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The mucosal-associated lymphoid tissues of the upper respiratory tract, including adenoids and palatine tonsils, are considered as the first line of defense against respiratory infections, being important effector organs in both mucosal-type and systemic-type adaptive immunity. They are strategically located for mediating both local and regional immune functions, as they are exposed to antigens from both the inhaled air (allergens and pathogens) and the alimentary tract. Adenoids play a major role in the early and effective immune responses against viral and bacterial upper airway infections, as well as in the development of allergic reactions to respiratory allergens, being influenced by several environmental antigens and pollutants, such as tobacco smoke. In addition, recent studies have focused on new immune-modulating strategies for adenoidal cells as a preventive and therapeutic approach for chronic upper airways inflammation.:Herein, we aimed to summarize what is known about the cellular and molecular mechanisms regulating adenoidal immune responses in the context of inflammation and allergy, with particular reference to scientific literature published within the last five years.

In the last decade, the secreting activity of mesenchymal stem/stromal cells (MSCs) has been widely investigated, due to its possible therapeutic role. In fact, MSCs release extracellular vesicles (EVs) containing relevant biomolecules such as mRNAs, microRNAs, bioactive lipids, and signaling receptors, able to restore physiological conditions where regenerative or anti-inflammatory actions are needed. An actual advantage would come from the therapeutic use of EVs with respect to MSCs, avoiding the possible immune rejection, the lung entrapment, improving the safety, and allowing the crossing of biological barriers. A number of concerns still have to be solved regarding the mechanisms determining the beneficial effect of MSC-EVs, the possible alteration of their properties as a consequence of the isolation/purification methods, and/or the best approach for a large-scale production for clinical use. Most of the preclinical studies have been successful, reporting for MSC-EVs a protecting role in acute kidney injury following ischemia reperfusion, a potent anti-inflammatory and anti-fibrotic effects by reducing disease associated inflammation and fibrosis in lung and liver, and the modulation of both innate and adaptive immune responses in graft versus host disease (GVHD) as well as autoimmune diseases. However, the translation of MSC-EVs to the clinical stage is still at the initial phase. Herein, we discuss the therapeutic potential of an acellular product such as MSC derived EVs (MSC-EVs) in acute and chronic pathologies.

Respiratory infections, mainly in children, are a demanding challenge for physicians. Commonly, a relative immune-defect sustains their recurrence. At present, there is no standardized treatment for their prevention acting on the immune system. Citomix is a low-dose multicomponent medication largely used in this issue. The current study evaluated its ex vivo effect on adenoidal mononuclear cells recovered from children operated for adenoid hypertrophy. B cell phenotype, and IFN-γ, IL-6, IL-10, IgG, IgA, IgM in culture supernatants were evaluated. Citomix was able to significantly increase the expression of B memory cells, IFN-γ, IL-6, IgA and IgM, and significantly decrease IL-10 and IgG. The current outcomes could be consistent with a strategy deputed to improve the early immune response to pathogens. In conclusion, the present ex vivo study suggests that Citomix might be a promising medication in preventing and early treating respiratory infections.

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.

BackgroundSpecific HLA-DQ genes have been recognized as necessary - but not sufficient - factors for the occurrence of Celiac Disease (CD). Through a meta-analysis, evaluating the distribution of CD-related HLA genotypes in children, we aimed at providing insights for a potential widened screening strategy.MethodsAfter a systematic search on the association between class II HLA genes and CD in children, 46 publications were obtained and assessed for eligibility. A total of 13 eligible studies were submitted to data extraction and analysis (10 case-control studies and 3 cohort studies). Case-control studies collectively enrolled 740 CD patients and 943 controls.ResultsIn the population-stratified analysis, the following alleles conferred a significantly increased risk for CD: HLA-DQB1*02 (odds ratio [OR]=10.28) and HLA-DQB1*03:02 (OR=2.24). By drafting a risk gradient to develop CD according to HLA genetic background, the highest risk is confirmed to exist for DQ2/DQ2 homozygous subjects, regardless of the ethnicities (OR=5.4). Actually, the genotype DQ2/β2 showed basically the same risk (OR=5.3). Indeed, no differences have been found in CD risk between DQ2/β2 and DQ2/DQ2, as well as between DQ8/β2 and DQ2/DQ8, and between β2/DQX and DQ2/X.ConclusionThe HLA-DQB1*02:01 allele is present in more than 90% CD children. In the perspective of a widened pediatric population screening for CD, a double-step process might be suggested: HLA-DQB1*02:01 might be investigated first and, only if this result is positive, children might be candidate for a prospective serologic screening, as a second step.

The aim of the present study is to evaluate the effects of 60-day artichoke leaf extract (ALE) supplementation (250mg, twice daily) on cytokines levels, natural killer cell (NK) response, and lipo-metabolic profile (HDL, LDL, and total-cholesterol, triglycerides (TG), ApoB, ApoA, lipid accumulation product (LAP), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)) in twenty adults (9/11 males/females, age=49.10 ± 13.74 years, and BMI=33.12 ± 5.14 kg/m2) with low HDL-C and mild hypercholesterolemia. Hierarchical generalized linear model, adjusted for sex, BMI, and age, has been used to evaluate pre-post treatment changes. A significant increase for HDL-C (β=0.14, p=0.0008) and MCP-1 (β=144.77, p=0.004) and a significant decrease for ApoB/ApoA (β=-0.07, p=0.03), total-C/HDL-C ratio (β=-0.58, pβ=0.43, p=0.04), medium (β=0.40, pβ=0.42, p=0.001) have been found. These results support the benefits of ALE supplementation on metabolic profile.

Rhinella icterica is a poisonous toad whose toxic secretion has never been studied against entomotoxic potential. Sublethal doses of Rhinella icterica toxic secretion (RITS) were assayed in Nauphoeta cinerea cockroaches, in order to understand the physiological and behavioral parameters, over the insect central and peripheral nervous system. RITS (10 μg/g) injections, induced behavioral impairment as evidenced by a significant decrease (38 ± 14%) in the distance traveled (p .05), followed by an increase (90 ± 6%) of immobile episodes (p .001, n = 28, respectively). In cockroaches semi-isolated heart preparations, RITS (16 μg/200 μl) induced a significant irreversible dose-dependent negative chronotropism, reaching ~40% decrease in heart rate in 20 min incubation. In in vivo cockroach neuromuscular preparations, RITS (20, 50 and 100 μg/g of animal weight) induced a time-dependent inhibition of twitch tension that was complete for 20 μg/g, in 120 min recordings. RITS (10 μg/g) also induced a significant increase in the insect leg grooming activity (128 ± 10%, n = 29, p .01), but not in the antennae counterparts. The RITS increase in leg grooming activity was prevented in 90% by the pretreatment of cockroaches with phentolamine (0.1 μg/g). The electrophysiological recordings of spontaneous neural compound action potentials showed that RITS (20 μg/g) induced a significant increase in the number of events, as well as in the rise time and duration of the potentials. In conclusion, RITS showed to be entomotoxic, being the neuromuscular failure and cardiotoxic activity considered the main deleterious effects. The disturbance of the cockroaches' behavior together with the electrophysiological alterations, may unveil the presence of some toxic components present in the poison with inherent biotechnological potentials.

Background: Evidence suggests a role of intestinal microbiota-host interactions in the pathophysiology and symptoms of irritable bowel syndrome (IBS). Objective: The objective of this article is to assess the effects of Lactobacillus paracasei CNCM I-1572 on clinical and gut microbiota-related factors in IBS. Methods: We conducted a multicenter, randomized, double-blind, cross-over, 18-week, placebo-controlled, pilot trial assessing the effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota composition, fecal short chain fatty acid (SCFA), immunoglobulin A, and cytokines in IBS. The intestinal microbial ecosystem was characterized by 16S rRNA gene profiling. Results: Forty IBS patients were enrolled from five Italian centers. Lactobacillus paracasei CNCM I-1572 did not significantly improve IBS symptoms, including primary efficacy variables worst abdominal pain/discomfort and IBS degree of relief. Interestingly, Lactobacillus paracasei CNCM I-1572 induced a significant reduction in genus Ruminococcus, dominated by taxa related to Ruminococcus bromii and Ruminococcus callidus, a significant increase in the SCFAs acetate and butyrate, and a significant reduction in the pro-inflammatory cytokine interleukin-15. Conclusions: This pilot study shows that Lactobacillus paracasei CNCM I-1572 is able to modulate gut microbiota structure/function and reduce immune activation in IBS. As no statistically significant effect on IBS-symptoms was found, further studies are necessary to determine the role of this probiotic in IBS. The study was registered at ClinicalTrials.gov registry under identifier NCT02371499.

Intestinal microbiota is composed by symbiotic innocuous bacteria and potential pathogens also called pathobionts. The human gut normally hosts roughly 1014 bacterial organisms of up to 1000 different species. The genome size of this microbial organ, collectively named microbiome, exceeds the size of the human nuclear genome by 2 orders of magnitude.