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HPVs representing the most common sexually transmitted disease are a group of carcinogenic viruses with different oncogenic potential. The immune system and the vaginal microbiome represent the modifiable and important risk factors in HPV-induced carcinogenesis. HPV infection significantly increases vaginal microbiome diversity, leading to gradual increases in the abundance of anaerobic bacteria and consequently the severity of cervical dysplasia. Delineation of the exact composition of the vaginal microbiome and immune environment before HPV acquisition, during persistent/progressive infections and after clearance, provides insights into the complex mechanisms of cervical carcinogenesis. It gives hints regarding the prediction of malignant potential. Relative high HPV prevalence in the general population is a challenge for modern and personalized diagnostics and therapeutic guidelines. Identifying the dominant microbial biomarkers of high-grade and low-grade dysplasia could help us to triage the patients with marked chances of lesion regression or progression. Any unnecessary surgical treatment of cervical dysplasia could negatively affect obstetrical outcomes and sexual life. Therefore, understanding the effect and role of microbiome-based therapies is a breaking point in the conservative management of HPV-associated precanceroses. The detailed evaluation of HPV capabilities to evade immune mechanisms from various biofluids (vaginal swabs, cervicovaginal lavage/secretions, or blood) could promote the identification of new immunological targets for novel individualized diagnostics and therapy. Qualitative and quantitative assessment of local immune and microbial environment and associated risk factors constitutes the critical background for preventive, predictive, and personalized medicine that is essential for improving state-of-the-art medical care in patients with cervical precanceroses and cervical cancer. The review article focuses on the influence and potential diagnostic and therapeutic applications of the local innate immune system and the microbial markers in HPV-related cancers in the context of 3P medicine. [ABSTRACT FROM AUTHOR]

Key message: Studied organic molecules in Pinus sylvestris L. seem to have acted as a safety net for metal transport, chelation and sequestration, allowing adaptation and growth under highly polluted conditions. Pinus sylvestris L. is known for its ability to survive in areas of highly elevated metal pollution, such as flotation tailings. The aim of the study was to estimate the content of selected organic molecules (including aliphatic low molecular weight organic acids (ALMWOAs), phenolic compounds and terpenes) and the physiological mechanisms underlying differences in metal/metalloid tolerance of P. sylvestris growing in unpolluted (soil) and polluted (flotation tailings) areas. The dominant ALMWOAs in rhizosphere soil extracts were citric acid followed by malic and oxalic acids, whereas in flotation tailings malic and oxalic acids. In roots and needles, the content of ALMOWAs was significantly higher in P. sylvestris L. tissue from flotation tailings in comparison to soil. Phenolic compounds were detected only in roots and needles, with a generally higher content of nearly all detected compounds from flotation tailings. The composition of roots did not contain all the compounds detected in needles. The profile of needles additionally contained four hydroxybenzoic, protocatechuic and salicylic acids. In pine needles, 24 volatile terpenes were identified in total. The content of these compounds in pine needles from the polluted area was markedly different from the unpolluted area. The dominant volatile monoterpenes in P. sylvestris L. needles from the unpolluted area was three carene, while in pine needles from the polluted area monoterpenes α-pinene was dominant. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the phytoextraction abilities of six tree species ( Acer platanoides L., Acer pseudoplatanus L., Betula pendula Roth, Quercus robur L., Tilia cordata Miller, Ulmus laevis Pall.), cultivated on mining sludge contaminated with arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), thallium (Tl), and zinc (Zn). All six tree species were able to survive on such an unpromising substrate. However, A. platanoides and T. cordata seedlings grown on the polluted substrate showed significantly lower biomass than control plants (55.5 and 45.6%, respectively). As, Cd, Cu, Pb, and Tl predominantly accumulated in the roots of all the analyzed tree species with the following highest contents: 1616, 268, 2432, 547, and 856 mg kg, respectively. Zn was predominantly localized in shoots with the highest content of 5801 and 5732 mg kg for U. laevis and A. platanoides, respectively. A. platanoides was the most effective in Zn phytoextaction, with a bioconcentration factor (BCF) of 8.99 and a translocation factor (TF) of 1.5. Furthermore, with the exception of A. pseudoplatanus, the analyzed tree species showed a BCF > 1 for Tl, with the highest value for A. platanoides (1.41). However, the TF for this metal was lower than 1 in all the analyzed tree species. A. platanoides showed the highest BCF and a low TF and could, therefore, be a promising species for Tl phytostabilization. In the case of the other analyzed tree species, their potential for effective phytoextraction was markedly lower. Further studies on the use of A. platanoides in phytoremediation would be worth conducting. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing that miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities.

Mushrooms are known to accumulate various concentrations of different arsenic (As) species depending on the metalloid residue level in the substrate. These species are of different toxicity to humans and may represent a significant health problem. In the present study, edible fungal species ( Agaricus bisporus, Pleurotus ostreatus, Pleurotus eryngii and Hericium erinaceus) grown separately on substrate containing different As species (As(III), As(V) and dimethylarsinic acid-DMA; each form individually) at different concentrations (0.1-0.8 mM) exhibited different accumulation of total As, the lowest being in A. b isporus (1.97 ± 0.14 mg kg DW) and the highest in P. o streatus HK35 (68.8 ± 19.0 mg kg DW) and P. e ryngii (68.0 ± 31.0 mg kg DW). The highest biomass was observed for A. b isporus, regardless of the As forms and their concentration (from 341.24 ± 13.16 to 378.49 ± 14.57 g). This confirms that A. b isporus is highly resistant to As due to low metalloid uptake and accumulation. To ensure quality of cultivated mushroom species and safety of final food product to human health, there is a necessity to control the level of substrate contamination with As. [ABSTRACT FROM AUTHOR]

Fibroblast growth factors (FGFs) deliver extracellular signals that govern many developmental and regenerative processes, but the mechanisms regulating FGF signaling remain incompletely understood. Here, we explored the relationship between intrinsic stability of FGF proteins and their biological activity for all 18 members of the FGF family. We report that FGF1, FGF3, FGF4, FGF6, FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22 exist as unstable proteins, which are rapidly degraded in cell cultivation media. Biological activity of FGF1, FGF3, FGF4, FGF6, FGF8, FGF10, FGF16, FGF17, and FGF20 is limited by their instability, manifesting as failure to activate FGF receptor signal transduction over long periods of time, and influence specific cell behavior in vitro and in vivo. Stabilization via exogenous heparin binding, introduction of stabilizing mutations or lowering the cell cultivation temperature rescues signaling of unstable FGFs. Thus, the intrinsic ligand instability is an important elementary level of regulation in the FGF signaling system. [ABSTRACT FROM AUTHOR]

In chronic lymphocytic leukemia (CLL), the worst prognosis is associated with TP53 defects with the affected patients being potentially directed to alternative treatment. Therapy administration was shown to drive the selection of new TP53 mutations in CLL. Using ultra-deep next-generation sequencing (NGS), we performed a detailed analysis of TP53 mutations' clonal evolution. We retrospectively analyzed samples that were assessed as TP53-wild-type (wt) by FASAY from 20 patients with a new TP53 mutation detected in relapse and 40 patients remaining TP53-wt in relapse. Minor TP53-mutated subclones were disclosed in 18/20 patients experiencing later mutation selection, while only one minor-clone mutation was observed in those patients remaining TP53-wt (n=40). We documented that (i) minor TP53 mutations may be present before therapy and may occur in any relapse; (ii) the majority of TP53-mutated minor clones expand to dominant clone under the selective pressure of chemotherapy, while persistence of minor-clone mutations is rare; (iii) multiple minor-clone TP53 mutations are common and may simultaneously expand. In conclusion, patients with minor-clone TP53 mutations carry a high risk of mutation selection by therapy. Deep sequencing can shift TP53 mutation identification to a period before therapy administration, which might be of particular importance for clinical trials. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 2 (FGF2) is one of the most studied growth factors to date. Most attention has been dedicated to the smallest, 18kDa FGF2 variant that is released by cells and acts through activation of cell-surface FGF-receptor tyrosine kinases. There are, however, several higher molecular weight (HMW) variants of FGF2 that rarely leave their producing cells, are retained in the nucleus and act independently of FGF-receptors (FGFR). Despite significant evidence documenting the expression and intracellular trafficking of HMW FGF2, many important questions remain about the physiological roles and mechanisms of action of HMW FGF2. In this review, we summarize the current knowledge about the biology of HMW FGF2, its role in disease and areas for future investigation. [ABSTRACT FROM AUTHOR]

Background Dysregulation of the balance between cell growth and death in the colonic epithelium is associated with cancer promotion. Understanding how cell death in this self-renewing tissue is regulated and how it is influenced by interaction of specific dietary components, especially fat and fibre, could lead to improved treatment and prevention strategies for cancer. Aim of the study The effects of two types of polyunsaturated fatty acids (PUFA5) - arachidonic (AA, 20:4, n-6) or docosahexaenoic (DHA, 22:6, n-3) - on the response of human colon adenocarcinoma HT-29 cells to sodium butyrate (NaBt) were investigated. Methods The parameters reflecting cell proliferation and cell death were studied together with oxidative response, mitochondrial membrane potential (MMP) and changes of selected regulatory molecules associated with cell cycle (p27Kipl and p21Cipl/WAF1) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose) polymerase - PARP, Bcl-2, Bax, Bak, Mcl-1). Results We demonstrated that pre-treatment with either AA or DHA attenuated cell cycle arrest caused by NaBt which is associated with modulation of p27Kipl, but not p21Cipl/WAF1 protein expression. On the other hand, PUFAs sensitised HT-29 cells to NaBt-induced apoptosis. An increased amount of floating cells and cells in the subG0/G1 population was associated with increased reactive oxygen species production, lipid peroxidation, decrease of MMP, activation of caspase-3 and -9, PARP cleavage, and decrease in the expression of anti-apoptotic Mcl-1 protein. The observed effects were modulated by the addition of a protein synthesis inhibitor, cycloheximide, and partially reversed by the antioxidant Trolox. Conclusions PUFAs may have beneficial effects in the colon enhancing apoptosis induced by NaBt. Alteration of cell membrane lipid composition and potentiation of oxidative processes accompanied by changes in mitochondria followed by stimulation of apoptotic cascade components play a role in these effects. [ABSTRACT FROM AUTHOR]