Characterizing the human intestinal chondroitin sulfate glycosaminoglycan sulfation signature in inflammatory bowel disease.

The intestinal extracellular matrix (ECM) helps maintain appropriate tissue barrier function and regulate host-microbial interactions. Chondroitin sulfate- and dermatan sulfate-glycosaminoglycans (CS/DS-GAGs) are integral components of the intestinal ECM, and alterations in CS/DS-GAGs have been shown to significantly influence biological functions. Although pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD), it is unknown whether changes in the intestinal CS/DS-GAG composition are also linked to IBD in humans.

Assessing translational applicability of perineuronal net dysfunction in Alzheimer's disease across species.

In the context of aging and age-associated neurodegenerative disorders, the brain's extracellular matrix (ECM) serves as a critical regulator for neuronal health and cognitive function. Within the extracellular space, proteoglycans and their glycosaminoglycan attachments play essential roles in forming, stabilizing, and protecting neural circuits throughout neurodevelopment and adulthood. Recent studies in rodents reveal that chondroitin sulfate-glycosaminoglycan (CS-GAG) containing perineuronal nets (PNNs) exhibit both structural and compositional differences throughout the brain.

Diabetes exacerbates inflammatory bowel disease in mice with diet-induced obesity.

Background: The increased prevalence of inflammatory bowel disease (IBD) among patients with obesity and type 2 diabetes suggests a causal link between these diseases, potentially involving the effect of hyperglycemia to disrupt intestinal barrier integrity.

Aim: To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced obesity.

Methods: Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia.

Enteric Endocrinopathy: A Rare Case of Pediatric Congenital Diarrhea and Diabetes Mellitus.

Disorders of intestinal enteroendocrine cells (EEC) are a rare cause of congenital diarrhea and diabetes. The gene is essential in EEC differentiation, and mutations in this gene lead to a paucity of EEC in the intestine and pancreas, often presenting clinically as congenital diarrhea and diabetes mellitus. We present the earliest known diagnosis of -associated enteric endocrinopathy, which was identified on a neonatal diabetes genetic panel sent at 4 weeks of age.

Decoding perineuronal net glycan sulfation patterns in the Alzheimer's disease brain.

The extracellular matrix (ECM) of the brain comprises unique glycan "sulfation codes" that influence neurological function. Perineuronal nets (PNNs) are chondroitin sulfate-glycosaminoglycan (CS-GAG) containing matrices that enmesh neural networks involved in memory and cognition, and loss of PNN matrices is reported in patients with neurocognitive and neuropsychiatric disorders including Alzheimer's disease (AD). Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we show that patients with a clinical diagnosis of AD-related dementia undergo a re-coding of their PNN-associated CS-GAGs that correlates to Braak stage progression, hyperphosphorylated tau (p-tau) accumulation, and cognitive impairment.