Endothelial dysfunction is one of the major factors in the pathogenesis of metabolic syndrome (MetS), and its molecular mechanisms are not completely understood. The present study aimed to examine the connection between nuclear factor2-related factor2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), heme oxygenase 1 (HO-1), and plasma asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) in people with MetS. Participants in the study were as follows: with MetS (n = 30) and without MetS (Control) (n = 14). Expression of Nrf2, NF-kB, and HO-1 was measured in peripheral blood mononuclear cells (PBMCs). Plasma ADMA was determined using the ELISA technique and MDA via the thiobarbituric acid method. Our study showed that mRNA of NF-kB, Nrf2, and HO-1 levels in PBMCs in the MetS group were significantly higher than in the controls by 53%, 130%, and 185% (p < 0.05), respectively. Similarly, elevated levels of MDA (by 78%, p < 0.001) and ADMA (by 18.7%, p < 0.001) were established in the MetS group. Our findings show the importance of transcription factor Nrf2, playing an integral role in the protection of the endothelium, and of NF-κB, a transcription factor mediating the inflammatory response in MetS. Knowledge of complex cellular–molecular mechanisms would allow the use of biomarkers such as Nrf2, NF-kB, HO-1, and ADMA for the assessment of endothelial dysfunction in clinical practice.

Infectious diseases have been treated using plants and their compounds for thousands of years. This knowledge has enabled modern techniques to identify specific antiviral remedies and to understand their molecular mechanism of action. Numerous active phytochemicals, such as alkaloids, terpenoids, polyphenols (phenolic acids, flavonoids, stilbenes, and lignans), coumarins, thiophenes, saponins, furyl compounds, small proteins, and peptides, are promising options for treating and preventing viral infections. It has been shown that plant-derived products can prevent or inhibit viral entry into and replication by host cells. Biotechnological advances have made it possible to engineer plants with an increased capacity for the production and accumulation of natural antiviral compounds. Plants can also be engineered to produce various types of antivirals (cytokines, antibodies, vaccines, and lectins). This study summarizes the current understanding of the antiviral activity of specific plant-derived metabolites, emphasizing their mechanisms of action and exploring the enormous potential of plants as biological factories.

The wound-healing effect of St. John’s Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how “free” HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract “protected” by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the “free” SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

Cyanoprokaryotes are distributed worldwide and they produce various bioactive compounds, including cyanotoxins. The major route of human exposure to cyanotoxins is the oral intake by using contaminated drinking water, by incidental intake of contaminated water during recreational and professional activities, and by consuming contaminated food or dietary supplements prepared from cyanobacteria. The prolonged chronic exposure to low concentrations of cyanotoxins provokes cell damage and may increase the risk for cancer development. Due to the variety of cyanotoxin chemical structures, different mechanisms of their toxic effects are known. At the same time, some of the natural compounds produced by cyanoprokaryotes have anticancer potential and are promising sources for the development of novel drugs. This chapter is dedicated to the target mechanisms behind the effects of the widely distributed cyanotoxins with an impact on human health, microcystins, nodularins, and cylindrospermopsin.

Introduction: Elevated plasma levels of uric acid (UA) are considered an independent risk factor for hypertension, diabetes, cardiovascular disease, endothelial and vascular damage, obesity, and metabolic syndrome. Even physiological concentrations of soluble UA have been proved to induce gene expression of macrophage-secreted inflammatory cytokines and stimulate production of reactive oxygen species in mature adipocytes. UA is also described as a powerful endogenous plasma antioxidant, which reveals a paradox of duality for this parameter. Aim: The aim of this study was to investigate the effect of UA on expression of antioxidant defense related enzymes in cultured J744A.1 macrophage cell line. Materials and methods: Mouse macrophage J744A.1 cells were treated with uric acid at increasing concentrations of 200 to 800 μM. Changes in expression levels of genes related to the metabolism of glutathione – glutamate-cysteine ligase, catalytic subunit (GCLc), glutathione peroxidase 1 (GPx1), glutathione reductase (GR) and glutathione synthetase (GS) were analyzed. Gene expression levels were calculated using the 2^-ΔΔCt method. Results: When UA is applied in concentrations of 200 µM and 400 µM, cell viability did not change significantly. Higher, pathophysiological concentrations of 600 μM, 800 μM UA, and 1000 μM of UA caused significant decrease in cell viability to 95.81% (p<0.01), 76.22% (p<0.001), and 18.01% (p<0.001), respectively. UA treatment in concentrations of 200 μM, 400 μM, 500 μM, and 800 μM induced significant transcription levels of glutathione reductase – 8.14 (p<0.05), 7.15 (p<0.01), 22.07 (p<0.001), and 27.77 (p<0.01), respectively, and of glutathione synthetase – 13.71 (p<0.01), 13.05 (p<0.05), 18 (p<0.01), and 48.60 (p<0.01) folds, respectively. GCLc and GPx1 genes were transcriptionally activated by higher (500 μM and 800 μM) concentrations of UA. For these UA concentrations the measured levels of mRNA were 7.51 (p<0.05) and 12 fold (p<0.05) higher than the non-treated control for GCLc and 1.90 (p<0.05) and 1.93 (p<0.01) for GPx1. Significant difference in the GCLc expression was found between the 200 μM and 500 μM (p<0.05) and 800 μM (p<0.01) treated cells. mRNA levels were significantly different between 400 μM and 800 μM (p<0.05) for both GCLc and GR genes. Very strong correlation was found between GCLc and GR (0.974, p=0.005) and GS (0.935, p=0.020) expression and between GS and GR (0.886, p=0.045) expression levels. Conclusions: It appears that 500 μM and pathophysiological concentrations (800 μM) of UA induce antioxidant cell response in J744A.1 macrophages proved by the indicative elevation GCL, GPx1, GR, and GS transcription. GR and GS can be stimulated even by lower concentrations (200 μM and 400 μM) indicating that glutathione metabolism in macrophages is tightly regulated in order to keep adequate GSH levels.