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This article belongs to the Section Bioactives and Nutraceuticals., Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a “mucin-like” molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders.

Background: To assess the efects of Rhinosectan® spray, a medical device containing xyloglucan, on nasal ciliary function (in MucilAir Nasal cells). Methods: MucilAir Nasal, a three-dimensional organotypic airway tissue model (with diferent cell types), was treated with Rhinosectan® (30 µl) or with a control (saline solution). The efects of Rhinosectan® were evaluated at 15 and 60 min post-exposure by: measurement of the cilia beating frequency (Hz), mucin detection (Enzyme-Linked Lectin Assay ELLA), mucociliary clearance (µm/s) and phagocytosis assay (fuorescence). Results: Exposure of MucilAir to Rhinosectan® did not alter the cilia beating frequency at 15 and 60 min post-exposure (diluted and undiluted). Exposure to Rhinosectan® (undiluted) during 60 min increased mucociliary clearance (93.3±2.1 µm/s vs. 80.9±1.8 µm/s; p

Aim: To assess the properties of a medical device containing xyloglucan, propolis and hibiscus to create a bioprotective barrier to avoid the contact of uropathogenic Escherichia coli strains on cell walls in models of intestinal (CacoGoblet) and uroepithelial (RWPE-1) cells (derived from normal human prostate epithelium). Materials & methods: Two uropathogenic E. coli strains (expressing type 1 fimbriae and P fimbriae) were used to assess, by electronic microscopy and ELISA, the barrier properties of the medical device. The antimicrobial activity was assessed in broth dilution assays. Results: The three components (xyloglucan, propolis and hibiscus) did not alter E. coli cell integrity in intestinal and uroepithelial cell models and were devoid of antibacterial activity. The three components avoided bacterial contact in both cell monolayers. Conclusion: The nonpharmacological barrier properties of xyloglucan, propolis and hibiscus confirm the role of the medical device for the management of urinary tract infections.

Background: To evaluate barrier protective properties of Rhinosectan® spray, a medical device containing xyloglucan, on nasal epithelial cells (MucilAir). Methods: MucilAir-Nasal, a three-dimensional organotypic (with diferent cell types) airway tissue model, was treated with the medical device Rhinosectan® (30 µL) or with controls (Rhinocort budesonide or saline solution). The protective barrier efects of Rhinosectan® were evaluated by: TEER (trans-epithelial electrical resistance) (preservation of tight junctions), Lucifer Yellow assay (preservation of paracellular fux) and confocal immunofuorescence microscopy (localization of tight junction proteins). Results: Exposure of MucilAir with Rhinosectan® protected cell tight junctions (increases in TEER of 13.1% vs −6.3% with saline solution after 1 h of exposure), and preserved the paracellular fux, even after exposure with pro-infammatory compounds (TNF-α and LPS from Pseudomonas aeruginosa 10). Results of confocal immunofuorescence microscopy demonstrated that, after treatment with the pro-infammatory mixture, Rhinosectan® produced a slight relocation of zona occludens-1 in the cytosol compartment (while Rhinocort induced expression of zona-occludens-1), maintaining the localization of occludin (similarly to negative control). Conclusions: Results of our study indicates that Rhinosectan® creates a protective physical barrier on nasal epithelial cells in vitro, allowing the avoidance of allergens and triggering factors, thus confrming the utility of this medical device in the management of nasal respiratory diseases, as rhinitis or rhinosinusitis. Keywords: Nasal obstruction, Rhinitis, Rhinosinusitis, Orgatypic 3D airway tissue model (MucilAir), Rhinosectan®, Xyloglucan, Barrier properties, Allergy, Preventive measures

Aim: To evaluate whether Utipro®, a natural product approved to prevent urinary tract infections, protects intestinal epithelial cells from Escherichia coli adherence/intracellular invasion in vitro. Materials & methods: Caco-2 and CacoGobletTM cells were treated with Utipro (1.5 to 10 mg/ml) or untreated (controls). E. coli adherence/intracellular invasion was evaluated by Trans-Epithelial Electrical Resistance, Lucifer Yellow assay and microbial counts. Results: Utipro was noncytotoxic. Utipro 5 and 10 mg/ml protected cell tight junctions (mean ± SD Trans-Epithelial Electrical Resistance [Ω × cm2] 66.83 ± 0.29 and 71.33 ± 0.29, respectively), and protected cells from E. coli intracellular invasion (mean ± SD reductions in total bacteria counts [Log10] 0.9 ± 0.06 and 2.1 ± 0.56, respectively). Conclusion: Results indicate that Utipro creates a protective physical barrier on intestinal epithelial cells in vitro which reduces the settling of E. coli reservoirs. These results constitute the first step in the demonstration of the efficacy of Utipro to prevent urinary tract infections. Further research is needed in in vivo models and clinical trials.

Background. Xyloglucan, a film-forming agent, improves intestinal mucosa resistance to pathologic damage. The efficacy, safety, and time of onset of the antidiarrheal effect of xyloglucan were assessed in children with acute gastroenteritis receiving oral rehydration solution (ORS).Methods. This randomized, controlled, open-label, parallel-group, multicenter, clinical trial included children (3 months–12 years) with acute gastroenteritis of infectious origin. Children were randomized to xyloglucan and ORS, or ORS only, for 5 days. Diarrheal symptoms, including stool number/characteristics, and safety were assessed at baseline and after 2 and 5 days and by fulfillment of a parent diary card.Results. Thirty-six patients (58.33% girls) were included (n=18/group). Patients receiving xyloglucan and ORS had better symptom evolution than ORS-only recipients, with a faster onset of action. At 6 hours, xyloglucan produced a significantly greater decrease in the number of type 7 stools (0.11 versus 0.44;P=0.027). At days 3 and 5, xyloglucan also produced a significantly greater reduction in types 6 and 7 stools compared with ORS alone. Xyloglucan plus ORS was safe and well tolerated.Conclusions. Xyloglucan is an efficacious and safe option for the treatment of acute gastroenteritis in children, with a rapid onset of action in reducing diarrheal symptoms. This study is registered with ISRCTN number65893282.

Klebsiella pneumoniae strains typically express both smooth lipopolysaccharide (LPS) with O antigen molecules and capsule polysaccharide (K antigen) on the surface. A single mutation in a gene that codes for a UDP galacturonate 4-epimerase ( uge ) renders a strain with the O − :K − phenotype (lack of capsule and LPS without O antigen molecules and outer core oligosaccharide). The uge gene was present in all the K. pneumoniae strains tested. The K. pneumoniae uge mutants were unable to produce experimental urinary tract infections in rats and were completely avirulent in two different animal models (septicemia and pneumonia). Reintroduction of the single uge wild-type gene in the corresponding mutants completely restored the wild-type phenotype (presence of capsule and smooth LPS) independently of the O or K serotype of the wild type. Furthermore, complemented uge mutants recovered the ability to produce experimental urinary tract infections in rats and virulence in the septicemia and pneumonia animal models.

To determine the function of the wabG gene in the biosynthesis of the core lipopolysaccharide (LPS) of Klebsiella pneumoniae , we constructed wabG nonpolar mutants. Data obtained from the comparative chemical and structural analysis of LPS samples obtained from the wild type, the mutant strain, and the complemented mutant demonstrated that the wabG gene is involved in attachment toα - l -glycero- d -manno-heptopyranose II ( l , d -Hep p II) at the O-3 position of anα - d -galactopyranosyluronic acid (α- d -GalA p ) residue. K. pneumoniae nonpolar wabG mutants were devoid of the cell-attached capsular polysaccharide but were still able to produce capsular polysaccharide. Similar results were obtained with K. pneumoniae nonpolar waaC and waaF mutants, which produce shorter LPS core molecules than do wabG mutants. Other outer core K. pneumoniae nonpolar mutants in the waa gene cluster were encapsulated. K. pneumoniae waaC , waaF , and wabG mutants were avirulent when tested in different animal models. Furthermore, these mutants were more sensitive to some hydrophobic compounds than the wild-type strains. All these characteristics were rescued by reintroduction of the waaC , waaF , and wabG genes from K. pneumoniae .

Up to now only one major type of core oligosaccharide has been found in the lipopolysaccharide of all Klebsiella pneumoniae strains analyzed. Applying a different screening approach, we identified a novel Klebsiella pneumoniae core (type 2). Both Klebsiella core types share the same inner core and the outer-core-proximal disaccharide, GlcN-(1,4)-GalA, but they differ in the GlcN substituents. In core type 2, the Glc p N residue is substituted at the O-4 position by the disaccharide β-Glc p (1-6)-α-Glcp(1, while in core type 1 the Glc p N residue is substituted at the O-6 position by either the disaccharide α-He p (1-4)-α-Kdo(2 or a Kdo residue (Kdo is 3-deoxy- d -manno-octulosonic acid). This difference correlates with the presence of a three-gene region in the corresponding core biosynthetic clusters. Engineering of both core types by interchanging this specific region allowed studying the effect on virulence. The replacement of Klebsiella core type 1 in a highly type 2 virulent strain (52145) induces lower virulence than core type 2 in a murine infection model.

Background The evaluation of the interaction of new immunogens with dendritic cells is important for new vaccine strategies. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and Modified Vaccinia Ankara (MVA) expressing Gag or Tat, Nef and Rev in an ex vivo model of human monocyte-derived dendritic cells (MDDC) to compare two different loading strategies,either viral or synthetic derived.

Background There is a strong rationale for the use of agents with film-forming protective properties, like xyloglucan, for the treatment of acute diarrhea. However, few data from clinical trials are available. Methods A randomized, controlled, open-label, parallel group, multicentre, clinical trial was performed to evaluate the efficacy and safety of xyloglucan, in comparison with diosmectite and Saccharomyces in adult patients with acute diarrhea due to different causes. Patients were randomized to receive a 3-day treatment. Symptoms (stools type, nausea, vomiting, abdominal pain and flatulence) were assessed by a self-administered ad-hoc questionnaire 1, 3, 6, 12, 24, 48 and 72 h following the first dose administration. Adverse events were also recorded. Results A total of 150 patients (69.3 % women and 30.7 % men, mean age 47.3 ± 14.7 years) were included (n = 50 in each group). A faster onset of action was observed in the xyloglucan group compared with the diosmectite and S. bouliardii groups. At 6 h xyloglucan produced a statistically significant higher decrease in the mean number of type 6 and 7 stools compared with diosmectite (p = 0.031). Xyloglucan was the most efficient treatment in reducing the percentage of patients with nausea throughout the study period, particularly during the first hours (from 26 % at baseline to 4 % after 6 and 12 h). An important improvement of vomiting was observed in all three treatment groups. Xyloglucan was more effective than diosmectite and S. bouliardii in reducing abdominal pain, with a constant improvement observed throughout the study. The clinical evolution of flatulence followed similar patterns in the three groups, with continuous improvement of the symptom. All treatments were well tolerated, without reported adverse events. Conclusions Xyloglucan is a fast, efficacious and safe option for the treatment of acute diarrhea. Trial registration EudraCT number 2014-001814-24 (date: 2014-04-28) ISRCTN number: 90311828