Beclin 1 interactome controls the crosstalk between apoptosis,autophagy and inflammasome activation: Impact on the aging process

Autophagy and apoptosis are crucial cellular housekeeping and tissue survival mechanisms. There is emerging evidence of important crosstalk between apoptosis and autophagy which can be linked to inflammasome activation. Beclin 1 is a platform protein which assembles an interactome consisting of diverse proteins which control the initiation of autophagocytosis and distinct phases in endocytosis. Recent studies have demonstrated that the anti-apoptotic Bcl-2 family members can interact with Beclin 1 and inhibit autophagy. Consequently, impaired autophagy can trigger inflammasome activation. Interestingly, the hallmarks of the ageing process include a decline in autophagy, increased resistance to apoptosis and a low-grade inflammatory phenotype. Age-related stresses, e.g. genotoxic, metabolic and environmental insults, enhance the expression of NF-κB-driven anti-apoptotic Bcl-2 proteins which repress the Beclin 1-dependent autophagy. Suppression of autophagocytosis provokes inflammation including NF-κB activation which further potentiates anti-apoptotic defence. In a context-dependent manner, this feedback defence mechanism can enhance the aging process or provoke tumorigenesis or cellular senescence. We will review the role of Beclin 1 interactome in the crosstalk between apoptosis, autophagy and inflammasomes emphasizing that disturbances in Beclin 1-dependent autophagy can have a crucial impact on the aging process.     

Personal Values that Support and Counteract Utilization of a Screening Test for Prostate Cancer

The main aim of the current research was to discover the personal values that may support men's prostate cancer screening decisions in the future. We asked for participants’ past behavior and future behavioral intentions, and also considered their real-life behavior. The sample consisted of 371 men, of which 93 were first-time patients at the Andrology Unit. The results show that Security value was related to past participation, while Achievement, Stimulation, and Traditions counteracted this. Present prostate-testing behavior was related only to higher Security values. Predictors of future behavioral intentions were Security, Self-direction, and Benevolence, which described 21% of the total variability. Considering informed decision-making processes, our results suggest that men who hold Security, Self-direction, and Benevolence values are more likely to participate in office-based initial screening. The study indicates the need to offer office-based initial screening to those age-eligible men whose values do not support participation.     

Low-FODMAP vs regular rye bread in irritable bowel syndrome:Randomized SmartPill~ study

AIM To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome(IBS) symptoms and to study gastrointestinal conditions with Smart Pill?.METHODS Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion,lower intraluminal pressure,higher colonic p H,different transit times,and fewer IBS symptoms than regular rye bread.The study was a randomized,double-blind,controlled cross-over meal study.Female IBS patients(n = 7) ate study breads at three consecutive meals during one day.The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day.Intraluminal p H,transit time,and pressure were measured by Smart Pill,an indigestible motility capsule.RESULTS Hydrogen excretion(a marker of colonic fermentation) expressed as area under the curve(AUC)(0-630 min) was [median(range)] 6300(1785-10800) ppm?min for low-FODMAP rye bread and 10 635(4215-13080) ppm?min for regular bread(P = 0.028).Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption(P = 0.063).Intraluminal pressure correlated significantly with total symptom score after regular rye bread(ρ = 0.786,P = 0.036) and nearly significantly after lowFODMAP bread consumption(ρ = 0.75,P = 0.052).We found no differences in p H,pressure,or transit times between the breads.Gastric residence of Smart Pill was slower than expected.Smart Pill left the stomach in less than 5 h only during one measurement(out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus.CONCLUSION Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread.No difference was found in median values of intraluminal conditions of the gastrointestinal tract.     

Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease

Introduction. Currently the only treatment for celiac disease is a lifelong gluten-free diet. The diet is, however, often burdensome, and thus new treatment options are warranted. We isolated proteases from germinating wheat grain naturally meant for total digestion of wheat storage proteins and investigated whether these enzymes can diminish toxic effects of gluten in vitro and ex vivo.

Methods. Pepsin and trypsin digested (PT) gliadin was pretreated with proteases from germinating wheat, whereafter the degradation was analyzed by HPLC-MS (high-performance liquid chromatography and mass spectroscopy) and sodium dodecyl sulphate polyacrylamide gel electrophoresis. The toxicity of cleaved PT-gliadin products was assessed in Caco-2 epithelial cells, celiac patient-derived T cells, and in human small intestinal mucosal organ culture biopsies.

Results. Proteases from germinating wheat degraded gliadin into small peptide fragments, which, unlike unprocessed PT-gliadin, did not increase epithelial permeability, induce cytoskeletal rearrangement or changes in ZO-1 expression in Caco-2 cells. Pretreated gliadin did not stimulate T cell proliferation in vitro or enhance the production of autoantibodies to culture supernatants and the activation of CD25+ lymphocytes in the organ culture to the same extent as unprocessed PT-gliadin.

Discussion. Germinating wheat enzymes reduce the toxicity of wheat gliadin in vitro and ex vivo. Further studies are justified to develop an alternative therapy for celiac disease.