12 results on '"Oreste Gualillo"'
Search Results
2. Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival
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Alessandro Ottaiano, Mariachiara Santorsola, Luisa Circelli, Francesco Perri, Marco Cascella, Francesco Sabbatino, Maurizio Capuozzo, Vincenza Granata, Silvia Zappavigna, Angela Lombardi, Marianna Scrima, Nadia Petrillo, Monica Ianniello, Marika Casillo, Oreste Gualillo, Guglielmo Nasti, Michele Caraglia, and Giovanni Savarese
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hypertension ,type 2 diabetes ,obesity ,p53 ,prognosis ,NGS ,Medicine (General) ,R5-920 - Abstract
IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P < 0.05). At multivariate analysis, age (≥65 vs. 25 kg/m2) associated with occurrence of p53 mutations (P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence.
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- 2023
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3. Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects
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Mariam Farrag, Djedjiga Ait Eldjoudi, María González-Rodríguez, Alfonso Cordero-Barreal, Clara Ruiz-Fernández, Maurizio Capuozzo, Miguel Angel González-Gay, Antonio Mera, Francisca Lago, Ahmed Soffar, Amina Essawy, Jesus Pino, Yousof Farrag, and Oreste Gualillo
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asprosin ,adipokines ,metabolic diseases ,obesity ,diabetes ,PCOS ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Adipose tissue malfunction leads to altered adipokine secretion which might consequently contribute to an array of metabolic diseases spectrum including obesity, diabetes mellitus, and cardiovascular disorders. Asprosin is a novel diabetogenic adipokine classified as a caudamin hormone protein. This adipokine is released from white adipose tissue during fasting and elicits glucogenic and orexigenic effects. Although white adipose tissue is the dominant source for this multitask adipokine, other tissues also may produce asprosin such as salivary glands, pancreatic B-cells, and cartilage. Significantly, plasma asprosin levels link to glucose metabolism, lipid profile, insulin resistance (IR), and β-cell function. Indeed, asprosin exhibits a potent role in the metabolic process, induces hepatic glucose production, and influences appetite behavior. Clinical and preclinical research showed dysregulated levels of circulating asprosin in several metabolic diseases including obesity, type 2 diabetes mellitus (T2DM), polycystic ovarian syndrome (PCOS), non-alcoholic fatty liver (NAFLD), and several types of cancer. This review provides a comprehensive overview of the asprosin role in the etiology and pathophysiological manifestations of these conditions. Asprosin could be a promising candidate for both novel pharmacological treatment strategies and diagnostic tools, although developing a better understanding of its function and signaling pathways is still needed.
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- 2023
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4. Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis
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Verónica Pulito-Cueto, Sara Remuzgo-Martínez, Fernanda Genre, Belén Atienza-Mateo, Víctor M. Mora-Cuesta, David Iturbe-Fernández, Leticia Lera-Gómez, María Sebastián Mora-Gil, Diana Prieto-Peña, Virginia Portilla, Ricardo Blanco, Alfonso Corrales, J. Gonzalo Ocejo-Vinyals, Oreste Gualillo, Iván Ferraz-Amaro, José M. Cifrián, Raquel López-Mejías, and Miguel A. González-Gay
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VCAM-1 ,MCP-1 ,ADMA ,interstitial lung disease ,rheumatoid arthritis ,biomarkers ,Biology (General) ,QH301-705.5 - Abstract
Introduction: Early diagnosis of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA) constitutes a challenge for the clinicians. Pulmonary vasculopathy is relevant in the development of interstitial lung disease. Accordingly, we aimed to explore the role of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and asymmetric dimethylarginine (ADMA), key molecules in the vasculopathy, as potential biomarkers of pulmonary fibrosis in RA-ILD+.Methods: We included 21 RA-ILD+ patients and two comparative groups: 25 RA-ILD- patients and 21 idiopathic pulmonary fibrosis (IPF) patients. Serum levels of the molecules were determined by ELISA, and mRNA expression was quantified by qPCR.Results: VCAM-1, MCP-1 and ADMA serum levels were increased in RA-ILD+ patients in relation to RA-ILD- and IPF patients. Additionally, RA-ILD+ patients exhibited increased CCL2 (gene encoding MCP-1) and decreased PRMT1 (gene related to ADMA synthesis) mRNA expression in relation to RA-ILD- patients. A lower expression of VCAM1, CCL2, and PRMT1 was observed in RA-ILD+ patients when compared with those with IPF. Furthermore, MCP-1 serum levels and PRMT1 mRNA expression were positively correlated with RA duration, and ADMA serum levels were positively associated with C-reactive protein in RA-ILD+ patients.Conclusion: Our study suggests that VCAM-1, MCP-1 and ADMA could be considered as useful biomarkers to identify ILD in RA patients, as well as to discriminate RA-ILD+ from IPF, contributing to the early diagnosis of RA-ILD+.
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- 2022
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5. Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis
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Sara Remuzgo-Martínez, Javier Rueda-Gotor, Verónica Pulito-Cueto, Raquel López-Mejías, Alfonso Corrales, Leticia Lera-Gómez, Raquel Pérez-Fernández, Virginia Portilla, Íñigo González-Mazón, Ricardo Blanco, Rosa Expósito, Cristina Mata, Javier Llorca, Vanesa Hernández-Hernández, Carlos Rodríguez-Lozano, Nuria Barbarroja, Rafaela Ortega-Castro, Esther Vicente, Cristina Fernández-Carballido, María Paz Martínez-Vidal, David Castro-Corredor, Joaquín Anino-Fernández, Diana Peiteado, Chamaida Plasencia-Rodríguez, Eva Galíndez-Agirregoikoa, María Luz García-Vivar, Nuria Vegas-Revenga, Irati Urionaguena, Oreste Gualillo, Juan Carlos Quevedo-Abeledo, Santos Castañeda, Iván Ferraz-Amaro, Miguel Á. González-Gay, and Fernanda Genre
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irisin ,axial spondyloarthritis ,biomarker ,subclinical atherosclerosis ,cardiovascular risk ,disease severity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionPatients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients.MethodsA large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA.ResultsLow irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01).ConclusionsOur results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.
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- 2022
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6. The Treatment With the SGLT2 Inhibitor Empagliflozin Modifies the Hepatic Metabolome of Male Zucker Diabetic Fatty Rats Towards a Protective Profile
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Alana Aragón-Herrera, Manuel Otero-Santiago, Laura Anido-Varela, Sandra Moraña-Fernández, Manuel Campos-Toimil, Tomás García-Caballero, Luis Barral, Estefanía Tarazón, Esther Roselló-Lletí, Manuel Portolés, Oreste Gualillo, Isabel Moscoso, Ricardo Lage, José Ramón González-Juanatey, Sandra Feijóo-Bandín, and Francisca Lago
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empagliflozin ,diabetes ,liver ,metabolome ,inflammation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.
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- 2022
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7. Editorial: Inflammation and Biomarkers in Osteoarthritis
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Ali Mobasheri, João Eurico Fonseca, Oreste Gualillo, Yves Henrotin, Raquel Largo, Gabriel Herrero-Beaumont, and Francisco Airton Castro Rocha
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osteoarthritis ,biomarkers ,cartilage ,synovium ,inflammation ,Medicine (General) ,R5-920 - Published
- 2021
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8. Editorial: The Physiology of Inflammation—The Final Common Pathway to Disease
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Alexandrina Ferreira Mendes, Maria Teresa Cruz, and Oreste Gualillo
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aging ,low grade inflammation ,chronic diseases ,nutrition ,microbiota ,Physiology ,QP1-981 - Published
- 2018
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9. Obesity, Fat Mass and Immune System: Role for Leptin
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Vera Francisco, Jesús Pino, Victor Campos-Cabaleiro, Clara Ruiz-Fernández, Antonio Mera, Miguel A. Gonzalez-Gay, Rodolfo Gómez, and Oreste Gualillo
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adipokines ,adipose tissue ,immunometabolism ,leptin ,metabolism ,rheumatic diseases ,Physiology ,QP1-981 - Abstract
Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.
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- 2018
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10. Role of Toll-Like Receptor 4 on Osteoblast Metabolism and Function
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Ana Alonso-Pérez, Eloi Franco-Trepat, María Guillán-Fresco, Alberto Jorge-Mora, Verónica López, Jesús Pino, Oreste Gualillo, and Rodolfo Gómez
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osteoblast ,TLR4 ,inflammation ,LPS ,osteoclast ,MSCs ,Physiology ,QP1-981 - Abstract
Inflammation is a process whose main function is to fight against invading pathogens or foreign agents. Nonetheless, it is widely accepted that inflammation takes part in multiple processes in a physiological or pathophysiological context. Among these processes the inflammation has been closely related to bone metabolism. It is well-known that in systemic inflammatory diseases such as rheumatoid arthritis the inflammatory environment contributes to the reduction of the bone mineral density. This has been further evidenced in different animals models of osteoporosis where the deletion of key inflammatory molecules dramatically reduced the bone loss. On the contrary, it is also well-known that certain degree of inflammation is required to allow bone fractures healing. In fact, excessive use of anti-inflammatory drugs inhibits bone fracture consolidation. The innate immune responses (IIRs) contribute to the development and maintenance of the inflammation. These responses have been observed in cells of the musculoskeletal system. Chondrocytes and osteoblasts are equipped with the molecular repertoire necessary to setting up these IIR, including the expression of several toll-like receptors. Specifically, toll-like receptor 4 (TLR4) activation in mesenchymal stem cells, osteoblasts, and osteocytes has been involved in catabolic and anabolic process. Accordingly, in this review we have summarized the current knowledge about the physiology of TLR4, including its signaling, and its endogenous agonists. In addition we have focused on its role on osteoblast metabolism and function.
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- 2018
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11. The Physiology of Inflammation—The Final Common Pathway to Disease
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Alexandrina Ferreira Mendes, Maria Teresa Cruz, and Oreste Gualillo
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Physiology ,Inflammation ,Disease ,low grade inflammation ,Inflammatory bowel disease ,lcsh:Physiology ,Low grade inflammation ,chronic diseases ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,microbiota ,aging ,nutrition ,Healthy aging ,lcsh:QP1-981 ,business.industry ,Cancer ,medicine.disease ,3. Good health ,Editorial ,030104 developmental biology ,medicine.symptom ,business ,030215 immunology - Abstract
Healthy Aging 2020: CENTRO-01-0145-FEDER-000012 and POCI-01-0145-FEDER-028424 supported by Programa Operacional Competitividade e Internacionalização (COMPETE 2020) through FEDER and by the Portuguese Foundation for Science and Technology
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- 2018
12. Obesity, Fat Mass and Immune System: Role for Leptin
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Clara Ruiz-Fernández, Rodolfo Gómez, Oreste Gualillo, Victor Campos-Cabaleiro, Antonio Mera, Jesús Pino, Vera Francisco, Miguel A. González-Gay, and Universidad de Cantabria
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0301 basic medicine ,Physiology ,immunometabolism ,Adipose tissue ,Adipokine ,Inflammation ,leptin ,lcsh:Physiology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Physiology (medical) ,medicine ,adipokines ,Leptin receptor ,Innate immune system ,lcsh:QP1-981 ,business.industry ,Leptin ,Acquired immune system ,adipose tissue ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,rheumatic diseases ,medicine.symptom ,business ,metabolism - Abstract
Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases. OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). VF is a “Sara Borrell” Researcher funded by ISCIII and FEDER. RG is a “Miguel Servet” Researcher funded by Instituto de Salud Carlos III (ISCIII) and FEDER. OG, MG-G, and RG are members of RETICS Program, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG and JP (PIE13/00024 and PI14/00016, PI17/00409), and RG (PI16/01870 and CP15/00007) was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Program (Project No. 734899). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
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- 2018
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