Microbiological-Chemical Sourced Chondroitin Sulfates Protect Neuroblastoma SH-SY5Y Cells against Oxidative Stress and Are Suitable for Hydrogel-Based Controlled Release

Chondroitin sulfates (CS) are a class of sulfated glycosaminoglycans involved in many biological processes. Several studies reported their protective effect against neurodegenerative conditions like Alzheimer’s disease. CS are commonly derived from animal sources, but ethical concerns, the risk of contamination with animal proteins, and the difficulty in controlling the sulfation pattern have prompted research towards non-animal sources. Here we exploited two microbiological-chemical sourced CS (i.e., CS-A,C and CS-A,C,K,L) and Carbopol 974P NF/agarose semi-interpenetrating polymer networks (i.e., P.NaOH.0 and P.Ethanol.0) to set up a release system, and tested the neuroprotective role of released CS against H2O2-induced oxidative stress. After assessing that our CS (1–100 µM) require a 3 h pre-treatment for neuroprotection with SH-SY5Y cells, we evaluated whether the autoclave type (i.e., N- or B-type) affects hydrogel viscoelastic properties. We selected B-type autoclaves and repeated the study after loading CS (1 or 0.1 mg CS/0.5 mL gel). After loading 1 mg CS/0.5 mL gel, we evaluated CS release up to 7 days by 1,9-dimethylmethylene blue (DMMB) assay and verified the neuroprotective role of CS-A,C (1 µM) in the supernatants. We observed that CS-A,C exhibits a broader neuroprotective effect than CS-A,C,K,L. Moreover, sulfation pattern affects not only neuroprotection, but also drug release.

Marine Sulfated Polysaccharides: Preventive and Therapeutic Effects on Metabolic Syndrome: A Review

Metabolic syndrome is the pathological basis of cardiovascular and cerebrovascular diseases and type 2 diabetes. With the prevalence of modern lifestyles, the incidence of metabolic syndrome has risen rapidly. In recent years, marine sulfate polysaccharides (MSPs) have shown positive effects in the prevention and treatment of metabolic syndrome, and they mainly come from seaweeds and marine animals. MSPs are rich in sulfate and have stronger biological activity compared with terrestrial polysaccharides. MSPs can alleviate metabolic syndrome by regulating glucose metabolism and lipid metabolism. In addition, MSPs prevent and treat metabolic syndrome by interacting with gut microbiota. MSPs can be degraded by gut microbes to produce metabolites such as short chain fatty acids (SCFAs) and free sulfate and affect the composition of gut microbiota. The difference between MSPs and other polysaccharides lies in the sulfation pattern and sulfate content, therefore, which is very important for anti-metabolic syndrome activity of MSPs. This review summarizes the latest findings on effects of MSPs on metabolic syndrome, mechanisms of MSPs in treatment/prevention of metabolic syndrome, interactions between MSPs and gut microbiota, and the role of sulfate group and sulfation pattern in MSPs activity. However, more clinical trials are needed to confirm the potential preventive and therapeutic effects on human body. It may be a better choice to develop new functional foods containing MSPs for dietary intervention in metabolic syndrome.

Three-Dimensional Human Neural Stem Cell Models to Mimic Heparan Sulfate Proteoglycans and the Neural Niche

Heparan sulfate proteoglycans (HSPGs) are a diverse family of polysaccharides, consisting of a core protein with glycosaminoglycan (GAG) side chains attached. The heterogeneous GAG side-chain carbohydrates consist of repeating disaccharides, with each side chain possessing a specific sulfation pattern. It is the variable sulfation pattern that allows HSPGs to interact with numerous ligands including growth factors, cytokines, chemokines, morphogens, extracellular matrix (ECM) glycoproteins, collagens, enzymes, and lipases. HSPGs are classified according to their localization within an individual cell, and include the membrane bound syndecans (SDCs) and glypicans (GPCs), with perlecan, agrin, and type-XVIII collagen secreted into the ECM. The stem cell niche is defined as the environment that circumscribes stem cells when they are in their naïve state, and includes the ECM, which provides a complex contribution to various biological processes during development and throughout life. These contributions include facilitating cell adhesion, proliferation, migration, differentiation, specification, and cell survival. In contrast, HSPGs play an anticoagulant role in thrombosis through being present on the luminal surface of cells, while also playing roles in the stimulation and inhibition of angiogenesis, highlighting their varied and systemic roles in cellular control. To fully understand the complexities of cell-cell and cell–matrix interactions, three-dimensional (3D) models such as hydrogels offer researchers exciting opportunities, such as controllable 3D in vitro environments, that more readily mimic the in vivo/in situ microenvironment. This review examines our current knowledge of HSPGs in the stem cell niche, human stem cell models, and their role in the development of 3D models that mimic the in vivo neural ECM.

Heparan Sulfate Biosynthesis in Zebrafish

The biosynthesis of heparan sulfate (HS) proteoglycans occurs in the Golgi compartment of cells and will determine the sulfation pattern of HS chains, which in turn will have a large impact on the biological activity of the proteoglycans. Earlier studies in mice have demonstrated the importance of HS for embryonic development. In this review, the enzymes participating in zebrafish HS biosynthesis, along with a description of enzyme mutants available for functional studies, are presented. The consequences of the zebrafish genome duplication and maternal transcript contribution are briefly discussed as are the possibilities of CRISPR/Cas9 methodologies to use the zebrafish model system for studies of biosynthesis as well as proteoglycan biology.