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a b s t r a c tWild Meripilus giganteus Karst belongs to the order Polyporales, in which some members are known to possess a wide range of pharmacological properties. M. giganteus showed to be rich in carbohydrates (74.49 g/100 g) and proteins (15.94 g/100 g), presenting low fat content (1.51 g/100 g). Chemical composition was determined by using chromatographic techniques. Also, various bioactive compounds were detected including all four tocopherol isoforms with d-and g-tocopherols being predominant (123.35 and 77.80 mg/100 g, respectively); five organic acids (oxalic, malic, quinic, citric and fumaric acids) with predominant malic acid (3.17 g/100 g); and three phenolic acids and related compounds (phydroxybenzoic, p-coumaric and cinnamic acids; 1010, 2420 and 340 mg/100 g, respectively). M. giganteus methanolic extract exhibited antioxidant activity tested by five different assays with the strongest potential in TBARS assay (EC 50 0.31 mg/mL); and antimicrobial activities (MIC/MBC 0.0125e5 mg/mL; MIC/ MFC 0.025e0.4 mg/mL). Furthermore, treatment of cervical carcinoma cell line (HeLa) led to reduction in cell's viability in MTT assay (IC 50 0.41 mg/mL after 48 h), induced process of apoptosis and inhibited cell's migration in vitro. The analysed extract was not toxic for zebrafish embryos (at 0.5 mg/mL), indicating its biosafety and potential application as a dietary supplement in chemoprevention.

Sox3/SOX3 gene is considered to be one of the earliest neural markers in vertebrates and it is implicated in the genetic cascades that direct brain formation. We have previously shown that early phases of differentiation and neural induction of NT2/D1 embryonal carcinoma cells by retinoic acid (RA) involve up‐regulation of the SOX3 gene expression. Here, we present identification of a novel positive regulatory promoter element involved in RA‐dependent activation of the SOX3 gene expression in NT2/D1 cells. This element represents a direct repeat 3‐like motif that directly interacts with retinoid X receptor (RXR) α in a sequence‐specific manner. It is capable of independently mediating the RA effect in a heterologous promoter context and its disruption caused significant reduction of RA/RXR transactivation of the SOX3 promoter. Furthermore, by using synthetic antagonists of retinoid receptors, we have shown for the first time, that RA‐induced SOX3 gene expression could be significantly down‐regulated by the synthetic antagonist of RXR. Also, this data showed that RXRs, but not RA receptors, are mediators of RA effect on the SOX3 gene up‐regulation in NT2/D1 cells. Presented data will be valuable for future investigation of SOX3 gene expression, not only in NT2/D1 model system, but also in diverse developmental, physiological and pathological settings.

Glioblastoma (GBM) is the most common, most aggressive and deadliest brain tumor. Recently, remarkable progress has been made towards understanding the cellular and molecular biology of gliomas. GBM tumor initiation, progression and relapse as well as resistance to treatments are associated with glioma stem cells (GSCs). GSCs exhibit a high proliferation rate and self-renewal capacity and the ability to differentiate into diverse cell types, generating a range of distinct cell types within the tumor, leading to cellular heterogeneity. GBM tumors may contain different subsets of GSCs, and some of them may adopt a quiescent state that protects them against chemotherapy and radiotherapy. GSCs enriched in recurrent gliomas acquire more aggressive and therapy-resistant properties, making them more malignant, able to rapidly spread. The impact of SOX transcription factors (TFs) on brain tumors has been extensively studied in the last decade. Almost all SOX genes are expressed in GBM, and their expression levels are associated with patient prognosis and survival. Numerous SOX TFs are involved in the maintenance of the stemness of GSCs or play a role in the initiation of GSC differentiation. The fine-tuning of SOX gene expression levels controls the balance between cell stemness and differentiation. Therefore, innovative therapies targeting SOX TFs are emerging as promising tools for combatting GBM. Combatting GBM has been a demanding and challenging goal for decades. The current therapeutic strategies have not yet provided a cure for GBM and have only resulted in a slight improvement in patient survival. Novel approaches will require the fine adjustment of multimodal therapeutic strategies that simultaneously target numerous hallmarks of cancer cells to win the battle against GBM.