The Arab American experience with diabetes: Perceptions, myths and implications for culturally-specific interventions

Culturally-specific lifestyle diabetes prevention programs require an assessment of population disease perceptions and cultural influences on health beliefs and behaviors. The primary objectives were to assess Arab Americans’ knowledge and perceptions of diabetes and their preferences for a lifestyle intervention

A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests

Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity.Stanley Medical Research InstituteNational Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01DA030321

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

The Arab American experience with diabetes: Perceptions, myths and implications for culturally-specific interventions

AIMS: Culturally-specific lifestyle diabetes prevention programs require an assessment of population disease perceptions and cultural influences on health beliefs and behaviors. The primary objectives were to assess Arab Americans’ knowledge and perceptions of diabetes and their preferences for a lifestyle intervention. METHODS: Sixty-nine self-identified Arab or Arab Americans ≥ 30 years of age and without diabetes participated in 8 focus groups. RESULTS: Emerging themes from the data included myths about diabetes etiology, folk remedies, and social stigma. The main barrier to healthcare was lack of health insurance and/or cost of care. Intervention preferences included gender-specific exercise, group-delivered education featuring religious ideology, inclusion of the family, and utilization of community facilities. CONCLUSION: Lifestyle interventions for Arab Americans need to address cultural preferences, diabetes myths, and folk remedies. Interventions should incorporate Arabic cultural content and gender-specific group education and exercise. Utilization of family support and religious centers will enable culturally-acceptable and cost-effective interventions

BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors

Background: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. Methods: A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. Results: Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. Conclusions: The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.Fil: Bertran Alamillo, Jordi. Quiron Dexeus University Hospital; EspañaFil: Giménez Capitán, Ana. Quiron Dexeus University Hospital; EspañaFil: Román, Ruth. Quiron Dexeus University Hospital; EspañaFil: Talbot, Sara. Quiron Dexeus University Hospital; EspañaFil: Whiteley, Rebecca. Quiron Dexeus University Hospital; EspañaFil: Floch, Nicolas. Astrazeneca; Reino UnidoFil: Martinez Perez, Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Martin, Matthew J.. Astrazeneca; Reino UnidoFil: Smith, Paul D.. Astrazeneca; Reino UnidoFil: Sullivan, Ivana. Hospital de la Santa Creu I Sant Pau; España. Hospital Universitari Dexeus; EspañaFil: Terp, Mikkel G.. University of Southern Denmark; DinamarcaFil: Saeh, Jamal. Astrazeneca; Reino UnidoFil: Marino Buslje, Cristina. Fundación Instituto Leloir; ArgentinaFil: Fabbri, Giulia. Astrazeneca; Reino UnidoFil: Guo, Grace. Astrazeneca; Reino UnidoFil: Xu, Man. Astrazeneca; Reino UnidoFil: Tornador, Cristian. Teresa Moretó Foundation And Wholegenix Sl; EspañaFil: Aguilar Hernández, Andrés. Hospital Universitari Dexeus; EspañaFil: Reguart, Noemí. Hospital Clinic Barcelona; EspañaFil: Ditzel, Henrik J.. University of Southern Denmark,; Dinamarca. Odense University Hospital; DinamarcaFil: Martínez Bueno, Alejandro. Hospital Universitari Dexeus; EspañaFil: Nabau Moretó, Núria. Teresa Moretó Foundation And Wholegenix Sl; EspañaFil: Gascó, Amaya. Astrazeneca; Reino UnidoFil: Rosell, Rafael. Germans Trias I Pujol Research Institute; España. Hospital Universitari Dexeus; EspañaFil: Pease, J. Elizabeth. Astrazeneca; Reino UnidoFil: Polanska, Urszula M.. Astrazeneca; Reino UnidoFil: Travers, Jon. Astrazeneca; Reino UnidoFil: Urosevic, Jelena. Astrazeneca; Reino UnidoFil: Molina Vila, Miguel A.. Hospital Universitari Dexeus; Españ