Development of a Local Health-Enhancing Physical Activity Policy Analysis Tool in France: CAPLA-Santé.

The promotion of health-enhancing physical activity (HEPA) has become a key objective in public health policy. Therefore, based on the national HEPA Policy Audit Tool Version 2 (HEPA PAT v2) of the World Health Organization, a tool was designed to support local governments in assessing HEPA policies. This study aims to describe the adaptation and testing of the HEPA policy analysis tool (CAPLA-Santé) at the local level in France. The work was conducted in three stages: (1) an intersectoral group of experts was constituted, and the group adapted each item of the HEPA PAT v2 tool to the local level; (2) a testing phase with seven local governments helped to collect data and feedback on the tool; and (3) a final workshop was organized to adjust and finalize the tool. The final version of CAPLA-Santé contains 21 items divided into six major sections: overview of HEPA stakeholders in the local government area, policy documents, policy contents, funding and political engagement, studies and measures relating to physical activity in the local government area, and progress achieved and future challenges. CAPLA-Santé allows the collection and in-depth analysis of local level policies to assess the progress in promoting HEPA and intersectoral collaboration as well as identifying successful policy levers and remaining challenges.

K092A and K092B, Two Peptides Isolated from the Dogfish (Scyliorhinus canicula L.), with Potential Antineoplastic Activity Against Human Prostate and Breast Cancer Cells.

Cancer therapy is currently a major challenge within the research community, especially in reducing the side effects of treatments and to develop new specific strategies against cancers that still have a poor prognosis. In this context, alternative strategies using biotechnologies, such as marine peptides, have been developed based on their promise of effectivity associated with a low toxicity for healthy cells. The purpose of the present paper is to investigate the active mechanism of two peptides that were isolated from the epigonal tissue of the lesser spotted dogfish Scyliorhinus canicula L., identified NFDTDEQALEDVFSKYG (K092A) and EAPPEAAEEDEW (K092B) on the in vitro growth inhibition of ZR-75-1 mammary carcinoma cells and MDA-Pca-2b prostate cancer cells. The effects of the peptides on cell proliferation and cell death mechanisms were studied by the flow cytometry and immunofluorescence microscopy approaches. The results have shown the onset of both K092A- and K092B-induced early cytoskeleton changes, and then cell cycle perturbations followed by non-apoptotic cell death. Moreover, impedance perturbation and plasma membrane perforation in ZR-75-1 K092A-treated cell cultures and autophagy inhibition in MDA-Pca-2b K092B-treated cells have been observed. In conclusion, these two bioactive peptides from dogfish exhibit antineoplastic activity on the human prostate and breast cancer cells in vitro.

A Potential Antineoplastic Peptide of Human Prostate Cancer Cells Derived from the Lesser Spotted Dogfish (Scyliorhinus canicula L.).

The purpose of the present paper is to investigate the mechanism of action of a pyroglutamate-modified peptide (pE-K092D) on in vitro growth inhibition of MDA-Pca-2b prostate cancer cells. This peptide was derived from a peptide previously isolated from the testis of the lesser spotted dogfish and identified as QLTPEALADEEEMNALAAR (K092D). The effect of the peptide on cell proliferation and cell death mechanisms was studied by flow cytometry. Cellular morphology and cytoskeleton integrity of peptide-treated cells were observed by immunofluorescence microscopy. Results showed the onset of peptide induced early cytoskeleton perturbation, inhibition of autophagy, inhibition of cell proliferation and, at the end, non-apoptotic cell death mechanisms (membrane destabilization and necrosis). All those mechanisms seem to contribute to MDA-Pca-2b growth inhibition by a main cytostatic fate.

Antibodies preventing the interaction of tissue-type plasminogen activator with N-methyl-D-aspartate receptors reduce stroke damages and extend the therapeutic window of thrombolysis.

BACKGROUND AND PURPOSE: Tissue-type plasminogen activator (tPA) is the only drug approved for the acute treatment of ischemic stroke but with two faces in the disease: beneficial fibrinolysis in the vasculature and damaging effects on the neurovascular unit and brain parenchyma. To improve this profile, we developed a novel strategy, relying on antibodies targeting the proneurotoxic effects of tPA. METHODS: After production and characterization of antibodies (αATD-NR1) that specifically prevent the interaction of tPA with the ATD-NR1 of N-methyl-d-aspartate receptors, we have evaluated their efficacy in a model of murine thromboembolic stroke with or without recombinant tPA-induced reperfusion, coupled to MRI, near-infrared fluorescence imaging, and behavior assessments. RESULTS: In vitro, αATD-NR1 prevented the proexcitotoxic effect of tPA without altering N-methyl-d-aspartate-induced neurotransmission. In vivo, after a single administration alone or with late recombinant tPA-induced thrombolysis, antibodies dramatically reduced brain injuries and blood-brain barrier leakage, thus improving long-term neurological outcome. CONCLUSIONS: Our strategy limits ischemic damages and extends the therapeutic window of tPA-driven thrombolysis. Thus, the prospect of this immunotherapy is an extension of the range of treatable patients.

Tissue-type plasminogen activator induces plasmin-dependent proteolysis of intracellular neuronal nitric oxide synthase.

BACKGROUND INFORMATION: Despite its pro-fibrinolytic activity, tPA (tissue plasminogen activator) is a serine protease known to influence a number of physiological and pathological functions in the central nervous system. Accordingly, tPA was reported to mediate some of its functions in the central nervous system through NMDA (N-methyl-D-aspartate) receptors, LRP (low-density lipoprotein receptor-related protein) or annexin II. RESULTS: We provide here both in vitro and in vivo evidence that tPA could mediate proteolysis and subsequent delocalization of neuronal nitric oxide synthase, thereby reducing endogenous neuronal nitric oxide release. We also demonstrate that although this effect is independent of NMDA receptors, LRP signalling and calpain-mediated proteolysis, it is dependent on the ability of tPA to promote the conversion of plasminogen into plasmin. CONCLUSION: Altogether, these results demonstrate a new function for tPA in the central nervous system, which most likely contributes to its pleiotropic functions.