Investigating the correlation between Xrn1-resistant RNAs and frameshifter pseudoknots.

Xrn1-resistant RNA structures are multifunctional elements employed by an increasing number of RNA viruses. One of such elements is the coremin motif, discovered in plant virus RNAs, of which the structure has been hypothesized to form a yet unelucidated pseudoknot. Recently, the coremin motif was shown to be capable of stalling not only Xrn1, but scanning ribosomes as well.

Food-Derived Uremic Toxins in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a higher cardiovascular risk compared to the average population, and this is partially due to the plasma accumulation of solutes known as uremic toxins. The binding of some solutes to plasma proteins complicates their removal via conventional therapies, e.g.

Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential.

Interest in gut microbiome dysbiosis and its potential association with the development and progression of chronic kidney disease (CKD) has increased substantially in the past 6 years. In parallel, the microbiome field has matured considerably as the importance of host-related and environmental factors is increasingly recognized. Past research output in the context of CKD insufficiently considered the myriad confounding factors that are characteristic of the disease.

Microbial-Derived Tryptophan Catabolites, Kidney Disease and Gut Inflammation.

Uremic metabolites, molecules either produced by the host or from the microbiota population existing in the gastrointestinal tract that gets excreted by the kidneys into urine, have significant effects on both health and disease. Tryptophan-derived catabolites are an important group of bacteria-produced metabolites with an extensive contribution to intestinal health and, eventually, chronic kidney disease (CKD) progression. The end-metabolite, indoxyl sulfate, is a key contributor to the exacerbation of CKD via the induction of an inflammatory state and oxidative stress affecting various organ systems.

Exposure of Intestinal Epithelial Cells to 2'-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development.

Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2'-fucosyllactose (2'-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with αCD3/CD28-activated peripheral blood mononuclear cells (PBMC), were apically exposed to NDOs and CpG, washed and co-cultured with immature monocyte-derived dendritic cells (moDC).

Combined Exposure of Activated Intestinal Epithelial Cells to Nondigestible Oligosaccharides and CpG-ODN Suppresses Th2-Associated CCL22 Release While Enhancing Galectin-9, TGF, and Th1 Polarization.

Background: Short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS) and CpG-ODN affect intestinal epithelial cells (IEC). Epithelial IL1 may contribute to allergic sensitization via autocrine mediator release affecting dendritic cells (DC). We studied whether IL1 contributes to Th2-associated mediator release by activated IEC and IEC/DC cocultures and possible modulation by scGOS/lcFOS±CpG-ODN.

The Combination of 2'-Fucosyllactose with Short-Chain Galacto-Oligosaccharides and Long-Chain Fructo-Oligosaccharides that Enhance Influenza Vaccine Responses Is Associated with Mucosal Immune Regulation in Mice.

Background: A critical role for host-microbe interactions and establishment of vaccine responses has been postulated. Human milk oligosaccharides, of which 2'-fucosyllactose (2'FL) is the most prevalent, are known to alter host-associated microbial communities and play a critical role in the immunologic development of breastfed infants.

Objectives: Dietary supplementation with a combination of 2'FL and prebiotic short-chain (sc) galacto-oligosaccharides (GOS) and long-chain (lc) fructo-oligosaccharides (FOS) was employed to examine human milk oligosaccharide effects on immune responsiveness, within a murine influenza vaccination model.

Human milk oligosaccharides promote immune tolerance via direct interactions with human dendritic cells.

Human milk oligosaccharides (HMOS) are a complex mixture of bioactive components supporting the immune development of breastfed-infants. Dendritic cells (DCs) play a central role in the regulation of immune responses, being specialized in antigen presentation and driving T-cell priming as well as differentiation. However, little is known about the direct effects of HMOS on human DC phenotypes and functions.

Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis.

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines.

Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE).

Exposure of Intestinal Epithelial Cells to Short- and Long-Chain Fructo-Oligosaccharides and CpG Oligodeoxynucleotides Enhances Peanut-Specific T Helper 1 Polarization.

Background: Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative.

Human Milk Oligosaccharide 2'-Fucosyllactose Improves Innate and Adaptive Immunity in an Influenza-Specific Murine Vaccination Model.

Background: Human milk is uniquely suited to provide optimal nutrition and immune protection to infants. Human milk oligosaccharides are structural complex and diverse consisting of short chain and long chain oligosaccharides typically present in a 9:1 ratio. 2'-Fucosyllactose (2'FL) is one of the most prominent short chain oligosaccharides and is associated with anti-infective capacity of human milk.

T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis.

There is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity.

Bifidobacterium breve attenuates murine dextran sodium sulfate-induced colitis and increases regulatory T cell responses.

While some probiotics have shown beneficial effects on preventing or treating colitis development, others have shown no effects. In this study, we have assessed the immunomodulating effects of two probiotic strains, Lactobacillus rhamnosus (L. rhamnosus) and Bifidobacterium breve (B.

Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease.

Objective: Proline-glycine-proline (PGP) has been shown to have chemotactic effects on neutrophils via CXCR2 in several lung diseases. PGP is derived from collagen by the combined action of matrix metalloproteinase (MMP) 8 and/or MMP9 and prolyl endopeptidase (PE). We investigated the role of PGP in inflammatory bowel disease (IBD).

Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?

Background: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP). The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE).

Chemo-attractant N-acetyl proline-glycine-proline induces CD11b/CD18-dependent neutrophil adhesion.

Background: Chronic inflammation in lung diseases contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated proline-glycine-proline (N-ac-PGP). In the current study, we investigate whether N-ac-PGP influences β(2)-integrin activation and function in neutrophilic firm adhesion to endothelium.

Methods: Human polymorphonuclear leukocytes (PMNs) were isolated from fresh human blood.

Targeting chemokine receptors in chronic inflammatory diseases: an extensive review.

The traffic of the different types of immune cells is an important aspect in the immune response. Chemokines are soluble peptides that are able to attract cells by interaction with chemokine receptors on their target cells. Several different chemokines and receptors exist enabling the specific trafficking of different immune cells.

Cigarette smoke induces β2-integrin-dependent neutrophil migration across human endothelium.

Background: Cigarette smoking induces peripheral inflammatory responses in all smokers and is the major risk factor for neutrophilic lung disease such as chronic obstructive pulmonary disease. The aim of this study was to investigate the effect of cigarette smoke on neutrophil migration and on β2-integrin activation and function in neutrophilic transmigration through endothelium.

Methods And Results: Utilizing freshly isolated human PMNs, the effect of cigarette smoke on migration and β2-integrin activation and function in neutrophilic transmigration was studied.

CXCR2 antagonists block the N-Ac-PGP-induced neutrophil influx in the airways of mice, but not the production of the chemokine CXCL1.

Neutrophils are innate immune cells in chronic inflammatory diseases including chronic obstructive pulmonary disease (COPD) and can be attracted to the site of inflammation via the collagen breakdown product N-acetyl Proline-Glycine-Proline (N-Ac-PGP). To elucidate whether CXCR2 is involved in N-Ac-PGP-induced neutrophil migration and activation, studies using specific antagonists were performed in vivo. N-Ac-PGP and keratinocyte cell-derived chemokine (KC; CXCL1) were administered in C57Bl/6 mice via oropharyngeal aspiration.

β₂-Agonists and physical performance: a systematic review and meta-analysis of randomized controlled trials.

Inhaled β₂-agonists are commonly used as bronchodilators in the treatment of asthma. Their use in athletes, however, is restricted by anti-doping regulations. Controversies remain as to whether healthy elite athletes who use bronchodilators may gain a competitive advantage.

The collagen-breakdown product N-acetyl-Proline-Glycine-Proline (N-alpha-PGP) does not interact directly with human CXCR1 and CXCR2.

Neutrophils transmigrate from the blood into inflamed tissue via the interaction of chemokines produced in this tissue with chemokine receptors, such as CXCR1 and CXCR2, that are expressed on the membranes of neutrophils. Subsequently, activation of neutrophils will in turn lead to increased tissue damage and thereby enhanced clinical symptoms of inflammatory diseases like chronic obstructive pulmonary disease, inflammatory bowel disease and psoriasis. Besides chemokines, also the collagen-breakdown product N-acetyl-Proline-Glycine-Proline (N-alpha-PGP) attracts neutrophils.

Four weeks' corticosteroid inhalation does not augment maximal power output in endurance athletes.

Objective: To assess possible ergogenic properties of corticosteroid administration.

Design: A balanced, double-blind, placebo-controlled design was used.

Participants: 28 well-trained cyclists and rowers.