Moreover, hepatic expression of the apoptotic BAX significantly increased and the anti-apoptotic Bcl-2 significantly decreased in the liver specimen; biomarkers of intrinsic apoptosis. In conclusion; crocin attenuates experimentally induced hepato-carcinogenesis via modulation of oxidative/apoptotic signaling. Namely, crocin induced hepatic expression of Nrf2 with downstream modulation of endogenous HO-1 and Keap-1 signaling with modulation of various key players of apoptosis including; c-JNK, p53, TRAIL, caspase-8, BAX, and Bcl-2.Immobilisation of natural compounds on solid supports to amplify antimicrobial properties has reported successful results, but modifications to physico-chemical properties can also imply modifications from a toxicological viewpoint. This work aimed to study the immobilising process of gallic acid in the antibacterial activity of L. innocua and its toxicological properties in vivo using Caenorhabditis elegans. The experiment was based on obtaining the minimum bactericidal concentration for free and immobilised gallic acid by comparing lethality, locomotion behaviour, chemotaxis and thermal stress resistance on C.elegans at those concentrations. The results showed a lowering minimum bactericidal concentration and modifications to nematode responses. Increased lethality and velocity of movements was observed. Immobilisation increased the repellent effect of gallic acid with a negative chemotaxis index. Thermal stress resistance was also affected, with higher mortality for immobilised gallic acid compared to bare particles and free gallic acid. Thus despite evidencing a generalised increase in the toxicity of gallic acid in vivo, lowering the minimum bactericidal concentration allowed a bacterial reduction of 99 % with less than one third of mortality for the nematodes exposed to free gallic acid.A BCS-based biowaiver allows extrapolation of drug product bioequivalence (when applicable) based on the BCS class of the drug and in vitro dissolution testing. Drug permeability and solubility considerations for adult BCS might not apply directly to paediatric subpopulations and bridging of adult and paediatric formulations should be undertaken with caution.  https://www.selleckchem.com/products/gsk-lsd1-2hcl.html  The aims of this study were to (i.) identify compounds which would change drug solubility classification in the paediatric population, and (ii.) to assess the risk of extending BCS-based biowaiver criteria into paediatric products of these compounds. Amoxicillin, prednisolone, and amlodipine were selected as the model compounds. Dissolution studies of IR formulations of these compounds were conducted with USP II (paddle) and mini-paddle apparatus, in media of three pHs (pH 1.2, 4.5 and 6.8). Three dissolution setups were tested (1) 'typical' BCS-based biowaiver conditions, (2) "BE" setup derived from BE study protocols (volume 250 mL), and (3) "paediatric" setup based on representative volume for the paediatric population (50 mL). Results revealed that extension of regulated BCS-based biowaiver criteria for paediatric application is not as simple as scaling down volumes. It was further shown that BCS-based biowaiver criteria should not be applied when there is the risk of change of the drug solubility class, from the adult to paediatric populations. A deeper knowledge of the paediatric gastrointestinal environment is still lacking and would assist in refining the biopharmaceutical tools needed to appropriately evaluate formulation performance across age groups. This would potentially reduce the number of clinical studies required and speed up formulation development.Systemic exposure of inhaled drugs is used to estimate the local lung exposure and assess systemic side effects for drugs with local pharmacological targets. Predicting systemic exposure is therefore central for successful development of drugs intended to be inhaled. Currently, these predictions are based mainly on data from in vitro experiments, but the accuracy of these predictions might be improved if they were based on data with higher physiological relevance. In this study, systemic exposure was simulated by applying biopharmaceutics input parameters from isolated perfused rat lung (IPL) data to a lung model developed in MoBi® as an extension to the full physiologically-based pharmacokinetic (PBPK) model in PK-Sim®. These simulations were performed for a set of APIs with a variety of physicochemical properties and formulation types. Simulations based on rat IPL data were also compared to simulations based on in vitro data. The predictive performances of the simulations were evaluated by comparing simulated plasma concentration-time profiles to clinical observations after pulmonary administration. Simulations using IPL-based input parameters predicted systemic exposure well, with predicted AUCs within two-fold of the observed value for nine out of ten drug compounds/formulations, and predicted Cmax values within two-fold for eight out of ten drug compounds/formulations. Simulations using input parameters based on IPL data performed generally better than simulations based on in vitro input parameters. These results suggest that the developed model in combination with IPL data can be used to predict human lung absorption for compounds with different physicochemical properties and types of inhalation formulations.Epigenetics is mainly comprised of features that regulate genomic interactions thereby playing a crucial role in a vast array of biological processes. Epigenetic mechanisms such as DNA methylation and histone modifications influence gene expression by modulating the packaging of DNA in the nucleus. A plethora of studies have emphasized the importance of analyzing epigenetics data through genome-wide studies and high-throughput approaches, thereby providing key insights towards epigenetics-based diseases such as cancer. Recent advancements have been made towards translating epigenetics research into a high throughput approach such as genome-scale profiling. Amongst all, bioinformatics plays a pivotal role in achieving epigenetics-related computational studies. Despite significant advancements towards epigenomic profiling, it is challenging to understand how various epigenetic modifications such as chromatin modifications and DNA methylation regulate gene expression. Next-generation sequencing (NGS) provides accurate and parallel sequencing thereby allowing researchers to comprehend epigenomic profiling.