Differential Biological Effects of Dietary Lipids and Irradiation on the Aorta, Aortic Valve, and the Mitral Valve

peer reviewedAimsDietary cholesterol and palmitic acid are risk factors for cardiovascular diseases (CVDs) affecting the arteries and the heart valves. The ionizing radiation that is frequently used as an anticancer treatment promotes CVD. The specific pathophysiology of these distinct disease manifestations is poorly understood. We, therefore, studied the biological effects of these dietary lipids and their cardiac irradiation on the arteries and the heart valves in the rabbit models of CVD.Methods and ResultsCholesterol-enriched diet led to the thickening of the aortic wall and the aortic valve leaflets, immune cell infiltration in the aorta, mitral and aortic valves, as well as aortic valve calcification. Numerous cells expressing α-smooth muscle actin were detected in both the mitral and aortic valves. Lard-enriched diet induced massive aorta and aortic valve calcification, with no detectable immune cell infiltration. The addition of cardiac irradiation to the cholesterol diet yielded more calcification and more immune cell infiltrates in the atheroma and the aortic valve than cholesterol alone. RNA sequencing (RNAseq) analyses of aorta and heart valves revealed that a cholesterol-enriched diet mainly triggered inflammation-related biological processes in the aorta, aortic and mitral valves, which was further enhanced by cardiac irradiation. Lard-enriched diet rather affected calcification- and muscle-related processes in the aorta and aortic valve, respectively. Neutrophil count and systemic levels of platelet factor 4 and ent-8-iso-15(S)-PGF2α were identified as early biomarkers of cholesterol-induced tissue alterations, while cardiac irradiation resulted in elevated levels of circulating nucleosomes.ConclusionDietary cholesterol, palmitic acid, and cardiac irradiation combined with a cholesterol-rich diet led to the development of distinct vascular and valvular lesions and changes in the circulating biomarkers. Hence, our study highlights unprecedented specificities related to common risk factors that underlie CVD

Quantitative technologies and reflexivity: The role of tools and their layouts in the case of credit risk management

International audienceThe development of quantitative technologies is increasingly challenging professional practices and raises questions about whether and how organizations may foster plural and reflexive practices. In this paper, we outline the role played by tools and their layouts in this process. Tools can sustain the enactment of plural views, logics and evaluative principles. However, it is not clear why, in some cases, designing or using these tools triggers intractable conflicts instead of helping to sustain reflexivity in a “productive” way. To address this issue, we explore the case of a French bank that introduced in its credit management processes a new statistical approach of risk management, which conflicted with the professional approach that prevailed at the time. Relying on Boltanski’s (2011) work on critique, we highlight how “productive” reflexivity emerges, not only from critique, but from a dynamic relationship between critique, confirmation and practical action. This framework allows us to bring a fresh look at the layouts identified in the literature as able to sustain pluralism by exposing their differences regarding whether and how they may contribute to trigger reflexivity. We especially show that, when quantitative technologies are involved, the creation of compromising accounts may prompt dynamics of escalating conflict, while combinations may help organising a pluralism of modes of evaluation that nurtures reflexivity without inhibiting action. Moreover, our study shows how, in credit risk management, quantitative technologies can be implemented, even in the most operational processes, without bringing about an unreflexive “illusion” of control

N-(2-{3-[3,5-Bis(Tifluoromethyl)Phenyl]Ureido}Ethyl)-Glycyrrhetin-amide: A novel anticancer glycyrrhetinic acid derivative that targets the proteasome.

info:eu-repo/semantics/nonPublishe

Growth inhibitory activities of oxyprenylated and non-prenylated naturally occurring phenylpropanoids in cancer cell lines

info:eu-repo/semantics/publishe

Enrichment of methylated molecules using enhanced- ice

International audienceAim: The detection of specific DNA methylation patterns bears great promise as biomarker for personalized management of cancer patients. Co-amplification at lower denaturation temperature-PCR (COLD-PCR) assays are sensitive methods, but have previously only been able to analyze loss of DNA methylation. Materials & methods: Enhanced (E)-ice-COLD-PCR reactions starting from 2 ng of bisulfite-converted DNA were developed to analyze methylation patterns in two promoters with locked nucleic acid (LNA) probes blocking amplification of unmethylated CpGs. The enrichment of methylated molecules was compared to quantitative (q)PCR and quantified using serial dilutions.Results: E-ice-COLD-PCR allowed the multiplexed enrichment and quantification of methylated DNA. Assays were validated in primary breast cancer specimens and circulating cell-free DNA from cancer patients. Conclusion: E-ice-COLD-PCR could prove a useful tool in the context of DNA methylation analysis for personalized medicine

Dampening type 2 properties of group 2 innate lymphoid cells by a gammaherpesvirus infection reprograms alveolar macrophages.

peer reviewedImmunological dysregulation in asthma is associated with changes in exposure to microorganisms early in life. Gammaherpesviruses (γHVs), such as Epstein-Barr virus, are widespread human viruses that establish lifelong infection and profoundly shape host immunity. Using murid herpesvirus 4 (MuHV-4), a mouse γHV, we show that after infection, lung-resident and recruited group 2 innate lymphoid cells (ILC2s) exhibit a reduced ability to expand and produce type 2 cytokines in response to house dust mites, thereby contributing to protection against asthma. In contrast, MuHV-4 infection triggers GM-CSF production by those lung ILC2s, which orders the differentiation of monocytes (Mos) into alveolar macrophages (AMs) without promoting their type 2 functions. In the context of γHV infection, ILC2s are therefore essential cells within the pulmonary niche that imprint the tissue-specific identity of Mo-derived AMs and shape their function well beyond the initial acute infection

Bariatric Surgery is feasible in patients with Ehlers-Danlos Syndrome

International audienceBackground: Ehlers-Danlos syndrome (EDS) is a heterogeneous disease affecting connective tissues. EDS patients have a high susceptibility for developing anastomotic leak after visceral surgery. Although patients with EDS can also develop severe obesity and might be referred to bariatric surgery, there is just 1 case report in the literature regarding the outcomes of bariatric surgery in this specific context.Objective: To report the cases of patients with EDS and severe obesity that underwent bariatric surgery.Setting: Five French hospitals (University Hospital of Nantes, APHP Pitié Salpêtrière Hospital, APHP Bichat Hospital, Clinique St Gregoire Rennes, and Clinique Mutualiste de l'Estuaire St Nazaire).Methods: We report the cases of 7 patients with EDS and severe obesity who underwent surgery.Results: All patients showed classical postoperative course except for 1 case of excessive bleeding. There was no increased pain, leak, and solid parietal healing was achieved in all patients at 1 month postoperatively. The percent excess weight loss at 1 and 6 months were 13.9 ± 3.8% and 45.3 ± 16%, respectively.Conclusion: Our study shows that bariatric surgery is a relevant and apparently safe surgical option to consider in severely obese patients with EDS

Overlap between differentially methylated DNA regions in blood B lymphocytes and genetic at-risk loci in primary Sjögren's syndrome

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N-(2-{3-[3,5-Bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b): A Novel Anticancer Glycyrrhetinic Acid Derivative that Targets the Proteasome and Displays Anti-Kinase Activity.

18-β-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in cancer cells. The current study aims to characterize the anticancer effects of 17 novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be the most potent compound, with IC(50)in vitro growth inhibitory concentrations in single-digit micromolarity in a panel of 8 cancer cell lines. Compound 6b is cytostatic and displays similar efficiency in apoptosis-sensitive versus apoptosis-resistant cancer cell lines through, at least partly, the inhibition of the activity of a cluster of a dozen kinases that are implicated in cancer cell proliferation and in the control of the actin cytoskeleton organization. Compound 6b also inhibits the activity of the 3 proteolytic units of the proteasome. Compound 6b thus represents an interesting hit from which future compounds could be derived to improve chemotherapeutic regimens that aim to combat cancers associated with poor prognoses.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe