43 research outputs found

    Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy

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    Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes to placental vascularization and growth and that its aberrant expression is associated with pregnancy pathologies including preeclampsia and fetal growth restriction. These findings strongly suggested that antagonization of its receptors may constitute a potential therapy for the pregnancy pathologies. Two specific antagonists of PROKR1 (PC7) and for PROKR2 (PKRA) were reported to reverse PROKs adverse effects in other systems. In the view of using these antagonists to treat pregnancy pathologies, a proof of concept study was designed to determine the biological significances of PC7 and PKRA in normal pregnancy outcome. PC7 and PKRA were tested independently or in combination in trophoblast cells and during early gestation in the gravid mouse. Both independent and combined treatments uncovered endogenous functions of EG-VEGF. The independent use of antagonists distinctively identified PROKR1 and PROKR2-mediated EG-VEGF signaling on trophoblast differentiation and invasion; thereby enhancing feto-placental growth and pregnancy outcome. Thus, our study provides evidence for the potential safe use of PC7 or PKRA to improve pregnancy outcome

    A highly prevalent filamentous algal endophyte in natural populations of the sugar kelp Saccharina latissima is not detected during cultivation in Northern Brittany

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    The sugar kelp Saccharina latissima is cultivated in Europe for food, feed and ultimately the production of chemical commodities and bioenergy. Being cultivated in the open sea, S. latissima is exposed to potentially harmful organisms, such as Laminarionema elsbetiae, a filamentous brown algal endophyte with a very high prevalence in wild populations of European S. latissima. As it was shown previously that S. latissima sporophytes get infected by L. elsbetiae very early in their life, seeding the spores on collectors and keeping them under controlled conditions during the critical time of a possible infection with filamentous endophytes could be advantageous over direct seeding techniques, where the ropes are deployed within days after seeding. We used a qPCR-assay to assess the prevalence of the endophyte L. elsbetiae in S. latissima cultivated during winter in Northern Brittany, comparing individuals from direct-seeded ropes and collector-seeded lines that were kept in laboratory conditions for different time spans. No DNA of the endophyte was detected in the samples, suggesting that either the kelps were not infected or the amount of endophytic filaments were below the detection rate of the qPCR assay. Furthermore, L. elsbetiae could not be detected in the seawater surrounding the kelp farm, indicating that L. elsbetiae is not fertile or disperses at a very small scale in Northern Brittany during the deployment time of young kelps. Our results suggest that infections of cultivated S. latissima with the endophyte L. elsbetiae might be a minor problem in kelp farms in Northern Brittany if the seeding production is kept under controlled conditions without external contamination

    A systematic approach to the evaluation of the coronary microcirculation using bolus thermodilution: CATH CMD

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    Coronary microvascular dysfunction (CMD) can cause myocardial ischemia in patients presenting with angina without obstructive coronary artery disease (ANOCA). Evaluating for CMD by using the thermodilution technique offers a widely accessible means of assessing microvascular resistance. Through this technique, 2 validated indices, namely coronary flow reserve and the index of microcirculatory resistance, can be computed, facilitating investigation of the coronary microcirculation. The index of microcirculatory resistance specifically estimates minimum achievable microvascular resistance within the coronary microcirculation. We aim to review the bolus thermodilution method, outlining the fundamental steps for conducting measurements and introducing an algorithmic approach (CATH CMD) to systematically evaluate the coronary microcirculation. Embracing a standardized approach, exemplified by the CATH CMD algorithm, will facilitate adoption of this technique and streamline the diagnosis of CMD

    Effect of surface chemistry on the thermodynamics and conductivity of water in silica nanopores

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    International audienceThe thermodynamics and conductivity of water confined in nanoporous silicas SBA-15 are studied using differential scanning calorimetry and impedance spectroscopy. The effect of the water/surface interaction is addressed by investigating samples with different surface chemistries

    EG-VEGF maternal levels predict spontaneous preterm birth in the second and third trimesters in pregnant women with risk factors for placenta-mediated complications

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    International audienceAbstract Prediction of spontaneous preterm birth in asymptomatic women remains a great challenge for the public health system. The aim of the study was to determine the informational value of EG-VEGF circulating levels for prediction of spontaneous preterm birth in the second and third trimesters in pregnant women at high risk for placenta-mediated complications. A prospective multicenter cohort study including 200 pregnant patients with five-serum sampling per patient. Women with spontaneous preterm birth have higher concentrations of serum EG-VEGF than uncomplicated patients at 24 weeks, 28 weeks and 32 weeks (p = 0.03, 0.02 and < 0.001). The areas under the curve reached 0.9 with 100% sensitivity at 32 weeks for the prediction of spontaneous preterm birth. Serum EG-VEGF concentrations could be considered as a reliable biomarker of spontaneous preterm birth in high-risk for placenta-mediated complications pregnant women

    A clickable C-glycosyl scaffold for RGD peptide dimer labelling and application in bimodal [18F]PET/NIRF imaging

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    International audienceObjective A trend in molecular imaging is to combined two modalities, advantages of one compensate limitations of the second. Combining PET (Positron Emission Tomography) and NIRF (Near Infra-Red Fluorescence) imaging conjugates the non-invasive diagnosis of PET with the intraoperative imaging guided surgery or ex vivo histopathology of NIRF imaging.2,3 We developed a dual [18F]PET/NIRF imaging agent based on a single probe detectable with both modalities, which is the best way to facilitate the use of bimodal imaging. Methods 18F is a suitable isotope to form stable C-F bond and provide radiotracers with molar activity.3 A cyanine which is one of the most used fluorophores for biomedical applications was selected as the fluorescent dye. A C-glycosyl scaffold is functionalized in a regiocontrolled manner in order to introduce the fluorescent derivative (Cy-5) and the fluorine bound to a carbon, optimal for in vivo stability. Two c(RGDfK) peptides targeting integrins, overexpressed in some malignant tumours, were introduced by CuAAC. Results and ConclusionThe binding affinities towards integrins are higher than c(RGDfK) peptide reference, highlighting the benefit of the divalence (IC50 10-16 nM vs 40 nM for the reference c(RGDfK). The in vitro optical imaging of the synthetic dual agents evaluated in U87MG cells shows a great cellular incorporation. The 18F-radiofluoration was successfully performed on the radiolabeling precursor displaying the cyanine moiety. The radiosynthesis automation in an AllInOne (AIO) synthesizer and the in vivo PET and NIRF imaging are in development. According to in vitro data and promising radiofluoration, this dual tool could be a valuable agent in bimodal imaging for diagnosis and guided surgery
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