Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

Amaranth functional cookies exert potential antithrombotic and antihypertensive activities

In this study, amaranth flour was used as an ingredient to prepare gluten-free cookies. The production process and attributes of amaranth cookies were characterised, and the potential use of amaranth flour as a functional ingredient was analysed. Cookies exhibited a non-uniform reddish brown colour and a cookie factor ratio of 4.5 ± 0.6. Storage studies indicated that after 3 weeks at room temperature cookies presented slight variations in the texture. Simulated gastrointestinal digestion of this product was able to release peptides capable of exerting potential antithrombotic and antihypertensive activities, IC₅₀ values of 0.22 ± 0.04 and 0.23 ± 0.03 mg mL⁻¹ protein, respectively. This work demonstrates for the first time that food made with amaranth flour exerts potential antithrombotic and antihypertensive activity. In conclusion, these amaranth cookies could be an alternative way of incorporating potentially health beneficial products for people who choose a conscious diet, including coeliac or vegan consumers.     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Optimised anaerobic treatment of house-sorted biodegradable waste and slaughterhouse waste in a high loaded half technical scale digester.

Anaerobic co-digestion of organic wastes from households, slaughterhouses and meat processing industries was optimised in a half technical scale plant. The plant was operated for 130 days using two different substrates under organic loading rates of 10 and 12 kgCOD.m(-3).d(-1). Since the substrates were rich in fat and protein components (TKN: 12 g.kg(-1) the treatment was challenging. The process was monitored on-line and in the laboratory. It was demonstrated that an intensive and stable co-digestion of partly hydrolysed organic waste and protein rich slaughterhouse waste can be achieved in the balance of inconsistent pH and buffering NH4-N. In the first experimental period the reduction of the substrate COD was almost complete in an overall stable process (COD reduction >82%). In the second period methane productivity increased, but certain intermediate products accumulated constantly. Process design options for a second digestion phase for advanced degradation were investigated. Potential causes for slow and reduced propionic and valeric acid degradation were assessed. Recommendations for full-scale process implementation can be made from the experimental results reported. The highly loaded and stable codigestion of these substrates may be a good technical and economic treatment alternative.     

A stochastic model for localized disturbances and its applications

A stochastic model for local disturbances, particularly for a temporal harmonic with random modulations in amplitude and/or phase, is proposed in this paper. Results for the second moment responses of a linear single-degree-of-freedom system to this type of stochastic loading demonstrate a significant change in response characteristics due to a small uncertainty. A local phenomenon may last much longer and resonance may be smeared to a broad range. Integrated with wavelet transform, the proposed approach may be used to model a random process with non-stationary frequency content. Especially, it can be effectively used for Monte Carlo simulation to generate large size of samples that have similar characteristics in time and frequency domains as a pre-selected mother sample has. The technique has a great potential for the case where uncertainty study is warranted but the available samples are limited.     

Profiling Voids Embedded in a Slab by a Non-Linear Model

In this paper, by applying a non linear model for the electromagnetic inverse scattering, a technique for the dielectric profiling of a planarly layered medium is investigated and applied to void localization and diagnostics inside a homogeneous lossless slab (one-dimensional geometry). Data are collected under plane wave multifrequency normal incidence. Suitable finite dimensional representations for the unknown functions are introduced and their influence on the model is discussed. The resulting functional equation is solved by the method of weighted residuals and the solution algorithm amounts to minimizing a non quadratic function, where particular attention is devoted to reduce the occurrence of local minima. Finally, the inversion algorithm is validated by applications to both simulated and experimental data.     

Retrograde Amnesia Induced by Drugs Acting on Different Molecular Systems.

The gamma aminobutyric acid-A (GABAA) agonist, muscimol, the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), and the inhibitor of the extracellularly regulated kinases (ERKs), UO 126, cause retrograde amnesia when administered to the hippocampus. In the present study, the authors found that they all cause retrograde amnesia for 1-trial inhibitory avoidance, not only when infused into the dorsal CA1 region of the hippocampus, but also when infused into the basolateral amygdala or the entorhinal, parietal, and posterior cingulate cortices. The posttraining time course of the effect of each drug was, however, quite different across brain structures. Thus, in all of them, NMDA receptors and the ERK pathway are indispensable for memory consolidation, and GABAA receptor activation inhibits memory consolidation: but in each case, their influence is interwoven differently. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The specific antibacterial proliferation of reactive arthritis synovial T cells is not due to their higher proportion of CD45RO+ cells compared to peripheral blood

OBJECTIVE: To determine the role of synovial fluid (SF) compared to peripheral blood (PB) CD45RO+ T cells in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: We examined SF and PB of 8 patients with a specific lymphocyte proliferation to Yersinia enterocolitica (n = 5) and Chlamydia trachomatis (n = 3). After depletion of the CD45RA+ T cell subset by dynabeads, the remaining T cells (> 95% CD45RO+) from PB and SF of these patients were again stimulated with these bacterial antigens. RESULTS: The mean stimulation index (SI) of these 8 patients with ReA (n = 5) and undifferentiated oligoarthritis (n = 3) was 30.3 +/- 21.86 in SF compared to 1.36 +/- 0.75 in PB. The enrichment of CD45RO+ cells influenced the antigen specific proliferative response of T cells neither in PB (SI = 1.75 +/- 1.35) nor in SF (26.1 +/- 24.05); the initial difference remained unchanged. CONCLUSION: Our findings suggest that the antigen specific lymphocyte proliferation obtained with SF cells is not due to abundance of nonspecific CD45RO+ T cells but can rather be taken as an indication of specific recognition of local bacterial antigens in ReA.     

Reliability Potential Of Epoxy Based Encapsulants For Automotive Applications

Automotive under-the-hood electronics often have to withstand temperatures up to 175 °C in combination with harsh environment conditions. This paper gives an overview about the reliability potential of epoxy based encapsulants for automotive applications. Therefore the resistance of epoxy molding compound against typical automotive fluids at temperature of use is analyzed. Six epoxy molding compounds available on the market, showing high temperature automotive potential have been carefully selected to undergo a media resistance testing. For this purpose a dedicated mold tool has been designed and manufactured to prepare these encapsulants for material testing. Thermo-mechanical, mechanical and thermal properties had been determined in initial state directly after molding and after storage in aggressive fluids typical for automotive applications as e.g. gas oil, automatic transmission fluid (ATF), brake fluid or accumulator acid at the respective temperature of use.