Does Dietary Provision of Guanidinoacetic Acid Induce Global DNA Hypomethylation in Healthy Men and Women?

Background/Aims: Guanidinoacetic acid (GAA) is an experimental dietary additive and has been reported to induce methyl depletion when provided by the diet. However, no study evaluated whether supplemental GAA affects DNA methylation, a critical epigenetic process for genome regulation. Methods: In this open-label, repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA supplementation on global DNA methylation in 14 healthy participants (8 women and 6 men, age 22.2 +/- 2.3 years, body mass index 24.8 +/- 5.7). Results: Dietary provision of GAA had no effect on global DNA methylation, with 5-methylcytosine (m5C) nonsignificantly increased by 13.4% at postadministration when averaged across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14 participants at follow-up. Conclusion: Global DNA methylation seems to be unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men and women

Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells

Sox3/SOX3 is one of the earliest neural markers in vertebrates. Together with the Sox1/ SOX1 and Sox2/SOX2 genes it is implicated in the regulation of stem cell identity. In the present study, we performed the first analysis of epigenetic mechanisms (DNA methylation and histone marks) involved in the regulation of the human SOX3 gene expression during RA-induced neural differentiation of NT2/D1 cells. We show that the promoter of the human SOX3 gene is extremely hypomethylated both in undifferentiated NT2/D1 cells and during the early phases of RA-induced neural differentiation. By employing chromatin immunoprecipitation, we analyze several histone modifications across different regions of the SOX3 gene and their dynamics following initiation of differentiation. In the same timeframe we investigate profiles of selected histone marks on the promoters of human SOX1 and SOX2 genes. We demonstrate differences in histone signatures of SOX1, SOX2 and SOX3 genes. Considering the importance of SOXB1 genes in the process of neural differentiation, the present study contributes to a better understanding of epigenetic mechanisms implicated in the regulation of pluripotency maintenance and commitment towards the neural lineage

Structural, optical, and bioimaging characterization of carbon quantum dots solvothermally synthesized from o-phenylenediamine

Carbon quantum dots as a novel type of carbon nanomaterials have attracted the attention of many researchers because of their unique optical, antibacterial, and anticancer properties as well as their biocompatibility. In this study, for the first time, carbon quantum dots were prepared from o-phenylenediamine dissolved in toluene by a solvothermal route. Subsequently, the prepared carbon quantum dots were encapsulated into polyurethane films by a swelling–encapsulation–shrink method. Analyses of the results obtained by different characterization methods (AFM, TEM, EDS, FTIR, photoluminescence, and EPR) indicate the significant influence of the precursor on structural, chemical, and optical properties. Antibacterial and cytotoxicity tests showed that these dots did not have any antibacterial potential, because of the low extent of reactive oxygen species production, and showed low dark cytotoxicity. By investigating the cellular uptake, it was established that these dots penetrated the HeLa cells and could be used as probes for bioimaging

Employing Gamma-Ray-Modified Carbon Quantum Dots to Combat a Wide Range of Bacteria

Nowadays, it is a great challenge to develop new medicines for treating various infectious diseases. The treatment of these diseases is of utmost interest to further prevent the development of multi-drug resistance in different pathogens. Carbon quantum dots, as a new member of the carbon nanomaterials family, can potentially be used as a highly promising visible-light-triggered antibacterial agent. In this work, the results of antibacterial and cytotoxic activities of gamma-ray-irradiated carbon quantum dots are presented. Carbon quantum dots (CQDs) were synthesized from citric acid by a pyrolysis procedure and irradiated by gamma rays at different doses (25, 50, 100 and 200 kGy). Structure, chemical composition and optical properties were investigated by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, UV-Vis spectrometry and photoluminescence. Structural analysis showed that CQDs have a spherical-like shape and dose-dependent average diameters and heights. Antibacterial tests showed that all irradiated dots had antibacterial activity but CQDs irradiated with dose of 100 kGy had antibacterial activity against all seven pathogen-reference bacterial strains. Gamma-ray-modified CQDs did not show any cytotoxicity toward human fetal-originated MRC-5 cells. Moreover, fluorescence microscopy showed excellent cellular uptake of CQDs irradiated with doses of 25 and 200 kGy into MRC-5 cells

Highly Efficient Antibacterial Polymer Composites Based on Hydrophobic Riboflavin Carbon Polymerized Dots

Development of new types of antimicrobial coatings is of utmost importance due to increasing problems with pathogen transmission from various infectious surfaces to human beings. In this study, new types of highly potent antimicrobial polyurethane composite films encapsulated by hydrophobic riboflavin-based carbon polymer dots are presented. Detailed structural, optical, antimicrobial, and cytotoxic investigations of these composites were conducted. Low-power blue light triggered the composites to eradicate Escherichia coli in 30 min, whereas the same effect toward Staphylococcus aureus was reached after 60 min. These composites also show low toxicity against MRC-5 cells. In this way, RF-CPD composites can be used for sterilization of highly touched objects in the healthcare industry

Facile synthesis of L-cysteine functionalized graphene quantum dots as a bioimaging and photosensitive agent

Nowadays, a larger number of aggressive and corrosive chemical reagents as well as toxic solvents are used to achieve structural modification and cleaning of the final products. These lead to the production of residual, waste chemicals, which are often reactive, cancerogenic, and toxic to the environment. This study shows a new approach to the modification of graphene quantum dots (GQDs) using gamma irradiation where the usage of reagents was avoided. We achieved the incorporation of S and N atoms in the GQD structure by selecting an aqueous solution of L-cysteine as an irradiation medium. GQDs were exposed to gamma-irradiation at doses of 25, 50 and 200 kGy. After irradiation, the optical, structural, and morphological properties, as well as the possibility of their use as an agent in bioimaging and photodynamic therapy, were studied. We measured an enhanced quantum yield of photoluminescence with the highest dose of 25 kGy (21.60%). Both S- and N-functional groups were detected in all gamma-irradiated GQDs: amino, amide, thiol, and thione. Spin trap electron paramagnetic resonance showed that GQDs irradiated with 25 kGy can generate singlet oxygen upon illumination. Bioimaging on HeLa cells showed the best visibility for cells treated with GQDs irradiated with 25 kGy, while cytotoxicity was not detected after treatment of HeLa cells with gamma-irradiated GQDs

Graphene quantum dots as singlet oxygen producer or radical quencher - The matter of functionalization with urea/thiourea

Due to their low cost and possible green synthesis, high stability and resistance to photobleaching, graphene quantum dots (GQDs) can be considered as one of the class of carbon nanomaterials which may have great potential as an agent for photosensitized oxygen activation. In such a way, GQDs can be used as a theranostic agent in photodynamic therapy. In this work pristine GQDs, GQDs irradiated with gamma rays and GQDs doped with N and N, S atoms are produced using a simple, green approach. By using different techniques (AFM, HR-TEM, SEM-EDS, FTIR, XRD, PL and UV–Vis) we investigated structural and optical properties of the new types of GQDs. We showed that GQDs functionalized with thiourea (GQDs-TU) completely lost the ability to produce singlet oxygen (1O2) upon photoexcitation while functionalization with urea (GQDs-U) improves the capability of GQDs to produce 1O2 upon the same conditions. Thus, presented GQDs modification with urea seems like a promising approach for the production of the efficient photosensitizer. On the opposite, GQDs-TU are efficient [rad]OH quencher. Due to high singlet oxygen production and low cytotoxicity below 100 μg/mL against HeLa cells, GQDs-U is a good candidate as an agent in photodynamic therapy at this concentration. © 201

Graphene oxide size and structure pro-oxidant and antioxidant activity and photoinduced cytotoxicity relation on three cancer cell lines

Photoactive materials called photosensitizers can be used for treatment of different types of cancer in combination with light source. In this paper, we have investigated pro-oxidant and antioxidant potentials of four graphene based nanomaterials (graphene oxide-GO, graphene quantum dots-GQDs, carbon quantum dots-CQDs and N-doped carbon quantum dots-N-CQDs) depending on the presence/absence of visible light source. Structural and optical properties of these materials and their potentials for reactive oxygen species generation/quenching are investigated by applying different microscopy and spectroscopy techniques (transmission electron microscopy, FTIR, UV-Vis, photoluminescence, electron paramagnetic resonance). Results show that all types of quantum dots has pro-oxidant and antioxidant potentials whereas GO demonstrated only moderate antioxidant effect. The best free radical scavenger is CQDs sample in the absence of light. CQDs are the best singlet oxygen generator under blue light irradiation as well. To check photo-cytotoxicity of these materials, photo-cytotoxic concentrations of the GO, GQDs, CQDs and N-CQDs were determined for three cellular lines: human rhabdomyosarcoma (RD), cell line derived from human cervix carcinoma Hep2c (HeLa) and fibroblast cell line from murine (L2OB). Cytotoxicity test has indicated that all samples are much less photocytotoxic than cis-diamminedichloroplatinum (cis-DPP). The production method and doping of quantum dots affect the photodynamic activity of tested samples very much

Na+/K+-ATPase 2-subunit (AMOG) expression abrogates invasion of glioblastoma-derived brain tumor-initiating cells

BACKGROUND: Mechanisms of glioma invasion remain to be fully elucidated. Glioma cells within glioblastoma multiforme (GBM) range from well-differentiated tumor cells to less-differentiated brain tumor-initiating cells (BTICs). The β2-subunit of Na(+)/K(+)-ATPase, called the adhesion molecule on glia (AMOG), is highly expressed in normal glia but is thought to be universally downregulated in GBM. To test our hypothesis that expression of AMOG is heterogeneous in GBM and confers a less invasive phenotype, we compared it between BTICs and differentiated cells from patient-matched GBM and then tested GBM invasion in vitro after AMOG overexpression. METHODS: Immunohistochemistry, immunoblotting, and real-time PCR were used to characterize AMOG protein and mRNA expression in tumor samples, BTICs, and differentiated cells. Matrigel invasion assay, scratch assay, and direct cell counting were used for testing in vitro invasion, migration, and proliferation, respectively. RESULTS: While AMOG expression is heterogeneous in astrocytomas of grades II–IV, it is lost in most GBM. BTICs express higher levels of AMOG mRNA and protein compared with patient-matched differentiated tumor cells. Overexpression of AMOG decreased GBM cell and BTIC invasion without affecting migration or proliferation. Knockdown of AMOG expression in normal human astrocytes increased invasion. CONCLUSIONS: AMOG expression inhibits GBM invasion. Its downregulation increases invasion in glial cells and may also represent an important step in BTIC differentiation. These data provide compelling evidence implicating the role of AMOG in glioma invasion and provide impetus for further investigation