41 research outputs found
PEMANFAATAN TEBON TANAMAN JAGUNG UNTUK PRODUKSI PAKAN TERNAK SILASE DI DESA ANA ENGGE, KABUPATEN SUMBA BARAT DAYA
No full textPEMANFAATAN TEBON TANAMAN JAGUNG UNTUK PRODUKSI PAKAN TERNAK SILASE DI DESA ANA ENGGE, KABUPATEN SUMBA BARAT DAY
IMINOSUGAR-BASED INHIBITORS OF CERAMIDE GLUCOSYL-TRANSFERASE (GLCCERT) AND NONLYSOSOMAL GLUCOSYLCERAMIDASE (GBA2) REDUCE THE INFLAMMATORY RESPONSE TO P. AERUGINOSA IN CF BRONCHIAL EPITHELIAL CELLS
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Role of adipose tissue in melanoma cancer microenvironment and progression
No full textBackground:An epidemiological association between excess weight and increased risk of cancer has been described in melanoma, for which the physiopathological mechanisms are still unknown. The study of tumor microenvironment and of the role of adipocytes in cancer development, progression and metastasis has recently received great interest. However, the role of peritumoral adipocytes has been characterized only in a few types of cancer, and in melanoma it still remains to be defined.Methods:We investigated the interactions between adipocytes and melanoma cells using an in vitro co-culture system. We studied the morphological and functional properties of 3T3-L1 adipocytes before and after co-culture with A375 melanoma cells, in order to assess the role of adipocytes on melanoma migration.Results:Morphological analysis showed that after 6 days of co-culture 3T3-L1 adipocytes were reduced in number and size. Moreover, we observed the appearance of dedifferentiated cells with a fibroblast-like phenotype that were not present in controls and that had lost the expression of some adipocyte-specific genes, and increased the expression of collagen, metalloproteinases and genes typical of dedifferentiation processes. Through the Matrigel Invasion Test, as well the Scratch Test, it was possible to observe that co-culture with adipocytes induced in melanoma cells increased migratory capacity, as compared with controls. In particular, the increase in migration observed in co-culture was suppressed after adding the protein SFRP-5 in the medium, supporting the involvement of the Wnt5a pathway. The activation of this pathway was further characterized by immunofluorescence and western blot analysis, showing in melanocytes in co-culture the activation of β-catenin and LEF-1, two transcription factors involved in migration processes, neo-angiogenesis and metastasis.Conclusions:These data allow us to hypothesize a dedifferentiation process of adipocytes toward fibroblast-like cells, which can promote migration of melanoma cells through activation of Wnt5a and the intracellular pathways of β-catenin and LEF-1
Pseudomonas aeruginosa reduces the expression of CFTR via post-translational modification of NHERF1
No full textPseudomonas aeruginosa infections of the airway cells decrease apical expression of both wild-type (wt) and F508del CFTR through the inhibition of apical endocytic recycling. CFTR endocytic recycling is known to be regulated by its interaction with PDZ domain containing proteins. Recent work has shown that the PDZ domain scaffolding protein NHERF1 finely regulates both wt and F508delCFTR membrane recycling. Here, we investigated the effect of P. aeruginosa infection on NHERF1 post-translational modifications and how this affects CFTR expression in bronchial epithelial cells and in murine lung. Both in vitro in bronchial cells, and in vivo in mice, infection reduced CFTR expression and increased NHERF1 molecular weight through its hyper-phosphorylation and ubquitination as a consequence of both bacterial pilin- and flagellin-mediated host-cell interaction. The ability of P. aeruginosa to down-regulate mature CFTR expression was reduced both in vivo in NHERF1 knockout mice and in vitro after silencing NHERF1 expression or mutations blocking its phosphorylation at serines 279 and 301. These studies provide the first evidence that NHERF1 phosphorylation may negatively regulate its action and, therefore, the assembly and function of multiprotein NHERF1 complexes in response to infection. The identification of molecular mechanisms responsible for these effects could identify novel targets to block potential P. aeruginosa interference with the efficacy of potentiator and/or corrector compounds. © 2014 Springer-Verlag Berlin Heidelberg
The antimicrobial resistance travel tool, an interactive evidence-based educational tool to limit antimicrobial resistance spread
No full textBACKGROUND: International travel has been recognized as a risk factor contributing to the spread of antimicrobial resistance (AMR). However, tools focused on AMR in the context of international travel and designed to guide decision-making are limited. We aimed at developing an evidence-based educational tool targeting both healthcare professionals (HCPs) and international travellers to help prevent the spread of AMR. METHODS: A literature review on 12 antimicrobial-resistant bacteria (ARB) listed as critical and high tiers in the WHO Pathogen Priority List covering four key areas was carried out: AMR surveillance data; epidemiological studies reporting ARB prevalence data on carriage in returning travellers; guidance documents reporting indications on screening for ARB in returning travellers and recommendations for ARB prevention for the public. The evidence, catalogued at country-level, provided the content for a series of visualizations that allow assessment of the risk of AMR acquisition through travel. RESULTS: Up to January 2021, the database includes data on: (i) AMR surveillance for 2.018.241 isolates from 86 countries; (ii) ARB prevalence of carriage from 11.679 international travellers and (iii) 15 guidance documents published by major public health agencies. The evidence allowed the development of a consultation scheme for the evaluation of risk factors, prevalence of carriage, proportion and recommendations for screening of AMR. For the public, pre-travel practical measures to minimize the risk of transmission were framed. CONCLUSIONS: This easy-to-use, annually updated, freely accessible AMR travel tool (https://epi-net.eu/travel-tool/overview/), is the first of its kind to be developed. For HCPs, it can provide a valuable resource for teaching and a repository that facilitates a stepwise assessment of the risk of AMR spread and strengthen implementation of optimized infection control measures. Similarly, for travellers, the tool has the potential to raise awareness of AMR and outlines preventive measures that reduce the risk of AMR acquisition and spread
PSEUDOMONAS AERUGINOSA MODULATES THE PHOSPHORYLATION CHANGES OF SCAFFOLDING PROTEINS AND APICAL EXPRESSION OF CFTR IN AIRWAYS
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Phospholipase C-β3 is a key modulator of IL-8 expression in cystic fibrosis bronchial epithelial cells.
No full textRespiratory insufficiency is the major cause of morbidity and mortality in patients affected by cystic fibrosis (CF). An excessive neutrophilic inflammation, mainly orchestrated by the release of IL-8 from bronchial epithelial cells and amplified by chronic bacterial infection with Pseudomonas aeruginosa, leads to progressive tissue destruction. The anti-inflammatory drugs presently used in CF patients have several limitations, indicating the need for identifying novel molecular targets. To address this issue, we preliminarily studied the association of 721 single nucleotide polymorphisms from 135 genes potentially involved in signal transduction implicated in neutrophil recruitment in a cohort of F508del homozygous CF patients with either severe or mild progression of lung disease. The top ranking association was found for a nonsynonymous polymorphism of the phospholipase C-β3 (PLCB3) gene. Studies in bronchial epithelial cells exposed to P. aeruginosa revealed that PLCB3 is implicated in extracellular nucleotide-dependent intracellular calcium signaling, leading to activation of the protein kinase Cα and Cβ and of the nuclear transcription factor NF-κB p65. The proinflammatory pathway regulated by PLCB3 acts by potentiating the Toll-like Receptors' signaling cascade and represents an interesting molecular target to attenuate the excessive recruitment of neutrophils without completely abolishing the inflammatory response
PLCB3 cooperates with the Toll-like receptors' signaling cascade enhancing P.aeruginosa-dependent IL-8 expression in bronchial epithelial cells
No full textAn excessive neutrophilic inflammation, initially orchestrated by bronchial epithelial cells and amplified by chronic bacterial infection with P.aeruginosa, leads to progressive tissue destruction in the lungs of patients affected by Cystic Fibrosis. The discovery of novel molecular targets may help to develop more effective anti-inflammatory drugs. In this issue, we report that association study conducted on a cohort of F508del homozygous cystic fibrosis patients with either severe or mild progression of lung disease, showed the implication of the nonsynonymous single-nucleotide polymorphism C2534T of the phospholipase C-3 (PLCB3) gene in the neutrophil recruitment. Studies performed in IB3-1 and CuFi-1 bronchial epithelial cells exposed to P.aeruginosa revealed that PLCB3 is implicated in ATP releasing from the cells and subsequent activation of purinergic receptors, intracellular calcium (Ca2+)i signaling, activation of the protein kinase C and C and of the nuclear transcription factor NF-B p65. Thus, the pro-inflammatory pathway regulated by PLCB3 acts by potentiating the Toll-like Receptors’ signaling cascade leading to enhanced IL-8 expression in bronchial epithelial cells. Concluding, PLCB3 may represent an interesting molecular target to attenuate the excessive recruitment of neutrophils without completely abolishing the immune response
