Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

The influence of lateral forces on the cell stiffness measurement by optical tweezers vertical indentation

We studied the lateral forces arising during the vertical indentation of the cell membrane by an optically trapped microbead, using back focal plane interferometry to determine force components in all directions. We analyzed the cell-microbead interaction and showed that indeed the force had also lateral components. Using the Hertz model, we calculated and compared the elastic moduli resulting from the total and vertical forces, showing that the differences are important and the total force should be considered. To confirm our results we analyzed cells from two breast cancer cell lines: MDA-MB-231 and HBL-100, known to have different cancer aggressiveness and hence stiffness.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.     

Thermal instabilities in semiconductor amplifiers

We introduce here a model which includes the thermal dynamics in the time evolution of a semiconductor multiple quantum well microresonator, driven by a coherent holding beam. The active layer is electrically pumped, in order to obtain population inversion, but it is maintained below the lasing threshold. We show that the inclusion of thermal effects introduces a Hopf instability which may dominate the dynamical behaviour of the system in some operational regimes. In those cases our numerical simulations show that both spatial patterns and cavity solitons perform a drift motion in the transverse direction. This motion develops over the slow time scale which characterizes thermal effects.     

Antioxidant activity of phenolic and phenylethanoid glycosides from Teucrium polium L

In the present study, the chemical composition and antioxidant activities of Teucrium polium L. (Lamiaceae) were assessed. Fractionation of methanol extract obtained from the aerial parts of T. polium yielded one new phenylethanoid glycoside, named poliumoside B, together with four known flavonoids, two iridoid glycosides and a known poliumoside. The structures of all of these compounds were elucidated on the basis of spectroscopic data from 1D and 2D NMR experiments and MS spectral analyses. The antioxidant activities of the crude extracts and of the isolated compounds were evaluated through tests such as DPPH radical-scavenging capability, reducing power, xanthine oxidase inhibitory effect and inhibition of linoleic acid peroxidation. The highest antioxidant activity was found in the n-butanol extract, which also contained active polyphenols, thus suggesting that this plant could be used as a source of natural molecules, to provide safe antioxidant additives and nutraceuticals. The structure–activity relationships of the isolated compounds are also discussed.     

Fuzzy mathematical morphology for biological image segmentation

Due to the imaging devices, real-world images such as biological images may have poor contrast and be corrupted by noise, so that regions in the images present soft edges and their segmentation turns out to be quite difficult. Fuzzy mathematical morphology can be successfully applied to segment biological images having such characteristics of vagueness and imprecision. In this work we introduce an approach based on fuzzy mathematical morphology to segment images of human oocytes in order to extract the oocyte region from the entire image. The approach applies fuzzy morphological operators to detect soft edges in the oocyte images, followed by morphological reconstruction operators to isolate the oocyte region. The main concepts from fuzzy mathematical morphology are briefly introduced and the results of applying fuzzy morphological operators are reported in low-contrast images of human oocytes.