The role of miRNA-221 and miRNA-126 in patients with benign metastasizing leiomyoma of the lung: an overview with new interesting scenarios

Molecular Biology Reports - Benign metastasizing leiomyoma (BML) is a rare disease characterized by extrauterine benign leiomyomatosis in patients with a previous or concomitant history of uterine...     

Effects of coupled upper limbs movements on postural stabilisation

The preference for in-phase association of coupled cyclic limbs movements is well described (mirror-symmetrical patterns) and this is demonstrated by the ease of performing in-phase movements compared to anti-phase ones. The hypothesis of this study is that the easiest movement patterns are those with minor postural activity. The aim of this study was to describe postural activity in standing subjects in the sagittal and frontal planes during the execution of three upper limbs tasks (single arm, in-phase, anti-phase) at four different frequencies (from 0.6 to 1.2 Hz).We employed six infrared cameras for recording kinematics information, a force platform for measuring forces exerted on the ground, and a system for surface electromyography (SEMG). Outcome measures were: upper limb range of movement and relative-phase, centre of pressure displacement (COP), screw torque (T_z) exerted on the ground, and SEMG recordings of postural muscles (adductor longus, gluteus medius, rectus femoris, and biceps femoris).Our results show that in both the planes the in-phase task resulted in less COP displacement, torque production, and postural muscles involvement than the anti-phase and single arm tasks. This reduced need of postural control could explain the ease of performing in-phase coupled limb movements compared with anti-phase movements.     

Detailed finite element modelling of deep needle insertions into a soft tissue phantom using a cohesive approach

Detailed finite element modelling of needle insertions into soft tissue phantoms encounters difficulties of large deformations, high friction, contact loading and material failure. This paper demonstrates the use of cohesive elements in high-resolution finite element models to overcome some of the issues associated with these factors. Experiments are presented enabling extraction of the strain energy release rate during crack formation. Using data from these experiments, cohesive elements are calibrated and then implemented in models for validation of the needle insertion process. Successful modelling enables direct comparison of finite element and experimental force–displacement plots and energy distributions. Regions of crack creation, relaxation, cutting and full penetration are identified. By closing the loop between experiments and detailed finite element modelling, a methodology is established which will enable design modifications of a soft tissue probe that steers through complex mechanical interactions with the surrounding material.     

Inflammation-induced reactive nitrogen species cause proteasomal degradation of dimeric peroxiredoxin-1 in a mouse macrophage cell line

Peroxiredoxin 1 (PRDX1) is an antioxidant enzyme that, when secreted, can act as a proinflammatory signal. Here we studied the regulation of intracellular PRDX1 by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) in the RAW 264.7 mouse macrophage cell line. While LPS or IFN-γ alone did not affect PRDX1 protein levels, their combination led to an almost complete loss of the PRDX1 dimer. This was likely mediated by the increased production of nitric oxide (NO) as it was reversed by the NO synthase inhibitor L-N-methylarginine (L-NMMA), while a NO-releasing agent decreased PRDX1 levels. Inhibition of the proteasome with MG132 also prevented the loss of the PRDX1 dimer, suggesting that the decrease is due to a NO-activated proteasomal degradation pathway. By contrast with the decrease in protein levels, LPS increased PRDX1 mRNA and this effect was amplified by IFN-γ. Two other Nrf2 target genes, thioredoxin reductase (TXNRD1) and haem oxygenase (HMOX1), were also induced by LPS but IFN-γ did not increase their expression further. This study shows that inflammation differentially regulates PRDX1 at the levels of protein stability and gene expression, and that NO plays a key role in this mechanism.     

Calibration of the comet assay for the measurement of DNA damage in mammalian cells

We used X-rays from a linear accelerator and from a low energy therapeutic source to calibrate the single cell gel electrophoresis (comet assay), a widely used method to measure DNA damage. γ-Rays from ⁶⁰Co, with known efficiency in inducing DNA breakage, were used as reference. Human lymphocytes and one murine tumour cell line, F10-M3 cells, were irradiated under different experimental conditions. A similar relationship between radiation dose and induced DNA damage was obtained with γ- and X-rays. A calibration curve was constructed to convert the comet assay raw data into break frequency. The median levels of DNA breaks and oxidative damage in circulating lymphocytes from healthy volunteers were calculated to be 0.76 and 0.80 breaks/10⁹ Da, respectively, (0.50 and 0.52 breaks/10⁶ bp). The values of oxidative DNA damage were in the same order of magnitude as those found by others with HPLC methods.     

2- and 3-[(Aryl)(azolyl)methyl]indoles as Potential Non-steroidal Aromatase Inhibitors

The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a–h and 28a–h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC₅₀ and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28?g) was a highly potent and selective aromatase inhibitor with IC₅₀ value of 0.025?μM. 28?g was also a weak inhibitor of androstenedione synthesis.     

Immobilization and stabilization of a bimolecular aggregate of the lipase from Pseudomonas fluorescens by multipoint covalent attachment

The soluble lipase from Pseudomonas fluorescens (PFL) forms bimolecular aggregates in which the hydrophobic active centers of the enzyme monomers are in close contact. This bimolecular aggregate could be immobilized by multipoint covalent linkages on glyoxyl supports at pH 8.5. The monomer of PFL obtained by incubation of the soluble enzyme in the presence of detergent (0.5% TRITON X-100) could not be immobilized under these conditions. The bimolecular aggregate has two amino terminal residues in the same plane. A further incubation of the immobilized derivative under more alkaline conditions (e.g., pH 10.5) allows a further multipoint attachment of lysine (Lys) residues located in the same plane as the amino terminal residues. Monomeric PFL was immobilized at pH 10.5 in the presence of 0.5% TRITON X-100. The properties of both PFL derivatives were compared. In general, the bimolecular derivatives were more active, more selective and more stable both in water and in organic solvents than the monomolecular ones. The bimolecular derivative showed twice the activity and a much higher selectivity (100 versus 20) for the hydrolysis of R,S-2-hydroxy-4-phenylbutyric acid ethyl ester (HPBEt) in aqueous media at pH 5.0 compared to the monomeric derivative. In experiments measuring thermal inactivation at 75 °C, the bimolecular derivative was 5-fold more stable than the monomeric derivative (and 50-fold more stable than a one-point covalently immobilized PFL derivative), and it had a half-life greater than 4 h. In organic solvents (cyclohexane and tert-amyl alcohol), the bimolecular derivative was much more stable and more active than the monomeric derivative in catalyzing the transesterification of olive oil with benzyl alcohol.