Alfonso Carleo

A system biology study of BALF from patients affected by idiopathic pulmonary fibrosis (IPF) and healthy controls

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by progressive loss of the alveolar integrity, recruitment, and activation of myofibroblast, and excessive collagen deposition that resulted in loss of parenchymal architecture and lung function. Although etiology is unknown, major risk factor of disease development is represented by cigarette smoke or exposure to dust.

Biomarkers in sarcoidosis: the contribution of system biology.

Purpose of review System biology is an interdisciplinary approach with the purpose to evaluate the experimental results of ‘-omics’ sciences as a whole. The ‘-omics’ sciences do not start generally from a-priori assumptions and are aimed to study the constituents of a specific biological domain (genome, transcriptome, proteome and metabolome) in a given state, using different high-throughput technologies (as polymerase chain reaction, arrays, liquid chromatography, mass spectrometry, etc.) and allowing a hermeneutical integration and recomposition of the experimental information. The aim of the present review is to explore the main new findings of system biology studies applied to sarcoidosis in the last year. Recent findings The main new findings of sarcoidosis that were highlighted by different studies in the last year (including miRNAs, TGF-&bgr; pathway, TNF-&agr; and related proteins, vesicle trafficking, vitamin D and lipid metabolism, analyzed by system biology) are presented in this article. Summary System biology is a useful approach to combine different experimental results to study the pathogenesis of sarcoidosis and to identify groups of new molecules and mediators with potential clinical application as biomarkers.

What makes A. guillouiae SFC 500-1A able to co-metabolize phenol and Cr(VI)? A proteomic approach

Acinetobacter guillouiae SFC 500-1A is an environmental bacterium able to efficiently co-remediate phenol and Cr(VI). To further understand the molecular mechanisms triggered in this strain during the bioremediation process, variations in the proteomic profile after treatment with phenol and phenol plus Cr(VI) were evaluated. The proteomic analysis revealed the induction of the β-ketoadipate pathway for phenol oxidation and the assimilation of degradation products through TCA cycle and glyoxylate shunt. Phenol exposure increased the abundance of proteins associated to energetic processes and ATP synthesis, but it also triggered cellular stress. The lipid bilayer was suggested as a target of phenol toxicity, and changing fatty acids composition seemed to be the bacterial response to protect the membrane integrity. The involvement of two flavoproteins in Cr(VI) reduction to Cr(III) was also proposed. The results suggested the important role of chaperones, antioxidant response and SOS-induced proteins in the ability of the strain to mitigate the damage generated by phenol and Cr(VI). This research contributes to elucidate the mechanisms involved in A. guillouiae SFC 500-1A tolerance and co-remediation of phenol and Cr(VI). Such information may result useful not only to improve its bioremediation efficiency but also to identify putative markers of resistance in environmental bacteria.

Sarcoidosis: proteomics and new perspectives for improving personalized medicine

ABSTRACT Introduction: Through synergistic approaches integrating biomedical data from omics sciences to the clinical practice, precision medicine aims at more accurate identification of risk factors, characterization of endotypes, patient stratification, establishment of individualized therapy, and prediction of outcomes. Areas covered: This review evaluates the potential role of different omics approaches for the development and application of precision medicine to sarcoidosis patients. This systemic and heterogeneous inflammatory disease is of unknown etiology, affects people of any age, and requires genotypic and phenotypic characterization. The latter can be achieved through the integration of genomic (i.e. information about genes and their mutations potentially involved in sarcoidosis), transcriptomic (reflecting the dynamic state of a cell and measuring the transcribed genes over time), and proteomic data (i.e. proteins in bronchoalveolar lavage, lung tissues, lung cells, serum and immunity system). Expert commentary: Genomic studies have revealed numerous aspects of sarcoidosis; however, for precision medicine, it is necessary to implement genomics with other omic approaches. The improving reliability of omics data, their storage, and their bioinformatics processing represents the next step to recapitulate in silico biological systems, with the final aim to simulate potential molecular pathways involved in the pathology and useful for clinical purposes.

Familial and sporadic IPF: A proteomic comparison

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic interstitial lung disease characterized by progressive parenchymal fibrosis leading to a severe and irreversible decline of respiratory function. Familial cases of IPF have been associated with several gene mutations, that represent about 4% of total IPF population. Genetic mutations have been observed only in few sporadic IPF cases. Aims: The aim of this study is to verify different pathobiological aspects of sporadic and familial IPF forms by comparing their BronchoAleolar Lavage Fluid (BALF) proteomes. Methods: The comparative analysis of BALF obtained by sporadic and familial IPF patients was perfomed through a classical two-dimensional electrophoresis approach. The differentially expressed proteins were identified using mass spectrometry. Results of the differential analysis were then elaborated by the different Multivariate analysis systems in order to identify specific protein profiles characteristic of each condition. Results: The comparison of BALF proteomic profiles revealed 88 protein spots differentially expressed among the 2 groups. Proteins up-regulated in familial IPF than sporadic patients resulted polymeric immunoglobulin receptor, surfactant protein A, fibrinogen γ chain, transthyretin, and actin whereas isocitrate dehydrogenase, selenium binding protein1, complement factor B, andα-1-antitrypsin were down-regulated proteins in familial cohort than sporadic IPF. Conclusions: The early characterization of different IPF subtypes could help to develop more accurate and personalized therapeutic treatments. This study represents a contribution to this topic and to the analysis of the pathogenetic mechanisms and potential biomarkers of familial and sporadic IPF.