5 research outputs found

    Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)

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    International audienceHeart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts

    A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells

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    International audienceA good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophypromoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1

    Biochar and compost addition increases soil organic carbon content and substitutes P and K fertilizer in three French cropping systems

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    International audienceAbstractBiochar and compost are increasingly considered sustainable amendments to improve soil fertility, while reducing agrochemical use. However, the efficiency of biochar, compost, and especially their mixtures under field conditions in temperate regions is still poorly studied. The objective of this study was to evaluate the effects of biochar/compost mixtures on crop yield and soil properties in French temperate cropping systems and to compare the amendment effects to soils receiving mineral potassium and phosphorus fertilization. To this end, green waste compost alone (8 t.ha−1) or in mixture with three contrasted biochars (8 t.ha−1 compost and 4 t.ha−1 biochar) were applied to maize-wheat cropping systems located in three major agricultural territories in France. Results showed that maize and wheat yields were predominantly site specific. Within each site, compost and biochar application led to similar yields and nutrient uptakes as compared to the mineral fertilization, suggesting that compost-biochar mixtures might be as efficient as mineral fertilizers to supply potassium and phosphorus, while biochar did not improve compost benefits to plant yield. Moreover, the effects of compost-biochar mixtures on soil organic carbon concentrations were site specific and led to no effect or increase by up to 53%. We conclude that compost-biochar mixtures may increase carbon content in soil and substitute phosphorus and potassium mineral fertilizers for crop production in temperate cropping systems, even though their effects are site specific
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