Central focus in modern anticancer nanosystems is given to certain types of nanomaterials such as graphene oxide (GO). Its functionalization with polyethylene glycol (PEG) demonstrates high delivery efficiency and controllable release of proteins, bioimaging agents, chemotherapeutics and anticancer drugs. GO–PEG has a good biological safety profile, exhibits high NIR absorbance and capacity in photothermal treatment. To investigate the bioactivity of PEGylated GO NPs in combination with NIR irradiation on colorectal cancer cells we conducted experiments that aim to reveal the molecular mechanisms of action of this nanocarrier, combined with near-infrared light (NIR) on the high invasive Colon26 and the low invasive HT29 colon cancer cell lines. During reaching cancer cells the phototoxicity of GO–PEG is modulated by NIR laser irradiation. We observed that PEGylation of GO nanoparticles has well-pronounced biocompatibility toward colorectal carcinoma cells, besides their different malignant potential and treatment times. This biocompatibility is potentiated when GO–PEG treatment is combined with NIR irradiation, especially for cells cultured and treated for 24 h. The tested bioactivity of GO–PEG in combination with NIR irradiation induced little to no damages in DNA and did not influence the mitochondrial activity. Our findings demonstrate the potential of GO–PEG-based photoactivity as a nanosystem for colorectal cancer treatment.
GDP-mannose is the mannosyl donor for the glycosylation reactions and is synthesized by GDP-mannose pyrophosphorylase from GTP and d-mannose-1-phosphate; in Saccharomyces cerevisiae this enzyme is encoded by the PSA1/VIG9/SRB1 gene. We isolated the Kluyveromyces lactis KlPSA1 gene by complementing the osmotic growth defects of S. cerevisiae srb1/psa1 mutants. KlPsa1p displayed a high degree of similarity with other GDP-mannose pyrophosphorylases and was demonstrated to be the functional homologue of S. cerevisiae Psa1p. Phenotypic analysis of a K. lactis strain overexpressing the KlPSA1 gene revealed changes in the cell wall assembly. Increasing the KlPSA1 copy number restored the defects in O-glycosylation, but not those in N-glycosylation, that occur in K. lactis cells depleted for the hexokinase Rag5p. Overexpression of GDP-mannose pyrophosphorylase also enhanced heterologous protein secretion in K. lactis as assayed by using the recombinant human serum albumin and the glucoamylase from Arxula adeninivorans.
30 August 2022 in Oxidative Medicine and Cellular Longevity
Nowadays, the environmentally friendly approach to everyday life routines including body supplementation with pharma‐, nutraceuticals and dietary supplements gains popularity. This trend is implemented in pharmaceutical as well as cosmetic and antiageing industries by adopting a newly developed green chemistry approach. Following this trend, a new type of solvents has been created, called Natural Deep Eutectic Solvents (NADES), which are produced by plant primary metabolites. These solvents are becoming a much better alternative to the already established organic solvents like ethanol and ionic liquids by being nontoxic, biodegradable, and easy to make. An interesting fact about NADES is that they enhance the biological activities of the extracted biological compounds. Here, we present our results that investigate the potential antiageing effect of CiAPD14 as a NADES solvent and three plant extracts with it. The tested NADES extracts are from propolis and two well‐known medicinal plants—Sideritis scardica and Plantago major. Together with the solvent, their antiageing properties have been tested during the chronological lifespan of four Saccharomyces cerevisiae yeast strains—a wild type and three chromatin mutants. The chromatin mutants have been previously proven to exhibit characteristics of premature ageing. Our results demonstrate the potential antiageing activity of these NADES extracts, which was exhibited through their ability to confer the premature ageing phenotypes in the mutant cells by ameliorating their cellular growth and cell cycle, as well as by influencing the activity of some stress‐responsive genes. Moreover, we have classified their antiageing activity concerning the strength of the observed bioactivities.
Complex interactions among DNA and nuclear proteins maintain genome organization and stability. The nuclear proteins, particularly the histones, organize, compact, and preserve the stability of DNA, but also allow its dynamic reorganization whenever the nuclear processes require access to it. Five histone classes exist and they are evolutionarily conserved among eukaryotes. The linker histones are the fifth class and over time, their role in chromatin has been neglected. Linker histones interact with DNA and the other histones and thus sustain genome stability and nuclear organization. Saccharomyces cerevisiae is a brilliant model for studying linker histones as the gene for it is a single-copy and is non-essential. We, therefore, created a linker histone-free yeast strain using a knockout of the relevant gene and traced the way cells age chronologically. Here we present our results demonstrating that the altered chromatin dynamics during the chronological lifespan of the yeast cells with a mutation in ARP4 (the actin-related protein 4) and without the gene HHO1 for the linker histone leads to strong alterations in the gene expression profiles of a subset of genes involved in DNA repair and autophagy. The obtained results further prove that the yeast mutants have reduced survival upon UVA/B irradiation possibly due to the accelerated decompaction of chromatin and impaired proliferation. Our hypothesis posits that the higher-order chromatin structure and the interactions among chromatin proteins are crucial for the maintenance of chromatin organization during chronological aging under optimal and UVA-B stress conditions.