1,720,971 research outputs found
Phloretin, a nutritional lipid modulator that suppresses neuroinflammation and promotes remyelination
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Phloretin, a nutritional lipid modulator that suppresses neuroinflammation and promotes remyelination
No full textnot availabl
Inhibition of carcinoma cell growth and promotion of inflammatory properties of macrophages by Silene vulgaris (Moench) Garcke subsp. macrocarpa ethanolic extract
No full textIntroduction: Silene vulgaris (Moench) Garcke subsp. macrocarpa is a wild herbaceous plant known for its nutraceutical properties, and use in folk medicine. This study investigates the anti-cancer properties of S. vulgaris extracts.Methods: The leaves and roots of S. vulgaris were extracted by the Soxhlet extractor with ethanol, their phenolic content was determined by RTHPLC-DAD. By using squamous cell carcinoma cells and bone marrow-derived macrophages, we defined the ability of S. vulgaris extracts to kill tumour cells and suppress the tumour -promoting phenotype of macrophages.Results: A total of 21 phenolic compounds were detected, among which dihydrochalcones phloredzin and phloretin were most abundant, encompassing about 70% of the whole polyphenolic content in leaf extract. In the root extract, 45.75% of the polyphenolic compounds are flavonoids (epicatechin, epicatechin gallate, and avicularin). The leaf and the root extracts exhibit cytotoxic activity against A431 tumour cells. The highest cytotoxic activity was observed by root extract (IC50 =102.65 vs 173.26 mu g /mL). Interestingly, this extract also most potently induces the anti-tumour properties of BMDMs by decreasing the expression of genes typically expressed by tumour-associated macrophages, such as ARG1, CD163, CD209, TREM2, FIZZ1, MMP9, and CCL17, and suppressing the expression of the angiogenic factors EGF and VEGF. In contrast, the leaf extract promotes the expression of pro-inflammatory mediators IL-6, TNF-alpha, and iNOS in macrophages.Conclusions: The results highlight the anti-tumour properties of S. vulgaris leaves and roots, which underscore its effectiveness in traditional medicine and may open new avenues for its use in therapeutic anti-cancer applications.This work was carried out within the program of the institutional cooperation (CUI-UMI-UHasselt), and financially supported by VLIRUOS. The authors gratefully thank Prof. Jalal el Oualidi for plant identification
Phloretin enhances remyelination by stimulating OPC differentiation
No full textthe number of activated and quiescent NSCs, indicating that ET-1 signaling is required for maintenance of NSCs in the healthy adult mouse. Following focal demyelination of the corpus callosum, SVZ NSCs upregulated expression of ET-1. Ablation of ET-1 reduced the percentages of proliferating NSCs and proliferating OPCs in the SVZ, suggesting that ET-1 plays a critical role in the SVZ proliferative response to injury. RNAseq of cultured primary NSCs and OPCs treated with ET-1 identified genes involved in stem cell maintenance, including Notch signaling, and OPC migration. Lastly, we confirmed that ET-1 and EDNRB expression are conserved in the adult human SVZ, indicating that this pathway may be a potential target for promoting SVZ-mediated cellular repair. Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequency fail in these disorders is poorly understood, however, there is now strong evidence that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries reduces neuroinflammation by driving macrophages towards an anti-inflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animals models. However, improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred autonomously from alterations in microglia function and inflammation. Mechanistically, phloretin activated the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma PPARy, thereby promoting the maturation of OPC. Altogether, our findings indicate that phloretin has pro-regenerative properties in CNS disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions
Targeting lipophagy in macrophages improves repair in multiple sclerosis
No full textFoamy macrophages containing abundant intracellular myelin remnants are an important pathological hallmark of multiple sclerosis. Reducing the intracellular lipid burden in foamy macrophages is considered a promising therapeutic strategy to induce a phagocyte phenotype that promotes central nervous system repair. Recent research from our group showed that sustained intracellular accumulation of myelin-derived lipids skews these phagocytes toward a disease-promoting and more inflammatory phenotype. Our data now demonstrate that disturbed lipophagy, a selective form of autophagy that helps with the degradation of lipid droplets, contributes to the induction of this phenotype. Stimulating autophagy using the natural disaccharide trehalose reduced the lipid load and inflammatory phenotype of myelin-laden macrophages. Importantly, trehalose was able to boost remyelination in the ex vivo brain slice model and the in vivo cuprizone-induced demyelination model. In summary, our results provide a molecular rationale for impaired metabolism of myelin-derived lipids in macrophages, and identify lipophagy induction as a promising treatment strategy to promote remyelination.The work has been supported by the Flemish Fund for ScientificResearch (FWO Vlaanderen; 1141920N, 12U7718N and 1502120N), theBelgian Charcot Foundation (Fondation Charcot 2020-0004), and thespecial research fund UHasselt (BOF
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
ApoA-I mimetic peptide 5A boosts remyelination by promoting myelin debris clearance
No full textArticle The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris Graphical abstract Highlights d ApoA-I mimetic peptide 5A enhances remyelination in a phagocyte-dependent manner d In addition to promoting lipid efflux, peptide 5A enhances clearance of myelin debris d Peptide 5A drives clearance of myelin debris via the fatty acid translocase CD3
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