The role of statins on helicobacter pylori eradication: Results from the european registry on the management of h. pylori (hp-eureg)

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1-1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59-0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4-2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3-5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservation

We have constructed a comparative map in mouse of the critical region of human 22q11 deleted in DiGeorge (DGS) and Velocardiofacial (VCFS) syndromes. The map includes 11 genes potentially haploinsufficient in these deletion syndromes. We have localized all the conserved genes to mouse Chromosome (Chr) 16, bands B1-B3. The determination of gene order shows the presence of two regions (distal and proximal), containing two groups of conserved genes. The gene order in the two regions is not completely conserved; only in the proximal group is the gene order identical to human. In the distal group the gene order is inverted. These two regions are separated by a DNA segment containing at least one gene which, in the human DGS region, is the most proximal of the known deleted genes. In addition, the gene order within the distal group of genes is inverted relative to the human gene order. Furthermore, a clathrin heavy chain-like gene was not found in the mouse genome by DNA hybridization, indicating that there is an inconsistent level of gene conservation in the region. These and other independent data obtained in our laboratory clearly show a complex evolutionary history of the DGS-VCFS region. Our data provide a framework for the development of a mouse model for the 22q11 deletion with chromosome engineering technologies

Structure and chromosomal locations of mouse steroid receptor coactivator gene family

The newly recognized steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) belong to a homologous gene family and are important transcriptional mediators for nuclear receptors. Through fluorescence in situ hybridization, we have mapped the mouse SRC-1, SRC-2, and SRC-3 genes to chromosomal locations 12A2-A3, 1A3-A5, and 2H2-H4, respectively. By screening a mouse genomic DNA library, performing long-range polymerase chain reaction and sequencing, we have cloned and characterized the mouse SRC-3 gene. The SRC-3 gene contains 19 exons and spans more than 38 kilobases (kb). Intron sizes are variable. Intron 1 (13.5 kb) and intron 15 (4.6 kb) contribute to almost half the total length of the gene. Among 20 exons identified, exon 10 is the largest (869 bp) and encodes the receptor interaction domain. The start and stop codons for translation are in exon 2 and 20, respectively. The relationship between SRC-3 gene structure and its functional protein domains suggests that many functional domains or subdomains are encoded by individual exons. The correlation between gene structure and alternative splice variants is also discussed. In summary, we have defined the structure of mouse SRC-3 gene and found that the genes in the SRC family are located in different mouse chromosomes. This information is important for developing valuable animal models harboring multiple: disruptions of the SRC gene family to study their biological functions

Congenital heart disease in mice deficient for the DiGeorge Syndrome region

The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering