Comprehensive mass spectrometric metabolomic profiling of a chemically diverse collection of plants of the Celastraceae family.

Natural products exhibit interesting structural features and significant biological activities. The discovery of new bioactive molecules is a complex process that requires high-quality metabolite profiling data to properly target the isolation of compounds of interest and enable their complete structural characterization. The same metabolite profiling data can also be used to better understand chemotaxonomic links between species.

Integration of Wnt-inhibitory activity and structural novelty scoring results to uncover novel bioactive natural products: new Bicyclo[3.3.1]non-3-ene-2,9-diones from the leaves of .

In natural products (NPs) research, methods for the efficient prioritization of natural extracts (NEs) are key for discovering novel bioactive NPs. In this study a biodiverse collection of 1,600 NEs, previously analyzed by UHPLC-HRMS metabolite profiling was screened for Wnt pathway regulation. The results of the biological screening drove the selection of a subset of 30 non-toxic NEs with an inhibitory IC ≤ 5 g/mL.

Profiling of pyrrolizidine alkaloids using a retronecine-based untargeted metabolomics approach coupled to the quantitation of the retronecine-core in medicinal plants using UHPLC-QTOF.

Pyrrolizidine alkaloids (PA) are secondary metabolites of high toxicological relevance. Several PA quantitative methodologies were developed based on a limited number of certified standards, including time consuming solid phase extraction (SPE) purification steps. Herein, we shed light on the variability of PA in herbal extracts and propose a quantification methodology based on ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) for the evaluation of the total PA content as retronecine-equivalents (RE) directly from crude matrices.

Tumor Cells Hijack Macrophage-Produced Complement C1q to Promote Tumor Growth.

Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure.

Cerebrovascular β-amyloid deposition and associated microhemorrhages in a Tg2576 Alzheimer mouse model are reduced with a DHA-enriched diet.

Cerebral amyloid angiopathy (CAA) is a major contributor to Alzheimer's disease (AD) pathogenesis. Like AD, CAA is often accompanied by marked inflammation, aggravating associated vasculopathies. No evidence-based prevention or treatment strategies are available.

Actinic keratosis modelling in mice: A translational study.

Background: Actinic keratoses (AK) are pre-malignant cutaneous lesions caused by prolonged exposure to ultraviolet radiation. As AKs lesions are generally accepted to be the initial lesions in a disease continuum that progresses to squamous cell carcinoma (SCC), AK lesions have to be treated. They are also the second most common reason for visits to the dermatologist.

The DNA-Binding Polyamine Moiety in the Vectorized DNA Topoisomerase II Inhibitor F14512 Alters Reparability of the Consequent Enzyme-Linked DNA Double-Strand Breaks.

Poisons of topoisomerase II (TOP2) kill cancer cells by preventing religation of intermediate DNA breaks during the enzymatic process and thus by accumulating enzyme-drug-DNA complexes called TOP2 cleavage-complex (TOP2cc). F14512 is a highly cytotoxic polyamine-vectorized TOP2 inhibitor derived from etoposide and currently in clinical trials. It was shown that F14512 has acquired DNA-binding properties and that the stability of TOP2cc was strongly increased.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

Background: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline.

Methods: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco.

A Myrtus communis extract enriched in myrtucummulones and ursolic acid reduces resistance of Propionibacterium acnes biofilms to antibiotics used in acne vulgaris.

Background: Recent works present evidence of Propionibacterium acnes growing as a biofilm in cutaneous follicles. This formation of clusters is now considered as an explanation for the in vivo resistance of P. acnes to the main antimicrobials prescribed in acne vulgaris.

Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization.

GPR88 is a neuronal cerebral orphan G-protein-coupled receptor (GPCR) that has been linked to various psychiatric disorders. However, no extensive description of its localization has been provided so far. Here, we investigate the spatiotemporal expression of the GPR88 in prenatal and postnatal rat tissues by using in situ hybridization and immunohistochemistry.

Anticancer properties of lamellarins.

In 1985 the first lamellarins were isolated from a small oceanic sea snail. Today, more than 50 lamellarins have been inventoried and numerous derivatives synthesized and tested as antiviral or anticancer agents. The lead compound in the family is lamellarin D, characterized as a potent inhibitor of both nuclear and mitochondrial topoisomerase I but also capable of directly interfering with mitochondria to trigger cancer cell death.

ESLAV/ECLAM/LAVA/EVERI recommendations for the roles, responsibilities and training of the laboratory animal veterinarian and the designated veterinarian under Directive 2010/63/EU.

Directive 2010/63/EU was adopted in September 2010 by the European Parliament and Council, and became effective in January 2013. It replaces Directive 86/609/EEC and introduces new requirements for the protection of animals used for scientific purposes. In particular, it requires that establishments that breed, supply or use laboratory animals have a designated veterinarian (DV) with expertise in laboratory animal medicine, or a suitably qualified expert where more appropriate, charged with advisory duties in relation to the well-being and treatment of the animals.

Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings.

The dopamine D3 receptor is located in the limbic area and apparently mediates selective effects on motivation to take drugs and drug-seeking behaviors, so that there has been considerable interest on the possible use of D3 receptor ligands to treat drug addiction. However, only recently selective tools allowing studying this receptor have been developed. This chapter presents an overview of findings that were presented at a symposium on the conference Dopamine 2013 in Sardinia in May 2013.

F14512, a polyamine-vectorized anti-cancer drug, currently in clinical trials exhibits a marked preclinical anti-leukemic activity.

Chemotherapy remains mainly used for the treatment of acute myeloid leukemia (AML). However, in the past 3 decades limited progress has been achieved in improving the long-term disease-free survival. Therefore the development of more effective drugs for AML represents a high level of priority.

A multitechnique evaluation of topical corticosteroid treatment.

Background/purpose: Corticosteroids are widely prescribed for systemic or local treatment of inflammatory autoimmune disorders. Long-term therapy is associated with side effects and causes cutaneous atrophy of the epidermis and the dermis. The present study aims to evaluate with several noninvasive techniques, the skin modifications observed during corticosteroids treatment.

Validation of a non-contact technique for local skin temperature measurements.

Unlabelled: Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers.

Objectives: To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL).

Methods: A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL.

Comparison of perceived itch induced by skin prick-tests with histamine and codeine.

The role of personal factors makes it difficult to correlate subjective data, such as those obtained with the use of a visual analogue scale, and objective data, such as a quantity of injected histamine. In this study, prick tests with histamine and codeine on the forearms allowed a coherent variation in itch scores to be obtained over time, with highly significant differences from controls and with a peak at 4 minutes. These tests are therefore valuable for screening anti-pruritic agents.

Image analysis of scaly skin using Dsquame(R) samplers: technical and physiological validation.

An image analysis-based technique for evaluating skin scaliness using Dsquame(R) instant testers is presented, with four surface texture parameters characterizing this condition. Studies on the variability of the technique were carried out to determine the influence of instrumental and physiological factors. Parameters of texture, optical density, number and surface area of squames are calculated from images of obliquely lit Dsquame(R) samples.

Image analysis of skin scaling using D-Squame samplers: comparison with clinical scoring and use for assessing moisturizer efficacy.

The severity of scaling disorders can be evaluated objectively using the D-Squame technique coupled with image analysis. The parameters of scaling derived using this approach need to be clinically relevant and should have greater discrimination than visual grading. Improvements to an existing method that fulfil these requirements are presented.

Sensitive skin is not limited to the face.

Background: Sensitive skin (or reactive or hyper-reactive skin) is defined as skin that reacts by erythema and/or subjective symptoms (pricking, burning, pain, pruritus etc.) to stimuli that are not pathogens in themselves (e.g.

Use of a 3-D imaging technique for non-invasive monitoring of the depth of experimentally induced wounds.

Background/purpose: Experimental studies of wound healing lack methods for standardized wounding and in situ depth assessment. Consequently, in this pilot study, an Erbium (Er):YAG laser has been used for wound induction with a non-invasive 3-D imaging technique as an alternative to histology.

Methods: Erbium:YAG ablation of human skin ex vivo was performed with total fluences of 10, 50 and 200 J/cm(2), removing the stratum corneum, epidermis/papillary dermis and deeper dermis, respectively.

Anti-angiogenic, vascular-disrupting and anti-metastatic activities of vinflunine, the latest vinca alkaloid in clinical development.

The aim of this study was to investigate the anti-angiogenic, vascular-disrupting and anti-metastatic properties of vinflunine, the latest vinca alkaloid in phase III clinical development. The effects of vinflunine on in vitro endothelial cell functions relevant to the performance of an already formed vasculature and to the angiogenic process were evaluated. The in vivo anti-angiogenic properties of vinflunine were also investigated, as were its activity against a model of experimental metastasis.

Efficacy and safety of a topically applied Avène spring water spray in the healing of facial skin after laser resurfacing.

Background: Although laser resurfacing is a well-accepted treatment, tolerance problems may preclude patient's acceptance of the procedure. Post-laser protracted erythema is a prime problem, associated with the symptoms of pain, itching, stinging and tightening.

Objective: The present study was conducted to evaluate a low-salt medical spring water (Avène, Avène-les-Bains, France), in conjunction with the standard use of an emollient, to improve tolerance by hydrating the postlaser skin.