Epigenetic changes in the early stage of silica-induced cell transformation

The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil^® 5. Short-term treatment by Min-U-Sil^® 5 decreased global DNA methylation and increased the expression of the two de novo DNMTs, DNMT3a and DNMT3b. NM-203 treatment affected neither the expression of these enzymes nor DNA methylation. Moreover, modified global histone H4 acetylation status and HDAC protein levels were observed only in the Min-U-Sil^® 5-treated cells. Finally, both types of particle treatment induced strong c-Myc expression in the early stage of cell transformation and this correlated with enrichment in RNA polymerase II as well as histone active marks on its promoter. Lastly, almost all parameters that were modulated in the early stage were restored in transformed cells suggesting their involvement mainly in the first steps of cell transformation.     

Frailty in older population: a brief position paper from the French society of geriatrics and gerontology

Frailty in the older population is a clinical syndrome which evaluate a risk level. The Frailty syndrome defines a reduction of the adaptation capacity to a stress. It can be modulated by physical, psychological and social factors. The screening of the frailty syndrome is relevant for older people without disability for basic activities of daily living. The clinical criteria of frailty must be predictive of the risk of functional decline and adverse outcomes, consensual at the international level, and easy to perform in primary care as well as in the clinical researches.     

Arterial stiffness and systolic hypertension: Determinants, assessment, and clinical consequences

Large-artery stiffness, a major consequence of aging, involves changes in the structural organization of various components of the arterial wall. The development of arterial stiffness is manifested by an acceleration of pulse wave velocity, a rise in systolic and pulse pressure, and a decline in diastolic blood pressure. These events observed during aging are more pronounced in patients with accelerated arterial aging. Thus, while chronologic age is a major determinant of arterial stiffness, genetic and environmental determinants can accelerate or attenuate arterial aging. Clinical studies have demonstrated a direct relationship between these clinical manifestations of arterial stiffness and cardiovascular morbidity and mortality. Hence, noninvasive techniques for measuring arterial stiffness could rapidly become a very useful step in the development of more accurate ways to assess cardiovascular risk.     

Laboratory evaluation of Fendona 6SC® treated bednets and Interceptor® long-lasting nets against Anopheles gambiae s.l. in Burkina Faso

Insecticide-treated bednets play a cornerstone role in the efforts to control malaria. Bednets entomological efficacy is the determinant factor of their use to control malaria. In this study, we compared under laboratory conditions, the efficacy of two long-lasting nets (PermaNet® versus Interceptor®) and two treatments kits K-O TAB® (deltamethrin) versus Fendona 6SC® (alpha-cypermethrin) against Anopheles gambiae s.l. malaria vectors. The efficacy of washed and unwashed bednets was assessed by contact bioassays using World Health Organization (WHO) cones. Three to five-days-old mosquitoes were exposed to the netting for 3 min; the median and 95 % knockdown time, the after 24 h mortality was recorded for each type of bednet. The mortality after 24 h was equivalent for the Fendona 6SC® treated bednets and the K-O TAB® treated bednets [79.4 % confidence limits (CL) (73.9–84.6) and 74 % CL (68.3–80.0), respectively]. However, the Fendona 6SC® treated bednets were superior in 50 % knockdown time to the K-O TAB® treated bednets [7.8 min, CL (6.5–9.0) and 15. 2 min, CL (14.0–16.4), respectively]. Washed Interceptor® and PermaNet® bednets showed similar efficacy in terms of 50 % knockdown times. Mortality after 24 h was similar from the fifth to the twentieth wash, but PermaNet® performed better than Interceptor® for the first four washes and for unwashed bednets. This study showed that Fendona 6SC® kit and the Interceptor® bednets have exhibited consistent comparable efficacy in the laboratory compared to the well known and in use K-O TAB® kit and PermaNet® bednets.     

Angiotensin II type 1 receptor-153A/G and 1166A/C gene polymorphisms and increase in aortic stiffness with age in hypertensive subjects

OBJECTIVES: Arterial stiffness is associated with excess morbidity and mortality, independently of other cardiovascular risk factors. Age is the main determinant responsible for arterial wall changes leading to arterial stiffening. Environmental and genetic factors may however influence the magnitude of the effects of age on large artery stiffness. DESIGN AND METHODS: The present study assessed whether or not the relationship between age and aortic stiffness was influenced by genetic variants of angiotensinogen (AGT 174T/M, 235M/T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1 1166A/C, -153A/G) and aldosterone synthase (CYP11B2 -344T/C). This study was realized in 441 untreated hypertensive subjects of European origin (aged 18-74 years). Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). RESULTS: Carriers of the angiotensin II type 1 receptor -153G allele showed a steeper age/PWV relationship than the AT1 -153AA subjects. The effect of the AT1 -153A/G polymorphism on aortic stiffness became apparent after the age of 55 years. In subjects with the AT1 1166C allele, the relationship age/PWV is shifted upward, indicating higher values of aortic stiffness at any age compared to the AT1 1166AA patients. Carriers of both the AT1 1166C and -153G alleles presented the additive effects of these 2 genotypes on aortic stiffness. Angiotensinogen, ACE and CYP11B2 genotypes did not influence the effects of age on PWV. CONCLUSIONS: AT1 receptor genotypes could influence arterial ageing in hypertensive subjects. These results also show that the association between genotypes and arterial stiffness may manifest itself later in life.     

Effects of valsartan on mechanical properties of the carotid artery in spontaneously hypertensive rats under high-salt diet

The aim of this investigation was to evaluate the influence of a high-salt diet (HSD) on the effects of valsartan, an angiotensin II type 1 (AT(1)) receptor antagonist, on carotid arterial stiffness and structure in spontaneous hypertensive rats (SHR). Carotid arterial stiffness was studied in SHR receiving a HSD or a normal-salt diet (NSD) from the 10th to 20th week of age. Within each of the 2 groups, the animals received treatment with either placebo or valsartan (30 mg. kg(-1). d(-1)) administered on the 4th to 20th week of age. Arterial pressure, wall stress, incremental elastic modulus (Einc), medial cross-sectional area, and EIIIA fibronectin isoform were significantly increased in placebo-HSD rats compared with placebo-NSD rats with no change in the ratio of collagen to elastin. Valsartan reduced mean arterial pressure in both NSD and HSD rats but reduced pulse pressure only in NSD rats. In NSD rats, valsartan reduced Einc and medial cross-sectional area. In HSD, valsartan increased Einc and did not modify medial cross-sectional area and fibronectin. In valsartan-treated rats, the ratio of collagen to elastin was greater in HSD than in NSD rats. In conclusion, the effects of AT(1) blockade are greatly influenced by salt intake in SHR. Despite a reduction in mean arterial pressure in HSD rats, AT(1) blockade was not able to prevent the effects of a HSD on pulse pressure, carotid artery stiffness, and hypertrophy.     

Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid—an Experimental Study

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 μg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20?±?0.12 vs 1.17?±?0.78,p?=?0.29), while AV calcification progressed in the placebo group (1.22?±?0.15 vs 1.53?±?0.23,p?=?0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.