The generally accepted mechanism of metformin’s effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin’s beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects. The aim of this review is to describe the potential anti-cancer and anti-aging properties of metformin and discuss the possible underlying mechanisms.

B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

Propolis is a natural bee-produced substance with antimicrobial, anti-inflammatory, and wound-healing properties, containing some components from the leaves, buds and resins of plants. It has been used for centuries for various health benefits. In this manuscript, our group reviewed the radioprotective effect of propolis using PubMed and Embase, and our review was conducted according to the PRISMA statement. Finally, 27 articles were included in this review, which includes the radioprotective effect of propolis from cell-based studies (n = 8), animal models (n = 14), and human trials (n = 5). Results reflected that the dosage forms of propolis extracted in the scientific literature were ethanolic extracts of propolis, a water-soluble derivate of propolis, or capsules. The efficacy of the radioprotective properties from propolis is extracted from the bibliography, as several compounds of this resinous mixture individually or synergistically are possible candidates that have the radioprotective effect. In fact, studies prior to 2011 lacked a comprehensive characterization of propolis due to the variability in active compounds among different batches of propolis and were limited to analytical techniques. Furthermore, in this manuscript, we have selected studies to include primarily propolis types from Brazil, Croatia, Egypt, European countries, and those commercialized in Spain. They all contained ethanolic extract of propolis (EEP) and were influenced by different dosage forms. EEP showed a significant presence of lipophilic bioactive compounds like flavones, flavonols, and flavanones.

Purpose: The ICRU 89 recommends reporting a set of vaginal dose points for cervical cancer treatments in order to quantify the goodness of implant. This vaginal dose reporting method for combined external beam radiotherapy and brachytherapy has been adopted by the EMBRACE II study protocol. Large variations in dose between patients and centers have been reported. The aim of this study was to determine possible discrepancies with consensus observers from the same institution. Therefore, the inter-and intra-observer variability were analyzed. Material and methods: For five patients, five experienced observers reported dose at the proposed vaginal points twice. The effect of inter-and intra-observer variations on total dose was analyzed by estimating biologically equivalent dose EQD 2 (α/β = 3 Gy). Coefficient of variation (CV) was used to provide a measure of data dispersion as a proportion to the mean. Results: The maximum inter-observer deviation among all patients and all points ranged from 0.5 Gy to 24.1 Gy in EQD 2. The higher inter-observer discrepancies were found at points at 3 o'clock and at 6 o'clock, with respect to ovoids. In case of the maximum intra-observer deviation, it ranged from 0.5 Gy to 14.2 Gy, with higher deviation points at 12 o'clock and 9 o'clock, with respect to ovoids. Conclusions: There is a need to ensure consistency in vaginal points reporting. The impact of the dosimetric inter-and intra-observer variability should also be considered when dealing with dose tolerances and limits due to the potential dose gradient.