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21.
Elisa Boschetti Leonardo Caporali Roberto DAngelo Carolina Malagelada Anna Accarino Maria Teresa Dotti Roberta Costa Giovanna Cenacchi Loris Pironi Rita Rinaldi Vincenzo Stanghellini Stefano Ratti Lucia Manzoli Valerio Carelli Roberto De Giorgio 《International journal of molecular sciences》2022,23(15)
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. 相似文献
22.
Roberta J. Ward David T. Dexter Robert R. Crichton 《International journal of molecular sciences》2022,23(13)
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. 相似文献
23.
Ian Stoppa Casimiro Luca Gigliotti Nausicaa Clemente Deepika Pantham Chiara Dianzani Chiara Monge Chiara Puricelli Roberta Rolla Salvatore Sutti Filippo Ren Renzo Boldorini Elena Boggio Umberto Dianzani 《International journal of molecular sciences》2022,23(13)
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. 相似文献
24.
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. 相似文献
25.
Roberta Gonnella Roberta Zarrella Roberta Santarelli Concetta Anna Germano Maria Saveria Gilardini Montani Mara Cirone 《International journal of molecular sciences》2022,23(12)
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. 相似文献
26.
Ornaghi Heitor L. Almeida José Humberto S. Monticeli Francisco M. Neves Roberta M. Cioffi Maria Odila H. 《Mechanics of Time-Dependent Materials》2021,25(4):601-615
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.... 相似文献
27.
28.
Roberta Roesler Luciana G. Malta Luciana C. Carrasco Gláucia Pastore 《Journal of food science》2006,71(2):C102-C107
Annona crassiflora, known commonly as araticum, is an exotic tropical fruit consumed mainly by native people of the Brazilian Cerrado (2nd biggest biome of Brazil). In this study, pulp, seed, and peel of slight ripe and overripe fruits were extracted using ethanol and water. The extracts showed high content of total phenols and were screening for their potential as antioxidants using the in vitro model 1,1‐ dipheniyl‐2‐picryl hydrazyl (DPPH). The ethanol extracts of peel and seeds showed IC50 of 48.82 μg/mL and 31.14 μg/mL, respectively, for the slightly ripe fruits. As the ethanolic fractions of araticum showed the highest antioxidant activity, they were selected for testing of its effect on lipid peroxidation. The ethanolic extracts of slightly ripe fruits showed IC50 of 4.44 μg/mL, 1.72 μg/mL, and 8.62 μg/mL for the peel, seed, and pulp, respectively. This is the 1st report on the antioxidant properties of the extracts of araticum. Owing to these properties, the studies can be further extending to exploit them for their possible application as natural antioxidant for cosmetic, supplements, and functional ingredients for food products. 相似文献
29.
The effective thermal diffusivity of foodstuffs was estimated from time-temperature histories in the geometric center of samples exposed to heating and cooling processes.Transfer functions methodology was used as an alternative method to estimate the thermal diffusivity assuming that conduction was the main heat transfer mechanism. The samples were characterized as delayed first-order systems with unit gain, dead time (L) and time constant (τ).The results were compared with those obtained from the fh value and with results reported in the literature. 相似文献
30.
Jessica Maiuolo Francesca Oppedisano Cristina Carresi Micaela Gliozzi Vincenzo Musolino Roberta Macrì Federica Scarano Annarita Coppoletta Antonio Cardamone Francesca Bosco Rocco Mollace Carolina Muscoli Ernesto Palma Vincenzo Mollace 《International journal of molecular sciences》2022,23(24)
Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2. 相似文献