المؤلفون: Estelle Guillot, Anna Lemay, Manon Allouche, Sara Vitorino Silva, Hanna Coppola, Florence Sabatier, Françoise Dignat-George, Alexandre Sarre, Anne-Christine Peyter, Stéphanie Simoncini, Catherine Yzydorczyk

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 11, p 9747 (2023)

مصطلحات موضوعية: intrauterine growth restriction, developmental programming, endothelial colony-forming cells, oxidative stress, stress-induced premature senescence, resveratrol, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Individuals born after intrauterine growth restriction (IUGR) are at risk of developing cardiovascular diseases (CVDs). Endothelial dysfunction plays a role in the pathogenesis of CVDs; and endothelial colony-forming cells (ECFCs) have been identified as key factors in endothelial repair. In a rat model of IUGR induced by a maternal low-protein diet, we observed an altered functionality of ECFCs in 6-month-old males, which was associated with arterial hypertension related to oxidative stress and stress-induced premature senescence (SIPS). Resveratrol (R), a polyphenol compound, was found to improve cardiovascular function. In this study, we investigated whether resveratrol could reverse ECFC dysfunctions in the IUGR group. ECFCs were isolated from IUGR and control (CTRL) males and were treated with R (1 μM) or dimethylsulfoxide (DMSO) for 48 h. In the IUGR-ECFCs, R increased proliferation (5′-bromo-2′-deoxyuridine (BrdU) incorporation, p < 0.001) and improved capillary-like outgrowth sprout formation (in Matrigel), nitric oxide (NO) production (fluorescent dye, p < 0.01), and endothelial nitric oxide synthase (eNOS) expression (immunofluorescence, p < 0.001). In addition, R decreased oxidative stress with reduced superoxide anion production (fluorescent dye, p < 0.001); increased Cu/Zn superoxide dismutase expression (Western blot, p < 0.05); and reversed SIPS with decreased beta-galactosidase activity (p < 0.001), and decreased p16ink4a (p < 0.05) and increased Sirtuin-1 (p < 0.05) expressions (Western blot). No effects of R were observed in the CTRL-ECFCs. These results suggest that R reverses long-term ECFC dysfunctions related to IUGR.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/11/9747Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/2866b67c094849b7afe38233ae367330Test

المؤلفون: Anouck Coulange Zavarro, Mélanie Velier, Robin Arcani, Maxime Abellan Lopez, Stéphanie Simoncini, Audrey Benyamine, Quentin Gomes De Pinho, Raphael Coatmeur, Jiucun Wang, Jingjing Xia, Ludovica Barone, Dominique Casanova, Françoise Dignat-George, Florence Sabatier, Brigitte Granel, Jérémy Magalon, Aurélie Daumas

المصدر: Biomedicines, Vol 11, Iss 2, p 348 (2023)

مصطلحات موضوعية: systemic sclerosis, adipose tissue, adipose-tissue-derived cell therapy, fat grafting, stromal vascular fraction, adipose-derived stromal/stem cell, Biology (General), QH301-705.5

الوصف: Adipose tissue is recognized as a valuable source of cells with angiogenic, immunomodulatory, reparative and antifibrotic properties and emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. The use of adipose-tissue-based therapy is expanding in autoimmune diseases, particularly in Systemic Sclerosis (SSc), a disease in which hands and face are severely affected, leading to disability and a decrease in quality of life. Combining the advantage of an abundant supply of fat tissue and a high abundance of stem/stromal cells, fat grafting and adipose tissue-derived cell-based therapies are attractive therapeutic options in SSc. This review aims to synthesize the evidence to determine the effects of the use of these biological products for face and hands treatment in the context of SSc. This highlights several points: the need to use relevant effectiveness criteria taking into account the clinical heterogeneity of SSc in order to facilitate assessment and comparison of innovative therapies; second, it reveals some impacts of the disease on fat-grafting success; third, an important heterogeneity was noticed regarding the manufacturing of the adipose-derived products and lastly, it shows a lack of robust evidence from controlled trials comparing adipose-derived products with standard care.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2227-9059/11/2/348Test; https://doaj.org/toc/2227-9059Test

الوصول الحر: https://doaj.org/article/a236661e4c394a7ab6396b0ef07745e4Test

المؤلفون: Stéphanie Simoncini, Simon Toupance, Carlos Labat, Sylvie Gautier, Chloé Dumoulin, Laurent Arnaud, Maria G. Stathopoulou, Sophie Visvikis-Siest, Pascal M. Rossi, Athanase Benetos, Françoise Dignat-George, Florence Sabatier

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 16, p 8969 (2022)

مصطلحات موضوعية: endothelial progenitor cells, atherosclerosis, senescence, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Endothelial dysfunction is a key factor in atherosclerosis. However, the link between endothelial repair and severity of atherosclerotic cardiovascular disease (ASCVD) is unclear. This study investigates the relationship between ASCVD, markers of inflammation, and circulating endothelial progenitor cells, namely hematopoietic cells with paracrine angiogenic activity and endothelial colony forming cells (ECFC). Two hundred and forty-three subjects from the TELARTA study were classified according to the presence of clinical atherosclerotic disease. ASCVD severity was assessed by the number of involved vascular territories. Flow cytometry was used to numerate circulating progenitor cells (PC) expressing CD34 and those co-expressing CD45, CD34, and KDR. Peripheral blood mononuclear cells ex vivo culture methods were used to determine ECFC and Colony Forming Unit- endothelial cells (CFU-EC). The ECFC subpopulation was analyzed for proliferation, senescence, and vasculogenic properties. Plasma levels of IL-6 and VEGF-A were measured using Cytokine Array. Despite an increased number of circulating precursors in ASCVD patients, ASCVD impaired the colony forming capacity and the angiogenic properties of ECFC in a severity-dependent manner. Alteration of ECFC was associated with increased senescent phenotype and IL-6 levels. Our study demonstrates a decrease in ECFC repair capacity according to ASCVD severity in an inflammatory and senescence-associated secretory phenotype context.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/16/8969Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/a213f1552d95450ca1683c45d4e246a6Test

المؤلفون: Stephanie Simoncini, Hanna Coppola, Angela Rocca, Isaline Bachmann, Estelle Guillot, Leila Zippo, Françoise Dignat-George, Florence Sabatier, Romain Bedel, Anne Wilson, Nathalie Rosenblatt-Velin, Jean-Baptiste Armengaud, Steeve Menétrey, Anne-Christine Peyter, Umberto Simeoni, Catherine Yzydorczyk

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 18, p 10159 (2021)

مصطلحات موضوعية: intrauterine growth restriction, developmental programming, arterial hypertension, endothelial colony-forming cells, oxidative stress, stress-induced premature senescence, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/18/10159Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/3f5ff10b6558492eabb427a42b272a33Test

المؤلفون: Stéphanie Simon, Abdel Aissat, Fanny Degrugillier, Benjamin Simonneau, Pascale Fanen, André-Patrick Arrigo

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 8, p 4252 (2021)

مصطلحات موضوعية: cystic fibrosis, CFTR, sHsps, HspB1, HspB4, HspB5, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Human small heat shock proteins are molecular chaperones that regulate fundamental cellular processes in normal and pathological cells. Here, we have reviewed the role played by HspB1, HspB4 and HspB5 in the context of Cystic Fibrosis (CF), a severe monogenic autosomal recessive disease linked to mutations in Cystic Fibrosis Transmembrane conductance Regulator protein (CFTR) some of which trigger its misfolding and rapid degradation, particularly the most frequent one, F508del-CFTR. While HspB1 and HspB4 favor the degradation of CFTR mutants, HspB5 and particularly one of its phosphorylated forms positively enhance the transport at the plasma membrane, stability and function of the CFTR mutant. Moreover, HspB5 molecules stimulate the cellular efficiency of currently used CF therapeutic molecules. Different strategies are suggested to modulate the level of expression or the activity of these small heat shock proteins in view of potential in vivo therapeutic approaches. We then conclude with other small heat shock proteins that should be tested or further studied to improve our knowledge of CFTR processing.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/8/4252Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/d0ef91c87f654dc9825a015d13ae6ae4Test

المؤلفون: Tomasz Miksa, Stephanie Simms, Daniel Mietchen, Sarah Jones

المصدر: PLoS Computational Biology, Vol 15, Iss 3, p e1006750 (2019)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Data management plans (DMPs) are documents accompanying research proposals and project outputs. DMPs are created as free-form text and describe the data and tools employed in scientific investigations. They are often seen as an administrative exercise and not as an integral part of research practice. There is now widespread recognition that the DMP can have more thematic, machine-actionable richness with added value for all stakeholders: researchers, funders, repository managers, research administrators, data librarians, and others. The research community is moving toward a shared goal of making DMPs machine-actionable to improve the experience for all involved by exchanging information across research tools and systems and embedding DMPs in existing workflows. This will enable parts of the DMP to be automatically generated and shared, thus reducing administrative burdens and improving the quality of information within a DMP. This paper presents 10 principles to put machine-actionable DMPs (maDMPs) into practice and realize their benefits. The principles contain specific actions that various stakeholders are already undertaking or should undertake in order to work together across research communities to achieve the larger aims of the principles themselves. We describe existing initiatives to highlight how much progress has already been made toward achieving the goals of maDMPs as well as a call to action for those who wish to get involved.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test

الوصول الحر: https://doaj.org/article/0f94eb66755a450c95f069ed84de4caeTest

المؤلفون: Fanny Degrugillier, Abdel Aissat, Virginie Prulière-Escabasse, Lucie Bizard, Benjamin Simonneau, Xavier Decrouy, Chong Jiang, Daniela Rotin, Pascale Fanen, Stéphanie Simon

المصدر: International Journal of Molecular Sciences, Vol 21, Iss 14, p 4844 (2020)

مصطلحات موضوعية: cystic fibrosis, CFTR, HspB5, alpha B-crystallin, CRYAB, phosphorylation, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Cystic Fibrosis is a lethal monogenic autosomal recessive disease linked to mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The most frequent mutation is the deletion of phenylalanine at position 508 of the protein. This F508del-CFTR mutation leads to misfolded protein that is detected by the quality control machinery within the endoplasmic reticulum and targeted for destruction by the proteasome. Modulating quality control proteins as molecular chaperones is a promising strategy for attenuating the degradation and stabilizing the mutant CFTR at the plasma membrane. Among the molecular chaperones, the small heat shock protein HspB1 and HspB4 were shown to promote degradation of F508del-CFTR. Here, we investigated the impact of HspB5 expression and phosphorylation on transport to the plasma membrane, function and stability of F508del-CFTR. We show that a phosphomimetic form of HspB5 increases the transport to the plasma membrane, function and stability of F508del-CFTR. These activities are further enhanced in presence of therapeutic drugs currently used for the treatment of cystic fibrosis (VX-770/Ivacaftor, VX-770+VX-809/Orkambi). Overall, this study highlights the beneficial effects of a phosphorylated form of HspB5 on F508del-CFTR rescue and its therapeutic potential in cystic fibrosis.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/21/14/4844Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/4e0e1cdb46b343a79e2df89bc9ce3b2bTest

المؤلفون: Paul A Clarke, Maria-Jesus Ortiz-Ruiz, Robert TePoele, Olajumoke Adeniji-Popoola, Gary Box, Will Court, Stephanie Czasch, Samer El Bawab, Christina Esdar, Ken Ewan, Sharon Gowan, Alexis De Haven Brandon, Phillip Hewitt, Stephen M Hobbs, Wolfgang Kaufmann, Aurélie Mallinger, Florence Raynaud, Toby Roe, Felix Rohdich, Kai Schiemann, Stephanie Simon, Richard Schneider, Melanie Valenti, Stefan Weigt, Julian Blagg, Andree Blaukat, Trevor C Dale, Suzanne A Eccles, Stefan Hecht, Klaus Urbahns, Paul Workman, Dirk Wienke

المصدر: eLife, Vol 5 (2016)

مصطلحات موضوعية: CDK8, inhibitor, Mediator complex, Wnt, super-enhancer, Medicine, Science, Biology (General), QH301-705.5

الوصف: Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts. Altered gene expression was consistent with CDK8/19 inhibition, including profiles associated with super-enhancers, immune and inflammatory responses and stem cell function. In a mouse model expressing oncogenic beta-catenin, treatment shifted cells within hyperplastic intestinal crypts from a stem cell to a transit amplifying phenotype. In two species, neither probe was tolerated at therapeutically-relevant exposures. The complex nature of the toxicity observed with two structurally-differentiated chemical series is consistent with on-target effects posing significant challenges to the clinical development of CDK8/19 inhibitors.

وصف الملف: electronic resource

العلاقة: https://elifesciences.org/articles/20722Test; https://doaj.org/toc/2050-084XTest

الوصول الحر: https://doaj.org/article/a201fbf6b4ca430996a70dd003f4f498Test

المؤلفون: Olivier Andréoletti, Leonor Orge, Sylvie L Benestad, Vincent Beringue, Claire Litaise, Stéphanie Simon, Annick Le Dur, Hubert Laude, Hugh Simmons, Séverine Lugan, Fabien Corbière, Pierrette Costes, Nathalie Morel, François Schelcher, Caroline Lacroux

المصدر: PLoS Pathogens, Vol 7, Iss 2, p e1001285 (2011)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrP(Sc) negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347349/pdf/?tool=EBITest; https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/30d9590d064043eba600ccc38db17639Test

المؤلفون: Caroline Lacroux, Stéphanie Simon, Sylvie L Benestad, Séverine Maillet, Jacinthe Mathey, Séverine Lugan, Fabien Corbière, Hervé Cassard, Pierrette Costes, Dominique Bergonier, Jean-Louis Weisbecker, Torffin Moldal, Hugh Simmons, Frederic Lantier, Cécile Feraudet-Tarisse, Nathalie Morel, François Schelcher, Jacques Grassi, Olivier Andréoletti

المصدر: PLoS Pathogens, Vol 4, Iss 12, p e1000238 (2008)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (TSE)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. However, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. Here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several months prior to clinical onset. Additionally, abnormal PrP was detected, by immunohistochemistry and PET blot, in lacteal ducts and mammary acini. This PrP(Sc) accumulation was detected only in ewes harbouring mammary ectopic lymphoid follicles that developed consequent to Maedi lentivirus infection. However, bioassay revealed that prion infectivity was present in milk and colostrum, not only from ewes with such lympho-proliferative chronic mastitis, but also from those displaying lesion-free mammary glands. In milk and colostrum, infectivity could be recovered in the cellular, cream, and casein-whey fractions. In our samples, using a Tg 338 mouse model, the highest per ml infectious titre measured was found to be equivalent to that contained in 6 microg of a posterior brain stem from a terminally scrapie-affected ewe. These findings indicate that both colostrum and milk from small ruminants incubating TSE could contribute to the animal TSE transmission process, either directly or through the presence of milk-derived material in animal feedstuffs. It also raises some concern with regard to the risk to humans of TSE exposure associated with milk products from ovine and other TSE-susceptible dairy species.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC2587713?pdf=renderTest; https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/3afbbeba89524a31b9545854bc204aa9Test