Due to increased lactate production during glucose metabolism, tumor cells heavily rely on efficient lactate transport to avoid intracellular lactate accumulation and acidification. Monocarboxylate transporter 4 (MCT4/SLC16A3) is a lactate transporter that plays a central role in tumor pH modulation. The discovery and optimization of a novel class of MCT4 inhibitors (hit 9a), identified by a cellular screening in MDA-MB-231, is described. Direct target interaction of the optimized compound 18n with the cytosolic domain of MCT4 was shown after solubilization of the GFP-tagged transporter by fluorescence cross-correlation spectroscopy and microscopic studies. In vitro treatment with 18n resulted in lactate efflux inhibition and reduction of cellular viability in MCT4 high expressing cells. Moreover, pharmacokinetic properties of 18n allowed assessment of lactate modulation and antitumor activity in a mouse tumor model. Thus, 18n represents a valuable tool for investigating selective MCT4 inhibition and its effect on tumor biology.

Ceylon leadwort (Plumbago zeylanica) is ornamental plant known for its pharmacological properties arising from the abundant production of various secondary metabolites. It often grows in lead polluted areas. The aim of presented study was to evaluate the survival strategy of P. zeylanica to lead toxicity via photosynthetic apparatus acclimatization. Shoots of P. zeylanica were cultivated on media with different Pb concentrations (0.0, 0.05, and 0.1 g Pb∙l−1). After a four-week culture, the efficiency of the photosynthetic apparatus of plants was evaluated by Chl a fluorescence measurement, photosynthetic pigment, and Lhcb1, PsbA, PsbO, and RuBisCo protein accumulation, antioxidant enzymes activity, and chloroplast ultrastructure observation. Plants from lower Pb concentration revealed no changes in photosynthetic pigments content and light-harvesting complex (LHCII) size, as well as no limitation on the donor side of Photosystem II Reaction Centre (PSII RC). However, the activity and content of antioxidant enzymes indicated a high risk of limitation on the acceptor side of Photosystem I. In turn, plants from 0.1 g Pb∙l−1 showed a significant decrease in pigments content, LHCII size, the amount of active PSII RC, oxygen-evolving complex activity, and significant remodeling of chloroplast ultrastructure indicated limitation of PSII RC donor side. Obtained results indicate that P. zeylanica plants acclimate to lead toxicity by Pb accumulation in roots and, depending on Pb concentration, by adjusting their photosynthetic apparatus via the activation of alternative (cyclic and pseudocyclic) electron transport pathways.

The study aimed at evaluating the response of common plum (Prunus domestica L.) microshoots during in vitro rooting in the presence of two phytoactive medium supplements, i.e. a dialyzate of pineapple pulp and a conditioned medium containing green algae Desmodesmus subspicatus exudates. Rooting efficiency was evaluated after 4 weeks of culture. During the root induction phase the content of phenolic compounds in shoot bases was determined and anatomical studies were conducted. Medium supplements were analyzed for the content of carbohydrates and phenolic acids. Both supplements were efficient in rooting induction of shoots of a difficult-to-root cultivar 'Węgierka Zwykła'. Medium supplementation allowed a significant reduction in the exogenous auxin content required for rooting. The highest rooting efficiencies on supplemented media were 28.9 and 27.8 %, in comparison with 33.3 % obtained in the control medium with doubled concentration of exogenous auxins. In the easy-to-root plum cultivar 'Węgierka Dąbrowicka' the rooting rate was slightly reduced in the presence of pineapple dialyzate, while in the presence of algal conditioned medium the rooting rate decreased substantially compared with the nonsupplemented medium. Approximately 30 % of 'Węgierka Dąbrowicka' shoots rooted on supplemented auxin-free media. The content of phenolic compounds accumulated in shoot bases during the root induction stage reflected the differences in rooting ability between both plum cultivars, indicating potential stressful conditions of the culture generated by the presence of phytoactive natural supplements. Anatomical study allowed to recognize the mode of dedifferentiation leading to adventitious rhizogenesis in the common plum. The results are discussed in relation to the composition of medium supplements and their potential root-promoting activity.

Generative processes have been evaluated in six European buttercup species in order to verify the hypothesis that the reproduction efficiency of clonal species is lower than that of nonclonal ones. The study covered common species (Ficaria verna, Ranunculus auricomus, R. bulbosus, R. cassubicus, R. lanuginosus) and the endangered R. illyricus. The following properties have been assessed: pollen viability (staining method), pollen grain germination and the pollen-tube elongation in pistil tissues (fluorescence microscopy), seed formation efficiency, seed viability (tetrazolium test) and germination ability by introducing factors interrupting dormancy (low temperature and gibberellin application). Additionally, the pistil morphology was documented for R. bulbosus, R. illyricus and R. cassubicus using SEM techniques. It was demonstrated that the reproductive efficiency, expressed as the production of viable seeds able to germinate, was significantly higher in the species reproducing sexually (especially in R. lanuginosus) compared to the clonal ones. However, the complexity observed leads to separation of an additional group (cluster) of apomictic species: R. auricomus and R. cassubicus, distinguished by the lowest pollen viability and a low ability of the seeds to germinate. In the vegetatively reproducing R. illyricus, the seed formation efficiency was just 13.2% despite the having highest number of pistils in its flowers. The developed seeds of this species observed in our experiment were viable, but in general effective methods to stimulate their germination have not been proposed yet. Here, the first comparative study concerning the biology of sexual reproduction of R. illyricus is presented in the context of its decreasing distribution in natural habitats.

The bird's-eye primrose (Primula farinosa L.) is an endangered species in Poland. The sole remaining, and critically endangered, population of approximately 300 flowering plants is located in the Beskid Sądecki Mountains (Jaworki, Poland). The genetic investigation was performed using highly variable microsatellite markers on a total of four populations: the Polish population and its three nearest known Slovak counterparts. We hypothesize that the Polish population is a relic of the previously much wider Central European mountain/lowland range and is thus genetically distinct from the rest of the Slovak stock. Clarification of this issue is needed before active protection interventions such as artificial supplementation can be carried out. Our results, particularly those from STRUCTURE Bayesian clustering, showed clear population structure within the dataset: all three Slovak populations were dominated by one genetic group, while the Polish population comprised mostly individuals dominated by the second genetic group. Only limited gene flow was observed between the Polish and Slovak populations. This demonstrates the distinct genetic makeup of the Jaworki population, which is probably the result of prolonged isolation from the rest of the P. farinosa range and admixture of genes from various lineages. Their origin could be determined by including plant material from the rest of the P. farinosa range, i.e., Scandinavian, Baltic, and Alpine/Carpathian locations, in a future study. The immediate practical application of our results is the recommendation that all supplementation interventions to the Jaworki population must be limited to plants produced from locally collected seeds.