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Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The changes in protein synthesis and degradation associated with proteinase activity and protein synthesis may derive from alteration of the membrane permeability of the various organelles in the neurons from the damaged peripheral nerve.270 Proteinases contain proteolipids which may be responsible for their enzyme activity. Therefore, the primary modifications of the macromolecular organization of the neuronal structures and denaturation of lipoproteins occuring during early stages of neuron injury are associated with conformational changes of these complex molecules. Reduced enzyme activity may represent unmasking of the enzyme function. Later, increased enzyme activity may be related to changes in membrane permeability due to the injury or release of proteolipid from protein binding through the action of cytolytic substances, such as lysolecithin or lysophosphatidylethanolamine. These phospholipids are normally present in small amounts in the nervous system and exert a direct cytolytic or myelinolytic action on the cell, releasing enzymes from lysosomes of myelin. This step may be the initiator of the demyelinating process, indicating the participation of neural lysosomes in events of Wallerian degeneration. Lysosome-like particles are described in neuronal cells, axon, and glial cells and in the Schwann cell. It may be that lysosomal activity largely of axonal origin is responsible for the degradation and enzyme changes manifesting in the early stage of degeneration.
Nature, Function, and Biosynthesis of Surfactant Lipids
Published in Jacques R. Bourbon, Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
Recent findings, however, suggest that the processing of low molecular weight associated proteins (surfactant proteolipids) would differ notably from that of the major protein, SP-A. Thus, changes in protein composition may accompany functional changes in surfactant in the alveoli55 and it appears that surfactant-associated proteins 15 (SP-B) and 35 kDa (SP-A) would be concentrated in different organelles in type II cells.57 The surfactant proteolipid 6 to 15 kDa would be secreted as a 42-kDa precursor subsequently cleaved in alveolar spaces into the functional forms which are then reassociated with lamellar bodies via reuptake from the lumen.3 Further experiments therefore appear necessary to reach a final, comprehensive view of the packaging, assembly, and functional interactions of the various surfactant components.
CD4+ T Regulatory Cells and Modulation of Undesired Immune Responses
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Rosa Bacchetta, Megan K. Levings, Maria-Grazia Roncarolo
Another subset of CD4+ Tr cells was identified in studies of oral tolerance. Th3-cell clones, isolated from mice that were orally tolerised to myelin basic protein, suppress induction of EAE via a TGF-β-dependent mechanism.78 CD4+ Tr cells which protect from EAE also arise in mice or rats, following oral administration of copolymer 1 (Cop-1).79 Interestingly, T-cell lines generated from Cop-1-tolerant animals produce high levels of IL-10 and TGF-β, but little IL-2 or IL-4. Th3, like Tr1 cells and CD4+CD25+ Tr cells, must be activated via the TCR to be suppressive and mediate bystander suppression.80 In patients suffering from multiple sclerosis, oral treatment with myelin basic protein (MBP) and proteolipid protein (PLP) induces a significant increase in the frequency of MBP or PLP-specific T cells that secrete TGF-β.81 These data suggest that cells equivalent to murine TGF-β-producing Th3 cells78 also exist in humans. The specialized environment of the oral mucosa and the selected subsets of resident DC are likely important factors for the differentiation of Th3 cells. Further studies are required to clarify whether the Th3 cells induced during oral tolerance are related to Tr1 or CD4+CD25+ Tr cells. One important difference between Th3 and Tr1 cells appears to be that Th3 cells require IL-4 for their differentiation.80
Extracellular vesicles: emerging anti-cancer drugs and advanced functionalization platforms for cancer therapy
Published in Drug Delivery, 2022
Manling Wu, Min Wang, Haoyuan Jia, Peipei Wu
Cancer is one of the most significant burdens that a human could experience all over the world (Torre et al., 2015). In particular, with the change of disease patterns and the trend of population aging, cancer prevention and treatment are facing a grim situation. During the past several decades, despite years of investigations, the scientists still have not developed effective therapies for many types of tumors. Currently, lacks of specificity and effectiveness remain the main limitations of clinical tumor therapy. Therefore, there is an urgent need to find new therapeutic regimens for the precise treatment of tumors. EVs are nanoscale to micron-sized membrane structure vesicles with a size ranging from 30 to 5000 nm (Cocozza et al., 2020), which are shed from cell membranes or secreted by almost all bacteria, archaea and eukaryotic cells in a constitutive or fine-tuning manner (van Niel et al., 2018). EVs are spherical, bilayered proteolipids that harbor multiple biomolecules including proteins, nucleic acids, lipids and metabolites. The interaction between tumor cells and tumor microenvironment is closely related to tumor initiation, development, metastasis and drug resistance. As one of the important components of tumor microenvironment, EVs play an important role in tumor relapse and drug resistance, angiogenesis, immune monitoring and other aspects. In addition, EVs are also the main content of tumor liquid biopsy, which can provide new insights for the diagnosis, treatment and prognosis of tumor.
Physical exercise counteracts the increase in velocity of propagation of cortical spreading depression imposed by early over-nutrition in rats
Published in Nutritional Neuroscience, 2020
Heloísa Mirelle Costa Monteiro, Débora Carneiro de Mendonça, Mariana Séfora Bezerra Sousa, Angela Amancio-dos-Santos
Regarding nutrition-related effects on brain excitability, HF diet intake accelerated CSD velocity (group HF/S versus group C/S). In fact, the lactation period, which in rats corresponds to the three first weeks of life, is considered very critical and sensitive to adverse environmental conditions.30 HF diet exposure exclusively during lactation has been associated with significant effects in the cerebral environment of the offspring.31 For example, Soares et al.29 have suggested that conjugated linoleic acid treatment carried out during lactation may impair myelin synthesis in the progeny, and this would causally involve CSD acceleration. In our study, the HF diet used contained higher amounts of palmitic, stearic, and oleic acids than the C diet. All these are constituents of the proteolipid encountered in myelin in the central nervous system of the rat brain.32,33 It is possible that fat imbalance during suckling may influence myelination negatively and so promote long-lasting brain electrophysiological effects. Myelin content is reported to be inversely associated to CSD propagation velocity.34
Progress towards the development of Klebsiella vaccines
Published in Expert Review of Vaccines, 2019
Myeongjin Choi, Sharon M Tennant, Raphael Simon, Alan S Cross
A crude outer membrane protein (OMP) vaccine from an unencapsulated KP strain provided complete protection from bacterial challenge [75]. Since OmpA has been considered an antigen which is involved in host defense mechanism with cytokine production and neutrophil recruitment, it was considered a good vaccine candidate [76]. KP OmpA was first cloned in 1998 [77]. Recombinant OmpK17 and OmpK36 [78] as well as OmpA [79] were used as vaccine candidates against lung infection and sepsis caused by KP in murine models with little [78] to modest [79] protective efficacy. OmpA also has been considered a good carrier protein for polysaccharide haptens that induces CD4 + T cell lymphoproliferative and Th1/Th2 responses as well as primes for cytotoxic T lymphocytes (CTL) epitopes in mice [80]. KP recombinant rP40 OMP has been reported to be an effective carrier protein for other important bacterial polysaccharide vaccine antigens such as a peptide of respiratory syncytial virus [81] or a polysaccharide derived from Haemophilus [80]. KP-derived extracellular vesicles, spherical, nanometer-sized proteolipids enriched in OMPs and LPS, induced innate immune responses and both humoral and cellular immunity leading to protection against homologous KP challenge [82].