China
Africa
Explore chapters and articles related to this topic
Pharmacologic vitreolysis
Published in A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha, Vitreoretinal Surgical Techniques, 2019
It has been shown that a 240 kDa chondroitin sulfate proteoglycan is associated with the vitreoretinal interface.8 The greatest immunoreactivity of this proteoglycan has been observed in regions of firm vitreoretinal adhesion, such as the vitreous base and the papillary margin, suggesting a major role in vitreoretinal adhesion. Chondroitinase cleaves this proteoglycan and has been studied as an adjunct in vitrectomy in 2 human donor eyes and in 57 cynomolgus monkeys.8 Intravitreal injection of the enzyme caused separation of the vitreous from the retina, including the vitreous base, without damage to the internal limiting membrane (ILM). Three monkeys have been followed for 14–16 months after surgery. The eyes remained quiet and clear, and electroretinograms were indistinguishable from controls.8 Moreover, chondroitinase has been used to detach epiretinal membranes in the eyes of four monkeys, providing evidence that the chondroitin sulfate proteoglycan participates in the adhesion of epiretinal membranes to the ILM.8 Chondroitinase has been studied in phase I human trials, but results have not yet been reported.
Cellular and Molecular Basis of Human Biology
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
Structural proteins are responsible for creating a functional frameworks of human structure and function, like muscles, tendon, bone, cartilage, skin, hair, nail, etc. Although the major skeletal muscle proteins include common contractile proteins of slow type 1 and fast types 2A and 2X myosins, actins, tropomyosins, troponin complexes, and metabolic proteins, there is a high variability in terms of relative composition since muscle protein types vary with age, activity type and level, and gender (Gelfi et al. 2011). In bone, about 90% of protein is in the form of type I collagen (Lammi et al. 2006). In cartilage, type II collagen and aggrecans (large aggregating chondroitin sulfate proteoglycan) predominate (Lammi et al. 2006). In tendon, the major proteins are type I (most abundant), II, and III collagens (Buckley et al. 2013). For the skin, collagen is one of the major protein components. Hair and nail proteins are primarily keratins.
Structural and Functional Consequences of Streptozotocin-Induced Diabetes on the Kidney
Published in John H. McNeill, Experimental Models of Diabetes, 2018
Kumar Sharma, Dong Cheol Han, András Mogyorósi, Fuad N. Ziyadeh
In normal rats, basement membrane–specific chondroitin sulfate proteoglycan (CSPG) is localized to the basement membrane of Bowman’s capsule and the mesangial matrix but not to the pericapillary GBM. However, in STZ diabetic rats, glomerular CSPG immunofluorescence staining can be found within the pericapillary GBM, where it forms a thin continuous rim that outlines the perimeter of affected capillaries.101 Immunoelectron microscopy of diabetic glomeruli has revealed that CSPG tends to deposit within areas where the GBM is ostensibly thickened.101 CSPG accumulation displaces endothelial cells from the GBM and results in loss of endothelial cell fenestration in some areas. Effacement of the epithelial podocyte foot processes is also observed.101 Recent ultrastructural morphological studies with serial detergents revealed that the subendothelial layer is continuous with the mesangial matrix.103 Hyperglycemia may cause altered metabolism of HSPG by glomerular cells and result in abnormal synthesis and/or removal of CSPG in the GBM by mesangial cells.
Advances in engineering and delivery strategies for cytokine immunotherapy
Published in Expert Opinion on Drug Delivery, 2023
Margaret Bohmer, Yonger Xue, Katarina Jankovic, Yizhou Dong
PLGA-based cytokine NPs have been studied as a potentiator of chimeric antigen receptor (CAR)-T cell therapy. While CAR-T therapy is effective for treating B-cell leukemias and lymphomas, its implementation in solid tumor treatment has been limited by the immunosuppressive TME, which leads to T-cell exhaustion [125]. In one study, IL-15 was encapsulated in PLGA NPs and added to a modified hyaluronic acid-based hydrogel containing platelet-conjugated anti-PDL1 blocking antibody (aPDL1), as well as CAR-T cells targeting human chondroitin sulfate proteoglycan 4 (CSPG4) [126]. The purpose of the IL-15 was to prevent T-cell exhaustion by promoting proliferation of the CAR-T cells. When this hydrogel was implanted into the surgical bed post-tumor resection in mice, it demonstrated improved T-cell persistence when compared to free CAR-T cells [126].
Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies
Published in OncoImmunology, 2022
Rebecca Adams, Gabriel Osborn, Bipashna Mukhia, Roman Laddach, Zena Willsmore, Alicia Chenoweth, Jenny L C Geh, Alastair D MacKenzie Ross, Ciaran Healy, Linda Barber, Sophia Tsoka, Victoria Sanz-Moreno, Katie E Lacy, Sophia N Karagiannis
Chondroitin sulfate proteoglycan 4 (CSPG4) is a cancer antigen which may be more selective for cancer cells. CSPG4 is expressed in 70% of the melanomas with a low and restricted expression profile in healthy tissue.133 Monoclonal antibodies designed against this target which can engage the FcRs on immune cells, including monocytes and macrophages, are under development in preclinical models. An anti-CSPG4 IgG1 monoclonal antibody has been reported to increase macrophage recruitment in a fully humanized mouse model of melanoma,118 and repeated administration of an anti-CSPG4 IgE monoclonal antibody therapy is well tolerated in immunocompetent animal models.133 The exact effect of anti-CSPG4 mAbs on macrophages remains unknown but warrants exploration, since polarizing TAMs and enhancing their antitumor properties may be a potential mechanism by which anti-CSPG4 can exert therapeutic effects.
Skin proteomics – analysis of the extracellular matrix in health and disease
Published in Expert Review of Proteomics, 2020
Jörn Dengjel, Leena Bruckner-Tuderman, Alexander Nyström
Additional key regulators of collagen fibrillogenesis are proteoglycans and matricellular proteins. Decorin, a dermatan sulfate/chondroitin sulfate SLRP, and versican, a chondroitin sulfate proteoglycan, are the most abundant proteoglycans in the skin [84]. Decorin shows a higher abundance in the papillary ECM and versican in the reticular ECM [84,85]. The importance of these proteoglycans in the skin is reflected by skin fragility in decorin-deficient mice [86] and in dermatan sulfate-deficient humans [87]. Despite being of lower abundance, also other proteoglycans are important regulators of collagen fibrillogenesis in the dermis. These include the SLRPs biglycan, lumican and fibromodulin [88]. Proteoglycans can be present without GAG substitution as just the protein core. Furthermore, although not a protein, the GAG hyaluronan, which is distributed throughout the skin, shows its highest abundance in the papillary dermis [89].