Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activi...Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activity, and altered CD56Dim and CD56Bright NK cell phenotypes. This current project, for the first time, investigates the NK cell cytotoxicity, calcium mobilisation and transient receptor potential melastatin 3 (TRPM3) surface expression. Methods: NK cell cytotoxic activity and calcium signaling were examined in CD56Dim and CD56Bright NK cells before and after stimulation using Ionomycin, Pregnenolone sulphate, 2-Aminoethoxydiphenyl borate and Thapsigargin. Purified NK cells were labelled with antibodies to determine TRPM3, CD69 and CD107a surface expression using flow cytometry. Results: Twenty-two MS patients and 22 healthy controls were recruited for this project. Twelve of the 22 previously received Alemtuzumab (Lemtrada®) and the remaining ten reported nil medication. We report TRPM3 was significantly increased in untreated MS patients compared with healthy controls and treated MS patients (p-value 0.034). There was a significant decrease in CD69 surface expression on CD56Dim NK cell phenotype for untreated MS patients (p-value 0.031) and treated MS patients (p-value 0.036). We report altered calcium mobilisation in CD56Bright NK cells and to a lesser extent CD56Dim NK cells between healthy controls, treated and untreated MS patients. Conclusion: This investigation suggests variations in TRPM3 expression and calcium mobilisation of NK cells may be implicated in the pathogenesis of MS. Further investigation is required to determine the mechanism by which alemtuzumab alters calcium signaling in NK cells.展开更多
A variety of skin substitutes are used in the treatment of full-thickness burns. Substitutes made from skin can harbor latent viruses, and artificial skin grafts can heal with extensive scarring, failing to regenerate...A variety of skin substitutes are used in the treatment of full-thickness burns. Substitutes made from skin can harbor latent viruses, and artificial skin grafts can heal with extensive scarring, failing to regenerate structures such as glands, nerves, and hair follicles. Biodegradable and biocompatible hydrogels, however, rarely mimic the strength of the epidermis. Therefore, novel and practical skin scaffold materials remain to be developed. Polysaccharides form hydrogels with predicted inherent biocompatibility. This paper describes the preparation and biocompatibility of unique hydrogel skin scaffolds from plant-extracted polysaccharide mixtures of specific sources, types, and molecular weight fractions. These hydrogels have a range of mechanical and degradation properties with the potential to fulfill the multiple, diverse functions of artificial skin, including protection, compatibility with different cell types, biodegradation, and release of needed signals for cell growth and wound healing.展开更多
文摘Background: Natural killer (NK) cell phenotypes have reported to be implicated in the pathomechanism of Multiple Sclerosis (MS). Several investigators have observed reduced peripheral numbers, reduced cytotoxic activity, and altered CD56Dim and CD56Bright NK cell phenotypes. This current project, for the first time, investigates the NK cell cytotoxicity, calcium mobilisation and transient receptor potential melastatin 3 (TRPM3) surface expression. Methods: NK cell cytotoxic activity and calcium signaling were examined in CD56Dim and CD56Bright NK cells before and after stimulation using Ionomycin, Pregnenolone sulphate, 2-Aminoethoxydiphenyl borate and Thapsigargin. Purified NK cells were labelled with antibodies to determine TRPM3, CD69 and CD107a surface expression using flow cytometry. Results: Twenty-two MS patients and 22 healthy controls were recruited for this project. Twelve of the 22 previously received Alemtuzumab (Lemtrada®) and the remaining ten reported nil medication. We report TRPM3 was significantly increased in untreated MS patients compared with healthy controls and treated MS patients (p-value 0.034). There was a significant decrease in CD69 surface expression on CD56Dim NK cell phenotype for untreated MS patients (p-value 0.031) and treated MS patients (p-value 0.036). We report altered calcium mobilisation in CD56Bright NK cells and to a lesser extent CD56Dim NK cells between healthy controls, treated and untreated MS patients. Conclusion: This investigation suggests variations in TRPM3 expression and calcium mobilisation of NK cells may be implicated in the pathogenesis of MS. Further investigation is required to determine the mechanism by which alemtuzumab alters calcium signaling in NK cells.
文摘A variety of skin substitutes are used in the treatment of full-thickness burns. Substitutes made from skin can harbor latent viruses, and artificial skin grafts can heal with extensive scarring, failing to regenerate structures such as glands, nerves, and hair follicles. Biodegradable and biocompatible hydrogels, however, rarely mimic the strength of the epidermis. Therefore, novel and practical skin scaffold materials remain to be developed. Polysaccharides form hydrogels with predicted inherent biocompatibility. This paper describes the preparation and biocompatibility of unique hydrogel skin scaffolds from plant-extracted polysaccharide mixtures of specific sources, types, and molecular weight fractions. These hydrogels have a range of mechanical and degradation properties with the potential to fulfill the multiple, diverse functions of artificial skin, including protection, compatibility with different cell types, biodegradation, and release of needed signals for cell growth and wound healing.
