Chapter One - Glycan-based biomarkers for diagnosis of cancers and other diseases: Past, present, and future
* Glycans are essential biomolecules in regulating human physiology and pathology ranging from signal transduction to microbial infections. Developing complex human diseases, such as cancer, diabetes, and cardiovascular diseases, are a combination of genetic and environmental factors. Genetics dominates embryonic development and the passing of genes to the next generation whereas the information in glycans reflects the impact of internal and external environmental factors, such as diseases, lifestyle, and social factors, on a person's health and disease. The reason behind this is that glycans are not directly encoded in a genetic template. Instead, they are assembled dynamically by hundreds of enzymes organized in more than 10 complex biosynthetic pathways. Any environmental changes affecting enzymatic activities or the availability of high-energy monosaccharide donors in a specific location will disturb the final structure of glycans. The glycan structure-dependent biological activities subsequently enable or disable gene expressions, which partially explain that it is difficult to pinpoint specific genetic defects to aging-associated diseases. Glycan-based biomarkers are currently used for diagnosis of diabetes, cancers, and other complex diseases. We will recapitulate the discovery of glucose, glycated proteins, glycan-, and glycoprotein-based biomarkers followed by summarizing clinically used glycan/glycoprotein-based biomarkers. The potential serum/plasma-derived N- and O-linked glycans as biomarkers will also be discussed.
Chapter Two - Desialylation in physiological and pathological processes: New target for diagnostic and therapeutic development
- Desialylation is a pivotal part of sialic acid metabolism, which initiates the catabolism of glycans by removing the terminal sialic acid residues on glycans, thereby modulating the structure and functions of glycans, glycoproteins, or glycolipids. The functions of sialic acids have been well recognized, whereas the function of desialylation process is underappreciated or largely ignored. However, accumulating evidence demonstrates that desialylation plays an important role in a variety of physiological and pathological processes. This chapter summarizes the current knowledge pertaining to desialylation in a variety of physiological and pathological processes, with a focus on the underlying molecular mechanisms. The potential of targeting desialylation process for diagnostic and therapeutic development is also discussed.
T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies. 2013
IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell–dependent (TD) protein antigens and proinflammatory costimulation.