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Mechanistically, p38 mitogen-activated protein kinase (MAPK) activation is critical for EF-24-triggered apoptosis via activating protein phosphatase 2A (PP2A) to attenuate extracellular-regulated protein kinase (ERK) activities in HL-60 AML cells. In the clinic, patients with AML expressing high level of PP2A have the most favorable prognoses compared to various solid tumors. Taken together, our results indicate that EF-24 is a potential therapeutic agent for treating AML, especially for cancer types that lose the function of the PP2A tumor suppressor.Infection with hepatitis B virus (HBV) remains a global health challenge. Approximately 292 million people worldwide are chronically infected with HBV and the annual mortality from the infection is approaching 900,000. Despite the availability of an effective prophylactic vaccine, millions of individuals are at risk of potentially fatal complicating cirrhosis and hepatocellular carcinoma. Current drug treatments can suppress viral replication, slow the progression of liver fibrosis, and reduce infectivity, but can rarely clear the viral covalently closed circular DNA (cccDNA) that is responsible for HBV persistence. Alternative therapeutic strategies, including those based on viral gene silencing by harnessing the RNA interference (RNAi) pathway, effectively suppress HBV replication and thus hold promise. RNAi-based silencing of certain viral genes may even lead to disabling of cccDNA during chronic infection. This review summarizes different RNAi activators that have been tested against HBV, the advances with vectors used to deliver artificial potentially therapeutic RNAi sequences to the liver, and the current status of preclinical and clinical investigation.Roads do not only have a detrimental effect on nature (fragmenting habitats, isolating populations and threatening biodiversity), but the increasing numbers of wildlife-vehicle collisions are also a direct threat to humans and property. Therefore, mitigation measures should be placed with respect to animal distribution and movements across the roads. We simulated red deer, roe deer and wild boar movements in Lithuania, focusing on the two main highways A1 and A2. Using regional habitat suitability and linkage models, we calculated movement pathways and the most probable crossing zones in 2009. The prognostic value of these models was tested by comparing the pathway predictions to the real roadkill and roadkill cluster locations in 2002-2009 and 2010-2017. Across both periods and on both highways, the roe deer roadkill locations were significantly closer to the model-predicted pathways than to randomly selected points. The prediction of roadkill locations was also good for wild boar. The roe deer roadkill clusters and multi-species clusters were significantly better represented by the model than by random distribution. On both highways, the biggest differences in distance from the predicted locations were near big cities. We recommended wildlife movement models as an additional tool for planning wildlife-vehicle collision mitigation measures and we advise measures for increasing their predicting power.Streptococcus mutans is the principal biofilm forming oral pathogen associated with dental caries. Studies have shown that Candida albicans, a commensal oral fungus is capable of forming pathogenic mixed-species biofilms with S. mutans. The treatment of bacterial and fungal infections using conventional antimicrobial agents has become challenging due to the antimicrobial resistance of the biofilm mode of growth. The present study aimed to evaluate the efficacy of secretory components of Lactobacillus plantarum 108, a potentially promising probiotic strain, against S. mutans and C. albicans single and mixed-species biofilms. L. plantarum 108 supernatant inhibited S. mutans and C. albicans single-species biofilms as shown by XTT reduction assay, crystal violet assay, and colony forming units counting. The probiotic supernatant significantly inhibited the S. mutans and C. albicans mixed-species biofilm formation. The pre-formed mixed-species biofilms were also successfully reduced. Confocal microscopy showed poorly developed biofilm architecture in the probiotic supernatant treated biofilms. Moreover, the expression of S. mutans genes associated with glucosyltransferase activity and C. albicans hyphal specific genes (HWP1, ALS1 and ALS3) were down-regulated in the presence of the probiotic supernatant. Altogether, the data demonstrated the capacity of L. plantarum 108 supernatant to inhibit the S. mutans and C. albicans mixed-species biofilms. Herein, we provide a new insight on the potential of probiotic-based strategies to prevent bacterial-fungal mixed-species biofilms associated with dental caries.The influence of a change in nutrition on the oral microbiota are discussed in literature, but usually only changes of population mean values are reported. This paper introduces simple methods to also analyse and report the variability of patients' reactions considering data from the culture analysis of oral biofilm. The framework was illustrated by an experimental study exposing eleven participants to different nutrition schemes in five consecutive phases. Substantial inter-individual variations in the individual reactions were observed. A new coherence index made it possible to identify 14 instances where the direction of individual changes tended to coincide with the direction of the mean change with more than 95% probability. Ciforadenant The heterogeneity in variability across different bacteria species was limited. This allowed us to develop recommendations for sample sizes in future studies. For studies measuring the concentration change of bacteria as a reaction to nutrition change, the use of replications and analysis of the variability is recommended. In order to detect moderate effects of a change in nutrition on the concentration of single bacterial taxa, 30 participants with three repetitions are often adequate. Insights into the relationship between nutrition and the microbial composition can be helpful for the development of dietary habits that promote the establishment of a healthy microbial flora and can therefore prevent the initiation of oral diseases such as caries and periodontitis.
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