Cytoprotective Effects and Intranuclear Localization of Sulfur-Containing Derivative of Buckminsterfullerene.

Background: There is a growing interest in exploring the biological characteristics of nanoparticles and exploring their potential applications. However, there is still a lack of research into the potential genotoxicity of fullerene derivatives and their impact on gene expression in human cells. In this study, we investigated the effects of a water-soluble fullerene derivative, C60[C6H4SCH2COOK]5H (F1), on human embryonic lung fibroblasts (HELF).

Dose-Response Effect of Various Concentrations of Cl-Containing Water-Soluble Derivatives of C Fullerenes on a Selective Regulation of Gene Expression in Human Embryonic Lung Fibroblasts (HELF).

Background: The new synthesized water-soluble derivatives of C fullerenes are of a great interest to researchers since they can potentially be promising materials for drug delivery, bioimaging, biosonding, and tissue engineering. Surface functionalization of fullerene derivatives changes their chemical and physical characteristics, increasing their solubility and suitability for different biological systems applications, however, any changes in functionalized fullerenes can modulate their cytotoxicity and antioxidant properties. The toxic or protective effect of fullerene derivatives on cells is realized through the activation or inhibition of genes and proteins of key signaling pathways in cells responsible for regulation of cellular reactive oxygen species (ROS) level, proliferation, and apoptosis.

East Asian forest-steppe outpost in the Khanka Lowland (Russia) and its conservation.

The Khanka Lowland forest-steppe is the most eastern outpost of the Eurasian steppe biome. It includes unique grassland plant communities with rare steppe species. These coenosis have changed under the influence of anthropogenic activity, especially during the last 100 years and included both typical steppe species and nemoral mesophytic species.

Satellite III (1q12) Copy Number Variation in Cultured Human Skin Fibroblasts from Schizophrenic Patients and Healthy Controls.

Background: The chromosome 1q12 region harbors the genome's largest pericentromeric heterochromatin domain that includes tandemly repeated satellite III DNA [SatIII (1)]. Increased SatIII (1) copy numbers have been found in cultured human skin fibroblasts (HSFs) during replicative senescence. The aim of this study was to analyze the variation in SatIII (1) abundance in cultured HSFs at early passages depending on the levels of endogenous and exogenous stress.

Antipsychotics Affect Satellite III (1q12) Copy Number Variations in the Cultured Human Skin Fibroblasts.

The fragment of satellite III (f-SatIII) is located in pericentromeric heterochromatin of chromosome 1. Cell with an enlarged f-SatIII block does not respond to various stimuli and are highly stress-susceptible. The fraction of f-SatIII in the cells of schizophrenia patients changed during antipsychotic therapy.

Effects of Aqueous Dispersions of C, C, and Gd@C Fullerenes on DNA Oxidative Damage/Repair and Apoptosis in Human Embryonic Lung Fibroblasts.

Fullerenes and metallofullerenes play an active role in homeostasis of reactive oxygen species and may cause oxidative damage to cells. As pristine fullerenes are a basis for derivatization, studying oxidative DNA damage/repair and apoptosis is important in terms of genotoxicity and cytotoxicity for their biomedical application. Aqueous dispersions of C, C, and Gd@C (5 nM and 1.

The Phosphonate Derivative of C Fullerene Induces Differentiation towards the Myogenic Lineage in Human Adipose-Derived Mesenchymal Stem Cells.

Inductors of myogenic stem cell differentiation attract attention, as they can be used to treat myodystrophies and post-traumatic injuries. Functionalization of fullerenes makes it possible to obtain water-soluble derivatives with targeted biochemical activity. This study examined the effects of the phosphonate C fullerene derivatives on the expression of myogenic transcription factors and myogenic differentiation of human mesenchymal stem cells (MSCs).

Effects of Aqueous Dispersions of C, C and Gd@C Fullerenes on Genes Involved in Oxidative Stress and Anti-Inflammatory Pathways.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory responses are of particular importance.

Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C, C, and Gd@C in concentrations of 5 nM and 1.

Water-soluble fullerene-based nanostructures with promising antiviral and myogenic activity.

Here we report a straightforward method for the synthesis of a water-soluble C60 fullerene derivative decorated with five residues of phosphonic acid. Self-assembly of the synthesized compound in aqueous solution leads to the formation of nanostructures with unprecedented myogenic and antiviral activity.

Effects of Functionalized Fullerenes on ROS Homeostasis Determine Their Cytoprotective or Cytotoxic Properties.

Background: Functionalized fullerenes (FF) can be considered regulators of intracellular reactive oxygen species (ROS) homeostasis; their direct oxidative damage-as well as regulation of oxidant enzymes and signaling pathways-should be considered.

Methods: Uptake of two water-soluble functionalized C fullerenes with different types of aromatic addends (ethylphenylmalonate and thienylacetate) in human fetal lung fibroblasts, intracellular ROS visualization, superoxide scavenging potential, NOX4 expression, NRF2 expression, oxidative DNA damage, repair genes, cell proliferation and cell cycle were studied.

Results & Conclusion: The intracellular effects of ethylphenylmalonate C derivative (FF1) can be explained in terms of upregulated NOX4 activity.

Diversion of the Arbuzov reaction: alkylation of C-Cl instead of phosphonic ester formation on the fullerene cage.

We report an "inversed" Arbuzov reaction of the fullerene derivatives CArCl with trialkyl phosphites P(OR) producing alkylated fullerene derivatives CArR (R = Me, Et, iPr, nBu) with almost quantitative yields. This reaction provides a convenient synthetic route for the preparation of a large variety of functionalized fullerene derivatives with tailored properties, e.g.

Antioxidant Properties of Fullerene Derivatives Depend on Their Chemical Structure: A Study of Two Fullerene Derivatives on HELFs.

Oxidative stress is a major issue in a wide number of pathologies (neurodegenerative, cardiovascular, immune diseases, and cancer). Because of this, the search for new antioxidants is an important issue. One of the potential antioxidants that has been enthusiastically discussed in the past twenty years is fullerene and its derivatives.

Changes of and /NF-B Expression Levels Induced by Cell-Free DNA in Different Cell Types.

Cell-free DNA (cfDNA) is a circulating DNA of nuclear and mitochondrial origin mainly derived from dying cells. Recent studies have shown that cfDNA is a stress signaling DAMP (damage-associated molecular pattern) molecule. We report here that the expression profiles of cfDNA-induced factors NRF2 and NF-B are distinct depending on the target cell's type and the GC-content and oxidation rate of the cfDNA.

Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response.

We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis.

Multiple Ways of cfDNA Reception and Following ROS Production in Endothelial Cells.

Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells.

GC-Rich DNA Fragments and Oxidized Cell-Free DNA Have Different Effects on NF-kB and NRF2 Signaling in MSC.

It has been established that cell-free DNA circulating in the bloodstream affects cells. The characteristics of cfDNA depend on the physiological state of the organism. As we showed previously, diseases can cause either GC-enrichment of the cell-free DNA pool or its oxidation.

Functionalized Fullerene Increases NF-κB Activity and Blocks Genotoxic Effect of Oxidative Stress in Serum-Starving Human Embryo Lung Diploid Fibroblasts.

The influence of a water-soluble [60] fullerene derivative containing five residues of 3-phenylpropionic acid and a chlorine addend appended to the carbon cage (F-828) on serum-starving human embryo lung diploid fibroblasts (HELFs) was studied. Serum deprivation evokes oxidative stress in HELFs. Cultivation of serum-starving HELFs in the presence of 0.

Toxic and DNA damaging effects of a functionalized fullerene in human embryonic lung fibroblasts.

Water-soluble fullerenes have been studied as potential nanovectors and therapeutic agents, but their possible toxicity is of concern. We have studied the effects of F-828, a soluble fullerene [C60] derivative, on diploid human embryonic lung fibroblasts (HELFs) in vitro. F-828 causes complex time-dependent changes in ROS levels.

GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells.

Background: Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA.

Principal Findings: Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay and γH2AX, foci).

Oxidized extracellular DNA suppresses nitric oxide production by endothelial NO synthase (eNOS) in human endothelial cells (HUVEC).

Circulating DNA from patients with cardiovascular diseases reduce the synthesis of NO in endothelial cells, which is probably related to oxidative modification of DNA. To test this hypothesis, HUVEC cells were cultured in the presence of DNA containing ~1 (nonoxidized DNA), 700, or 2100 8-oxodG/10(6) nucleosides. Nonoxidized DNA stimulated the synthesis of NO, which was associated with an increase in the expression of endothelial NO synthase.

[Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate TLR-dependent signal pathway and supress apoptosis].

Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood.

Enhanced expression of iNOS in human endothelial cells during long-term culturing with extracellular DNA fragments.

NO synthesis by endothelial cells plays an important role in normal function of the cardiovascular system. This work was designed to evaluate the role of variations in properties of extracellular DNA in the regulation of NO synthesis. We studied the effect of four DNA samples with various base sequences (50 ng/ml) on functional activity of endothelial cells HUVEC during 24-h culturing.

[Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation].

Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes.

[The response of human cancer stem cells on low-dose X-ray exposure].

Recently we found that transposition of homologous chromosomes 1q12 loci towards the nuclear centre and activation of the chromosomal nucleolus-forming regions (NFR) are observed in human lymphocytes after exposure to low doses of X-radiation (10 cGy). These cell reactions were studied for human breast cancer stem cell cultures. There are two cell types in cell culture from single donor: with two (type 1) and three (type 2) loci of 1q12.