Acceptive Immunity: The Role of Fucosylated Glycans in Human Host–Microbiome Interactions

The growth in the number of chronic non-communicable diseases in the second half of the past century and in the first two decades of the new century is largely due to the disruption of the relationship between the human body and its symbiotic microbiota, and not pathogens. The interaction of the human immune system with symbionts is not accompanied by inflammation, but is a physiological norm. This is achieved via microbiota control by the immune system through a complex balance of pro-inflammatory and suppressive responses, and only a disturbance of this balance can trigger pathophysiological mechanisms. This review discusses the establishment of homeostatic relationships during immune system development and intestinal bacterial colonization through the interaction of milk glycans, mucins, and secretory immunoglobulins. In particular, the role of fucose and fucosylated glycans in the mechanism of interactions between host epithelial and immune cells is discussed.     

Role of ABCA7 in Human Health and in Alzheimer’s Disease

Several studies, including genome wide association studies (GWAS), have strongly suggested a central role for the ATP-binding cassette transporter subfamily A member 7 (ABCA7) in Alzheimer’s disease (AD). This ABC transporter is now considered as an important genetic determinant for late onset Alzheimer disease (LOAD) by regulating several molecular processes such as cholesterol metabolism and amyloid processing and clearance. In this review we shed light on these new functions and their cross-talk, explaining its implication in brain functioning, and therefore in AD onset and development.     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

TGFβ-1 Induced Cross-Linking of the Extracellular Matrix of Primary Human Dermal Fibroblasts

Excessive cross-linking is a major factor in the resistance to the remodelling of the extracellular matrix (ECM) during fibrotic progression. The role of TGFβ signalling in impairing ECM remodelling has been demonstrated in various fibrotic models. We hypothesised that increased ECM cross-linking by TGFβ contributes to skin fibrosis in Systemic Sclerosis (SSc). Proteomics was used to identify cross-linking enzymes in the ECM of primary human dermal fibroblasts, and to compare their levels following treatment with TGFβ-1. A significant upregulation and enrichment of lysyl-oxidase-like 1, 2 and 4 and transglutaminase 2 were found. Western blotting confirmed the upregulation of lysyl hydroxylase 2 in the ECM. Increased transglutaminase activity in TGFβ-1 treated ECM was revealed from a cell-based assay. We employed a mass spectrometry-based method to identify alterations in the ECM cross-linking pattern caused by TGFβ-1. Cross-linking sites were identified in collagens I and V, fibrinogen and fibronectin. One cross-linking site in fibrinogen alpha was found only in TGFβ-treated samples. In conclusion, we have mapped novel cross-links between ECM proteins and demonstrated that activation of TGFβ signalling in cultured dermal fibroblasts upregulates multiple cross-linking enzymes in the ECM.