Proteomics Reveals How the Tardigrade Damage Suppressor Protein Teaches Transfected Human Cells to Survive UV-C Stress.

The genome sequencing of the tardigrade Ramazzottius varieornatus revealed a unique nucleosome-binding protein named damage suppressor (Dsup), which was discovered to be crucial for the extraordinary abilities of tardigrades in surviving extreme stresses, such as UV. Evidence in Dsup-transfected human cells suggests that Dsup mediates an overall response in DNA damage signaling, DNA repair, and cell cycle regulation, resulting in an acquired resistance to stress. Given these promising outcomes, our study attempts to provide a wider comprehension of the molecular mechanisms modulated by Dsup in human cells and to explore the Dsup-activated molecular pathways under stress. We performed a differential proteomic analysis of Dsup-transfected and control human cells under basal conditions and at 24 h recovery after exposure to UV-C. We demonstrate via enrichment and network analyses, for the first time, that even in the absence of external stimuli, and more significantly, after stress, Dsup activates mechanisms involved with the unfolded protein response, the mRNA processing and stability, cytoplasmic stress granules, the DNA damage response, and the telomere maintenance. In conclusion, our results shed new light on Dsup-mediated protective mechanisms and increases our knowledge of the molecular machineries of extraordinary protection against UV-C stress.

Proteomics coupled with AhR-reporter gene bioassay for human and environmental safety assessment of sewage sludge and hydrochar.

Today application of sewage sludge (SL) and hydrochar (HC) in agriculture is a common practice for soil conditioning and crop fertilization, however safety concerns for human and environmental health due to the presence of toxic compounds have recently been expressed. Our aim was to test the suitability of proteomics coupled with bioanalytical tools for unravelling mixture effects of these applications in human and environmental safety assessment. We conducted proteomic and bioinformatic analysis of cell cultures used in the DR-CALUX® bioassay to identify proteins differentially abundant after exposure to SL and the corresponding HC, rather than only using the Bioanalytical Toxicity Equivalents (BEQs) obtained by DR-CALUX®. DR-CALUX® cells exposed to SL or HC showed a differential pattern of protein abundance depending on the type of SL and HC extract. The modified proteins are involved in antioxidant pathways, unfolded protein response and DNA damage that have close correlations with the effects of dioxin on biological systems and with onset of cancer and neurological disorders. Other cell response evidence suggested enrichment of heavy metals in the extracts. The present combined approach represents an advance in the application of bioanalytical tools for safety assessment of complex mixtures such as SL and HC. It proved successful in screening proteins, the abundance of which is determined by SL and HC and by the biological activity of legacy toxic compounds, including organohalogens.

BAL Proteomic Signature of Lung Adenocarcinoma in IPF Patients and Its Transposition in Serum Samples for Less Invasive Diagnostic Procedures.

Idiopathic pulmonary fibrosis (IPF) is a form of chronic and irreversible fibrosing interstitial pneumonia of unknown etiology. Although antifibrotic treatments have shown a reduction of lung function decline and a slow disease progression, IPF is characterize by a very high mortality. Emerging evidence suggests that IPF increases the risk of lung carcinogenesis. Both diseases show similarities in terms of risk factors, such as history of smoking, concomitant emphysema, and viral infections, besides sharing similar pathogenic pathways. Lung cancer (LC) diagnosis is often difficult in IPF patients because of the diffuse lung injuries and abnormalities due to the underlying fibrosis. This is reflected in the lack of optimal therapeutic strategies for patients with both diseases. For this purpose, we performed a proteomic study on bronchoalveolar lavage fluid (BALF) samples from IPF, LC associated with IPF (LC-IPF) patients, and healthy controls (CTRL). Molecular pathways involved in inflammation, immune response, lipid metabolism, and cell adhesion were found for the dysregulated proteins in LC-IPF, such as TTHY, APOA1, S10A9, RET4, GDIR1, and PROF1. The correlation test revealed a relationship between inflammation- and lipid metabolism-related proteins. PROF1 and S10A9, related to inflammation, were up-regulated in LC-IPF BAL and serum, while APOA1 and APOE linked to lipid metabolism, were highly abundant in IPF BAL and low abundant in IPF serum. Given the properties of cytokine/adipokine of the nicotinamide phosphoribosyltransferase, we also evaluated its serum abundance, highlighting its down-regulation in LC-IPF. Our retrospective analyses of BAL samples extrapolated some potential biomarkers of LC-IPF useful to improve the management of these contemporary pathologies. Their differential abundance in serum samples permits the measurement of these potential biomarkers with a less invasive procedure.

Multi-Omics Integrative Approach of Extracellular Vesicles: A Future Challenging Milestone.

In the era of multi-omic sciences, dogma on singular cause-effect in physio-pathological processes is overcome and system biology approaches have been providing new perspectives to see through. In this context, extracellular vesicles (EVs) are offering a new level of complexity, given their role in cellular communication and their activity as mediators of specific signals to target cells or tissues. Indeed, their heterogeneity in terms of content, function, origin and potentiality contribute to the cross-interaction of almost every molecular process occurring in a complex system. Such features make EVs proper biological systems being, therefore, optimal targets of omic sciences. Currently, most studies focus on dissecting EVs content in order to either characterize it or to explore its role in various pathogenic processes at transcriptomic, proteomic, metabolomic, lipidomic and genomic levels. Despite valuable results being provided by individual omic studies, the categorization of EVs biological data might represent a limit to be overcome. For this reason, a multi-omic integrative approach might contribute to explore EVs function, their tissue-specific origin and their potentiality. This review summarizes the state-of-the-art of EVs omic studies, addressing recent research on the integration of EVs multi-level biological data and challenging developments in EVs origin.

Bronchoalveolar-Lavage-Derived Fibroblast Cell Line (B-LSDM7) as a New Protocol for Investigating the Mechanisms of Idiopathic Pulmonary Fibrosis.

BACKGROUND: The use of BAL to study ILDs has improved our understanding of IPF pathogenesis. BAL fluid is routinely collected and can be considered a clinical and research tool. The procedure is well tolerated and minimally invasive. No specific cell lines from BAL or immortalized cell lines from IPF patients are available commercially. A method to quickly isolate and characterize fibroblasts from BAL is an unmet research need. MATERIALS AND METHODS: Here we describe a new protocol by which we isolated a cell line from IPF. The cell line was expanded in vitro and characterized phenotypically, morphologically and functionally. RESULTS: This culture showed highly filamentous cells with an evident central nucleus. From the phenotypic point of view, this cell line displays fibroblast/myofibroblast-like features including expression of alpha-SMA, vimentin, collagen type-1 and fibronectin. The results showed high expression of ROS in these cells. Oxidative stress invariably promotes extracellular matrix expression in lung diseases directly or through over-production of pro-fibrotic growth factors. CONCLUSIONS: Our protocol makes it possible to obtain fibroblasts BAL that is a routine non-invasive method that offers the possibility of having a large sample of patients. Standardized culture methods are important for a reliable model for testing molecules and eventual novel development therapeutic targets.

Serum Proteomic Profile of Asthmatic Patients after Six Months of Benralizumab and Mepolizumab Treatment.

Severe eosinophilic asthma is characterized by chronic airway inflammation, oxidative stress, and elevated proinflammatory cytokines, especially IL-5. Mepolizumab and benralizumab are both humanized IgG antibodies directed against IL-5 signaling, directly acting on eosinophils count. Together with the complexity of severe asthma classification and patient selection for the targeted treatment, there is also the urgency to clarify the follow-up of therapy to identify biomarkers, in addition to eosinophils, for the optimal duration of treatment, persistence of effectiveness, and safety. To this purpose, here we performed a follow-up study using differential proteomic analysis on serum samples after 1 and 6 months of both therapies and sera from healthy patients. Statistical analysis by PCA and heatmap analyses were performed, and identified proteins were used for enrichment analysis by MetaCore software. The analysis highlighted 82 differences among all considered conditions. In particular, 30 referred to benralizumab time point (T0, T1B, T6B) and 24 to mepolizumab time point (T0, T1M, T6M) analyses. t-SNE and heatmap analyses evidence that the differential serum protein profile at 6 months of both treatments is more similar to that of the healthy subjects. Among the identified proteins, APOAI, APOC-II, and APOC-III are upregulated principally after 6 months of benralizumab treatment, plasminogen is upregulated after 6 months of both treatments and ceruloplasmin, upregulated already after 1 month of benralizumab, becoming higher after 6 months of mepolizumab. Using enrichment analysis, identified proteins were related to lipid metabolism and transport, blood coagulation, and ECM remodeling.

Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients.

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidism, here we compared, by a preliminary proteomic analysis, eight sera of patients with reduced post-surgical FT3 to eight sera from patients with FT3 levels similar to pre-surgery levels, and six healthy controls. Proteomic analysis highlights a different serum protein profile among the considered conditions. By enrichment analysis, differential proteins are involved in coagulation processes (PLMN-1.61, -1.98 in reduced vs. stable FT3, p < 0.02; A1AT fragmentation), complement system activation (CFAH + 1.83, CFAB + 1.5, C1Qb + 1.6, C1S + 7.79 in reduced vs. stable FT3, p < 0.01) and in lipoprotein particles remodeling (APOAI fragmentation; APOAIV + 2.13, p < 0.003), potentially leading to a pro-inflammatory response. This study suggests that LT4 replacement therapy might restore biochemical euthyroid conditions in thyroidectomized patients, but in some cases without re-establishing body tissue euthyroidism. Since our results, this condition is reflected by the serum protein profile.

Peripheral and alveolar biomarkers of fibrotic hypersensitivity pneumonitis.

Fibrotic hypersensitivity pneumonitis (fHP) is a frequently misdiagnosed fibrosing interstitial pneumonia, which often remains undiagnosed due to the lack of uniformity of diagnostic criteria. Its features are similar to those of other ILDs, especially idiopathic pulmonary fibrosis (IPF), and biomarkers with potential clinical value have been proposed. We reviewed the recent literature on serum and BAL biomarkers, focusing on their clinical role in the diagnosis and management of fHP. We searched Medline/Pubmed results from 2005 until April 2020. The manuscripts of interest selected by our search were limited in number and proposed different clinical biomarkers in serum (IgG antibodies, macrophage inflammatory proteins-1, epithelial cell proteins) and BAL (lymphocytes, T-cell mediators). This is the first review to summarize all the serum and BAL biomarkers for fHP proposed in the literature. This review summarized the main biomarkers investigated in fibrotic hypersensitivity pneumonitis because an urgent aim of subsequent research will be to validate and standardize them for diagnostic purposes.

Bitter Taste Receptors Expression in Human Granulosa and Cumulus Cells: New Perspectives in Female Fertility.

Bitter taste receptors (TAS2RS) expression is not restricted to the oral cavity and the presence of these receptors in the male reproductive system and sperm provides insights into their possible role in human reproduction. To elucidate the potential role of TAS2Rs in the female reproductive system, we investigated the expression and localization of bitter taste receptors and the components of signal transduction cascade involved in the pathway of taste receptors in somatic follicular cells obtained from women undergoing assisted reproductive techniques. We found that TAS2R genes are expressed in both cumulus (CCs) and granulosa (GCs) cells, with TAS2R14 being the most highly expressed bitter receptor subtype. Interestingly, a slight increase in the expression of TAS2R14 and TAS2R43 was shown in both GCs and CCs in young women (p < 0.05), while a negative correlation may be established between the number of oocytes collected at the pickup and the expression of TAS2R43. Regarding α-gustducin and α-transducin, two Gα subunits expressed in the taste buds on the tongue, we provide evidence for their expression in CCs and GCs, with α-gustducin showing two additional isoforms in GCs. Finally, we shed light on the possible downstream transduction pathway initiated by taste receptor activation in the female reproductive system. Our study, showing for the first time the expression of taste receptors in the somatic ovarian follicle cells, significantly extends the current knowledge of the biological role of TAS2Rs for human female fertility.

Cockayne syndrome group A and ferrochelatase finely tune ribosomal gene transcription and its response to UV irradiation.

CSA and CSB proteins are key players in transcription-coupled nucleotide excision repair (TC-NER) pathway that removes UV-induced DNA lesions from the transcribed strands of expressed genes. Additionally, CS proteins play relevant but still elusive roles in other cellular pathways whose alteration may explain neurodegeneration and progeroid features in Cockayne syndrome (CS). Here we identify a CS-containing chromatin-associated protein complex that modulates rRNA transcription. Besides RNA polymerase I (RNAP1) and specific ribosomal proteins (RPs), the complex includes ferrochelatase (FECH), a well-known mitochondrial enzyme whose deficiency causes erythropoietic protoporphyria (EPP). Impairment of either CSA or FECH functionality leads to reduced RNAP1 occupancy on rDNA promoter that is associated to reduced 47S pre-rRNA transcription. In addition, reduced FECH expression leads to an abnormal accumulation of 18S rRNA that in primary dermal fibroblasts from CS and EPP patients results in opposed rRNA amounts. After cell irradiation with UV light, CSA triggers the dissociation of the CSA-FECH-CSB-RNAP1-RPs complex from the chromatin while it stabilizes its binding to FECH. Besides disclosing a function for FECH within nucleoli, this study sheds light on the still unknown mechanisms through which CSA modulates rRNA transcription.

Differential Proteomic Analysis of Astrocytes and Astrocytes-Derived Extracellular Vesicles from Control and Rai Knockout Mice: Insights into the Mechanisms of Neuroprotection.

Reactive astrocytes are a hallmark of neurodegenerative disease including multiple sclerosis. It is widely accepted that astrocytes may adopt alternative phenotypes depending on a combination of environmental cues and intrinsic features in a highly plastic and heterogeneous manner. However, we still lack a full understanding of signals and associated signaling pathways driving astrocyte reaction and of the mechanisms by which they drive disease. We have previously shown in the experimental autoimmune encephalomyelitis mouse model that deficiency of the molecular adaptor Rai reduces disease severity and demyelination. Moreover, using primary mouse astrocytes, we showed that Rai contributes to the generation of a pro-inflammatory central nervous system (CNS) microenvironment through the production of nitric oxide and IL-6 and by impairing CD39 activity in response to soluble factors released by encephalitogenic T cells. Here, we investigated the impact of Rai expression on astrocyte function both under basal conditions and in response to IL-17 treatment using a proteomic approach. We found that astrocytes and astrocyte-derived extracellular vesicles contain a set of proteins, to which Rai contributes, that are involved in the regulation of oligodendrocyte differentiation and myelination, nitrogen metabolism, and oxidative stress. The HIF-1α pathway and cellular energetic metabolism were the most statistically relevant molecular pathways and were related to ENOA and HSP70 dysregulation.

Proteome Characterization of BALF Extracellular Vesicles in Idiopathic Pulmonary Fibrosis: Unveiling Undercover Molecular Pathways.

In the longtime challenge of identifying specific, easily detectable and reliable biomarkers of IPF, BALF proteomics is providing interesting new insights into its pathogenesis. To the best of our knowledge, the present study is the first shotgun proteomic investigation of EVs isolated from BALF of IPF patients. Our main aim was to characterize the proteome of the vesicular component of BALF and to explore its individual impact on the pathogenesis of IPF. To this purpose, ultracentrifugation was chosen as the EVs isolation technique, and their purification was assessed by TEM, 2DE and LC-MS/MS. Our 2DE data and scatter plots showed considerable differences between the proteome of EVs and that of whole BALF and of its fluid component. Analysis of protein content and protein functions evidenced that EV proteins are predominantly involved in cytoskeleton remodeling, adenosine signaling, adrenergic signaling, C-peptide signaling and lipid metabolism. Our findings may suggest a wider system involvement in the disease pathogenesis and support the importance of pre-fractioning of complex samples, such as BALF, in order to let low-abundant proteins-mediated pathways emerge.

Emerging role of embryo secretome in the paracrine communication at the implantation site: a proof of concept.

OBJECTIVE: To assess the role of embryo secretome in modifying the molecular profile of glycodelin A (GdA) in endometrial organoids (ORG) mimicking the implantation window. To verify whether the use of embryo-conditioned culture medium at the time of the embryo transfer may increase in vitro fertilization outcome. DESIGN: Molecular study with human endometrial ORG and embryo-conditioned culture medium. Retrospective study using prospectively recorded data. SETTING: University hospital. PATIENT(S): For isolation and culture of endometrial glandular ORG, endometrial biopsy specimens from five white women of proven fertility undergoing laparoscopy for tubal sterilization. A total of 75 women undergoing intracytoplasmic sperm injection for tubal and/or male infertility factor. INTERVENTIONS(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): Pinopodes presence in human endometrial ORG. Glycodelin A expression profile by means of two-dimensional electrophoresis. In vitro fertilization outcome. RESULT(S): This in vitro study demonstrated that the treatment of endometrial ORG with the secretome of medium conditioned by the growing embryo increased the GdA relative abundance and induced a different glycoform pattern. Biochemical and clinical pregnancy rate significantly increased when the spent medium was loaded during the transfer (17.5% vs. 36.6% and 16.5% vs. 35.1%, respectively). CONCLUSION(S): This study demonstrated that the secretome of implanting embryos is able to induce the expression as well as to determine the relative abundance and the glycosilation profile of endometrial GdA, a protein having a key role in the embryo-endometrial cross talk. Moreover, a significant increase in pregnancy rate was observed when the embryo transfer was performed by using the culture medium conditioned by the growing embryo.

First Attempt to Couple Proteomics with the AhR Reporter Gene Bioassay in Soil Pollution Monitoring and Assessment.

A topsoil sample obtained from a highly industrialized area (Taranto, Italy) was tested on the DR-CALUX® cell line and the exposed cells processed with proteomic and bioinformatics analyses. The presence of polyhalogenated compounds in the topsoil extracts was confirmed by GC-MS/MS analysis. Proteomic analysis of the cells exposed to the topsoil extracts identified 43 differential proteins. Enrichment analysis highlighted biological processes, such as the cellular response to a chemical stimulus, stress, and inorganic substances; regulation of translation; regulation of apoptotic process; and the response to organonitrogen compounds in light of particular drugs and compounds, extrapolated by bioinformatics all linked to the identified protein modifications. Our results confirm and reflect the complex epidemiological situation occurring among Taranto inhabitants and underline the need to further investigate the presence and sources of inferred chemicals in soils. The combination of bioassays and proteomics reveals a more complex scenario of chemicals able to affect cellular pathways and leading to toxicities rather than those identified by only bioassays and related chemical analysis. This combined approach turns out to be a promising tool for soil risk assessment and deserves further investigation and developments for soil monitoring and risk assessment.

Oxidative Stress Measurement in Frozen/Thawed Human Sperm: The Protective Role of an In Vitro Treatment with Myo-Inositol.

Despite its widespread use, sperm cryopreservation induces serious detrimental alterations in sperm function; indeed, it is commonly associated with decreased sperm viability and motility, and DNA fragmentation. Mechanisms of human sperm cryodamage are thought to be multifactorial, but oxidative stress seems to have a prominent role. A huge amount of data supported the cryoprotective effect of different antioxidants able to minimize the detrimental effects of reactive oxygen species (ROS) and improve the quality of spermatozoa. Among others, myo-inositol is one of the most powerful and has been reported to be effective in improving sperm quality and motility when used both in vivo and in vitro. This study aimed to determine the in vitro impact of myo-inositol in ameliorating sperm oxidative status during sperm cryopreservation. In particular, we demonstrated a significant improvement of sperm parameters (vitality and motility) when myo-inositol was added after sperm thawing (p < 0.05). Moreover, we showed that myo-inositol induces a significant increase in oxygen consumption, the main index of oxidative phosphorylation efficiency and ATP production. Finally, by means of 2D-electrophoresis, we demonstrated a significant decrease in the level of carbonyl groups, the main structural changes occurring in conditions of oxidative stress (p < 0.05). In conclusion, the sperm cryopreservation procedure we developed, assuring the reduction of ROS-induced sperm modifications, may improve the in vitro procedure currently used in ART laboratory for sperm cryostorage.

Antithrombin III as predictive indicator of survival in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib: a preliminary study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. Although clotting processes are involved in wound healing and repair in the lung, there are no data on the role of antithrombin III (ATIII) in IPF patients treated with nintedanib. A previous proteomic analysis of serum of IPF patients before and after 1 year of nintedanib treatment showed differential protein expression of ATIII. AIMS: Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after 1 year of nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients. METHODS: Serum levels of ATIII were measured by enzyme-linked immunosorbent assay in 14 IPF patients before and after 1 year of nintedanib treatment. RESULTS: A statistically significant inverse correlation was found between serum ATIII concentrations and pulmonary function test parameters in all patients at baseline and follow up. Baseline serum ATIII and bronchoalveolar lavage (BAL) neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 µg/mL discriminated survivors from non-survivors. CONCLUSIONS: After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. The results of this preliminary study suggest that ATIII has potential as a biomarker of IPF severity and in predicting response to nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage.

Ceruloplasmin and oxidative stress in severe eosinophilic asthma patients treated with Mepolizumab and Benralizumab.

INTRODUCTION: Severe eosinophilic asthma has been associated with Th2 airway inflammation and elevated proinflammatory cytokines and chemokines, such as IL-5. Precision therapies have recently been shown to improve asthma symptoms with a steroid-sparing effect. Two such therapies, Benralizumab and Mepolizumab, humanized IgG antibodies directed against the IL-5 receptor and IL-5, have been approved for severe eosinophilic asthma. METHODS: Here we used a differential proteomic approach to analyse serum from patients with severe eosinophilic asthma treated with Benralizumab and Mepolizumab in a search for differential molecular modifications responsible of their effects. Enrichment analysis of differential proteins was performed for the two treatments. RESULTS AND DISCUSSION: After one month of Benralizumab treatment we detected up-regulation of certain protein species of the antioxidant ceruloplasmin. To investigate oxidative stress, we performed redox proteomics which detected lower oxidative burst after one month of Benralizumab treatment than in the pre-treatment phase or after one month of Mepolizumab therapy.

Adiponectin and leptin levels in idiopathic pulmonary fibrosis: A new method for BAL and serum assessment.

Adipokines (APN) are mainly secreted by adipocytes, macrophages and various other cells, along with their role in the regulation and mediation of inflammatory responses. APN is almost exclusively synthesized by adipocytes and regulated by peroxisome proliferator-activated receptor γ (PPARγ) that is involved in the epithelial-mesenchymal transition, linked lung fibrosis. Leptin is involved in acute lung injury with a role in lung fibrogenesis. Little is known about the relationship between APN/leptin and idiopathic pulmonary fibrosis (IPF) and the few studies available in the literature used ELISA to detect these lipid mediators. Our study is also the first to measure adipokines by the new multiplex assay and for the first time were performed in bronchoalveolar lavage (BAL) from IPF patients. This preliminary study suggests that APN levels in serum could be useful for predicting the prognosis of IPF, as they are inversely correlated with DLco percentages and BMI. Moreover, this first analysis of APN in BAL from IPF patients by a new method demonstrated an inverse correlation between these levels and BMI values and a direct correlation with eosinophil percentages, both of which are negative prognostic factors of IPF.

Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder limited to the lung. New findings, starting from our proteomics studies on IPF, suggest that systemic involvement with altered molecular mechanisms and metabolic disorder is an underlying cause of fibrosis. The role of metabolic dysregulation in the pathogenesis of IPF has not been extensively studied, despite a recent surge of interest. In particular, our studies on bronchoalveolar lavage fluid have shown that the renin-angiotensin-aldosterone system (RAAS), the hypoxia/oxidative stress response, and changes in iron and lipid metabolism are involved in onset of IPF. These processes appear to interact in an intricate manner and to be related to different fibrosing pathologies not directly linked to the lung environment. The disordered metabolism of carbohydrates, lipids, proteins and hormones has been documented in lung, liver, and kidney fibrosis. Correcting these metabolic alterations may offer a new strategy for treating fibrosis. This paper focuses on the role of metabolic dysregulation in the pathogenesis of IPF and is a continuation of our previous studies, investigating metabolic dysregulation as a new target for fibrosis therapy.

Mepolizumab and Benralizumab in Severe Eosinophilic Asthma: Preliminary Results of a Proteomic Study.

Benralizumab and mepolizumab are new therapies for severe eosinophilic asthma. They are both humanized IgG antibodies, targeting the IL-5 receptor and IL-5, respectively, suppressing the corresponding pathways. No specific biomarkers have been proposed to evaluate treatment response to benralizumab or mepolizumab. The aim of this proteomic study was to compare serum protein profiles of patients with severe eosinophilic asthma before and after anti-IL5 or anti-IL5R therapies. Proteomic analysis highlighted 22 differently abundant spots. Among the proteins identified, CAYP1, A1AT and A2M expression was significantly modified in both groups of patients after therapies while ceruloplasmin showed a significant modification in the group of benralizumab treatment. These differentially expressed proteins could be potential biomarkers of response to mepolizumab and benralizumab treatments and need further evaluation.