Betanin Attenuates Epigenetic Mechanisms and UV-Induced DNA Fragmentation in HaCaT Cells: Implications for Skin Cancer Chemoprevention.

Dermal photoaging refers to the skin's response to prolonged and excessive ultraviolet (UV) exposure, resulting in inflammation, changes to the tissue, redness, swelling, and discomfort. Betanin is the primary betacyanin in red beetroot (Beta vulgaris) and has excellent antioxidant properties. Yet, the specific molecular mechanisms of betanin in HaCaT cells have not been fully clarified. The objective of this study was to investigate the activity of betanin and the underlying mechanisms in HaCaT cells; furthermore, in this study, we explored the protective effect of various concentrations of betanin against UVB irradiation on HaCaT cells. Additionally, we assessed its influence on the transcription of various epigenetic effectors, including members of the DNA methyltransferase (DNMT) and histone deacetylase (HDAC) families. Our findings demonstrate a notable downregulation of genes in HaCaT cells, exhibiting diverse patterns upon betanin intake. We considered the involvement of DNMT and HDAC genes in distinct stages of carcinogenesis and the limited exploration of the effects of daily exposure dosages. Our results indicate that betanin may protect the skin from damage caused by UV exposure. Further investigation is essential to explore these potential associations.

Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes.

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2-1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

Effects of medicinal waters on the UV-sensitivity of human keratinocytes - a comparative pilot study.

Balneotherapy has been used to treat several diseases including locomotor, neurological and dermatological conditions. The basis of the "organic hypothesis" of medical balneology is that medicinal waters, especially thermal spa and hot spring waters, contain a high variability of organic components with possible biological effects, including UV photo-protection. The recent study aims to clarify this effect in a human keratinocyte cell line model. Results confirm that organic-rich extract of selected medicinal waters might protect skin-derived cells from DNA damage. These results give a clinical relevance to medicinal waters or pharmaceutical products prepared from them in preventing the adverse effects of solar or artificial UV radiation on the human skin.

Association between AIRE gene polymorphism and rheumatoid arthritis: a systematic review and meta-analysis of case-control studies.

Autoimmune regulator (AIRE) is a transcription factor that functions as a novel player in immunological investigations. In the thymus, it has a pivotal role in the negative selection of naive T-cells during central tolerance. Experimental studies have shown that single nucleotide polymorphism (SNP) alters transcription of the AIRE gene. SNPs thereby provide a less efficient negative selection, propagate higher survival of autoimmune T-cells, and elevate susceptibility to autoimmune diseases. To date, only rheumatoid arthritis (RA) has been analysed by epidemiological investigations in relation to SNPs in AIRE. In our meta-analysis, we sought to encompass case-control studies and confirm that the association between SNP occurrence and RA. After robust searches of Embase, PubMed, Cochrane Library, and Web of Science databases, we found 19 articles that included five independent studies. Out of 11 polymorphisms, two (rs2075876, rs760426) were common in the five case-control studies. Thus, we performed a meta-analysis for rs2075876 (7145 cases and 8579 controls) and rs760426 (6696 cases and 8164 controls). Our results prove that rs2075876 and rs760426 are significantly associated with an increased risk of RA in allelic, dominant, recessive, codominant heterozygous, and codominant homozygous genetic models. These findings are primarily based on data from Asian populations.

In Vivo Induction of Primary DNA Lesions upon Subchronic Oral Exposure to Multi-walled Carbon Nanotubes.

Comet assay was used for testing the potential genotoxicity of multi-walled carbon nanotubes after ingestion. Three rat strains were treated through oral gavage with 50 mg/kg/weekly nanoparticles for 90 days. Induced DNA lesions were studied in lymphocytes at 24 and 48 h following the first treatment. This was repeated at the end of the subchronic treatment in lymphocytes as well as peritoneal macrophages. A significant increase in the level of DNA lesions was measured in lymphocytes of Fischer-344 and Long-Evans rats in the first 24 h. Similar results were observed in their macrophages after 90 days. More significant differences were detected in the sensitivities of the strains. Fisher-344 rats proved the most sensitive and Wistar rats the most tolerant to the genotoxic effects of nanotubes. This may also have human relevance as populations with diverse genetic characteristics might present higher or lower susceptibility to the effects of exposure to ingested nanoparticles.

Natural UV-protective organic matter in thermal water.

Medical significance of the organic fractions of natural waters is still poorly understood. Nevertheless, there are putative biologically active organic compounds found in natural medical waters and related clay or mud samples. Organic fractions of five thermal (spa) water samples of different geochemical origin were tested for photo-biological effects. To study possible effects on the UV sensitivity of Salmonella typhimurium TA strains, the organic isolates were applied in the "plate incorporation" Ames test combined with UV-irradiation. Four samples showed measurable survival of TA100 his+ revertants following exposure to a normally lethal UV dose. Metabolic activation with a mammalian microsomal fraction (S9) elevated the effect detected (up to 61% survival). This is the first study to demonstrate the UV-protective property of organic matter in natural thermal water samples used in balneotherapy.

Can the use of medical muds cause genotoxicity in eukaryotic cells? A trial using comet assay.

Despite the lack of knowledge of their exact effects, peloids (natural muds) are widely applied in clinical treatment and prevention of different diseases, especially in rheumatic and gynecological disorders or skin diseases. Primarily we have information on their inorganic components, but only limited data are available on the organic components and nothing on their mechanism of chemical action. The objective of the present study was to detect the DNA-damaging effects (possible genotoxic effect) of peloid samples using the single-cell comet assay on Long Evans rat lymphocytes, human lymphocytes, and Eisenia fetida coelomocytes. Rat and human lymphocytes were exposed to the in toto peloid samples, in vitro. The Eisenia cells were extracted from the coelom of animals kept in the intact peloid sample. An indicator derived from the DNA fluorescence intensity was used in the statistical evaluation. The predominantly organic (Hévíz) sample showed a significant alteration from the negative control in several cases, while the inorganic (Kolop) applied did not. A higher quantity of organic compounds may have an important role in the emergence of DNA damage. The results revealed that medical muds have not only positive health effects but can also contain substances with potential human toxicity risk. Our research provides essential steps towards the creation of a toxicity profile and the possible safe use of peloids as medicinal therapy.