Genistein modulates gene activity in psoriatic patients

Despite the impressive advancements in the treatment of psoriasis over the past two decades, there is still a need for further improvement. As previously shown in the literature, genistein (5,7-dihydroxy-3-(4-hydroxyphenyl) chromen-4-one), naturally occurring plant compound displays multidirectional action, also in relation to alleviating psoriasis symptoms. In this work we focused our attention on genistein impact on expression of genes when treating moderate-to-severe psoriasis patients. Testing the effects of this isoflavone on transcript levels in both skin specimens and peripheral blood cells of four psoriatic subjects, we found that this compound modulated activities of genes coding for anti-psoriatic members and anti-inflammatory mediators of inflammation. It impairs the activity of certain genes which are overexpressed in psoriasis, while stimulating the expression of other transcripts that are repressed in dermatosis

Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids

Flavonoids were found previously to modulate efficiency of synthesis of glycosaminoglycans (GAGs), compounds which are accumulated in cells of patients suffering from mucopolysaccharidoses (MPSs). The aim of this work was to determine effects of different flavonoids (genistein, kaempferol, daidzein) used alone or in combinations, on expression of genes coding for proteins involved in GAG metabolism. Analyses with DNA microarray, followed by real-time qRT-PCR revealed that genistein, kaempferol and combination of these two compounds induced dose- and time-dependent remarkable alterations in transcript profiles of GAG metabolism genes in cultures of wild-type human dermal fibroblasts (HDFa). Interestingly, effects of the mixture of genistein and kaempferol were stronger than those revealed by any of these compounds used alone. Similarly, the most effective reduction in levels of GAG production, in both HDFa and MPS II cells, was observed in the presence of genistein, keampferol and combination of these compounds. Forty five genes were chosen for further verification not only in HDFa, but also inMPS II fibroblasts by using real-time qRT-PCR. Despite effects on GAG metabolism-related genes, we found that genistein, kaempferol and mixture of these compounds significantly stimulated expression of TFEB. Additionally, a decrease inMTOR transcript level was observed at these conditions

Effects of flavonoids on expression of genes involved in cell cycle regulation and DNA replication in human fibroblasts

Flavonoids have been studied as potential agents in medicine for many years. Among them, genistein was found to be active in various biological systems, mainly in prevention of cancer. Our recent work supported the idea that genistein also impacts multiple cellular processes in healthy fibroblasts; however, its effects on cell cycle related pathways remained to be elucidated. Thus, in this work, high throughput screening with microarrays coupled to real-time quantitative Reverse Transcription PCR analyses was employed to study the changes in expression of key genes associated with cell cycle regulation and/or DNA replication in response to genistein, kaempferol, daidzein, and mixtures of genistein and either kaempferol or daidzein. Among them, genistein was found as the most significantly modulating, in a time- and dosedependent manner, compound of activity of studied genes, whose products are involved in different phases of the cell cycle and/or in regulatory processes important for DNA replication and cell growth. It considerably reduced the efficiency of expression of genes coding for MCM2-7 and MCM10 helicases, as well as some other proteins involved in the S phase control. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of CDKN1A, CDKN1C, CDKN2A, CDKN2B, CDKN2C, and GADD45A genes, as well as down-regulation of several mRNAs specific for this stage, demonstrated by transcriptomic assessments. We believe that studies described in this paper will be helpful in elucidating molecular mechanisms of action of genistein as modulator of cell cycle and inhibitor of DNA replication in humans

Activities of genes controlling sphingolipid metabolism in human fibroblasts treated with flavonoids

Natural flavonoids such as genistein, kaempferol and daidzein were previously found to be able to reduce efficiency of glycosaminoglycan synthesis in cells of patients suffering from mucopolysaccharidoses, inherited metabolic diseases with often brain disease symptoms. This feature was employed to test these compounds as potential drugs for treatment other neuronopathic lysosomal storage disorders, in which errors in sphingolipid metabolism occur. In this report, on the basis of DNA microarray analyses and quantitative real time PCR experiments, we present evidence that these compounds modify expression of genes coding for enzymes required for metabolism of sphingolipids in human dermal fibroblasts (HDFa). Expression of several genes involved in sphingolipid synthesis was impaired by tested flavonoids. Therefore, it is tempting to speculate that they may be considered as potential drugs in treatment of LSD, in which accumulation of sphingolipids, especially glycosphingolipids, occurs. Nevertheless, further studies on more advances models are required to test this hypothesis and to assess a therapeutic potential for flavonoids in this group of metabolic brain diseases

Models in the Research Process of Psoriasis

Psoriasis is an ancient, universal chronic skin disease with a significant geographical variability, with the lowest incidence rate at the equator, increasing towards the poles. Insights into the mechanisms responsible for psoriasis have generated an increasing number of druggable targets and molecular drugs. The development of relevant in vitro and in vivo models of psoriasis is now a priority and an important step towards its cure. In this review, we summarize the current cellular and animal systems suited to the study of psoriasis. We discuss the strengths and limitations of the various models and the lessons learned. We conclude that, so far, there is no one model that can meet all of the research needs. Therefore, the choice model system will depend on the questions being addressed

Anti-SARS-CoV-2S Antibody Levels in Healthcare Workers 10 Months after the Administration of Two BNT162b2 Vaccine Doses in View of Demographic Characteristic and Previous COVID-19 Infection

Antibody levels that confer full protection against SARS-CoV-2 infection after the administration of different vaccine brands as well as the factors influencing the humoral immune response have been analyzed extensively ever since the vaccination program was launched in late 2020. The aim of this study was to determine anti-SARS-CoV-2S antibody titers in 100 healthcare workers 10 months after the administration of two BNT162b2 vaccine doses, and to investigate the influence of demographic characteristics, the presence of comorbidities and history of COVID-19 infection. The results were compared with antibody levels that were determined eight months after the administration of two BNT162b2 vaccine doses in our previous study. Antibody levels in venous blood serum were measured by the ECLIA method with the use of the Roche Cobas e411 analyzer. In all tested subjects, antibody titers remained high 10 months after vaccination, particularly in recovered COVID-19 patients, and only a minor decrease was observed relative to the values noted two months earlier

Impact of isoflavone genistein on psoriasis in in vivo and in vitro investigations

Genistein is applied worldwide as an alternative medicament for psoriasis (Ps) because of its anti‐ inflammatory activity and perceived beneficial impact on the skin. Hereby, we report our in vivo and in vitro investigations to supplement scientific research in this area. The reduction of clinical and biochemical scores in mild to moderate Ps patients taking genistein, its safety, good tolerability with no serious adverse events or discontinuations of treatment, no dose‐limiting toxicities, negligible changes in pharmacodynamic parameters and remarkable serum interleukin level alterations were documented in this study. A certain regression of the Ps phenotype was visible, based on photo‐documented Ps lesion evaluation. Through in vitro experiments, we found that genistein reduced IL‐17A and TNF‐α induced MAPK, NF‐κB, and PI3K activation in normal human epidermal keratinocytes. Moreover, at the mRNA level of genes associated with the early inflammatory response characteristic for Ps (CAMP, CCL20, DEFB4A, PIK3CA, S100A7, and S100A9) and key cellular signalling (MTORC1 and TFEB), we showed that this isoflavone attenuated the increased response of IL‐17A‐ and TNF‐α‐related pathways. This allows us to conclude that genistein is a good candidate for Ps treatment, being attractive for co‐pharmacotherapy with other drugs

Molecular action of isoflavone genistein in the human epithelial cell line HaCaT.

Due to its strong proliferation-reducing effects on keratinocytes, and also anti-inflammatory properties, the isoflavone genistein has already been proposed as a possible antipsoriatic compound. As there is still no detailed information on this topic, we examined the effects of genistein by using an in vitro model of both, normal and "psoriasis-like" keratinocytes at this stage of our work exhaustively testing the selected flavonoid in a mono-treated experimental design. Gene expression studies revealed transcriptional changes that confirms known disease-associated pathways and highlights many psoriasis-related genes. Our results suggested that aberrant expression of genes contributing to the progress of psoriasis could be improved by the action of genistein. Genistein prevented "cytokine mix" as well as TNF-α-induced NF-κB nuclear translocation, with no effect on the PI3K signaling cascade, indicating the luck of turning this pathway into NF-κB activation. It could have attenuated TNF-α and LPS-induced inflammatory responses by suppressing ROS activation. Regardless of the type of keratinocyte stimulation used, reduction of cytokine IL-8, IL-20 and CCL2 production (both at RNA and protein level) following genistein treatment was visible. Because investigations of other groups supported our commentary on potential administration of genistein as a potential weapon in the armamentarium against psoriasis, it is believed that this paper should serve to encourage researchers to conduct further studies on this subject

Interleukin (IL)-8, IL-20, and IL-CCL2 production determined in HaCaT cells treated correspondingly with 100 μM genistein (GEN), 1 μM methotrexate (MTX), proinflammatory “cytokine mix” at a concentration of 2 ng/mL in each compound of the mix (ACT) and incubated with 100 μM genistein (ACT + GEN) or 1 μM methotrexate (ACT + MTX), 10 ng/mL tumor necrosis factor-α (TNF-α) and incubated with 100 μM genistein (TNF-α + GEN) or 1 μM methotrexate (TNF-α + MTX), or 1 μg/mL lipopolysaccharide (LPS) alone, and incubated with 100 μM genistein (LPS + GEN) or 1 μM methotrexate (LPS + MTX).

<p>DMSO-treated, unstimulated cells were used as control (NACT). The data are presented as the means ± standard deviation (SD) from three independent experiments. Comparisons among groups were performed using a one-way ANOVA with Tukey’s HSD test and significant differences are marked with * for <i>p</i> ≤ 0.05 and with ** for <i>p</i> ≤ 0.001.</p