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.     

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)     

Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus

Aspergillus fumigatus possesses two catalases (described as fast and slow on the basis of their electrophoretic mobility). The slow catalase has been recognized as a diagnostic antigen for aspergillosis in immunocompetent patients. The antigenic catalase has been purified. The enzyme is a tetrameric protein composed of 90-kDa subunits. The corresponding cat1 gene was cloned, and sequencing data show that the cat1 gene codes for a 728-amino-acid polypeptide. A recombinant protein expressed in Pichia pastoris is enzymatically active and has biochemical and antigenic properties that are similar to those of the wild-type catalase. Molecular experiments reveal that CAT1 contains a signal peptide and a propeptide of 15 and 12 amino acid residues, respectively. cat1-disrupted mutants that were unable to produce the slow catalase were as sensitive to H2O2 and polymorphonuclear cells as the wild-type strain. In addition, there was no difference in pathogenicity between the cat1 mutant and its parental cat1+ strain in a murine model of aspergillosis.     

Elimination of organic matter present in wastewaters from the cork industry by membrane filtration

BACKGROUND: The first stage of the cork industrial process generates great volumes of wastewater with moderate to high organic pollutant content that must be purified using different procedures, such as filtration by membranes. RESULTS: The tangential filtration of these wastewaters was studied using two different laboratory equipments. In the first one, three ultrafiltration (UF) membranes were tested, with molecular weight cut‐off (MWCO) 100 kDa and 30 kDa, and two operating modes were used: total recycling of permeate and retentate streams, and in continuous mode, without recycling both streams. In the total recycling UF experiments, the influence of the operating variables on the permeate flux was first established. The effectiveness of the different membranes was determined by evaluating the rejection coefficients for several parameters that measure the global pollutant content of the effluent. The values found for these rejection coefficients were in the following order: ellagic acid and color > absorbance at 254 nm > tannic content > COD (chemical oxygen demand). In the continuous mode experiments, the fouling mechanism for each membrane was established by fitting the experimental data to various filtration fouling models given in the literature. The operating mode in the second equipment was batch concentration, and additional experiments were carried out with an UF membrane (2 kDa), and with a NF membrane (with MWCO in the range 150–300 Da). CONCLUSIONS: The three operating modes tested provided different rejection levels of organic matter; among them, the most effective procedure tested was batch concentration mode using a NF membrane. Copyright © 2007 Society of Chemical Industry     

Immunoelectron localization of mitochondrial F1 factor in cryosections of heart muscle cells

Immunocytochemistry was used to investigate the localization of F1 ATPase in mitochondria of cryosections of adult mouse heart muscle cells. The initial aldehyde fixation was the only denaturation step for antigens. The fine structure was preserved with contrast enhancement as the sections were maintained hydrated, with the advantage that the entire procedure is completed in one working day. The reaction was highly specific, and entire mitochondria were labeled with the Protein A-gold complex. A new analytical technique, electron spectroscopic imaging (ESI), contributed to a better visualization of the localization of the F1 factor.