Persistent H. pylori colonization in early acquisition age of mice related with higher gastric sialylated Lewis x, IL-10, but lower interferon-γ expressions

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection is less prevalent in childhood. This study validated whether the rates of <it>H. pylori </it>colonization depend on different acquisition ages, and correlate with the different gastric Lewis antigens or cytokine expressions after <it>H. pylori </it>acquisition.</p> <p>Methods</p> <p>We applied a young (7-day-old) C57BL/6 mice group (n = 50) and adult (6-week-old) C57BL/6 mice group (n = 50). In each group, 30 mice were challenged with <it>H. pylori </it>and 20 mice served as naïve control. The success of <it>H. pylori </it>colonization was assessed on the 2^ndweek and the 8^thweek, respectively. The intensity of the Lewis x, sialylated Lewis x<sup/>(sialyl-Le^x), and cytokine expressions, including TNF-α, IFN-γ, IL-6, IL-10, and IL-1β, were immunochemically stained and graded.</p> <p>Results</p> <p>On the 2^ndweek after <it>H. pylori </it>challenge, the colonization rates of <it>H. pylori </it>were similar between the young mice group and the adult mice group (89% vs. 100%, <it>P </it>> 0.05). However, on the 8^thweek, the <it>H. pylori </it>colonization rate was significantly lower in the young mice group than in the adult mice group (53% vs. 95%, <it>P </it>= 0.003). On the 8^thweek, the young mice with a persistence of <it>H. pylori </it>colonization had higher sialyl-Le^x, higher IL-10, and lower IFN-γ than those of the mice that lost colonization during the 2^ndto the 8^thweek (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>The persistence of <it>H. pylori </it>colonization could be an acquisition-age determinant process. After <it>H. pylori </it>exposure at an early acquisition age, the host response with a higher sialyl-Le^xand IL-10, but a lower IFN-γ correlates to the consequent persistence of <it>H. pylori </it>colonization.</p

Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve <it>H. pylori</it>-induced gastric inflammation by inactivating the Smad7 and NFκB pathways.</p> <p>Results</p> <p>Challenge with <it>H. pylori </it>increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after <it>H. pylori </it>infection in a dose-dependent manner. A higher dose (MOI 100) of <it>L. acidophilus </it>pre-treatment attenuated the <it>H. pylori</it>-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. <it>L. acidophilus </it>also inhibited <it>H. pylori</it>-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. <it>L. acidophilus </it>pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection induces Smad7, NFκB, IL-8, and TNF-α production <it>in vitro</it>. Higher doses of <it>L. acidophilus </it>pre-treatment reduce <it>H. pylori</it>-induced inflammation through the inactivation of the Smad7 and NFκB pathways.</p

Etiology and Treatment of Childhood Peptic Ulcer Disease in Taiwan: A Single Center 9-Year Experience

Background/PurposePeptic ulcer disease (PUD) in children is relatively rare as compared with adults. This study aimed to assess the etiology, clinical and histological characteristics, and treatment of PUD in children.MethodsAll children aged < 18 years with an endoscopic diagnosis of PUD were enrolled in a tertiary referral center. The demographic data, clinical, endoscopic, and histological findings were compared between patients with different causes of PUD.ResultsFrom 1234 endoscopic examinations, 67 (5.4%) children (median age, 11.4 years) with gastric ulcer (GU; n = 27) or duodenal ulcer (DU; n = 40) were included. Thirty-two (47.7%) of them had Helicobacter pylori infection and 11 (16.5%) had previous use of non-steroidal anti-inflammatory drugs (NSAIDs). Non-H. pylori, non-NSAID PUD was found in 24 (35.8%) patients. Children with H. pylori-related PUD had a significantly higher mean age, antral chronic inflammatory score, rate of familial PUD, and presence of DU and nodular gastritis than those with NSAID-related and non-H. pylori, non-NSAID PUD (p < 0.01). In contrast, children with NSAID-related PUD had a higher rate of upper gastrointestinal bleeding, associated with acute febrile disease, than those with H. pylori-related and non-H. pylori, non-NSAID PUD (p < 0.05). All but two patients with non-H. pylori, non-NSAID PUD were disease free after H. pylori eradication and proton pump inhibitor treatment for 1–2 months.ConclusionIn children, H. pylori-related PUD is associated with familial peptic ulcer and the presence of DU. However, short-term NSAID use is correlated highly with GU. The outcome of childhood PUD is good

Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis

Chiral Spin-Liquid-Like State in Pyrochlore Iridate Thin Films

The pyrochlore iridates have become ideal platforms to unravel fascinating correlated and topolog?ical phenomena that stem from the intricate interplay among strong spin-orbit coupling, electronic correlations, lattice with geometric frustration, and itinerancy of the 5d electrons. The all-in-all?out antiferromagnetic state, commonly considered as the magnetic ground state, can be dramatically altered in reduced dimensionality, leading to exotic or hidden quantum states inaccessible in bulk. Here, by means of magnetotransport, resonant elastic and inelastic x-ray scattering experiments, we discover an emergent quantum disordered state in (111) Y2Ir2O7 thin films (thickness less than 30 nm) per?sisting down to 5 K, characterized by dispersionless magnetic excitations. The anomalous Hall effect observed below an onset temperature near 135 K corroborates the presence of chiral short-range spin configurations expressed in non-zero scalar spin chirality, breaking the macroscopic time-reversal symmetry. The origin of this chiral state is ascribed to the restoration of magnetic frustration on the pyrochlore lattice in lower dimensionality, where the competing exchange interactions together with enhanced quantum fluctuations suppress any long-range order and trigger spin-liquid-like behavior with degenerate ground-state manifold

Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment

Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF

A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq

Deciphering the structure of gene regulatory networks across the tree of life remains one of the major challenges in postgenomic biology. We present a novel ChIP-seq workflow for the archaea using the model organism Halobacterium salinarum sp. NRC-1 and demonstrate its application for mapping the genome-wide binding sites of natively expressed transcription factors. This end-to-end pipeline is the first protocol for ChIP-seq in archaea, with methods and tools for each stage from gene tagging to data analysis and biological discovery. Genome-wide binding sites for transcription factors with many binding sites (TfbD) are identified with sensitivity, while retaining specificity in the identification the smaller regulons (bacteriorhodopsin-activator protein). Chromosomal tagging of target proteins with a compact epitope facilitates a standardized and cost-effective workflow that is compatible with high-throughput immunoprecipitation of natively expressed transcription factors. The Pique package, an open-source bioinformatics method, is presented for identification of binding events. Relative to ChIP-Chip and qPCR, this workflow offers a robust catalog of protein–DNA binding events with improved spatial resolution and significantly decreased cost. While this study focuses on the application of ChIP-seq in H. salinarum sp. NRC-1, our workflow can also be adapted for use in other archaea and bacteria with basic genetic tools