5 research outputs found
Transcriptomic profiling of white blood cells reveals new insights into the molecular mechanisms of thalidomide in children with inflammatory bowel disease
Thalidomide has emerged as an effective immunomodulator in the treatment of pediatric
patients with inflammatory bowel disease (IBD) refractory to standard therapies. Cereblon,
a component of E3 protein ligase complex that mediates ubiquitination and proteasomal
degradation of target proteins, has been identified as the primary target of thalidomide.
Cereblon plays a crucial role in thalidomide teratogenicity, however it is unclear whether it
is also involved in the therapeutic effects in IBD patients. This study aimed at identifying
the mechanisms underpinning thalidomide action in pediatric IBD. Ten IBD pediatric
patients clinically responsive to thalidomide were prospectively enrolled. RNA-sequencing
and functional enrichment analysis was carried out on peripheral blood mononuclear
cells obtained before and after treatment with thalidomide. RNA-sequencing analysis
revealed 378 differentially expressed genes after treatment with thalidomide. The
most deregulated pathways were cytosolic calcium ion concentration, cAMP-mediated
signaling, eicosanoid signaling and inhibition of matrix metalloproteinases. Neuronal
signaling mechanisms such as CREB signaling in neurons and axonal guidance signaling
also emerged. Connectivity Map analysis revealed that thalidomide gene expression
changes were similar to those induced by MLN4924, an inhibitor of NEDD8 activating
enzyme, suggesting that thalidomide exerts its immunomodulatory effects by acting on
the ubiquitin-proteasome pathway.
In vitro experiments on cell lines confirmed the effect of thalidomide on altered candidate
pathways observed in patients. These results represent a unique resource for enhanced
understanding of thalidomide mechanism in patients with IBD, providing novel potential
targets associated with drug response.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202
Role of tristetraprolin phosphorylation in paediatric patients with inflammatory bowel disease
Long Non-Coding RNA GAS5 and Intestinal MMP2 and MMP9 Expression: A Translational Study in Pediatric Patients with IBD
Ecosystem vulnerability to alien and invasive species: a case study on marine habitats along the Italian coast
1. Spread of alien species (AS) is a serious threat to marine habitats and analysis of principal descriptors of their occurrence is pivotal to set reliable conservation strategies.
2. In order to assess the susceptibility of marine habitats to biological invasions, a dataset was gathered of the occurrence of 3899 species from 29 phyla, taken from 93 marine sites located along the Italian coast in the period 2000\u20132012.
3. In total, 61 AS belonging to 11 phyla have been recorded. Invertebrates were the most represented (63%).
Alien species were found in all the habitats examined (EUNIS, level 2), although they showed highest abundance in benthic habitats. Most of the AS were associated with a single EUNIS habitat, while some of them were present in more than one habitat. Trans-habitat occurrence suggests the potential invasiveness of AS.
4. According to statistical analysis, AS recorded could have been more numerous, since some of the marine habitats seemed to be still unsaturated. The model that best describes the spread of AS takes account of both native species richness (Rn) and EUNIS habitat type as explanatory variables. The number of observed AS was directly related to Rn and it was highest in rocky circalittoral and infralittoral habitats.
5. The results of this macro-ecological study focus on the importance of performing large-scale studies, since adopting ecosystem approaches to marine invasion management seems especially fruitful.
6. The results, moreover, highlight the importance of AS monitoring of different habitats, from those subjected to anthropogenic pressure, historically considered to be hubs of introduction of AS, to the most biologically rich and diverse marine habitats. Indeed, it is necessary to set monitoring strategies to detect the introduction, the distribution and persistence of AS over time. These recommendations are especially
significant in the light of the strategic plans currently under formulation in Mediterranean countries with regard to AS monitorin