Introduction: Coinfection with certain members of the Flaviviridae, such as Dengue Virus (DV), West Nile Virus (WNV) Yellow Fever Virus (YFV) and most importantly, GBV-C have been documented to reduce HIV-1 viral load in vivo. Numerous studies strongly support the notion that persistent coinfection with non-pathogenic virus prolongs survival in HIV-1 infected individuals. Coinfected individuals show higher CD4+ cell counts, lower HIV-1 RNA viral loads and live three times longer than clinically matched HIV-1 monoinfected patients. We have previously shown that one of the major anti-HIV defenses conferred by GBV-C coinfection is the upregulation of intracellular miRNAs in CD4+ cells that share significant mutual homologies with GBV-C and HIV-1 (>80%) genomes. Methodology: Genome-wide bioinformatics analyses were carried out to search for miRNA binding sites in mutual homologies between HIV and several members of the Flaviviridae Results: Several miRNAs shared significant mutual homology with HIV-1 genetic sequences and GBV-A, B, C, DV, WNV and YFV. These may be responsible for beneficial effects in HIV-1 infected individuals. Three highly mutual homologous miRNAs (i.e. miR-627-5, miR-369-5 and miR-548f), expressed in CD4+ cell lines, reduce HIV-1 replication by up to 90% whereas miRNAs with low mutual homologies (i.e. miR-34-1 and miR-508) impart only slight inhibition of HIV-1. Conclusion: We hypothesize that a recombinant GBV-C-based vector can be constructed which expresses several beneficial genetic motifs of the Flaviviridae without causing any side effects while stimulating a wide array of beneficial miRNAs that can more efficiently prevent HIV-1 infection.
The male gender bias in autism may be due to preferential depletions of oxytocin and arginine‐vasopressin receptors positive neurons exposed to certain fragrances during fetal development Leanna Sealey and Omar Bagasra M.D. Ph.D. Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. There is also evidence of impoverished language and empathy, and a profound inability to adopt another's viewpoint ‐ a failure to construct a “theory of mind” for interpreting another person's thoughts and intentions. In developed countries, it is now reported that 1%–1.5% of children have ASD, and in the US 2013 CDC report, approximately one in 80 children suffer from ASD. Although there is no reliable neurophysiological marker associated with ASDs, low levels of plasma oxytocin (OXY) and arginine‐vasopressin (AVP) have been reported. We have hypothesized that synthetic fragrances, which many of us are exposed to on a daily have potential to cause neurological damage to developing fetuses.Notably, the alarming rise in ASD parallels the rise in production of synthetic fragrances from petrochemicals and carcinogenic benzene‐based compounds. Numerous studies have shown that children with autism have significantly lower levels of OXY in plasma samples than their typical peers. Furthermore, in normal children, lower concentrations of OXY in plasma are associated with lower social and cognitive functioning. Here we show that male neuroblastoma cell lines, but not the female, exposure to fentomoles concentrations of certain fragments results in depletions of both OXY and AVP receptor + neurons. Our studies are the first to reveal a direct connection between fragrance exposures as the potential neuropathic agent that may cause autism and explains the gender bias. Grant Funding Source: Department of Education
Cancer therapies are generally non-specific for cancer cells and affect all cells in the body, resulting in severe side effects. We are working on an alternate method to present and treat cancer. Hypothesis: All replicating cells require energy in the forms of ATP and row material to reproduce. Cancer in a human body generally is the most energy consuming foci; therefore, it will be logical to down regulate the highest energy output pathways that do not harm the human being treated for a cancer. Two of the most prevalent cancers in are adenocarcinomas of prostate and breast. We hypothesized that if we treat cancer cells to a partial electron transport inhibitor that results in reduction in total ATP output it may significantly reduce cancer cell proliferation without interfering with normal functioning of other physiologic and immune functions. We chose Amygdalin (D-mandelonitrile-β-gentiobioside) which is found in seeds of prunasin family plants, such as peaches, apricots, almonds, apples, and other rosaceous plants and have been used as a traditional alternate medicine for treating terminal cancers and other illnesses. We evaluated the optimal dose that can inhibit various breast and prostate cancer cell lines as well two stem cell lines derived from neuroblastomas. We determine that cancer cell line and stem cell line proliferation rates were significantly inhibited 0.9 μM concentration of Amygdalin. This level of Amygdalin can be achieved by consuming 4-6 bitter almond and 2-3 apricot seed daily. In addition, we observed that Amygdalin induced apoptosis in the prostate and breast cancer cell lines. Citation Format: Omar Bagasra, Kareem Heslop, Krystal Livingston, Keneisha Corbett, Amarachi O. Ejiawoko, Leanna Sealey. Inhibitory Effect of Partial Electron Decoupling Agents as an Alternate Therapy for Cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5568. doi:10.1158/1538-7445.AM2015-5568
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