Airway Smooth Muscle Inflammation Is Regulated by MicroRNA-145 in COPD.

Chronic obstructive pulmonary disease (COPD) is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease, in part caused by the aberrant function of airway smooth muscle (ASM) cells under the regulation of transforming growth factor (TGF)-β. MicroRNAs are short, non-coding gene transcripts involved in the negative regulation of specific target genes, through their interactions with messenger RNAs. Previous studies have proposed that microRNA-145 (miR-145) may interact with SMAD3, an important downstream signalling molecule of the TGF-β pathway. TGF-β was used to stimulate primary human ASM cells isolated from healthy non-smokers, healthy smokers and COPD patients. This resulted in a TGF-β-dependent increase in CXCL8 and IL-6 release, most notably in the cells from COPD patients. TGF-β stimulation increased SMAD3 expression, only in cells from COPD patients, with a concurrent increased miR-145 expression. Regulation of miR-145 was found to be negatively controlled by pathways involving the MAP kinases, MEK-1/2 and p38 MAPK. Subsequent, overexpression of miR-145 (using synthetic mimics) in ASM cells from patients with COPD suppressed IL-6 and CXCL8 release, to levels comparable to the non-smoker controls. Therefore, this study suggests that miR-145 negatively regulates pro-inflammatory cytokine release from ASM cells in COPD by targeting SMAD3

Drought Impact Is Alleviated in Sugar Beets (Beta vulgaris L.) by Foliar Application of Fullerenol Nanoparticles

Over the past few years, significant efforts have been made to decrease the effects of drought stress on plant productivity and quality. We propose that fullerenol nanoparticles (FNPs, molecular formula C-60(OH)(24)) may help alleviate drought stress by serving as an additional intercellular water supply. Specifically, FNPs are able to penetrate plant leaf and root tissues, where they bind water in various cell compartments. This hydroscopic activity suggests that FNPs could be beneficial in plants. The aim of the present study was to analyse the influence of FNPs on sugar beet plants exposed to drought stress. Our results indicate that intracellular water metabolism can be modified by foliar application of FNPs in drought exposed plants. Drought stress induced a significant increase in the compatible osmolyte proline in both the leaves and roots of control plants, but not in FNP treated plants. These results indicate that FNPs could act as intracellular binders of water, creating an additional water reserve, and enabling adaptation to drought stress. Moreover, analysis of plant antioxidant enzyme activities (CAT, APx and GPx), MDA and GSH content indicate that fullerenol foliar application could have some beneficial effect on alleviating oxidative effects of drought stress, depending on the concentration of nanoparticles applied. Although further studies are necessary to elucidate the biochemical impact of FNPs on plants; the present results could directly impact agricultural practice, where available water supplies are often a limiting factor in plant bioproductivity

Six-month programme on lifestyle changes in primary cardiovascular prevention: a telemedicine pilot study

Technology and information systems enabling transmission of patients' data and ability to provide and exchange professional support remotely to the general practitioners can improve quality and continuity of care.We set up a programme of primary prevention in 27 patients at risk for cardiovascular diseases by using Telemedicine Service for 6 months.Telemedicine Service enlisted the involvement of physicians and nurse-tutors. The following cardiovascular activity markers were assessed: (i) cardiovascular risk cards (Framingham Study and Progetto CUORE); (ii) blood pressure; (iii) physical activity (three sessions of bicycle exercise training and calisthenic exercises a week); and (iv) questionnaires on stress and quality of life.Both cardiovascular risk cards showed a statistically significant reduction of the score (p < 0.05). Systolic and diastolic blood pressures showed a statistically significant reduction (128 ± 10 mmHg vs. 121 ± 9 mmHg, p = 0.04; 80 ± 8 mmHg vs. 73 ± 7 mmHg, p = 0.001). There was a noticeable increase in patient compliance for reporting blood pressure data. 89\% of patients complied with the physical activity programme. Effort test significantly increased from 11.4 ± 3.5 to 12.7 ± 3.4 min (p = 0.02). There was a significant improvement in physical health (p = 0.04) and 85\% of patients were satisfied with the service.A home multidisciplinary programme for primary cardiovascular disease prevention is simple, efficacious, and very well accepted by the patients with the majority of patients showing reduction in cardiovascular risk scores

Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

<p>Abstract</p> <p>Background</p> <p>The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether <it>FAAH </it>alleles are associated with early and late onset obesity.</p> <p>Methods</p> <p>We initially assessed association of five single nucleotide polymorphisms (SNPs) in <it>FAAH </it>with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the <it>FAAH </it>coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity.</p> <p>Results</p> <p>The trio analysis revealed some evidence for an association of three SNPs in <it>FAAH </it>(rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in <it>FAAH </it>(rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05).</p> <p>Conclusions</p> <p>As we observed some evidence for an association of the <it>FAAH </it>variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the <it>FAAH </it>variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.</p