Slaughterbartlett1045

Liposomal doxorubicin (L-DOX) is a popular drug formulation for the treatment of several cancer types (e.g., recurrent ovarian cancer, metastatic breast cancer, multiple myeloma, etc.), but poor nuclear internalization has hampered its clinical applicability so far. Therefore, novel drug-delivery nanosystems are actively researched in cancer chemotherapy. Here we demonstrate that DOX-loaded graphene oxide (GO), GO-DOX, exhibits much higher anticancer efficacy as compared to its L-DOX counterpart if administered to cellular models of breast cancer. Then, by a combination of live-cell confocal imaging and fluorescence lifetime imaging microscopy (FLIM), we suggest that GO-DOX may realize its superior performances by inducing massive intracellular DOX release (and its subsequent nuclear accumulation) upon binding to the cell plasma membrane. Reported results lay the foundation for future exploitation of these new adducts as high-performance nanochemotherapeutic agents.Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus-infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment (p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value (p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.Enzymes are key proteins performing the basic functional activities in cells. In humans, enzymes can be also responsible for diseases, and the molecular mechanisms underlying the genotype to phenotype relationship are under investigation for diagnosis and medical care. Here, we focus on highlighting enzymes that are active in different metabolic pathways and become relevant hubs in protein interaction networks. We perform a statistics to derive our present knowledge on human metabolic pathways (the Kyoto Encyclopaedia of Genes and Genomes (KEGG)), and we found that activity aldehyde dehydrogenase (NAD(+)), described by Enzyme Commission number EC 1.2.1.3, and activity acetyl-CoA C-acetyltransferase (EC 2.3.1.9) are the ones most frequently involved. By associating functional activities (EC numbers) to enzyme proteins, we found the proteins most frequently involved in metabolic pathways. With our analysis, we found that these proteins are endowed with the highest numbers of interaction partners when compared to all the enzymes in the pathways and with the highest numbers of predicted interaction sites. As specific enzyme protein test cases, we focus on Alpha-Aminoadipic Semialdehyde Dehydrogenase (ALDH7A1, EC 2.3.1.9) and Acetyl-CoA acetyltransferase, cytosolic and mitochondrial (gene products of ACAT2 and ACAT1, respectively; EC 2.3.1.9). With computational approaches we show that it is possible, by starting from the enzyme structure, to highlight clues of their multiple roles in different pathways and of putative mechanisms promoting the association of genes to disease."The main conclusions are that the ageing atrophy begins as early as around 25 years of age and thereafter accelerates and, for this muscle, is caused mainly by a loss of fibers and to a lesser extent by a reduction in fiber size [...].Background Psychosis recognizes an interaction between biological and social environmental factors. Adversities are now recognized to be consistently associated with psychotic-like experiences (PLEs). The purpose of this study was to describe the contents of paranoid symptoms and to focus on their relationship with bullying and victimization in help-seeking adolescents. Methods Help-seeking adolescents who screened positive for PLEs participated in the study. They performed a battery self-report questionnaire for data collection (paranoia the Specific Psychotic Experiences Questionnaire (SPEQ); the content of paranoid thoughts the Details of Threat (DoT); bullying victimization the Multidimensional Peer Victimization Scale (MPVS); depression the Children's Depression Inventory (CDI); and anxiety the Multidimensional Anxiety Scale (MASC)). Results The participants were 50 adolescents (52% female; mean age 170 months). The contents of their paranoid symptoms were related to victimization and, in particular, thetherapeutic intervention. CDK assay From a social psychiatry perspective, the prevention of bullying victimization is necessary.The quality of seeds in gene banks gradually deteriorates during long-term storage, which is probably, at least in part, a result of the progressive development of oxidative stress. Here, we report a greenhouse study that was carried out to test whether a novel approach of seed invigoration using priming with cathodic water (cathodic portion of an electrolysed calcium magnesium solution) could improve seedling emergence and growth in two deteriorated crop seeds. Fresh seeds of Pisum sativum and Cucurbita pepo were subjected to controlled deterioration to 50% viability at 14% seed moisture content (fresh weight basis), 40 °C and 100% relative humidity. The deteriorated seeds were thereafter primed with cathodic water, calcium magnesium solution and deionized water. In addition, to study the mechanism of the impacts of invigoration, the effects of such priming on the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and on the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase and catalase were also determined in the fresh and deteriorated seeds.