Emerging evidence suggests that platelets, cytoplasmic fragments derived from megakaryocytes, can no longer be considered just as mediators in hemostasis and coagulation processes, but as key ...modulators of immunity. Platelets have received increasing attention as the emergence of new methodologies has allowed the characterization of their components and functions in the immune continuum. Platelet activation in infectious and allergic lung diseases has been well documented and associated with bacterial infections reproduced in several animal models of pulmonary bacterial infections. Direct interactions between platelets and bacteria have been associated with increased pulmonary platelet accumulation, whereas bacterial-derived toxins have also been reported to modulate platelet function. Recently, platelets have been found extravascular in the lungs of patients with asthma, and in animal models of allergic lung inflammation. Their ability to interact with immune and endothelial cells and secrete immune mediators makes them one attractive target for biomarker identification that will help characterize their contribution to lung diseases. Here, we present an original review of the last advances in the platelet field with a focus on the contribution of platelets to respiratory infections and allergic-mediated diseases.
Obesity is associated with a low-grade inflammatory status that affects vascular function. Previous studies have reported the beneficial effects of Psidium guajava L. (guava) on diabetes. Here we ...evaluate the how guava leaf extract at the dose of 5 mg/kg, affects vascular dysfunction in obese mice fed a high-fat diet for 7 weeks. Extract intake did not alter weight over time, although it reduced glycemia and insulin resistance, improving the serum lipid profile in obese mice. Additionally, guava leaf extract reversed the endothelial dysfunction found in obese mice in terms of endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings. In conclusion, the beneficial effects of guava leaf extract in obese mice were associated with improved vascular functions altered by obesity, probably due to its phenolic content.
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•Guava leaves improves the vascular dysfunction in obese mice.•Administration of guava leaf extract has a positive impact on metabolic functions in obese mice.•The beneficial effects ascribed to guava leaf extract in obese mice can be due to its phenolic content.
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•AFC proves intestinal anti-inflammatory effects on DSS-induced colitis.•This study exhibits, for the first time, the immunomodulatory properties of AFC.•This study is an important ...step towards the therapeutic use of AFC in human IBD.
Fumaria genus has been traditionally used for managing inflammatory and gastrointestinal disorders. The study evaluates the immunomodulatory potential of the total alkaloid fraction from Fumaria capreolata L. (AFC) in primary macrophages and the intestinal anti-inflammatory effect in a dextran sodium sulphate-induced colitis in mice. AFC inhibited LPS-stimulated bone marrow-derived macrophages gene expression program dose-dependently. In vivo, AFC markedly reduced macroscopic and microscopic signs of intestinal inflammation. Besides, it restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers. These results demonstrate the potential of AFC extract as a therapeutic tool for the management of inflammatory bowel disease.
Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not ...fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.
SCOPE: This study investigates the preventive effects of two pea (Pisum sativum) seed albumin extracts, either in the presence (pea seed extract PSE) or absence (albumin fraction from PSE AF‐PSE) of ...soluble polysaccharides, in the dextran sodium sulfate (DSS) induced colitis in mice. METHODS AND RESULTS: Male C57BL/6J mice were assigned to five groups: one noncolitic and four colitic. Colitis was induced by incorporating DSS (3.5%) in the drinking water for 4 days, after which DSS was removed. Treated groups received orally PSE (15 g/kg⋅day), or AF‐PSE (1.5 g/kg⋅day), or pure soy Bowman–Birk inhibitor (BBI; 50 mg/kg⋅day), starting 2 wk before colitis induction, and maintained for 9 days after. All treated groups showed intestinal anti‐inflammatory effect, evidenced by reduced microscopic histological damage in comparison with untreated colitic mice. The treatments ameliorated the colonic mRNA expression of different proinflammatory markers: cytokines, inducible enzymes, metalloproteinases, adhesion molecules, and toll‐like receptors, as well as proteins involved in maintaining the epithelial barrier function. Furthermore, the administration of PSE, AF‐PSE, or soy BBI restored bacterial counts, partially or totally, to values in healthy mice. CONCLUSION: PSE and AF‐PSE ameliorated DSS‐induced damage to mice, their effects being due, at least partially, to the presence of active BBI.
Scope
Propyl‐propane thiosulfonate (PTSO) is a component isolated from garlic (Allium sativum) with antioxidant, anti‐inflammatory, immunomodulatory, and antimicrobial properties. In consequence, ...PTSO can be a potential candidate for the treatment of inflammatory bowel diseases.
Methods and results
The anti‐inflammatory effects of PTSO are studied in two mice models of colitis: 2,4‐dinitrobenzene sulfonic acid (DNBS) (PTSO doses: 0.01–10 mg kg–1) and dextran sodium sulfate (DSS) (PTSO doses: 0.01–0.1 mg kg–1). The immunomodulatory effects of PTSO (0.1–25 µm) are also shown in vitro in Caco‐2 and THP‐1 cells, reducing the production of pro‐inflammatory mediators and downregulating mitogen‐activated protein kinases (MAPKs) signaling pathways. This compound displays beneficial effects in both models of mouse colitis by reducing the expression of different pro‐inflammatory mediators and improving the intestinal epithelial barrier integrity. Moreover, PTSO ameliorates the altered gut microbiota composition observed in DSS colitic mice.
Conclusion
PTSO exerts intestinal anti‐inflammatory activity in experimental colitis in mice. This anti‐inflammatory activity can be associated with the immunomodulatory properties of PTSO through the regulation of the activity of cells involved in the inflammatory response. Furthermore, PTSO is able to restore the intestinal epithelial barrier function and to ameliorate the intestinal microbiota homeostasis, thus supporting its future development in human IBD.
Propyl‐propane thiosulfonate (PTSO) shows intestinal anti‐inflammatory properties in two experimental models of mouse colitis, 2,4‐dinitrobenzene sulfonic acid and dextran sodium sulfate, which are associated with reduced expression of pro‐inflammatory mediators, improvement of intestinal epithelial barrier integrity, and amelioration of altered gut microbiota composition. In vitro assays in Caco‐2 and THP‐1 cells reveal that PTSO reduced the production of pro‐inflammatory mediators and downregulated mitogen‐activated protein kinases signaling pathways.
Scope
The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.
Methods and results
...Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium‐dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)‐driven superoxide production and Rho‐kinase‐mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T‐helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus‐induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate‐ and butyrate‐producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40‐treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.
Conclusion
LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.
Lactobacillus fermentum CECT5716 (LC40) treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased T‐helper 17 cells (Th17) and increased regulatory T (Treg) cells polarization in mesenteric lymph nodes.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients' life quality and requires sustained pharmacological and surgical treatments. ...Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects.
Aging is a biological process with high susceptibility to several infections. This risk increases in older patients in residential care facilities (RCF). Thus, there is a clear demand for developing ...preventive interventions with new therapeutic compounds that combine efficacy and safety. This could be the case of compounds derived from plants of the genus
spp. The purpose of this study was to evaluate the impact of a combination of a garlic and onion extract concentrate standardized in organosulfur compounds derived from propiin on the incidence of respiratory tract infections in elderly patients of RCF. Sixty-five volunteers were selected at random to receive a placebo or a single daily dose of the extract for thirty-six weeks. Different clinical visits were performed to evaluate the main respiratory diseases with an infectious origin, as well as the associated symptoms and their duration. The extract showed a clinical safety profile and significantly reduced the incidence of respiratory infections. Moreover, the treatment decreased the number and duration of the associated symptoms compared with the placebo group. For the first time, we demonstrated the protective effect of
extract in respiratory infectious diseases in elderly healthy volunteers, which could be used prophylactically against the most common infectious respiratory diseases.
Exopolysaccharide (EPS)-producing bifidobacteria, particularly Bifidobacterium animalis subsp. lactis strains, are used in the functional food industry as promising probiotics with purported ...beneficial effects. We used three isogenic strains of B. animalis subsp. lactis, with different EPS producing phenotypes (mucoid-ropy and non-ropy), in order to determine their capability to survive the murine gastrointestinal tract transit, as well as to evaluate their role in improving clinical outcomes in a chemically-induced colitis model. The three strains were able to survive in the intestinal tract of C57BL/6J mice during the course of the intervention study. Furthermore, the disease activity index (DAI) of the animal group treated with the ropy strain was significantly lower than of the DAI of the placebo group at the end of the treatment. However, no significant differences were found among the three strains. The analysis of several immune parameters, such as TNFα and IL-10 quantified in blood plasma and lymphocyte populations enumerated in mesenteric nodes, showed some significant variations among the four experimental animal groups. Remarkably, a higher capability of the ropy strain to increase regulatory T-cells in mesenteric lymphoid nodes was demonstrated, suggesting a higher ability of this strain to regulate inflammatory responses at mucosal level. Our data indicate that strains of B. animalis subsp. lactis producing EPS that confer a mucoid-ropy phenotype could represent promising candidates to perform further studies targeting intestinal inflammatory processes.
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