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Article ; Online: Rate-induced tracking for concave or d-concave transitions in a time-dependent environment with application in ecology.

Dueñas, J / Longo, I P / Obaya, R

2023 Volume 33, Issue 12

Abstract: This paper investigates biological models that represent the transition equation from a system in the past to a system in the future. It is shown that finite-time Lyapunov exponents calculated along a locally pullback attractive solution are efficient ... ...

Abstract	This paper investigates biological models that represent the transition equation from a system in the past to a system in the future. It is shown that finite-time Lyapunov exponents calculated along a locally pullback attractive solution are efficient indicators (early-warning signals) of the presence of a tipping point. Precise time-dependent transitions with concave or d-concave variation in the state variable giving rise to scenarios of rate-induced tracking are shown. They are classified depending on the internal dynamics of the set of bounded solutions. Based on this classification, some representative features of these models are investigated by means of a careful numerical analysis.
Language	English
Publishing date	2023-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0159237
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Article ; Online: Lung Inflammatory Phenotype in Mice Deficient in Fibulin-2 and ADAMTS-12.

Mohamedi, Yamina / Fontanil, Tania / Vega, José A / Cobo, Teresa / Cal, Santiago / Obaya, Álvaro J

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Interaction between extracellular matrix (ECM) components plays an important role in the regulation of cellular behavior and hence in tissue function. Consequently, characterization of new interactions within ECM opens the possibility of studying not ... ...

Abstract	Interaction between extracellular matrix (ECM) components plays an important role in the regulation of cellular behavior and hence in tissue function. Consequently, characterization of new interactions within ECM opens the possibility of studying not only the functional but also the pathological consequences derived from those interactions. We have previously described the interaction between fibulin2 and ADAMTS-12 in vitro and the effects of that interaction using cellular models of cancer. Now, we generate a mouse deficient in both ECM components and evaluate functional consequences of their absence using different cancer and inflammation murine models. The main findings indicate that mice deficient in both fibulin2 and ADAMTS12 markedly increase the development of lung tumors following intraperitoneal urethane injections. Moreover, inflammatory phenotype is exacerbated in the lung after LPS treatment as can be inferred from the accumulation of active immune cells in lung parenchyma. Overall, our results suggest that protective effects in cancer or inflammation shown by fibulin2 and ADAMTS12 as interactive partners in vitro are also shown in a more realistic in vivo context.
MeSH term(s)	Animals ; Mice ; Calcium-Binding Proteins ; Extracellular Matrix Proteins ; Inflammation/genetics ; Lung ; Neoplasms ; Phenotype ; Pneumonia ; ADAMTS Proteins/genetics ; ADAMTS Proteins/metabolism
Chemical Substances	Calcium-Binding Proteins ; Extracellular Matrix Proteins ; fibulin 2 ; Adamts12 protein, mouse (EC 3.4.24.-) ; ADAMTS Proteins (EC 3.4.24.-)
Language	English
Publishing date	2024-02-07
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/ijms25042024
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Article ; Online: Impacto de dapagliflozina en los factores de riesgo cardiovascular. Más allá del control de la glucemia.

Pallarés, V / Escobar, C / Egocheaga, I / Obaya, J C

Semergen

2021 Volume 47 Suppl 1, Page(s) 1–4

Abstract: Sodium-glucose transport protein 2 (SGLT2) inhibitors are a new class of oral hypoglycemic agents that increase urinary glucose excretion independently of insulin secretion, although an apparently simple mechanism, but with multiple metabolic effects. ... ...

Title translation	Impact of dapagliflozin on cardiovascular risk factors. Beyond glycemic control.
Abstract	Sodium-glucose transport protein 2 (SGLT2) inhibitors are a new class of oral hypoglycemic agents that increase urinary glucose excretion independently of insulin secretion, although an apparently simple mechanism, but with multiple metabolic effects. Dapagliflozin was the first SGLT2 inhibitor marketed in Europe in 2012 for the treatment of patients with type 2 diabetes, and consequently, with the greatest clinical experience. The results of different clinical trials and real-life studies have demonstrated its effectiveness in glycemic control, as they reduce glycosylated hemoglobin, while achieving a decrease in body weight and blood pressure, among others, providing a comprehensive metabolic protection.
MeSH term(s)	Benzhydryl Compounds/adverse effects ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Diabetes Mellitus, Type 2/drug therapy ; Glucosides ; Glycemic Control ; Heart Disease Risk Factors ; Humans ; Hypoglycemic Agents ; Risk Factors ; Sodium-Glucose Transporter 2 Inhibitors
Chemical Substances	Benzhydryl Compounds ; Glucosides ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors ; dapagliflozin (1ULL0QJ8UC)
Language	Spanish
Publishing date	2021-11-12
Publishing country	Spain
Document type	Journal Article
ISSN	1578-8865
ISSN (online)	1578-8865
DOI	10.1016/j.semerg.2021.09.009
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Article ; Online: Dapagliflozina en la prevención y tratamiento de la insuficiencia cardiaca.

Egocheaga, I / Escobar, C / Pallarés, V / Obaya, J C

Semergen

2021 Volume 47 Suppl 1, Page(s) 11–17

Abstract: To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied ... ...

Title translation	Dapagliflozin in the prevention and treatment of heart failure.
Abstract	To substantially reduce the risk of hospitalization and death among subjects with heart failure (HF) and reduced left ventricular ejection fraction, it is necessary to make a comprehensive approach of the different neurohormonal systems that are implied in its etiopathogenesis, including not only sympathetic nervous system, and renin-angiotensin system, but also vasoactive peptides and sodium-glucose transport protein 2. The DAPA-HF trial demonstrated that the addition of dapagliflozin to the standard treatment in HF with reduced left ventricular ejection fraction, markedly decreases the risk of cardiovascular death, HF hospitalization and overall death. In addition, dapagliflozin improves functional class and quality of life. Importantly, the prognostic benefit starts early after initiating treatment with dapagliflozin, regardless baseline therapy or the presence of diabetes. All these evidences make dapagliflozin as one of the mainstays of treatment for the management of HF with reduced left ventricular ejection fraction.
MeSH term(s)	Benzhydryl Compounds ; Glucosides ; Heart Failure/drug therapy ; Heart Failure/prevention & control ; Humans ; Quality of Life ; Stroke Volume ; Ventricular Function, Left
Chemical Substances	Benzhydryl Compounds ; Glucosides ; dapagliflozin (1ULL0QJ8UC)
Language	Spanish
Publishing date	2021-11-14
Publishing country	Spain
Document type	Journal Article
ISSN	1578-8865
ISSN (online)	1578-8865
DOI	10.1016/j.semerg.2021.10.001
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Article ; Online: Abordaje práctico de dapagliflozina en el tratamiento de la insuficiencia cardíaca. Papel del médico de atención primaria.

Obaya, J C / Escobar, C / Pallarés, V / Egocheaga, I

Semergen

2021 Volume 47 Suppl 1, Page(s) 5–10

Abstract: Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this ... ...

Title translation	Practical approach of dapagliflozin for the treatment of heart failure. Role of primary care physician.
Abstract	Despite traditional treatments, morbidity and mortality of patients with heart failure (HF) and reduced left ventricular ejection fraction remains unacceptably high. Traditionally, guidelines recommended a step by step approach in the management of this population. However, this approach could delay the prescription of some drugs with proven efficacy on morbidity and prognosis. As current HF guidelines recommend, an initial comprehensive approach with the aim of targeting all neurohormonal systems that are implied in the etiopathogenesis of HF seems necessary. The DAPA-HF trial demonstrated that dapagliflozin markedly reduces the risk of HF hospitalization, and also improves prognosis. Consequently, dapagliflozin should be considered as a first-line therapy in the management of these patients. On the other hand, primary care physicians are essential for the prevention and treatment of patients with HF and reduced left ventricular ejection fraction. As a result, it is mandatory that they know when and how dapagliflozin should be used. In this review, a practical approach for an appropriate use of this drug is provided.
MeSH term(s)	Benzhydryl Compounds ; Glucosides ; Heart Failure/drug therapy ; Humans ; Physicians, Primary Care ; Stroke Volume ; Ventricular Function, Left
Chemical Substances	Benzhydryl Compounds ; Glucosides ; dapagliflozin (1ULL0QJ8UC)
Language	Spanish
Publishing date	2021-11-19
Publishing country	Spain
Document type	Journal Article ; Review
ISSN	1578-8865
ISSN (online)	1578-8865
DOI	10.1016/j.semerg.2021.08.003
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Article: ADAMTS-12: Functions and Challenges for a Complex Metalloprotease.

Mohamedi, Yamina / Fontanil, Tania / Cal, Santiago / Cobo, Teresa / Obaya, Álvaro J

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 686763

Abstract: Nineteen members of the ADAMTS family of secreted zinc metalloproteinases are present in the human degradome. A wide range of different functions are being attributed to these enzymes and the number of their known substrates is considerably increasing in ...

Abstract	Nineteen members of the ADAMTS family of secreted zinc metalloproteinases are present in the human degradome. A wide range of different functions are being attributed to these enzymes and the number of their known substrates is considerably increasing in recent years. ADAMTSs can participate in processes such as fertility, inflammation, arthritis, neuronal and behavioral disorders, as well as cancer. Since its first annotation in 2001, ADAMTS-12 has been described to participate in different processes displayed by members of this family of proteinases. In this sense, ADAMTS-12 performs essential roles in modulation and recovery from inflammatory processes such as colitis, endotoxic sepsis and pancreatitis. ADAMTS-12 has also been involved in cancer development acting either as a tumor suppressor or as a pro-tumoral agent. Furthermore, participation of ADAMTS-12 in arthritis or in neuronal disorders has also been suggested through degradation of components of the extracellular matrix. In addition, ADAMTS-12 proteinase activity can also be modified by interaction with other proteins and thus, can be an alternative way of modulating ADAMTS-12 functions. In this review we revised the most relevant findings about ADAMTS-12 function on the 20th anniversary of its identification.
Language	English
Publishing date	2021-04-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.686763
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Article ; Online: Hyalectanase Activities by the ADAMTS Metalloproteases.

Fontanil, Tania / Mohamedi, Yamina / Espina-Casado, Jorge / Obaya, Álvaro J / Cobo, Teresa / Cal, Santiago

International journal of molecular sciences

2021 Volume 22, Issue 6

Abstract: The hyalectan family is composed of the proteoglycans aggrecan, versican, brevican and neurocan. Hyalectans, also known as lecticans, are components of the extracellular matrix of different tissues and play essential roles in key biological processes ... ...

Abstract	The hyalectan family is composed of the proteoglycans aggrecan, versican, brevican and neurocan. Hyalectans, also known as lecticans, are components of the extracellular matrix of different tissues and play essential roles in key biological processes including skeletal development, and they are related to the correct maintenance of the vascular and central nervous system. For instance, hyalectans participate in the organization of structures such as perineural nets and in the regulation of neurite outgrowth or brain recovery following a traumatic injury. The ADAMTS (A Disintegrin and Metalloprotease domains, with thrombospondin motifs) family consists of 19 secreted metalloproteases. These enzymes also perform important roles in the structural organization and function of the extracellular matrix through interactions with other matrix components or as a consequence of their catalytic activity. In this regard, some of their preferred substrates are the hyalectans. In fact, ADAMTSs cleave hyalectans not only as a mechanism for clearance or turnover of proteoglycans but also to generate bioactive fragments which display specific functions. In this article we review some of the physiological and pathological effects derived from cleavages of hyalectans mediated by ADAMTSs.
MeSH term(s)	ADAMTS Proteins/genetics ; ADAMTS Proteins/metabolism ; Brain/metabolism ; Brain Injuries, Traumatic/genetics ; Brain Injuries, Traumatic/metabolism ; Extracellular Matrix/genetics ; Extracellular Matrix/metabolism ; Humans ; Hyalectins/chemistry ; Hyalectins/metabolism ; Neuronal Outgrowth/genetics ; Thrombospondins/genetics ; Thrombospondins/metabolism ; Versicans/chemistry ; Versicans/metabolism
Chemical Substances	Hyalectins ; Thrombospondins ; Versicans (126968-45-4) ; ADAMTS Proteins (EC 3.4.24.-)
Language	English
Publishing date	2021-03-15
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/ijms22062988
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Article ; Online: Role of Leptin in Obesity, Cardiovascular Disease, and Type 2 Diabetes.

Vilariño-García, Teresa / Polonio-González, María L / Pérez-Pérez, Antonio / Ribalta, Josep / Arrieta, Francisco / Aguilar, Manuel / Obaya, Juan C / Gimeno-Orna, José A / Iglesias, Pedro / Navarro, Jorge / Durán, Santiago / Pedro-Botet, Juan / Sánchez-Margalet, Víctor

International journal of molecular sciences

2024 Volume 25, Issue 4

Abstract: Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached ... ...

Abstract	Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.
MeSH term(s)	Adult ; Humans ; Cardiovascular Diseases/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Leptin/metabolism ; Obesity/metabolism
Chemical Substances	Leptin
Language	English
Publishing date	2024-02-16
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/ijms25042338
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Article ; Online: Manejo de perfiles de pacientes con diabetes mellitus tipo2 en la práctica clínica de la atención primaria en España: Programa CONTROVERTI2.

Obaya Rebollar, J C / Miravet Jiménez, S / Aranbarri Osoro, I / Carramiñana Barrera, F C / García Soidán, F J / Cebrián Cuenca, A M

Semergen

2021 Volume 48, Issue 1, Page(s) 23–37

Abstract: Aim: To identify existing controversies in the routine management of patients with T2D and to contrast them with the latest scientific evidence and clinical guidelines, in order to help optimize and homogenize the treatment of patients with T2D in ... ...

Title translation	Management of patient profiles with type2 diabetes mellitus in Primary Care in Spain: CONTROVERTI2 Program.
Abstract	Aim: To identify existing controversies in the routine management of patients with T2D and to contrast them with the latest scientific evidence and clinical guidelines, in order to help optimize and homogenize the treatment of patients with T2D in Primary Care (PC) in Spain. Material and methods: 240 family doctors responded to an online questionnaire about the management of 6 patient profiles with T2D of increasing complexity. Results: The main drivers for the antihyperglycemic treatment choice are an HbA1c>10% and the presence of cardiovascular disease (CVD), although in evolved patients, the estimated glomerular filtration rate and the risk of hypoglycemia become more relevant. In newly diagnosed patients with an HbA1c>9%, treatment is still initiated with monotherapy (24%). In patients not controlled with metformin, dipeptidyl peptidase 4 inhibitors (DPP4-I, 54%) or sodium-glucose cotransporter 2 inhibitors (SGLT2-I, 39%) are usually added. On the other hand, type1 glucagon-like peptide receptor agonists (GLP1-RA) are mainly associated with obese patients with T2D. In patients not controlled with metformin+sulfonylurea (SU), SU replacement is preferred to adding a third antihyperglycemic agent to background therapy (77% vs. 23%). Conclusions: T2D treatment in PC is still focused on HbA1c reduction and treatment safety. Thus, DPP4-I are widely used. SGLT2-I are usually preferred for patients with T2D and CVD and GLP1-RA for patients with T2D and obesity, although their use in PC is low.
MeSH term(s)	Diabetes Mellitus, Type 2/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; Humans ; Hypoglycemic Agents ; Primary Health Care ; Sodium-Glucose Transporter 2 Inhibitors ; Spain
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors
Language	Spanish
Publishing date	2021-08-25
Publishing country	Spain
Document type	Journal Article
ISSN	1578-8865
ISSN (online)	1578-8865
DOI	10.1016/j.semerg.2021.07.009
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Article ; Online: New Insights into ADAMTS Metalloproteases in the Central Nervous System.

Mohamedi, Yamina / Fontanil, Tania / Cobo, Teresa / Cal, Santiago / Obaya, Alvaro J

Biomolecules

2020 Volume 10, Issue 3

Abstract: Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, ...

Abstract	Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of "A disintegrin and metalloproteinase with thrombospondin motifs" proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer's disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans).
MeSH term(s)	ADAMTS Proteins/metabolism ; Animals ; Axons/enzymology ; Axons/pathology ; Brain/enzymology ; Brain/pathology ; Brain Diseases/enzymology ; Brain Diseases/pathology ; Extracellular Matrix/enzymology ; Humans ; Proteoglycans/metabolism
Chemical Substances	Proteoglycans ; ADAMTS Proteins (EC 3.4.24.-)
Language	English
Publishing date	2020-03-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom10030403
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