Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la

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    Current state of cannabis use, policies, and research across sixteen countries: cross-country comparisons and international perspectives
    (2022) Jatchavala, C. (Chonnakarn); Filippis, R. (Renato) de; Handuleh, J.I.M. (Jibril I. M.); Shoib, S. (Sheikh); Pereira-Sánchez, V. (Víctor); Boujraf, S. (Said); Gupta, A.K. (Anoop Krishna); Vahdani, B. (Bita); Ransing, R. (Ramdas); Stowe, M.J. (M.J.); Sonmez-Gungor, E. (Ekin); Jaguga, F. (Florence); Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la; Karaliuniene, R. (Ruta); Peyron, E. (Eric); da-Silva, A.K. (Alexandre Kieslich); Dannatt, L. (Lisa); Jerotic, S. (Stefan); Yee, A. (Ane); Grandinetti, P. (Paolo)
    Introduction: Varying public views on cannabis use across countries may explain the variation in the prevalence of use, policies, and research in individual countries, and global regulation of cannabis. This paper aims to describe the current state of cannabis use, policies, and research across sixteen countries.Methods: PubMed and Google Scholar were searched for studies published from 2010 to 2020. Searches were conducted using the relevant country of interest as a search term (e.g., "Iran"), as well as relevant predefined keywords such as "cannabis," "marijuana," "hashish," "bhang "dual diagnosis," "use," "addiction," "prevalence," "co-morbidity," "substance use disorder," "legalization" or "policy" (in English and non-English languages). These keywords were used in multiple combinations to create the search string for studies' titles and abstracts. Official websites of respective governments and international organizations were also searched in English and non-English languages (using countries national languages) to identify the current state of cannabis use, policies, and research in each of those countries.Results: The main findings were inconsistent and heterogeneous reporting of cannabis use, variation in policies (e.g., legalization), and variation in intervention strategies across the countries reviewed. European countries dominate the cannabis research output indexed on PubMed, in contrast to Asian countries (Thailand, Malaysia, India, Iran, and Nepal).Conclusions: Although global cannabis regulation is ongoing, the existing heterogeneities across countries in terms of policies and epidemiology can increase the burden of cannabis use disorders disproportionately and unpredictably. There is an urgent need to develop global strategies to address these cross-country barriers to improve early detection, prevention, and interventions for cannabis use and related disorders.
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    Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells
    (2020) Ballaz, S.J. (Santiago J.); Rodríguez-Losada, N. (Noela); Aguirre, J.A. (José A.); Saez-Castresana, J. (Javier); Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la; Wendelbo, R. (Rune); Larriva-Hormigos, M. (María)
    Alpha-Synuclein (aSyn) is a chameleon-like protein. Its overexpression and intracellular deposition defines neurodegenerative alpha-synucleinopathies including Parkinson's disease. Whether aSyn upregulation is the cause or the protective reaction to alpha-synucleinopathies remains unresolved. Remarkably, the accumulation of aSyn is involved in cancer. Here, the neuroblastoma SH-SY5Y cell line was genetically engineered to overexpress aSyn at low and at high levels. aSyn cytotoxicity was assessed by the MIT and vital-dye exclusion methods, observed at the beginning of the sub-culture of low-aSyn overexpressing neurons when cells can barely proliferate exponentially. Conversely, high-aSyn overexpressing cultures grew at high rates while showing enhanced colony formation compared to low-aSyn neurons. Cytotoxicity of aSyn overexpression was indirectly revealed by the addition of pro-oxidant rotenone. Pretreatment with partially reduced graphene oxide, an apoptotic agent, increased toxicity of rotenone in low-aSyn neurons, but, it did not in high-aSyn neurons. Consistent with their enhanced proliferation, high-aSyn neurons showed elevated levels of SMP30, a senescence-marker protein, and the mitosis Ki-67 marker.
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    Sonic hedgehog inhibition reduces in vitro tumorigenesis and alters expression of GLI1-target genes in a desmoplastic medulloblastoma cell line
    (2013) Vacas, A. (Andrés); Alonso-Roldán, M.M. (Marta María); Rey-Martinez, J.A. (Jorge Alberto); Vera-Cano, B. (Beatriz); Saez-Castresana, J. (Javier); García-López, R. (Ricardo); Rosa-Fernández-Pacheco, F.J. (Francisco Javier) de la; Gallo, G.O. (Gabriel Osvaldo)
    Medulloblastoma is one of the most frequent and aggressive tumors of childhood. The Sonic hedgehog (Shh) pathway, related to human development, is altered in most medulloblastomas: genes like Ptch, Smo, or Sufu suffer mutations in 15% to 25% of these tumors. We tested Shh inhibition in the Daoy medulloblastoma cell line by two methods: a molecular one, direct Gli1 siRNA inhibition; and a pharmacological inhibition of Smo, upstream of Gli1, by cyclopamine. Afterwards, a comparison of cellular and molecular responses was done. In general, we proved that cell viability, cell migration and cell colony formation decreased after Shh inhibition, which might confer a less tumorigenic status to Daoy cells. Moreover, we assessed the expression of different Gli1 target genes and other genes and found that Shh shows a crosstalk with oncogenes and tumor suppressor genes that have been described in numerous tumors. All these experiments give an overview of the Shh pathway in medulloblastoma, together with the demonstration of the efficacy of cyclopamine and Gli1 siRNA Shh inhibition in vitro.