Psychological stress frequently causes intestinal dysfunction and perturbation of gut microbiota. Chronic social defeat stress (CSDS) is a widely used rodent model of human mood disorders and depression. We previously showed that CSDS induced alterations of cecal and fecal microbiota which was associated with suppression of gene involved in immune response in the distal intestine of C57BL/6J mice. We introduced lection microarray analysis to determine glycation profile in intestinal tract. We found that CSDS significantly reduced the α1,2-fucose in distal small intestinal mucosa, but not with mucosa from proximal small intestine and colon. The α1,2-fucosylation is a major glycosylation detected on the surface of intestinal epithelial cells and secreted proteins and is known as a critical communication factor between host and intestinal commensal bacteria. CSDS may alter the gut microbiota by down-regulating α1,2-fucosylated glycan in intestinal epithelium.

Mast cells are characterized by large, intracellular secretory granules that accumulate large amounts of glycosaminoglycans, heparin and highly sulfated chondroitin depending on the mast cell type. The granular complex, a kind of protein-polyelectrolyte complex, is composed of these glycosaminoglycans, proteases, biogenic amines, and other mediator molecules. Recent findings suggest that, after the granular complex is released, it may undergo various fates, i.e., components of the complex are either transferred into the blood flow; or they may be retained in the connective tissues near the mast cells; or ingested by epithelial, interstitial or immune cells to trigger the adaptive immune responses or to maintain tissue homeostasis; or they may be transferred to the draining lymph nodes through lymph flow. The choice of fate is greatly influenced by carbohydrates in the granular complex, especially by processed heparin via heparanase-mediated cleavage. The present review focuses on recent developments on the formation of granular complex, especially on the processing of the granular heparin, the fates and roles of the complex after being released, its potential role as an immunomodulator, and a recent attempt to mimic the complex as an artificial delivery system. The involvement of carbohydrates in these functions is also discussed.

Tumor-associated carbohydrate antigens (TACAs) are expressed in a majority of carcinoma-type malignancies, but not in normal tissue, and they play an important role in driving oncogenic transformation. A highly relevant TACA is the Tn antigen, which is ubiquitously expressed in many human carcinomas, and which likely represents a promising diagnostic biomarker and candidate for molecular-targeted therapy. Over the last several decades, a myriad of immunotherapies and vaccination therapies against the Tn antigen have been developed; however, these have not shown sufficient anti-tumor efficacy. This review presents a novel methodology for generating a defined anti-Tn monoclonal antibody (mAb) and presents the latest cancer immunotherapies with anti-Tn mAb (targeted therapy, CAR-T cell therapy, and antibody-drug conjugates) within the hostile tumor microenvironment.

Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix and is also seen in the tumor microenvironment. HA-rich matrix is widely observed in tumor tissues and is strongly related to the malignancy potential. HA production was closely associated with the regulation of cancer stem cells (CSCs). CSCs are a stem cell-like subpopulation of cancer cells and are considered to be responsible for tumor initiation, growth, and recurrence. Recent findings suggested that the regulation of CSC properties strongly depends on cancer metabolism. HA production markedly induces the reprogramming of glucose metabolism, including the hexosamine biosynthetic pathway (HBP). The end product of HBP is a nucleotide sugar UDP-N-acetylglucosamine (UDP-GlcNAc) which is utilized as a substrate for HA and glycosaminoglycans synthesis as well as for O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins. Protein O-GlcNAcylation is another essential factor for the regulation of CSC properties. In this minireview, I outline the significance of HA production and O-GlcNAcylation in CSC regulation.

Psychological stress frequently causes intestinal dysfunction and perturbation of gut microbiota. Chronic social defeat stress (CSDS) is a widely used rodent model of human mood disorders and depression. We previously showed that CSDS induced alterations of cecal and fecal microbiota which was associated with suppression of gene involved in immune response in the distal intestine of C57BL/6J mice. We introduced lection microarray analysis to determine glycation profile in intestinal tract. We found that CSDS significantly reduced the α1,2-fucose in distal small intestinal mucosa, but not with mucosa from proximal small intestine and colon. The α1,2-fucosylation is a major glycosylation detected on the surface of intestinal epithelial cells and secreted proteins and is known as a critical communication factor between host and intestinal commensal bacteria. CSDS may alter the gut microbiota by down-regulating α1,2-fucosylated glycan in intestinal epithelium.

Mast cells are characterized by large, intracellular secretory granules that accumulate large amounts of glycosaminoglycans, heparin and highly sulfated chondroitin depending on the mast cell type. The granular complex, a kind of protein-polyelectrolyte complex, is composed of these glycosaminoglycans, proteases, biogenic amines, and other mediator molecules. Recent findings suggest that, after the granular complex is released, it may undergo various fates, i.e., components of the complex are either transferred into the blood flow; or they may be retained in the connective tissues near the mast cells; or ingested by epithelial, interstitial or immune cells to trigger the adaptive immune responses or to maintain tissue homeostasis; or they may be transferred to the draining lymph nodes through lymph flow. The choice of fate is greatly influenced by carbohydrates in the granular complex, especially by processed heparin via heparanase-mediated cleavage. The present review focuses on recent developments on the formation of granular complex, especially on the processing of the granular heparin, the fates and roles of the complex after being released, its potential role as an immunomodulator, and a recent attempt to mimic the complex as an artificial delivery system. The involvement of carbohydrates in these functions is also discussed.

Tumor-associated carbohydrate antigens (TACAs) are expressed in a majority of carcinoma-type malignancies, but not in normal tissue, and they play an important role in driving oncogenic transformation. A highly relevant TACA is the Tn antigen, which is ubiquitously expressed in many human carcinomas, and which likely represents a promising diagnostic biomarker and candidate for molecular-targeted therapy. Over the last several decades, a myriad of immunotherapies and vaccination therapies against the Tn antigen have been developed; however, these have not shown sufficient anti-tumor efficacy. This review presents a novel methodology for generating a defined anti-Tn monoclonal antibody (mAb) and presents the latest cancer immunotherapies with anti-Tn mAb (targeted therapy, CAR-T cell therapy, and antibody-drug conjugates) within the hostile tumor microenvironment.

Hyaluronan (HA) is a major glycosaminoglycan in the extracellular matrix and is also seen in the tumor microenvironment. HA-rich matrix is widely observed in tumor tissues and is strongly related to the malignancy potential. HA production was closely associated with the regulation of cancer stem cells (CSCs). CSCs are a stem cell-like subpopulation of cancer cells and are considered to be responsible for tumor initiation, growth, and recurrence. Recent findings suggested that the regulation of CSC properties strongly depends on cancer metabolism. HA production markedly induces the reprogramming of glucose metabolism, including the hexosamine biosynthetic pathway (HBP). The end product of HBP is a nucleotide sugar UDP-N-acetylglucosamine (UDP-GlcNAc) which is utilized as a substrate for HA and glycosaminoglycans synthesis as well as for O-linked N-acetylglucosamine (O-GlcNAc) modification of proteins. Protein O-GlcNAcylation is another essential factor for the regulation of CSC properties. In this minireview, I outline the significance of HA production and O-GlcNAcylation in CSC regulation.