In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers.

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE's hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound's cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs' potential metastatic properties in concentrations below IC50 values. Despite relatively high IC50 values (63.3-1737.6 µM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.

Vimentin Association with Nuclear Grooves in Normal MEF 3T3 Cells.

Vimentin, an intermediate filament protein present in leukocytes, blood vessel endothelial cells, and multiple mesenchymal cells, such as mouse embryonic fibroblasts (MEF 3T3), is crucial for various cellular processes, as well as for maintaining the integrity and durability (stability) of the cell cytoskeleton. Vimentin intermediate filaments (VIFs) adhere tightly to the nucleus and spread to the lamellipodium and tail of the cell, serving as a connector between the nucleus, and the cell's edges, especially in terms of transferring mechanical signals throughout the cell. How these signals are transmitted exactly remains under investigation. In the presented work, we propose that vimentin is involved in that transition by influencing the shape of the nucleus through the formation of nuclear blebs and grooves, as demonstrated by microscopic observations of healthy MEF (3T3) cells. Grooved, or "coffee beans" nuclei, have, to date, been noticed in several healthy cells; however, these structures are especially frequent in cancer cells-they serve as a significant marker for recognition of multiple cancers. We observed 288 MEF3T3 cells cultured on polyhydroxyoctanoate (PHO), polylactide (PLA), and glass, and we identified grooves, coaligned with vimentin fibers in the nuclei of 47% of cells cultured on PHO, 50% of cells on glass, and 59% of cells growing on PLA. We also observed nuclear blebs and associated their occurrence with the type of substrate used for cell culture. We propose that the higher rate of blebs in the nuclei of cells, cultured on PLA, is related to the microenvironmental features of the substrate, pH in particular.

How sustainable are biopolymers? Findings from a life cycle assessment of polyhydroxyalkanoate production from rapeseed-oil derivatives.

The main purpose of the article was to compare different scenarios of biopolymer production and their impacts on the environment using Life Cycle Assessment. Three alternative polyhydroxyalkanoates (PHA: amorphous PHA and poly(3-hydroxybutyrate), P(3HB)) production scenarios were considered to assess its environmental impact: Scenario A - Production of mcl-PHA/P(3HB) from crude vegetable oil; Scenario B - Production of P(3HB) with biodiesel by-product; Scenario C - Production of mcl-PHA/P(3HB) from used vegetable oil. Subject to the scenario considered, it was shown that the environmental efficiency of PHA production is highly dependent on carbon sources used, and it is strongly supporting production of mcl-PHA instead of P(3HB). As LCA study shows, due to low yield of P(3HB) in comparison to mcl-PHA production in considered processes, all the P(3HB) production scenarios have higher impacts than the production of mcl-PHA. Production processes based on bacterial fermentation had its impacts related mostly to the raw materials used and to its separation phase. Additionally, using secondary materials instead of raw ones, namely used oil instead of virgin oil, gives significant improvement with regard to environmental impact. The resource efficiency is also the identified as the key factor with sensitivity analysis that indicates the possible increase of biopolymer yield as the most beneficial factor. Biobased polymers have big environmental potential but still need significant improvement with regard to their manufacturing processes in order to become more economically benign. Preferably production of these microbial polymers should be integrated into biorefinery blocks, where such waste stream arises (e.g. biodiesel production plant).