Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.     

Iron,Neuroinflammation and Neurodegeneration

Disturbance of the brain homeostasis, either directly via the formation of abnormal proteins or cerebral hypo-perfusion, or indirectly via peripheral inflammation, will activate microglia to synthesise a variety of pro-inflammatory agents which may lead to inflammation and cell death. The pro-inflammatory cytokines will induce changes in the iron proteins responsible for maintaining iron homeostasis, such that increased amounts of iron will be deposited in cells in the brain. The generation of reactive oxygen and nitrogen species, which is directly involved in the inflammatory process, can significantly affect iron metabolism via their interaction with iron-regulatory proteins (IRPs). This underlies the importance of ensuring that iron is maintained in a form that can be kept under control; hence, the elegant mechanisms which have become increasingly well understood for regulating iron homeostasis. Therapeutic approaches to minimise the toxicity of iron include N-acetyl cysteine, non-steroidal anti-inflammatory compounds and iron chelation.     

ICOSL Stimulation by ICOS-Fc Accelerates Cutaneous Wound Healing In Vivo

Background: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair. Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing. Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS^−/− and ICOSL^−/− knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice. Results: We show that, in wild type mice, treatment with ICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGF expression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; and increases the number of M2 vs. M1 macrophages. Fittingly, ICOS-Fc enhanced M2 macrophage migration, while it hampered that of M1 macrophages. ICOS^−/− and ICOSL^−/− KO, and NSG mice showed delayed wound healing, and treatment with ICOS-Fc improved wound closure in ICOS^−/− and NSG mice. Conclusion: These data show that the ICOS/ICOSL network cooperates in tissue repair, and that triggering of ICOSL by ICOS-Fc improves cutaneous wound healing by increasing angiogenesis and recruitment of reparative macrophages.     

Sugar and dietary fibre composition influence, by different hormonal response, the satiating capacity of a fruit-based and a β-glucan-enriched beverage

In this study the satiating capacity of three beverages containing 3 g barley β-glucan, or 2.5 g dietary fibre (DF) from fruit, or without DF (control) was evaluated. Fourteen healthy volunteers were randomized to have isocaloric breakfasts including one of the beverages in different occasions. Appetite ratings over 3 h post-breakfast and energy intakes at ad libitum lunch, blood glucose, insulin, ghrelin, PYY, GLP-1, GIP, and PP concentrations, and 24 h food intake, were assessed. The bevaerages containing DF increased fullness and satiety over 3 h post-breakfast, but only the β-glucan-enriched vs. the control significantly reduced energy intakes by 18% at lunch and 40% over the rest of the day. Blood ghrelin and PP responses were differently modulated by beverages. The fruit-based and the β-glucan-enriched beverage suppressed by 8.9% and 8.1% ghrelin response over the 3 h and the first hour post-breakfast, respectively, while only the latter increased PP response by 34.6%, compared to the control. A sucrose-sweetened beverage providing 3 g barley β-glucans can control food intake by modulating PP response and it can even reduce 24 h energy intake. Ghrelin suppression by fruit dietary fibre and mixed sugars was not sufficient to significantly reduce food intake compared to the control.     

Mechanisms of Sensitivity and Resistance of Primary Effusion Lymphoma to Dimethyl Fumarate (DMF)

PEL is a rare B cell lymphoma associated with KSHV that mainly arises in immune-deficient individuals. The search for new drugs to treat this cancer is still ongoing given its aggressiveness and the poor response to chemotherapies. In this study, we found that DMF, a drug known for its anti-inflammatory properties which is registered for the treatment of psoriasis and relapsing–remitting MS, could be a promising therapeutic strategy against PEL. Indeed, although some mechanisms of resistance were induced, DMF activated NRF2, reduced ROS and inhibited the phosphorylation of STAT3 and the release of the pro-inflammatory and immune suppressive cytokines IL-6 and IL-10, which are known to sustain PEL survival. Interestingly, we observed that DMF displayed a stronger cytotoxic effect against fresh PEL cells in comparison to PEL cell lines, due to the activation of ERK1/2 and autophagy in the latter cells. This finding further encourages the possibility of using DMF for the treatment of PEL.     

Time-temperature behavior of carbon/epoxy laminates under creep loading

Mechanics of Time-Dependent Materials - The time-temperature creep behavior of advanced composite laminates is herein determined through a comprehensive set of experiments and analytical modeling....     

Comparing the impact of bentonite addition for both must clarification and wine fining on the chemical profile of wine from Chambave Muscat grapes

The impact of bentonite fining is generally studied on final wines, and few studies have evaluated it throughout the winemaking process. This work studied the fate of proteins and terpenols, the main targets of bentonite addition, during the processing of Chambave Muscat aromatic grapes. The experimental trials were performed in two vintages (2006 and 2007) and included the following processes: bentonite addition to must only (100 g hL^?1 in both vintages), fining of wine only (100 g hL^?1 in both vintages), double bentonite treatment on must and wine (200 and 150 g hL^?1 in 2006 and in 2007, respectively) and no treatment (control). The results demonstrated that the treatment allowing the best removal of protein was the addition of bentonite to must only. Moreover, a lower removal of free terpenols was observed in samples from double treatment compared with wines fined with bentonite only after alcoholic fermentation.     

Synthesis and characterization of nanocomposites of thermoplastic polyurethane with both graphene and graphene nanoribbon fillers

Thermoplastic polyurethane (TPU) nanocomposites containing graphene and graphene nanoribbons were obtained by polymerizing 1,4-butanediol with two diisocyanates (namely, 1,6-hexane diisocyanate or isophorone diisocyanate), in which the nanofillers were previously dispersed. Raman spectroscopy and Transmission Electron Microscopy demonstrated the formation of few-layer graphene and graphene nanoribbons dispersed in the monomers. At variance to the methods commonly reported in literature, that used in this work consists of the direct exfoliation of graphite without any chemical manipulation. Apart from the obvious cost and ease advantages, the so-obtained graphene does not contain any carboxy or alkoxy groups formed during the exfoliation process, which, at variance, are typically present in the most commonly reported methods. This finding paves the way toward the large-scale production of graphene and its nanoribbons, which are considered even more interesting than graphene itself for many potential applications. The obtained nanocomposites show a peculiar thermal and rheological behavior due to the presence of the nanofillers and to their reinforcing or plasticizing effect exerted on the TPU matrices.     

Perfluoropolyether polymers by UV curing: design,synthesis and characterization

Perfluoropolyether (PFPE) structures can be functionalized with acrylic groups using appropriate hydrogenated acrylic monomers: the macromers obtained are highly reactive under UV irradiation, and fluorinated polymers can be obtained. In the first part of this work is described the synthesis of new PFPE (meth)acrylic oligomers by extending OH‐terminated fluorinated chains with urethane groups and reactive acrylic functions. The photopolymerization reaction of each product is then reported followed by the characterisation of the main thermal, mechanical and surface properties of UV‐cured coatings. The polymers have good thermal resistance and fair mechanical and chemical resistance. More interestingly they show very low refractive index and low surface tension. For these latter properties the products can be advantageously used in highly demanding applications such as photonic devices and nano‐patterning. Copyright © 2011 Society of Chemical Industry     

GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract

Nutritional research is currently entering the field of personalized nutrition, to a large extent driven by major technological breakthroughs in analytical sciences and biocomputing. An efficient launching of the personalized approach depends on the ability of researchers to comprehensively monitor and characterize interindividual variability in the activity of the human gastrointestinal tract. This information is currently not available in such a form. This review therefore aims at identifying and discussing published data, providing evidence on interindividual variability in the processing of the major nutrients, i.e., protein, fat, carbohydrates, vitamins, and minerals, along the gastrointestinal tract, including oral processing, intestinal digestion, and absorption. Although interindividual variability is not a primary endpoint of most studies identified, a significant number of publications provides a wealth of information on this topic for each category of nutrients. This knowledge remains fragmented, however, and understanding the clinical relevance of most of the interindividual responses to food ingestion described in this review remains unclear. In that regard, this review has identified a gap and sets the base for future research addressing the issue of the interindividual variability in the response of the human organism to the ingestion of foods.