Multilayered blow-spun vascular prostheses with luminal surfaces in Nano/Micro range: the influence on endothelial cell and platelet adhesion.

BACKGROUND: In this study, two types of polyurethane-based cylindrical multilayered grafts with internal diameters ≤ 6 mm were produced by the solution blow spinning (SBS) method. The main aim was to create layered-wall prostheses differing in their luminal surface morphology. Changing the SBS process parameters, i.e. working distance, rotational speed, volume, and concentration of the polymer solution allowed to obtain structures with the required morphologies. The first type of prostheses, termed Nano, possessed nanofibrous luminal surface, and the second type, Micro, presented morphologically diverse luminal surface, with both solid and microfibrous areas. RESULTS: The results of mechanical tests confirmed that designed prostheses had high flexibility (Young's modulus value of about 2.5 MPa) and good tensile strength (maximum axial load value of about 60 N), which meet the requirements for vascular prostheses. The influence of the luminal surface morphology on platelet adhesion and the attachment of endothelial cells was investigated. Both surfaces did not cause hemolysis in contact with blood, the percentage of platelet-occupied area for Nano and Micro surfaces was comparable to reference polytetrafluoroethylene (PTFE) surface. However, the change in morphology of surface-adhered platelets between Nano and Micro surfaces was visible, which might suggest differences in their activation level. Endothelial coverage after 1, 3, and 7 days of culture on flat samples (2D model) was higher on Nano prostheses as compared with Micro scaffolds. However, this effect was not seen in 3D culture, where cylindrical prostheses were colonized using magnetic seeding method. CONCLUSIONS: We conclude the produced scaffolds meet the material and mechanical requirements for vascular prostheses. However, changing the morphology without changing the chemical modification of the luminal surface is not sufficient to achieve the appropriate effectiveness of endothelialization in the 3D model.

Genetic Factors Associated with Response to Vitamin E Treatment in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is becoming the predominant liver disease worldwide, and vitamin E has been clinically shown to improve histological parameters in a subset of patients. In this narrative review, we investigate whether genetic factors may help to explain why some patients show histological improvements upon high-dose alpha-tocopherol (αT) treatment while others do not. In summary, we identified two factors that are associated with treatment response, including genetic variations in haptoglobin as well as fatty acid desaturase 1/2 (FADS1/FADS2). Other genetic variants such as in alpha-tocopherol transfer protein (αTTP), tocopherol associated protein (TAP), transmembrane 6 superfamily 2 (TM6SF2), cluster of differentiation 36 (CD36), and proteins involved in lipoprotein metabolism may also play a role, but have not yet been investigated in a clinical context. We propose to further validate these associations in larger populations, to then use them as a clinical tool to identify the subset of patients that will benefit the most from vitamin E supplementation.

Molecular links between allergy and cancer.

Epidemiologic studies show both positive and negative associations between allergies and cancer. Allergic diseases may protect against tumorigenesis by promoting the immune surveillance, while carcinogenesis may be promoted through inflammatory responses from allergies. Histamine receptor antagonists are the focus of recent cancer studies because of their promising beneficial effect on tumor development. Also, cytokines, particularly IL-4 or IL-33, IgE as well as allergy-related immune cells such as eosinophils can contribute to tumor growth suppression. Depending on cancer types, cancer therapy may be more beneficial when considering combinatorial immunotherapy. In this review, we give an overview on molecular links between allergies and cancer.

Resveratrol Attenuates Mast Cell Mediated Allergic Reactions: Potential for Use as a Nutraceutical in Allergic Diseases?

Allergic diseases are one of the most common health disorders affecting about 30% of the world population. Mast cells (MCs) are key effector cells of allergic reactions by releasing proinflammatory mediators including histamine, lipid mediators, and cytokines/chemokines. Natural substances like secondary plant substances such as resveratrol (RESV), which can contribute to prevention and treatment of diseases, are becoming increasingly interesting for use as nutraceuticals. In this review, the anti-inflammatory effects of RESV on MC-mediated allergic reactions in vitro and in vivo models are summarized. The studies indicate that RESV inhibits MC degranulation, synthesis of arachidonic acid metabolites, expression of cytokines and chemokines as well as activation of signal molecules involved in proinflammatory mechanisms. Also, beneficial impacts by this polyphenol are reported in randomized controlled trials with allergic rhinitis patients. Although it cannot yet be concluded that RESV can be used successfully in allergy patients in general, there are many results that indicate a possible role for RESV for use as an anti-inflammatory nutraceutical. However, strategies to favorably influence the poor bioavailability of RESV would be helpful.

The polyphenol quercetin protects from glucotoxicity depending on the aggresome in Caenorhabditis elegans.

PURPOSE: Impaired proteostasis, i.e., protein homeostasis, is considered as a consequence of high-glucose exposure and is associated with reduced survival. The previous studies demonstrated that the polyphenol quercetin can protect from glucotoxicity. The aim of the present study was to unravel the contribution of the aggresome, sequestering potentially cytotoxic aggregates and also acting as a staging center for eventual autophagic clearance from the cell. METHODS: Knockdown of the aggresome-relevant genes dnc-1 and ubql-1 was achieved in stress-sensitive mev-1 mutants of the nematode Caenorhabditis elegans by RNA interference (RNAi). Survival assay was conducted under heat stress at 37 °C, protein aggregation using ProteoStat® and chymotrypsin-like proteasomal activity according to the cleavage of a fluorogenic peptide substrate. RESULTS: Survival was reduced by knockdown of ubql-1 and even more by knockdown of dnc-1 which both were not further reduced by addition of glucose. The rescue of survival due to quercetin in glucose-exposed nematodes was completely prevented under RNAi versus ubql-1 or dnc-1. Both knockdowns caused an increase of aggregated protein and prevented the reduction of aggregated protein caused by quercetin in glucose-exposed animals. Finally, the knockdown of ubql-1 and dnc-1 blocked the increase of proteasomal activity achieved by quercetin in glucose-treated nematodes. CONCLUSIONS: The study provides evidence that quercetin protects C. elegans from glucotoxicity through the activation of the aggresome, thereby, quercetin prevents the aggregation and functional loss of proteins, which is typically caused by enhanced glucose concentrations.

Inhibition of mitophagy decreases survival of Caenorhabditis elegans by increasing protein aggregation.

Autophagy of mitochondria, i.e., mitophagy, plays a crucial role in coping with stressors in the aging process, metabolic disturbances, and neurological disorders. Impairments of the process might consequently lead to enhanced accumulation of aged and aggregated proteins and reduced cellular integrity in response to stress. In the present study, we used the stress-sensitive mutant mev-1 of Caenorhabditis elegans to assess the effects of the knockdown of mitophagy relevant genes on survival under heat stress, the amount of autophagosomes, and on protein aggregation. RNA interference for dct-1, drp-1, eat-3, fis-1, fzo1, glb-1, pink-1, and pgam-5 all resulted in a significant reduction of survival time at 37 °C. These effects were associated with a decrease in autophagosomal flux of proteins, as indicated by increased accumulation of GFP-tagged SQST-1, and a reduced amount of lysosomes demonstrating that autophagy was hampered. Moreover, the gene knockdowns led to increased levels of reactive oxygen species in mitochondria and an enhanced protein aggregation. In conclusion, our studies show that mitophagy is of central importance to keep mitochondria functional in order to prevent production of excess reactive oxygen species and protein aggregation and finally a reduction of survival under heat stress.

Cinnamon reduces inflammatory response in intestinal fibroblasts in vitro and in colitis in vivo leading to decreased fibrosis.

SCOPE: Intestinal fibrosis, a complication of inflammatory bowel disease, is currently being addressed by surgery alone, with no adequate alternative therapy available for patients. We propose that anti-inflammatory plant substances like cinnamon extract (CE) or its main compound cinnamaldeyde (CA) could aid in therapy. We recently found CE reducing inflammation in murine colitis. Here, we analyzed effects of CE on fibrosis in IL-10-/- colitis. METHODS AND RESULTS: IL-10-/- and wild-type (WT) mice were orally treated with/without vehicle or CE. Colonic tissue was analyzed for collagen deposition and expression of matrix metalloproteinases (MMPs). Influence of CE or CA on expression and release of cytokines, and phosphorylation of IκB in LPS-activated fibroblasts was assessed. Fibrosis score and mRNA expression of MMPs were down-regulated in colonic tissue of CE-treated IL-10-/- mice. Fibroblasts treated with CE or CA showed reduced expression and release of IL-6, KC/C-X-C motif ligand (CXCL) 8, and C-C motif ligand (CCL) 2 in response to LPS-treatment. CE and CA appear to act via reducing phosphorylation of IκB. CONCLUSIONS: Cinnamon decreases fibrotic symptoms and markers in murine colitis, and expression of inflammatory and fibrotic markers in hiFB. Thus, CE and CA could be potential anti-fibrotic agents in chronic colitis.