A5030157600- Parathyroid Disorders and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Muscle and Compartmental Disorders
- Magnesium in Health and Disease
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Biomedical Research and Pathophysiology
- Acute Kidney Injury Research
- Nicotinic Acetylcholine Receptors Study
- Free Radicals and Antioxidants
- Computational Drug Discovery Methods
- Medical Imaging and Pathology Studies
- Cardiovascular Health and Disease Prevention
- Chemical synthesis and alkaloids
- Thyroid Disorders and Treatments
- Chronic Kidney Disease and Diabetes
- Cytokine Signaling Pathways and Interactions
- ATP Synthase and ATPases Research
- NF-κB Signaling Pathways
- Genetic Syndromes and Imprinting
- Neurological and metabolic disorders
- Biochemical effects in animals
- Immune Response and Inflammation
- Dialysis and Renal Disease Management
- Mitochondrial Function and Pathology
Hospital Universitario 12 De Octubre
2019-2025
Research Institute Hospital 12 de Octubre
2018-2024
Universidad Autónoma de Madrid
2010-2017
Hospital Universitario de La Princesa
2012-2017
Hospital Universitario Fundación Jiménez Díaz
2016-2017
Fundación Renal
2016
Abstract Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is well‐known anti‐ageing factor with relevant cardioprotective actions, at least when renal dysfunction present, but its actions are much less known function preserved. This study investigated as biomarker potential novel treatment IHD‐associated complications after myocardial infarction (MI) under preserved function. Association between circulating levels cardiac injury was in patients ST‐elevation...
Aims: A loss in brain acetylcholine and cholinergic markers, subchronic inflammation, impaired mitochondrial function, which lead to low-energy production high oxidative stress, are common pathological factors several neurodegenerative diseases (NDDs). Glial cells important for homeostasis, microglia controls the central immune response, where α7 nicotinic receptors (nAChR) seem play a pivotal role; however, little is known about effects of this receptor metabolism. Therefore, aim study was...
Renal ischemia and reperfusion injury (IRI) is the main cause of acute kidney (AKI). AKI induces development cardiac hypertrophy (CH) during cardiorenal syndrome (CRS), cardiomyocyte calcium mishandling though systemic inflammation after 8 days renal IRI. Klotho has recently been described as an anti-inflammatory component. Given this, treatment could prevent or attenuate inflammation, thereby also preventing electrical outcomes incurred by CRS. The aim this study was to investigate...
An improved understanding of pathogenic pathways in AKI may identify novel therapeutic approaches. Previously, we conducted unbiased liquid chromatography-tandem mass spectrometry–based protein expression profiling the renal proteome mice with acute folate nephropathy. Here, analysis dataset identified enrichment involving NF κ B kidney cortex, and a targeted data mining approach components noncanonical pathway, including upstream kinase mitogen-activated 14 (MAP3K14), DNA binding...
The synthesis, molecular modeling, and pharmacological analysis of phenoxyalkylamino-4-phenylnicotinates (2–7), phenoxyalkoxybenzylidenemalononitriles (12, 13), pyridonepezils (14–18), quinolinodonepezils (19–21) are described. Pyridonepezils 15–18 were found to be selective moderately potent regarding the inhibition hAChE, whereas 19–21 poor inhibitors hAChE. most hAChE inhibitor was ethyl 6-(4-(1-benzylpiperidin-4-yl)butylamino)-5-cyano-2-methyl-4-phenylnicotinate (18) [IC50 (hAChE) = 0.25...
Klotho is a membrane-bound or soluble protein, originally identified as an age-suppressing factor and regulator of mineral metabolism. deficiency associated with the development renal disease, but its role in cardiac function context uraemic cardiomyopathy unknown.We explored effects on Ca2+ cycling. We analysed handling adult cardiomyocytes from Klotho-deficient (kl/kl) mice murine model 5/6 nephrectomy (Nfx). also studied effect exogenous supplementation, by chronic recombinant treatment,...
Abstract Background Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, fibroblast growth factor (FGF) 23 decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis development remains unknown....
Background: Neurodegenerative diseases share many pathological pathways, such as abnormal protein aggregation, mitochondrial dysfunction, extensive oxidative stress and neuroinflammation. Cells have an intrinsic mechanism of protection, the Nrf2 transcriptional factor, known master regulator redox homeostasis. Results: Based on common features these we designed a multi-target hybrid structure derived from melatonin ethyl cinnamate. The obtained derivatives were inducers potent-free radical...
We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for treatment Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca(2+) channels, classically studied neurodegenerative diseases, Ser/Thr phosphatases, which have been marginally aimed, even despite key role in protein τ dephosphorylation. Twenty-five compounds were synthesized, mostly neuroprotective profile exceeded that offered by head...
Abstract TNF-like weak inducer of apoptosis (TWEAK) receptor Fn14 is expressed by podocytes and deficiency protects from experimental proteinuric kidney disease. However, the downstream effectors TWEAK/Fn14 in are poorly characterized. We have explored TWEAK activation non-canonical NFκB signaling cultured podocytes. In podocytes, increased expression chemokines CCL21, CCL19 RANTES a time-dependent manner. The inhibitor canonical parthenolide inhibited early responses, but not CCL21 or late...
Benzothiazepine CGP37157 is widely used as tool to explore the role of mitochondria in cell Ca(2+) handling, by its blocking effect Na(+)/Ca(2+) exchanger. Recently, has shown exhibit neuroprotective properties. In trend improve neuroprotection profile, we have synthesized ITH12505, an isosteric analogue having a methyl instead chlorine at C2' phenyl ring. ITH12505 exerted properties similar chromaffin cells and hippocampal slices stressed with veratridine. Also, both compounds afforded...
Hemodialysis patients experience high oxidative stress because of systemic inflammation and depletion antioxidants. Little is known about the global status during dialysis or whether it linked to type dialysis. We investigated before (pre-) after (post-) one session in subjected high-flux (HFD) on-line hemodiafiltration (OL-HDF). analyzed carbonyls, oxidized LDL (oxLDL), 8-hydroxy-2'-deoxyguanosine, xanthine oxidase (XOD) activity as markers, total antioxidant capacity (TAC), catalase,...
Acute renal failure (ARF) following ischemia-reperfusion (I/R) injury is considered a relevant risk factor for cardiac damage, but the underlying mechanisms, particularly those triggered at cardiomyocyte level, are unknown.We examined intracellular Ca2+ dynamics in adult ventricular cardiomyocytes isolated from C57BL/6 mice 7 or 15 days unilateral I/R.After of I/R, cell contraction was significantly lower compared to sham-treated mice. It accompanied by significant decrease both systolic...
ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in vitro models of Alzheimer's disease. These effects were proposed be due part regulatory action on protein phosphatase 2A inhibition, as it prevented binding its inhibitor okadaic acid. We decided investigate the pharmacological properties ITH12246, evaluating ability counteract memory impairment evoked by...
Mitochondria regulate cellular Ca2+ oscillations, taking up through its uniporter and releasing it the mitochondrial sodium/calcium exchanger. The role of mitochondria in regulation cycle has received much attention recently, as is a central stage neuronal survival death processes. Over last decades, 4,1-benzothiazepine CGP37157 been only available blocker exchanger, although targets several other calcium transporters. We report synthesis derivatives with goal enhancing exchanger blockade...