Cytotoxic and proliferation-inhibitory activity of natural and synthetic fungal tropolone sesquiterpenoids in various cell lines.

Fungal specialized metabolites are known for their potent biological activities, among which tropolone sesquiterpenoids (TS) stand out for their diverse bioactivities. Here, we report cytotoxic and proliferation inhibitory effects of the recently discovered TS compounds 4-hydroxyxenovulene B and 4-dihydroxy norpycnidione, and the structurally related 4-hydroxy norxenovulene B and xenovulene B. Inhibition of metabolic activity after TS treatment was observed in Jurkat, PC-3 and FAIK3-5 cells, whereas MDA-MB-231 cells were unresponsive to treatment.

Prediction Intervals for Overdispersed Poisson Data and Their Application in Medical and Pre-Clinical Quality Control.

In pre-clinical and medical quality control, it is of interest to assess the stability of the process under monitoring or to validate a current observation using historical control data. Classically, this is done by the application of historical control limits (HCL) graphically displayed in control charts. In many applications, HCL are applied to count data, for example, the number of revertant colonies (Ames assay) or the number of relapses per multiple sclerosis patient.

In vivo alkaline comet assay: Statistical considerations on historical negative and positive control data.

The alkaline comet assay is frequently used as in vivo follow-up test within different regulatory environments to characterize the DNA-damaging potential of different test items. The corresponding OECD Test guideline 489 highlights the importance of statistical analyses and historical control data (HCD) but does not provide detailed procedures. Therefore, the working group "Statistics" of the German-speaking Society for Environmental Mutation Research (GUM) collected HCD from five laboratories and >200 comet assay studies and performed several statistical analyses.

The calculation of historical control limits in toxicology: Do's, don'ts and open issues from a statistical perspective.

For reporting toxicology studies, the presentation of historical control data and the validation of the concurrent control group with respect to historical control limits have become requirements. However, many regulatory guidelines fail to define how such limits should be calculated and what kind of target value(s) they should cover. Hence, this manuscript is aimed to give a brief review on the methods for the calculation of historical control limits that are in use as well as on their theoretical background.

Gap Junction Dependent Cell Communication Is Modulated During Transdifferentiation of Mesenchymal Stem/Stromal Cells Towards Neuron-Like Cells.

transdifferentiation of patient-derived mesenchymal stem/stromal cells (MSCs) into neurons is of special interest for treatment of neurodegenerative diseases. Although there are encouraging studies, little is known about physiological modulations during this transdifferentiation process. Here, we focus on the analysis of gap junction dependent cell-cell communication and the expression pattern of gap junction-building connexins during small molecule-induced neuronal transdifferentiation of human bone marrow-derived MSCs.

Prediction intervals for overdispersed binomial data with application to historical controls.

Bioassays are highly standardized trials for assessing the impact of a chemical compound on a model organism. In that context, it is standard to compare several treatment groups with an untreated control. If the same type of bioassay is carried out several times, the amount of information about the historical controls rises with every new study.