Epigenetic regulation of glycosylation and the impact on chemo-resistance in breast and ovarian cancer

Glycosylation is one of the most fundamental posttranslational modifications in cellular biology and has been shown to be epigenetically regulated. Understanding this process is important as epigenetic therapies such as those using DNA methyltransferase inhibitors are undergoing clinical trials for the treatment of ovarian and breast cancer. Previous work has demonstrated that altered glycosylation patterns are associated with aggressive disease in women presenting with breast and ovarian cancer. Moreover, the tumor microenvironment of hypoxia results in globally altered DNA methylation and is associated with aggressive cancer phenotypes and chemo-resistance, a feature integral to many cancers. There is sparse knowledge on the impact of these therapies on glycosylation. Moreover, little is known about the efficacy of DNA methyltransferase inhibitors in hypoxic tumors. In this review, we interrogate the impact that hypoxia and epigenetic regulation has on cancer cell glycosylation in relation to resultant tumor cell aggressiveness and chemo-resistance.     

Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction

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Field larvicidal and oviposition repellent efficacy of three essential oil formulations for the control of filaria vector mosquito Culex quinquefasciatus Say (Diptera: Culicidae): A kill and push concept

Biological control of larval mosquitoes is in great demand due to the development of resistance against synthetic insecticides, environmental toxicity and the inability to protect habitats from further oviposition. In the present study, three botanical essential oils (BEOs) – citronella, eucalyptus, and pine oils – were formulated for the assessment of larvicidal and oviposition repellent efficacies against Culex quinquefasciatus Say, the filaria vector. The GC–MS profiling of BEOs showed the presence of 16 – 19 compounds covering 87.7–93% of oil composition. The resistance status of Culex quinquefasciatus population was evaluated with temephos (LC₅₀ = 0.001 ppm, LC₉₀ = 0.01 ppm). Larval bioassay of emulsifiable concentrate (EC) formulations prepared from eucalyptus and pine oils showed promising efficacy (LC₅₀ = 22.7 and 23.2 ppm) and LC₉₀ (63.8 and 62.4 ppm) compared to citronella oil EC (LC₅₀ = 43.4 ppm and LC₉₀ = 199.0 ppm). The field trials of eucalyptus + pine (1:1 ratio) EC showed 100% larval mortality for 3 weeks at 300 ppm compared to 2 weeks of individual oils. Further, the oviposition attraction index (OAI) for ECs of eucalyptus, pine, and their combination showed complete protection of breeding habitats from oviposition at 1st week and ?0.9 to ?1.0 OAI at 2nd week with slight reduction to ?0.5 at 3rd week. Citronella EC provided shortest larvicidal and oviposition repellent efficacy under the field conditions. The promising mosquitocidal activities of EC formulations of eucalyptus and pine or their combination suggest them as potential biocontrol vector control candidates over citronella oil.     

Huntington’s Disease: The Past,Present, and Future Search for Disease Modifiers

Huntington’s disease (HD) is an autosomal dominant genetic disorder that specifically causes neurodegeneration of striatal neurons, resulting in a triad of symptoms that includes emotional, cognitive, and motor disturbances. The HD mutation causes a polyglutamine repeat expansion within the N-terminal of the huntingtin (Htt) protein. This expansion causes aggregate formation within the cytosol and nucleus due to the presence of misfolded mutant Htt, as well as altered interactions with Htt’s multiple binding partners, and changes in post-translational Htt modifications. The present review charts efforts toward a therapy that delays age of onset or slows symptom progression in patients affected by HD, as there is currently no effective treatment. Although silencing Htt expression appears promising as a disease modifying treatment, it should be attempted with caution in light of Htt’s essential roles in neural maintenance and development. Other therapeutic targets include those that boost aggregate dissolution, target excitotoxicity and metabolic issues, and supplement growth factors.