Left ventricular midwall mechanics at 24 weeks' gestation in high-risk normotensive pregnant women: Relationship to placenta-related complications of pregnancy

Most studies during pregnancy have assessed maternal left ventricular (LV) function by load-dependent indices, assessing only chamber function. The aim of this study was to assess afterload-adjusted LV myocardial and chamber systolic function at 24 weeks' gestation and 6 months postpartum in high-risk normotensive pregnant women

The Impact of Kidney Development on the Life Course: A Consensus Document for Action

Hypertension and chronic kidney disease (CKD) have a significant impact on global morbidity and mortality. The Low Birth Weight and Nephron Number Working Group has prepared a consensus document aimed to address the relatively neglected issue for the developmental programming of hypertension and CKD. It emerged from a workshop held on April 2, 2016, including eminent internationally recognized experts in the field of obstetrics, neonatology, and nephrology. Through multidisciplinary engagement, the goal of the workshop was to highlight the association between fetal and childhood development and an increased risk of adult diseases, focusing on hypertension and CKD, and to suggest possible practical solutions for the future. The recommendations for action of the consensus workshop are the results of combined clinical experience, shared research expertise, and a review of the literature. They highlight the need to act early to prevent CKD and other related noncommunicable diseases later in life by reducing low birth weight, small for gestational age, prematurity, and low nephron numbers at birth through coordinated interventions. Meeting the current unmet needs would help to define the most cost-effective strategies and to optimize interventions to limit or interrupt the developmental programming cycle of CKD later in life, especially in the poorest part of the world

MiR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid fibroblasts

Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound-healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol-mebutate has been used as a novel agent with anti-proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance between lesion formation and repair. A comprehensive understanding of the molecular mechanism underlying the Ingenol-mebutate response in keloid fibroblast following Ingenol-mebutate exposure has been established previously. Therefore, the present study analyzed changes in miRNAs and apoptotic gene regulation in Ingenol-mebutate treated keloid fibroblast, by reverse transcription-quantitative polymerase chain reaction and a DNA fragmentation assay. The range of upregulated miRNAs and downregulated genes encoding cell death appeared to be associated with the degree of the morphological alterations in Ingenol-mebutate treated keloids. In particular, the upregulation of miR-34a was detected in keloid fibroblasts during and following Ingenol-mebutate exposure. Keloid fibroblasts that overexpressed miR-34a showed differential expression of genes involved in the apoptotic signaling pathway such as p53. In conclusion, the Ingenol-mebutate treatment used here was effective in reducing keloid fibroblast growth in cell culture experiments and the expression of particular miRNAs modulated the pro-apoptotic gene expression following Ingenol-mebutate treatment

GSTA1, GSTO1 and GSTO2 gene polymorphisms in Italian asthma patients

1. Previous studies have established that genetic alterations in glutathione S-transferase enzymes may change the ability of the airway to deal with toxic substances and increase the risk of asthma. The present study analysed the association between asthma and GSTA1, GSTO1 and GSTO2 gene polymorphisms. 2. The GSTA1*-69C⁄T, GSTO1*A140D and GSTO2*N142D polymorphisms were detected by polymerase chain reaction– restriction fragment length polymorphism, whereas the GSTO1*E155del polymorphism was detected using the confronting two-pair primer method. 3. Distribution of the GSTA1*-69C ⁄T genotype differed significantly between asthmatics and controls. Subjects with at least one allele -69T in the GSTA1 genotype have an increased risk of asthma (odds ratio (OR) 3.45; 95% confidence interval (CI) 1.80– 6.62). The distribution of the GSTO1 genotype was nearly equal between the control group and asthmatics, however, the distribution of the GSTO2 gene differed significantly between asthmatics and controls (Chi-squared test). Subjects who had the GSTO2 homozygous D142 genotype were found to have an increased risk of asthma (OR 5.91; 95% CI 1.80–19.42). 4. The results show a potential association between the GST genes and asthma. This is particularly significant given that, in the literature, there are no epidemiological studies on alpha and omega classes of glutathione transferases in asthma

Lack of association between GSTM1, GSTP1, and GSTT1 gene polymorphisms and asthma in adult patients from Rome, central Italy

Asthma is a complex multifactorial disease that is not yet fully understood. Oxidative stress due to an imbalance between the oxidative forces and the antioxidant defense systems has been implicated in asthma pathogenesis. However, much debate still surrounds the key genetic factors involved in the development of this disease. Candidate genes include the glutathione S-transferases (GSTs). In particular, mu, pi, and theta classes of GSTs play an important role in regulating inflammatory responses. However, few and contradictory data are available on the association between asthma development and GST gene polymorphisms (GSTM1, GSTP1, and GST1)

Lack of association between GSTM1, GSTP1, and GSTT1 gene polymorphisms and asthma in adult patients from Rome, central Italy

Asthma is a complex multifactorial disease that is not yet fully understood. Oxidative stress due to an imbalance between the oxidative forces and the antioxidant defense systems has been implicated in asthma pathogenesis. However, much debate still surrounds the key genetic factors involved in the development of this disease. Candidate genes include the glutathione S-transferases (GSTs). In particular, mu, pi, and theta classes of GSTs play an important role in regulating inflammatory responses. However, few and contradictory data are available on the association between asthma development and GST gene polymorphisms (GSTM1, GSTP1, and GST1)

Wide-Ranging Analysis of MicroRNA Profiles in Sporadic Amyotrophic Lateral Sclerosis Using Next-Generation Sequencing

MicroRNA (miRNA) has emerged as an important regulator of gene expression in neurodegenerative disease as amyotrophic lateral sclerosis (ALS). In the nervous system, dysregulation in miRNA-related pathways is subordinated to neuronal damage and cell death, which contributes to the expansion of neurodegenerative disorders, such as ALS. In the present research, we aimed to profile dysregulation of miRNAs in ALS blood and neuromuscular junction as well as healthy blood control by next-generation sequencing (NGS). The expression of three upregulated miRNAs, as miR-338-3p, miR-223-3p, and miR-326, in the ALS samples compared to healthy controls, has been validated by qRT-PCR in a cohort of 45 samples collected previously. Bioinformatics tools were used to perform ALS miRNAs target analysis and to predict novel miRNAs secondary structure. The analysis of the NGS data identified 696 and 49 novel miRNAs which were differentially expressed in ALS tissues. In particular, in neuromuscular junction the differential expression of miR-338-3p, which we previously found upregulated in different types of ASL tissues, miR-223-3p, and miR-326 was elevated compared to normal control. ALS miRNAs gene target were significantly involved in neuronal related pathway as BDFN1 and HIF-1genes. This study presents the direct experimental evidence that, overall, miR-338-3p is highly expressed in ALS tissues including neuromuscular junction characterizing ALS from normal tissues. Beside, our analysis identified, for the first time, novel miRNAs highly expressed in ALS tissues. In conclusion, the results indicate that miRNAs has an important role in the diagnosis and treatment of ALS

Assessment of genetic diversity between wild and cultivated artichokes using SSR markers

Artichokes is an economically important crop, due to its value in polyphenols compounds and inulin whit marked antioxidant and prebiotic activities. Wild artichokes possess a source of genetic variation for biotic and abiotic stress and higher polyphenolic compounds. Here, we used 10 SSR microsatellite markers to assess genetic variation between cultivated and wild species. Specific molecular markers show efficient introgression of such traits in cultivated as well as wild artichokes species. Cluster analysis discriminated all 30 accessions and classified cultivated and wild species in distinct groups. Results from PCoA analysis suggested that artichoke genotype contains a higher number of unique alleles