immune response has been ascribed to GSH. Specifically, GSH depletion in antigen-presenting cells (APCs) correlates with altered antigen processing and reduced secretion of Th1 cytokines. Conversely, an increase in intracellular GSH content stimulates IL-12 and/or IL-27, which in turn induces differentiation of naive CD4+ T cells to Th1 cells. In addition, GSH has been shown to inhibit the replication/survival of several pathogens, i.e. viruses and bacteria. Hence, molecules able to increase GSH levels have been proposed as new tools to more effectively hinder different pathogens by acting as both immunomodulators and antimicrobials. Herein, the new role of GSH and its derivatives as immunotherapeutics will be discussed
Metodo di sintesi di derivati del glutatione [Method for the synthesis of glutathione derivatives]
No full textA synthesis method for the production of N-acyl glutathione, comprising an acylation step, during which, in a water solution with a pH ranging from 8 to 10, glutathione is caused to react with an anhydride with formula (RCO)2O with a formation of S,N-diacyl glutathione, and a subsequent S-acyl group selective alcoholysis step, during which the S,N-diacyl glutathione produced in the previous step is dissolved in an alkoxide/alcohol solution (R'O-/R'OH) and, subsequently, the obtained product is treated with a cation-exchange resin. R is H or a straight or branched hydrocarbon group with a number of carbon atoms ranging from C1 to C24 while R' is a straight or branched radical hydrocarbon group with a number of carbon atoms ranging from C1 to C4
Up-regulation of the ubiquitin-conjugating and proteolytic systems in murine acquired immunodeficiency syndrome
No full textLarge-Scale Preparation of N-Butanoyl-l-glutathione (C4-GSH)
No full textA novel two-step synthesis of N-butanoyl-l-glutathione (C4-GSH) was developed involving the chemical modification of the commercially available starting material l-glutathione (GSH). This process not only has the advantage of selective acylation of the GSH amino group without the use of previous solid-phase organic synthesis and/or protecting group chemistry but also highlights the use of inexpensive reagents such as butyric anhydride and sodium methoxide as well as environmentally acceptable solvents such as water and methanol. This chromatography- and salt-free synthesis of C4-GSH is cost-effective, safe, efficient, and easy to scale up
In vivo survival and in vitro phagocytosis of engineered erythrocytes.
No full textADVANCES IN BIOSCIENCE
Red Blood Cell Membrane Processing for Biomedical Applications
Full text linkRed blood cells (RBC) are actually exploited as innovative drug delivery systems with unconventional and convenient properties. Because of a long in vivo survival and a non-random removal from circulation, RBC can be loaded with drugs and/or contrasting agents without affecting these properties and maintaining the original immune competence. However, native or drug-loaded RBC, can be modified decorating the membrane with peptides, antibodies or small chemical entities so favoring the targeting of the processed RBC to specific cells or organs. Convenient modifications have been exploited to induce immune tolerance or immunogenicity, to deliver antibodies capable of targeting other cells, and to deliver a number of constructs that can recognize circulating pathogens or toxins. The methods used to induce membrane processing useful for biomedical applications include the use of crosslinking agents and bifunctional antibodies, biotinylation and membrane insertion. Another approach includes the expression of engineered membrane proteins upon ex vivo transfection of immature erythroid precursors with lentiviral vectors, followed by in vitro expansion and differentiation into mature erythrocytes before administration to a patient in need. Several applications have now reached the clinic and a couple of companies that take advantage from these properties of RBC are already in Phase 3 with selected applications. The peculiar properties of the RBC and the active research in this field by a number of qualified investigators, have opened new exciting perspectives on the use of RBC as carriers of drugs or as cellular therapeutics
Pharmaceutical composition or composition package containing a pyrimidine nucleoside analog and a purine nucleoside analog
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