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Article ; Online: Targeting Nrf2 and NF-κB Signaling Pathways in Cancer Prevention

Francesca Gado / Giulio Ferrario / Larissa Della Vedova / Beatrice Zoanni / Alessandra Altomare / Marina Carini / Giancarlo Aldini / Alfonsina D’Amato / Giovanna Baron

Molecules, Vol 28, Iss 1356, p

The Role of Apple Phytochemicals

2023 Volume 1356

Abstract: Plant secondary metabolites, known as phytochemicals, have recently gained much attention in light of the “circular economy”, to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and ... ...

Abstract	Plant secondary metabolites, known as phytochemicals, have recently gained much attention in light of the “circular economy”, to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included. This review aims to provide a thorough overview of the main studies reported in the literature concerning apple phytochemicals, mostly polyphenols, in cancer prevention. Although there are many different mechanisms targeted by phytochemicals, the Nrf2 and NF-κB signaling pathways are the ones this review will be focused on, highlighting also the existing crosstalk between these two systems.
Keywords	phytochemicals ; apple polyphenols ; Nrf2 signaling pathway ; NF-κB signaling pathway ; anti-cancer activity ; Nrf2/NF-κB crosstalk ; Organic chemistry ; QD241-441
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lipid peroxidation derived reactive carbonyl species in free and conjugated forms as an index of lipid peroxidation

Alessandra Altomare / Giovanna Baron / Erica Gianazza / Cristina Banfi / Marina Carini / Giancarlo Aldini

Redox Biology, Vol 42, Iss , Pp 101899- (2021)

limits and perspectives

2021

Abstract: Reactive carbonyl species (RCS) formed by lipidperoxidation as free forms or as enzymatic and non-enzymatic conjugates are widely used as an index of oxidative stress. Besides general measurements based on derivatizing reactions, more selective and ... ...

Abstract	Reactive carbonyl species (RCS) formed by lipidperoxidation as free forms or as enzymatic and non-enzymatic conjugates are widely used as an index of oxidative stress. Besides general measurements based on derivatizing reactions, more selective and sensitive MS based analyses have been proposed in the last decade. Untargeted and targeted methods for the measurement of free RCS and adducts have been described and their applications to in vitro and ex vivo samples have permitted the identification of many biological targets, reaction mechanisms and adducted moieties with a particular relevance to RCS protein adducts. The growing interest in protein carbonylation can be explained by considering that protein adducts are now recognized as being involved in the damaging action of oxidative stress so that their measurement is performed not only to obtain an index of lipid peroxidation but also to gain a deeper insight into the molecular mechanisms of oxidative stress. The aim of the review is to discuss the most novel analytical approaches and their application for profiling reactive carbonyl species and their enzymatic and non-enzymatic metabolites as an index of lipid-oxidation and oxidative stress. Limits and perspectives will be discussed.
Keywords	Lipid peroxidation ; Reactive carbonyl species ; Covalent adducts ; Protein carbonylation ; Analytical methods ; Biomarkers ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Data from docking simulations to develop an efficient strategy able to evaluate the interactions between RAGE and MDA-induced albumin adducts

Angelica Mazzolari / Crescenzo Coppa / Alessandra Altomare / Genny Degani / Giulio Vistoli

Data in Brief, Vol 12, Iss C, Pp 656-

2017 Volume 661

Abstract: This data article contains the results of docking simulations performed in order to develop a suitable in silico strategy able to assess the stability of the putative complexes between RAGE and MDA induced adducts on human albumin as experimentally ... ...

Abstract	This data article contains the results of docking simulations performed in order to develop a suitable in silico strategy able to assess the stability of the putative complexes between RAGE and MDA induced adducts on human albumin as experimentally determined doi:10.1016/j.redox.2016.12.017, (Degani et al., 2017) [1]. The docking simulations involved different approaches to give a simplified yet realistic representation of the protein adducts and their environment. With increasing complexity, simulations involved the corresponding albumin tripeptides and pentapeptides with the modified residue in the central position as well as pseudo-structures which were generated by collecting the albumin residues around the adducted residue within a sphere of 7.5 Å and 5 Å radius. The reliability of the tested approaches was assessed by monitoring the score differences between adducted and unmodified residues. The obtained results revealed the greater predictive power of the spherical pseudo-structures compared to the simple tri- or pentapeptidic sequences thus suggesting that RAGE recognition involves residues which are spatially close to the modified residue even though not necessarily adjacent in the primary sequence.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
Subject code	612
Language	English
Publishing date	2017-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of Bergamot Leaves ( Citrus bergamia ) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats

Juliana Silva Siqueira / Erika Tiemi Nakandakare-Maia / Taynara Aparecida Vieira / Thiago Luiz Novaga Palacio / Núbia Alves Grandini / Matheus Antônio Filiol Belin / Gisele Alborghetti Nai / Fernando Moreto / Alessandra Altomare / Giovanna Baron / Giancarlo Aldini / Fabiane Valentini Francisqueti-Ferron / Camila Renata Correa

Livers, Vol 3, Iss 17, Pp 258-

2023 Volume 270

Abstract: The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. ... ...

Abstract	The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect of Bergamot leaves extract (BLE) on the crosstalk in the adipose tissue–liver axis of obese rats. For 20 weeks, Wistar rats were distributed into two groups: control (Control) and high sugar–fat (HSF) diet groups. Afterwards, the animals were redistributed into three groups for 10 weeks: control diet + vehicle (Control, n = 08), HSF + vehicle (HSF, n = 08), and HSF + BLE (HSF + BLE, n = 08). The BLE was carried out daily by gavage (50 mg/kg). The HSF group presented obesity, hyperglycemia, hypertriglyceridemia, insulin resistance, hepatic microvesicular steatosis, higher inflammation and oxidative stress in the liver and adipose tissue. In comparison to the HSF group, HSF + BLE animals showed protection by reducing the triglyceride levels, insulin resistance, inflammation and oxidative stress in hepatic and adipose tissues. BLE acted on the inflammation and oxidative stress in the adipose tissue–liver axis in obese rats when compared to the HSF group, which may have reflected on the improvement of insulin resistance and dyslipidemia.
Keywords	inflammation ; leaf ; oxidative stress ; western diet ; bioactive compound ; Medicine (General) ; R5-920
Subject code	630
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells

Graziano Colombo / Alessandra Altomare / Emanuela Astori / Lucia Landoni / Maria Lisa Garavaglia / Ranieri Rossi / Daniela Giustarini / Maria Chiara Lionetti / Nicoletta Gagliano / Aldo Milzani / Isabella Dalle-Donne

International Journal of Molecular Sciences, Vol 24, Iss 1, p

2022 Volume 691

Abstract: Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the ... ...

Abstract	Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1). Urea (5 g/L) caused a reduction in the proliferation rate after 72 h of exposure and appeared to be a potential endothelial-to-mesenchymal transition (EndMT) stimulus. Moreover, urea induced actin filament rearrangement, a significant increase in matrix metalloproteinases 2 (MMP-2) expression in the medium, and a significant up- or down-regulation of other EndMT biomarkers (keratin, fibrillin-2, and collagen IV), as highlighted by differential proteomic analysis. Among proteins whose expression was found to be significantly dysregulated following exposure of HMEC-1 to urea, dimethylarginine dimethylaminohydrolase (DDAH) and vasorin turned out to be down-regulated. Both proteins have been directly linked to cardiovascular diseases (CVD) by in vitro and in vivo studies. Future experiments will be needed to deepen their role and investigate the signaling pathways in which they are involved to clarify the possible link between CKD and CVD.
Keywords	urea ; HMEC-1 ; CVD ; CKD ; vasorin ; differential proteomics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570 ; 610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: MS methods to study macromolecule-ligand interaction: Applications in drug discovery

Riccardi Sirtori, Federico / Alessandra Altomare / Giancarlo Aldini / Luca Regazzoni / Marina Carini

Methods. 2018 July 15, v. 144

2018

Abstract: The interaction of small compounds (i.e. ligands) with macromolecules or macromolecule assemblies (i.e. targets) is the mechanism of action of most of the drugs available today. Mass spectrometry is a popular technique for the interrogation of ... ...

Abstract	The interaction of small compounds (i.e. ligands) with macromolecules or macromolecule assemblies (i.e. targets) is the mechanism of action of most of the drugs available today. Mass spectrometry is a popular technique for the interrogation of macromolecule-ligand interactions and therefore is also widely used in drug discovery and development. Thanks to its versatility, mass spectrometry is used for multiple purposes such as biomarker screening, identification of the mechanism of action, ligand structure optimization or toxicity assessment. The evolution and automation of the instruments now allows the development of high throughput methods with high sensitivity and a minimized false discovery rate. Herein, all these approaches are described with a focus on the methods for studying macromolecule-ligand interaction aimed at defining the structure–activity relationships of drug candidates, along with their mechanism of action, metabolism and toxicity.
Keywords	automation ; biomarkers ; drugs ; ligands ; mass spectrometry ; mechanism of action ; metabolism ; screening ; structure-activity relationships ; toxicity
Language	English
Dates of publication	2018-0715
Size	p. 152-174.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2018.06.005
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Advanced lipoxidation end products (ALEs) as RAGE binders

Marco Mol / Genny Degani / Crescenzo Coppa / Giovanna Baron / Laura Popolo / Marina Carini / Giancarlo Aldini / Giulio Vistoli / Alessandra Altomare

Redox Biology, Vol 23, Iss , Pp - (2019)

Mass spectrometric and computational studies to explain the reasons why

2019

Abstract: Advanced Lipoxidation End-products (ALEs) are modified proteins that can act as pathogenic factors in several chronic diseases. Several molecular mechanisms have so far been considered to explain the damaging action of ALEs and among these a pathway ... ...

Abstract	Advanced Lipoxidation End-products (ALEs) are modified proteins that can act as pathogenic factors in several chronic diseases. Several molecular mechanisms have so far been considered to explain the damaging action of ALEs and among these a pathway involving the receptor for advanced glycation end products (RAGE) should be considered. The aim of the present work is to understand if ALEs formed from lipid peroxidation derived reactive carbonyl species (RCS) are able to act as RAGE binders and also to gain a deeper insight into the molecular mechanisms involved in the protein-protein engagement. ALEs were produced in vitro, by incubating human serum albumin (HSA) with 4-hydroxy-trans− 2-nonenal (HNE), acrolein (ACR) and malondialdehyde (MDA). The identification of ALEs was performed by MS. ALEs were then subjected to the VC1 Pull-Down assay (VC1 is the ligand binding domain of RAGE) and the enrichment factor (the difference between the relative abundance in the enriched sample minus the amount in the untreated one) as an index of affinity, was determined. Computation studies were then carried out to explain the factors governing the affinity of the adducted moieties and the site of interaction on adducted HSA for VC1-binding. The in silico analyses revealed the key role played by those adducts which strongly reduce the basicity of the modified residues and thus occur at their neutral state at physiological conditions (e.g. the MDA adducts, dihydropyridine-Lysine (DHPK) and N-2-pyrimidyl-ornithine (NPO), and acrolein derivatives, N-(3-formyl-3,4-dehydro-piperidinyl) lysine, FDPK). These neutral adducts become unable to stabilize ion-pairs with the surrounding negative residues which thus can contact the RAGE positive residues.In conclusion, ALEs derived from lipid peroxidation-RCS are binders of RAGE and this affinity depends on the effect of the adduct moiety to reduce the basicity of the target amino acid and on the acid moieties surrounding the aminoacidic target. Keywords: Advanced lipoxidation end products ...
Keywords	Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	540
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein network analyses of pulmonary endothelial cells in chronic thromboembolic pulmonary hypertension

Sarath Babu Nukala / Olga Tura-Ceide / Giancarlo Aldini / Valérie F. E. D. Smolders / Isabel Blanco / Victor I. Peinado / Manuel Castellà / Joan Albert Barberà / Alessandra Altomare / Giovanna Baron / Marina Carini / Marta Cascante / Alfonsina D’Amato

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction ... ...

Abstract	Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a vascular disease characterized by the presence of organized thromboembolic material in pulmonary arteries leading to increased vascular resistance, heart failure and death. Dysfunction of endothelial cells is involved in CTEPH. The present study describes for the first time the molecular processes underlying endothelial dysfunction in the development of the CTEPH. The advanced analytical approach and the protein network analyses of patient derived CTEPH endothelial cells allowed the quantitation of 3258 proteins. The 673 differentially regulated proteins were associated with functional and disease protein network modules. The protein network analyses resulted in the characterization of dysregulated pathways associated with endothelial dysfunction, such as mitochondrial dysfunction, oxidative phosphorylation, sirtuin signaling, inflammatory response, oxidative stress and fatty acid metabolism related pathways. In addition, the quantification of advanced oxidation protein products, total protein carbonyl content, and intracellular reactive oxygen species resulted increased attesting the dysregulation of oxidative stress response. In conclusion this is the first quantitative study to highlight the involvement of endothelial dysfunction in CTEPH using patient samples and by network medicine approach.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The secrets of Oriental panacea: Panax ginseng

Colzani, Mara / Alessandra Altomare / Elisa Fasoli / Giancarlo Aldini / Matteo Caliendo / Pier Giorgio Righetti

Journal of proteomics. 2016 Jan. 01, v. 130

2016

Abstract: The Panax ginseng root proteome has been investigated via capture with combinatorial peptide ligand libraries (CPLL) at three different pH values. Proteomic characterization by SDS-PAGE and nLC–MS/MS analysis, via LTQ-Orbitrap XL, led to the ... ...

Abstract	The Panax ginseng root proteome has been investigated via capture with combinatorial peptide ligand libraries (CPLL) at three different pH values. Proteomic characterization by SDS-PAGE and nLC–MS/MS analysis, via LTQ-Orbitrap XL, led to the identification of a total of 207 expressed proteins. This quite large number of identifications was achieved by consulting two different plant databases: P. ginseng and Arabidopsis thaliana. The major groups of identified proteins were associated to structural species (19.2%), oxidoreductase (19.5%), dehydrogenases (7.6%) and synthases (9.0%). For the first time, an exploration of protein–protein interactions was performed by merging all recognized proteins and building an interactomic map, characterized by 196 nodes and 1554 interactions. Finally a peptidomic analysis was developed combining different in-silico enzymatic digestions to simulate the human gastrointestinal process: from 661 generated peptides, 95 were identified as possible bioactives and in particular 6 of them were characterized by antimicrobial activity. The present report offers new insight for future investigations focused on elucidation of biological properties of P. ginseng proteome and peptidome.Ginseng is a traditional oriental herbal remedy whose use is very diffused in all the world for its numerous pharmacological effects. However, the exact mechanism of action of ginseng components, both ginsenosides and proteins, is still unidentified. So the common use of ginseng requires strict investigations to assess both its efficiency and its safety. Although many reports have been published regarding the pharmacological effects of ginseng, little is known about the biochemical pathways of root. Proteomics analysis could be useful to elucidate the physiological pathways. In this manuscript, an integrated approach to proteomics and peptidomics will usher in exploration of Panax ginseng proteins and proteolytic peptides, obtained by in-silico gastrointestinal digestion, characterized by antimicrobial action. The present research would pave the way for better knowledge of metabolic functions connected with ginseng proteome and provide with new information necessary to understand better antimicrobial activity of P. ginseng.
Keywords	anti-infective properties ; Arabidopsis thaliana ; biochemical pathways ; databases ; digestion ; gastrointestinal system ; ginsenosides ; humans ; mechanism of action ; Panax ginseng ; peptides ; pH ; polyacrylamide gel electrophoresis ; protein synthesis ; protein-protein interactions ; proteins ; proteolysis ; proteome ; proteomics
Language	English
Dates of publication	2016-0101
Size	p. 150-159.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2015.09.023
Database	NAL-Catalogue (AGRICOLA)

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Article: Thiol oxidation and di-tyrosine formation in human plasma proteins induced by inflammatory concentrations of hypochlorous acid

Colombo, Graziano / Aldo Milzani / Alessandra Altomare / Daniela Giustarini / Francesco Rusconi / Isabella Dalle-Donne / Marco Clerici / Maria Lisa Garavaglia / Nicola Portinaro / Ranieri Rossi

Journal of proteomics. 2017 Jan. 30, v. 152

2017

Abstract: In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol ... ...

Abstract	In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics. Mass spectrometry (MS) analysis was performed to elucidate the protein composition of HMW aggregates. α1-antitrypsin, transthyretin, and haptoglobin showed thiol oxidation at HOCl concentrations higher than those causing complete oxidation of albumin. At the highest HOCl concentrations, formation of carbonylated and di-tyrosine cross-linked HMW protein aggregates also occurred. MS analysis identified fibrinogen, complement C3 and apolipoprotein A-I as components of HMW protein aggregates. These results could be relevant for human diseases characterized by inflammatory conditions in which myeloperoxidase and HOCl are involved.In this study we evaluated the oxidative damage occurring on plasma proteins when reconstituted human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). Pathophysiological concentrations of HOCl are able to induce different modifications on plasma proteins such as carbonylation, sulfhydryl oxidation and formation of high molecular weight (HMW) protein aggregates characterized by di-tyrosine fluorescence. There are two relevant aspects emerging from this paper. The first one consists on identifying low abundant proteins undergoing sulfhydryl oxidation by biotin-maleimide derivatization followed by MALDI-TOF mass spectrometry. This approach suggests three low-abundant proteins undergoing HOCl-induced oxidation: transthyretin, α1-antitrypsin, and haptoglobin. In addition, we analysed HMW protein aggregates forming after HOCl exposure. These aggregates are characterized by carbonylation, intra- and/or intermolecular di-tyrosine bridges. After their isolation from SDS-PAGE gel electrophoresis, using electrospray tandem mass spectrometry coupled to reversed-phase nanoscale capillary liquid chromatography, we identified some protein constituents of these HMW aggregates such as α, β, γ fibrinogen chains, apolipoprotein A-I and complement C3. In particular, our work highlights how fibrinogen is an important constituent of HOCl-induced HMW protein aggregates validating the mass spectrometry result with additional experiments. Further investigations are required in order to evaluate the possibility to use carbonylated and di-Tyr cross-linked HMW protein aggregates as (early) biomarkers for disease progression in inflammatory conditions in which myeloperoxidase and HOCl are involved.
Keywords	apolipoprotein A-I ; biomarkers ; blood ; complement ; crosslinking ; derivatization ; disease course ; fibrinogen ; fluorescence ; gel chromatography ; haptoglobins ; high performance liquid chromatography ; human diseases ; humans ; matrix-assisted laser desorption-ionization mass spectrometry ; molecular weight ; myeloperoxidase ; oxidation ; polyacrylamide gel electrophoresis ; prealbumin ; protein aggregates ; protein composition ; proteomics ; tandem mass spectrometry ; thiols ; Western blotting
Language	English
Dates of publication	2017-0130
Size	p. 22-32.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2400835-7
ISSN	1876-7737 ; 1874-3919
ISSN (online)	1876-7737
ISSN	1874-3919
DOI	10.1016/j.jprot.2016.10.008
Database	NAL-Catalogue (AGRICOLA)

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