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Abstract: Among eukaryotic P450s, the greatest expansion has been in insects, providing useful model systems for the study of enzyme evolution in response to natural and anthropogenic pressures such as the chemical warfare against plant toxins and synthetic insecticides. To better understand diversification of the catalytic properties in the various P450 clades, insight into the molecular principles governing biotransformation of the array of endogenous and exogenous compounds is of paramount importance. Based on a general, CYP102A1-related construct, the majority of prospective substrate-docking residues were found to cluster near the distal heme face within the six known substrate recognition sites (SRSs) made up by the α-helical B′, F, G and I tetrad as well as the B′-C turn and strands of certain β-sheets. Highest proportion of contact sites, having a mean frequency of conservation of not more than 10%, was detected to be housed in the variable SRS-1 and SRS-2 domains, affording conformational mobility to meet the structural diversity in the bulk of substrates. Some key determinants may have a function in governing substrate access, positioning ligands toward the catalytic center to allow regioselective attack, and promoting dioxygen activation. Moreover, non-SRS elements occupying regions on the bowl-like proximal heme face may serve in recognition of electron delivery partners. Physico-chemical factors interfering with substrate anchoring mainly relate to the variably expressed lipophilicity/hydrophilicity profile of the diverse binding sites and bulkiness of the side chains of critical amino acids. Detailed knowledge about structure–function relationships in insect P450s, thus, may offer an incentive to tailoring of novel insecticides and synergistic enzyme inhibitors to more efficiently control insect pests. [Copyright &y& Elsevier]

Abstract: Study aims: The aim was to evaluate the in vitro effects of amoxicillin and its combination with clavulanic acid, two β-lactams intravenously injected, on the oxidative metabolism of polymorphonuclear neutrophils. These cells play the major role in the “respiratory burst” as they produce superoxide anion to kill the infectious agent. An activation of this process by the injected antibiotics could enhance the bactericidal action or explain some of adverse effects. Materials and methods: Two models were used to estimate the O2 – amounts produced in the presence of the antimicrobial agents. In the cellular model, O2 – was generated by neutrophils artificially stimulated or not (separated by a gradient centrifugation through Histopaque 1077). In the acellular model, O2 – was produced by the xanthine–xanthine oxidase system. O2 – was measured by spectrophotometry using the ferricytochrome C reduction. Results: The O2 – production by polymorphonuclear neutrophils was increased when both antibiotics were added to the reaction mixture. A significant activation of the cell oxidative metabolism was observed with amoxicillin using various stimulating agents, that was higher without stimulation and lower when amoxicillin and clavulanic acid were associated. Conclusion: Amoxicillin could either activate polymorphonuclear neutrophils NADPH-oxidase or cause its activation by a membrane effect, or interfere with the zymosan activation way. It could then be supposed that this antimicrobial agent intensified the bactericidal effects. [Copyright &y& Elsevier]

Objectives – There are now experimental evidences about the growth of capillary bed in response to increased functional load in skeletal muscle such as physical exercise. The objective of this review is to discuss the present state of our knowledge on the adaptive responses of the capillary bed to physical training.Topics – The skeletal muscle is known to respond to physical training and the adaptive response of the microcirculation in mammals is the high capillarity observed in trained skeletal muscles. The increase in the capillary bed after endurance training results mainly from angiogenesis, and only for a short part from changes in the capillary tortuosity. Capillary growth involves several molecular factors ; some are expressed and induced by alterations in local oxygen pressure. The specific role played by mechanical factors and shear stress for capillary growth stimulation remains the matter of debate.Future prospects – A better knowledge of molecular mechanisms involved in capillary growth is an important stage to examine the general responses to physical training. Researches on exercise-induced capillary growth have many important practical consequences, especially on therapeutic domain. [Copyright &y& Elsevier]

Cancer is a disease that can appear in several tissues and that kills more than 150 000 people in France every year. Cancer cells have mutations in their genome that lead to changes in their metabolism, compared to healthy cells. They use mostly glycolysis as their energy source, but not fatty acid oxidation. Currently, treatments used against cancer are nonspecific and have many side effects. Thus it appears increasingly important to find new strategies against cancer cells progression while protecting surrounding healthy cells and decreasing side effects. Ketogenic diet, which is a low-sugar high-fat diet, could be an interesting candidate as it alters the energy machinery of the cell and keeps away its primary energy source (glucose). This diet is largely used to treat refractory epilepsy and begins to be studied in oncology as well. This article describes the scientific evidence of the beneficial effects of the ketogenic diet and aims at showing how this complementary treatment could be useful against several cancers., (© Société de Biologie, 2020.)