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Article ; Online: Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Álvarez, J Victor / Bravo, Susana B / Chantada-Vázquez, María Pilar / Pena, Carmen / Colón, Cristóbal / Tomatsu, Shunji / Otero-Espinar, Francisco J / Couce, María L

International journal of molecular sciences

2024 Volume 25, Issue 6

Abstract: Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly ... ...

Abstract	Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.
MeSH term(s)	Humans ; Animals ; Mice ; Mucopolysaccharidosis IV/metabolism ; Cartilage Diseases ; Bone Diseases ; Chondroitinsulfatases/genetics ; Mice, Knockout
Chemical Substances	Chondroitinsulfatases (EC 3.1.6.-)
Language	English
Publishing date	2024-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25063232
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Article ; Online: SWATH-MS Protocols in Human Diseases.

Chantada-Vázquez, Maria Del Pilar / García Vence, María / Serna, Antonio / Núñez, Cristina / Bravo, Susana B

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2259, Page(s) 105–141

Abstract: Identification of molecular biomarkers for human diseases is one of the most important disciplines in translational science as it helps to elucidate their origin and early progression. Thus, it is a key factor in better diagnosis, prognosis, and ... ...

Abstract	Identification of molecular biomarkers for human diseases is one of the most important disciplines in translational science as it helps to elucidate their origin and early progression. Thus, it is a key factor in better diagnosis, prognosis, and treatment. Proteomics can help to solve the problem of sample complexity when the most common primary sample specimens were analyzed: organic fluids of easy access. The latest developments in high-throughput and label-free quantitative proteomics (SWATH-MS), together with more advanced liquid chromatography, have enabled the analysis of large sample sets with the sensitivity and depth needed to succeed in this task. In this chapter, we show different sample processing methods (major protein depletion, digestion, etc.) and a micro LC-SWATH-MS protocol to identify/quantify several proteins in different types of samples (serum/plasma, saliva, urine, tears).
MeSH term(s)	Biomarkers/analysis ; Biomarkers/blood ; Biomarkers/urine ; Blood Proteins/analysis ; Humans ; Mass Spectrometry/methods ; Proteins/analysis ; Proteinuria/diagnosis ; Proteome/analysis ; Proteomics/methods ; Saliva/chemistry ; Specimen Handling/methods ; Tears/chemistry
Chemical Substances	Biomarkers ; Blood Proteins ; Proteins ; Proteome
Language	English
Publishing date	2021-03-09
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1178-4_7
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Article ; Online: Proteomics in Inherited Metabolic Disorders.

Chantada-Vázquez, Maria Del Pilar / Bravo, Susana B / Barbosa-Gouveia, Sofía / Alvarez, José V / Couce, María L

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Inherited metabolic disorders (IMD) are rare medical conditions caused by genetic defects that interfere with the body's metabolism. The clinical phenotype is highly variable and can present at any age, although it more often manifests in childhood. The ... ...

Abstract	Inherited metabolic disorders (IMD) are rare medical conditions caused by genetic defects that interfere with the body's metabolism. The clinical phenotype is highly variable and can present at any age, although it more often manifests in childhood. The number of treatable IMDs has increased in recent years, making early diagnosis and a better understanding of the natural history of the disease more important than ever. In this review, we discuss the main challenges faced in applying proteomics to the study of IMDs, and the key advances achieved in this field using tandem mass spectrometry (MS/MS). This technology enables the analysis of large numbers of proteins in different body fluids (serum, plasma, urine, saliva, tears) with a single analysis of each sample, and can even be applied to dried samples. MS/MS has thus emerged as the tool of choice for proteome characterization and has provided new insights into many diseases and biological systems. In the last 10 years, sequential window acquisition of all theoretical fragmentation spectra mass spectrometry (SWATH-MS) has emerged as an accurate, high-resolution technique for the identification and quantification of proteins differentially expressed between healthy controls and IMD patients. Proteomics is a particularly promising approach to help obtain more information on rare genetic diseases, including identification of biomarkers to aid early diagnosis and better understanding of the underlying pathophysiology to guide the development of new therapies. Here, we summarize new and emerging proteomic technologies and discuss current uses and limitations of this approach to identify and quantify proteins. Moreover, we describe the use of proteomics to identify the mechanisms regulating complex IMD phenotypes; an area of research essential to better understand these rare disorders and many other human diseases.
Language	English
Publishing date	2022-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232314744
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Article: Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

Chantada-Vázquez, María Del Pilar / Conde-Amboage, Mercedes / Graña-López, Lucía / Vázquez-Estévez, Sergio / Bravo, Susana B / Núñez, Cristina

Cancers

2022 Volume 14, Issue 4

Abstract: Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens ... ...

Abstract	Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.
Language	English
Publishing date	2022-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14041087
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Article ; Online: Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network.

García-Vega, David / Sánchez-López, David / Rodríguez-Carnero, Gemma / Villar-Taibo, Rocío / Viñuela, Juan E / Lestegás-Soto, Adán / Seoane-Blanco, Ana / Moure-González, María / Bravo, Susana B / Fernández, Ángel L / González-Juanatey, José R / Eiras, Sonia

Cardiovascular diabetology

2024 Volume 23, Issue 1, Page(s) 1

Abstract: Background: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat ... ...

Abstract	Background: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells. Methods: EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide. Results: GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88. Conclusion: Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment.
MeSH term(s)	Humans ; Endothelial Cells/metabolism ; Epicardial Adipose Tissue ; Neutrophils ; Fibrinolytic Agents/therapeutic use ; Atherosclerosis/metabolism ; Glucagon-Like Peptides/pharmacology ; Glucagon-Like Peptides/therapeutic use ; Obesity/metabolism ; Glucose/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use
Chemical Substances	semaglutide (53AXN4NNHX) ; Fibrinolytic Agents ; Glucagon-Like Peptides (62340-29-8) ; Glucose (IY9XDZ35W2) ; Glucagon-Like Peptide-1 Receptor ; Hypoglycemic Agents
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-023-02096-9
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Article ; Online: Genetic linkage analysis of head and neck cancer in a Spanish family.

Pérez-Sayáns, Mario / Chamorro-Petronacci, Cintia M / Bravo, Susana B / Padín-Iruegas, María E / Guitián-Fernández, Esteban / Barros-Angueira, Francisco / Quintas-Rey, Rita / García-García, Abel

Oral diseases

2023

Abstract: Objectives: To describe the genetic variants that may be associated with the development of head and neck cancer (HNC) and functionally validating the molecular implications.: Materials and methods: A prospective observational study was carried out ... ...

Abstract	Objectives: To describe the genetic variants that may be associated with the development of head and neck cancer (HNC) and functionally validating the molecular implications. Materials and methods: A prospective observational study was carried out on a family of 3 generations in which 3 members had developed HNC. Peripheral blood sample was taken in a routine procedure for exome sequencing in one relative and genotyping in the remaining twelve relatives. For the functional analysis all-trans retinoic acid (atRA) was extracted from saliva and serum and measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The presence of HPV-DNA. Results: None of the patients smoked or consumed alcohol. The presence of HPV DNA was not detected in any of the biopsied samples. A total amount of 6 members out of 13 (46.15%) carried out the same mutation of CYP26B1 (2p13.2; G>T). The mean plasma concentration of atRA was 3.3109 ± 1.4791 pg/mL for the study family and 4.7370 ± 1.5992 pg/mL for the controls (p = 0.042). Conclusion: Lower levels of atRA were confirmed in the study family, which may open the way to the possible relationship between the polymorphism CYP26B1 (2p13.2; G>T) and HNC.
Language	English
Publishing date	2023-04-07
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1290529-x
ISSN	1601-0825 ; 1354-523X
ISSN (online)	1601-0825
ISSN	1354-523X
DOI	10.1111/odi.14572
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Article ; Online: Structural Similarities, in Relation with the Cross-Reactivity, of Hymenoptera Allergenic Dipeptidyl Peptidases IV-An Overall Comparison Including a New Dipeptidyl Peptidase IV Sequence from

Monsalve, Rafael I / Lombardero, Manuel / Christensen, Lars H / Núñez-Acevedo, Beatriz / González-de-Olano, David / Sobrino-García, Miriam / Castillo-Loja, Rosita M / Bravo, Susana B / Alonso-Sampedro, Manuela / Vidal, Carmen

Toxins

2023 Volume 15, Issue 11

Abstract: 1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs ... ...

Abstract	(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions have higher similarity among these proteins and present a comparison among them, including a new
MeSH term(s)	Humans ; Bees ; Animals ; Allergens/chemistry ; Hymenoptera/metabolism ; Wasps ; Dipeptidyl Peptidase 4 ; Proteomics ; Wasp Venoms/chemistry
Chemical Substances	Allergens ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; Wasp Venoms
Language	English
Publishing date	2023-11-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins15110656
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Article ; Online: Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers.

López-Valverde, Laura / Vázquez-Mosquera, María E / Colón-Mejeras, Cristóbal / Bravo, Susana B / Barbosa-Gouveia, Sofía / Álvarez, J Víctor / Sánchez-Martínez, Rosario / López-Mendoza, Manuel / López-Rodríguez, Mónica / Villacorta-Argüelles, Eduardo / Goicoechea-Diezhandino, María A / Guerrero-Márquez, Francisco J / Ortolano, Saida / Leao-Teles, Elisa / Hermida-Ameijeiras, Álvaro / Couce, María L

Translational research : the journal of laboratory and clinical medicine

2024 Volume 269, Page(s) 47–63

Abstract: Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the ... ...

Abstract	Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The >30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2024.02.006
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Article ; Online: Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue.

Aragón-Herrera, Alana / Feijóo-Bandín, Sandra / Vázquez-Abuín, Xocas / Anido-Varela, Laura / Moraña-Fernández, Sandra / Bravo, Susana B / Tarazón, Estefanía / Roselló-Lletí, Esther / Portolés, Manuel / García-Seara, Javier / Seijas, José / Rodríguez-Penas, Diego / Bani, Daniele / Gualillo, Oreste / González-Juanatey, José Ramón / Lago, Francisca

Biochemical pharmacology

2024 Volume 223, Page(s) 116157

Abstract: Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, ... ...

Abstract	Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.
MeSH term(s)	Humans ; Rats ; Animals ; Lipid Metabolism ; Proteome ; Intra-Abdominal Fat/metabolism ; Lipidomics ; Relaxin/pharmacology ; Relaxin/metabolism ; Rats, Sprague-Dawley ; Vasodilator Agents/pharmacology ; Cardiovascular Diseases/metabolism ; RNA, Messenger/genetics ; Adipose Tissue/metabolism ; Recombinant Proteins/metabolism
Chemical Substances	Proteome ; Relaxin (9002-69-1) ; Vasodilator Agents ; RNA, Messenger ; serelaxin protein, human ; Recombinant Proteins
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2024.116157
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Article: Quantitative Proteomic Study Unmasks Fibrinogen Pathway in Polycystic Liver Disease.

Cordido, Adrian / Vizoso-Gonzalez, Marta / Nuñez-Gonzalez, Laura / Molares-Vila, Alberto / Chantada-Vazquez, Maria Del Pilar / Bravo, Susana B / Garcia-Gonzalez, Miguel A

Biomedicines

2022 Volume 10, Issue 2

Abstract: 1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the ... ...

Abstract	(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH-MS technology were performed comparing hepatic proteomes of
Language	English
Publishing date	2022-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10020290
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