Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice.

Background: Dysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10-/-). Methods: Wild type (WT) and IL-10-/-. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3-V4 regions of 16S rDNA gene. Results: IL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups-derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result. Conclusion: Gut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD.

Liver X Receptor Exerts Anti-Inflammatory Effects in Colonic Epithelial Cells via ABCA1 and Its Expression Is Decreased in Human and Experimental Inflammatory Bowel Disease.

BACKGROUND: Liver X receptor (LXR) exerts anti-inflammatory effects in macrophages. The aim of this study was to explore the expression and function of LXR in the colonic epithelium under inflammatory conditions. METHODS: The expression of LXR was explored by Western blot and immunohistochemistry in colonic biopsies from patients diagnosed with inflammatory bowel disease (IBD) and control patients. In addition, LXR and its target gene expression were analyzed in the colon from interleukin (IL)-10-deficient (IL-10-/-) and wild-type mice. Caco-2 cells were pretreated with the synthetic LXR agonist GW3965 and further challenged with IL-1ß, the expression of IL-8 and chemokine (C-C motif) ligand (CCL)-28 chemokines, the activation of mitogen-activated protein (MAP) kinases, and the nuclear translocation of the p65 subunit of nuclear factor kappa B was evaluated. Glibenclamide was used as an ABCA1 antagonist. RESULTS: We found that LXR expression was downregulated in colonic samples from patients with IBD and IL-10-/- mice. The nuclear positivity of LXR inversely correlated with ulcerative colitis histologic activity. Colonic IL-1ß mRNA levels negatively correlated with both LXRα and LXRß in the colon of IL-10-/- mice, where a decreased mRNA expression of the LXR target genes ABCA1 and FAS was shown. In addition, IL-1ß decreased the expression of the LXR target gene ABCA1 in cultured intestinal epithelial cells. The synthetic LXR agonist GW3965 led to a decreased nuclear positivity of the p65 subunit of nuclear factor kappa B, a phosphorylation ratio of the p44-42 MAP kinase, and the expression of CCL-28 and IL-8 in IL-1ß-stimulated Caco-2 cells. The pharmacological inhibition of ABCA1 increased the phosphorylation of p44-42 after GW3965 treatment and IL-1ß stimulation. CONCLUSIONS: The LXR-ABCA1 pathway exerts anti-inflammatory effects in intestinal epithelial cells and is impaired in the colonic mucosa of patients with IBD and IL-10-/- mice.

No antibiotic and toxic metabolites produced by the biocontrol agent Pseudomonas putida strain B2017.

Pseudomonas putida and closely-related species such as Pseudomonas fluorescens and Pseudomonas brassicacearum have been reported as potential biocontrol agents and plant growth-promoters. Recently, we have described the biocontrol activity of P. putida B2017 against several phytopathogens of agricultural relevance. In this study, its ability to produce potential antibiotic / toxic metabolites was assessed by functional, chromatography-mass spectrometry and genomic analysis. Our results show that B2017 is not able to synthesize surfactants and common antibiotics produced by Pseudomonas spp., i.e. pyrrolnitrin, 2,4-diacetylphloroglucinol, pyoluteorin and pyocyanin, but it produces pyoverdine, a siderophore which is involved in its biocontrol activity. The non-production of other metabolites, such as cyanide, safracin, promysalin and lipopeptides between others, is also discussed. Our data suggest that the mode of action of B2017 is not mainly due to the production of antimicrobial / toxic metabolites. Moreover, these features make P. putida B2017 a promising biocontrol microorganism for plant protection without side effects on environment, non-target organisms and human health.

Cribado nutricional y su asociación con los resultados al alta hospitalaria / Nutritional screening and its association with outcome at discharge

Existen dos métodos de cribado nutricional validados para la identificación temprana de desnutrición al ingreso hospitalario. OBJETIVO: Determinar la prevalencia de desnutrición hospitalaria (DNTH) usando la Valoración Global Subjetiva (VGS) y el Nutricional Risk Screening 2002 (NRS-2002), así como determinar su asociación con resultados adversos hospitalarios: infecciones nosocomiales, ulceras por presión, estancia hospitalaria y fallecimiento. MATERIAL Y METODO: Estudio observacional y transversal de los pacientes, de 18 a mas años, que ingresen al Departamento de Medicina del Hospital Víctor Lazarte Echegaray de Trujillo - Perú. RESULTADOS: 90 pacientes fueron incluidos en el estudio, de los cuales 14 desarrollaron una infección nosocomial (15,6%), 3 presentaron Ulceras por Presión (3,3%) y 1/ fallecieron (12,2%). La estancia promedio de todos los pacientes fue 13,9 +/- 10,3 días, con rango de 3 a 60 días. La DNTH se encontró entre el 58% (NRS-2002) y el 72% (VGS) de los pacientes de acuerdo al método de cribaje usado. Los DNTH Severos, diagnosticados con la VGS y NRS-2002, tuvieron más infecciones, desarrollaron más Ulceras por Presión, mas mortalidad y estancia hospitalaria más prolongada al alta cuando se comparó con los No DNTH Severa. CONCLUSION: La DNTH fue prevalente en los pacientes hospitalizados en el Departamento de Medicina durante el periodo del estudio, encontrando asociación entre los pacientes con DNTH Severa y los resultados adversos al alta, versus los pacientes No DNTH severos, usando cualquiera de los dos métodos de cribado nutricional...

There are two validated methods of nutritional screening for early detection of malnutrition at admission. OBJECTIVE: To determine the hospital malnutrition (H MN) prevalence using the Subjective Global Assessment (SGA) and Nutritional Risk Screening 2002 (NRS-2002), and to determine their association with adverse outcomes hospital: nosocomial infections, pressure ulcers, hospital stay and death. METHODS: observational, cross-sectional study of patients over 18 years, admitted the Department of Medicine HospitalVictor Lazarte Echegaray Trujillo - Peru. RESULTS: Ninety patients were admitted to the study, of them 14 developed a nosocomial infection (15,6%), 3 presented pressure ulcers (3,3%) and 11 died (12,2%). The average stay for all patients was 13,9 +/- 10,3 days, range 3-60 days. The HMN resulted 58% (NRS-2002) and 72% (SGA) patients according to the screening method used. Severe HMN diagnosed with SGA and NRS-2002, had more infections, pressure ulcers, more deaths and longer hospital stay when compared with HMN No Severe. CONCLUSION: HMN was prevalent in hospitalized patients in the Medicine Department during the study period, exists association between HMN patients with severe adverse outcomes at discharge, patients versus DNTH not severe, using either methods nutritional screening...

Cilastatin protects against cisplatin-induced nephrotoxicity without compromising its anticancer efficiency in rats.

Cisplatin is an anticancer agent marred by nephrotoxicity; however, limiting this adverse effect may allow the use of higher doses to improve its efficacy. Cilastatin, a small molecule inhibitor of renal dehydropeptidase I, prevents proximal tubular cells from undergoing cisplatin-induced apoptosis in vitro. Here, we explored the in vivo relevance of these findings and the specificity of protection for kidney cells in cisplatin-treated rats. Cisplatin increased serum blood urea nitrogen and creatinine levels, and the fractional excretion of sodium. Cisplatin decreased the glomerular filtration rate, promoted histological renal injury and the expression of many pro-apoptotic proteins in the renal cortex, increased the Bax/Bcl2 ratio, and oxidative stress in kidney tissue and urine. All these features were decreased by cilastatin, which preserved renal function but did not modify the pharmacokinetics of cisplatin area under the curve. The cisplatin-induced death of cervical, colon, breast, and bladder-derived cancer cell lines was not prevented by cilastatin. Thus, cilastatin has the potential to prevent cisplatin nephrotoxicity without compromising its anticancer efficacy.