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1.
J Sci Food Agric ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087312

RESUMEN

BACKGROUND: The incorporation of functional food ingredients in chocolate that seek to eliminate, if not completely, most of the added sugar content, as well as the use of alternative chocolate production techniques, have gained popularity in recent years. This study aimed to incorporate red beetroot powder into dark chocolate and investigate the effect of red beetroot powder concentration and processing time in a melanger on the physicochemical properties, sensory profile and consumer acceptability of beetroot dark chocolate. RESULTS: The addition of red beetroot powder increased the moisture content, particle size distribution and hardness of the chocolates, while the opposite was true for processing time with no effect on the colour. Except for taste, which had an average score of 3.2 ± 1.8 on the 7-point hedonic scale, consumers scored all the other sensory attributes of the chocolates above 4.0. Among the chocolates with red beetroot powder, samples with a 15% red beetroot powder addition had a high average overall acceptability score of >5, while the 30% sample scored <4. CONCLUSION: Red beetroot powder can be used to replace sugar in dark chocolate without affecting its physicochemical properties, sensory profile or consumer acceptability. However, the target market should be considered when determining the level of red beetroot powder incorporation in terms of chocolate taste. This research has the potential to improve the overall health-promoting properties of dark chocolate by eliminating added sugar (partially or completely). It would also help to diversify beetroot utilization, allow small-scale processors to venture into chocolate production and expand the small-scale chocolate value chain. © 2024 Society of Chemical Industry.

2.
Int J Mol Sci ; 24(10)2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37240378

RESUMEN

The stimulator of interferon genes (STING) is an adaptor protein involved in the activation of IFN-ß and many other genes associated with the immune response activation in vertebrates. STING induction has gained attention from different angles such as the potential to trigger an early immune response against different signs of infection and cell damage, or to be used as an adjuvant in cancer immune treatments. Pharmacological control of aberrant STING activation can be used to mitigate the pathology of some autoimmune diseases. The STING structure has a well-defined ligand binding site that can harbor natural ligands such as specific purine cyclic di-nucleotides (CDN). In addition to a canonical stimulation by CDNs, other non-canonical stimuli have also been described, whose exact mechanism has not been well defined. Understanding the molecular insights underlying the activation of STING is important to realize the different angles that need to be considered when designing new STING-binding molecules as therapeutic drugs since STING acts as a versatile platform for immune modulators. This review analyzes the different determinants of STING regulation from the structural, molecular, and cell biology points of view.


Asunto(s)
Adyuvantes Inmunológicos , Nucleótidos Cíclicos , Animales , Sitios de Unión
3.
Molecules ; 28(17)2023 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-37687094

RESUMEN

Esterases are hydrolases that catalyze the hydrolysis of esters into the corresponding acids and alcohols. The development of fluorescent probes for detecting esterases is of great importance due to their wide spectrum of biological and industrial applications. These probes can provide a rapid and sensitive method for detecting the presence and activity of esterases in various samples, including biological fluids, food products, and environmental samples. Fluorescent probes can also be used for monitoring the effects of drugs and environmental toxins on esterase activity, as well as to study the functions and mechanisms of these enzymes in several biological systems. Additionally, fluorescent probes can be designed to selectively target specific types of esterases, such as those found in pathogenic bacteria or cancer cells. In this review, we summarize the recent fluorescent probes described for the visualization of cell viability and some applications for in vivo imaging. On the other hand, positron emission tomography (PET) is a nuclear-based molecular imaging modality of great value for studying the activity of enzymes in vivo. We provide some examples of PET probes for imaging acetylcholinesterases and butyrylcholinesterases in the brain, which are valuable tools for diagnosing dementia and monitoring the effects of anticholinergic drugs on the central nervous system.


Asunto(s)
Esterasas , Colorantes Fluorescentes , Tomografía de Emisión de Positrones , Hidrolasas , Butirilcolinesterasa
4.
J Sci Food Agric ; 103(13): 6263-6271, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37160731

RESUMEN

BACKGROUND: Black corn possesses potent antioxidants, but these are mostly lost during processing. In this study we evaluated the antioxidant content of two different black ('Millo Corvo') corn-based products (i.e. tortillas and cookies) subject to moderate processing. A parallel study on white and yellow corns was carried out for comparison. RESULTS: Raw 'Millo Corvo' flour exhibited higher contents of phenolic acids, flavonoids, and particularly anthocyanins than white and yellow flours did. Phenolic acids decreased in cookies but did not in tortillas; flavonoids did not exhibit a clear tendency, and anthocyanins were always preserved. Antioxidant activity (AA) obtained for 'Millo Corvo' samples was twice as high as the value measured in white and yellow corns in terms of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. The difference in AA was even more remarkable in terms of photochemiluminiscence antiradical activity. The conditions used during the cookie-making process enabled the natural antioxidant characteristics of 'Millo Corvo' to be preserved. However, the conditions applied to prepare tortillas resulted in major losses. CONCLUSIONS: The initial phenolics, in particular anthocyanins, and AA of 'Millo Corvo' flour can be maintained during processing as long as the conditions applied are 183 °C for 20 min in the absence of a high water content. Millo corvo products possess improved antioxidant characteristics compared with those from white and yellow corns. Millo corvo is a promising black corn type to prepare health-promoting corn-based foodstuffs. © 2023 Society of Chemical Industry.


Asunto(s)
Antioxidantes , Callosidades , Antocianinas , Zea mays/química , Fenoles , Flavonoides
5.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-36430843

RESUMEN

Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the cocoa products. It is, therefore, necessary to process cocoa beans to develop the characteristic color, taste, and flavor, and reduce the astringency and bitterness, which are desirable in cocoa products. Processing, however, affects the composition and quantities of the bioactive compounds, resulting in the modification of the health-promoting properties of cocoa beans and chocolate. In this advanced review, we sought to better understand the effect of cocoa's transformational process into chocolate on polyphenols and methylxanthine and the mechanism of action of the original flavanols and methylxanthines. More data on the cocoa processing effect on cocoa bioactives are still needed for better understanding the effect of each processing step on the final polyphenolic and methylxanthine composition of chocolate and other cocoa products. Regarding the mechanisms of action, theobromine acts through the modulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways, while flavanols mainly act though the protein kinases and antioxidant pathways. Both flavanols and theobromine seem to be involved in the nitric oxide and neurotrophin regulation.


Asunto(s)
Cacao , Chocolate , Polifenoles/farmacología , Teobromina/farmacología
6.
Molecules ; 27(3)2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35163980

RESUMEN

Histone deacetylases (HDACs) are a large family of epigenetic metalloenzymes that are involved in gene transcription and regulation, cell proliferation, differentiation, migration, and death, as well as angiogenesis. Particularly, disorders of the HDACs expression are linked to the development of many types of cancer and neurodegenerative diseases, making them interesting molecular targets for the design of new efficient drugs and imaging agents that facilitate an early diagnosis of these diseases. Thus, their selective inhibition or degradation are the basis for new therapies. This is supported by the fact that many HDAC inhibitors (HDACis) are currently under clinical research for cancer therapy, and the Food and Drug Administration (FDA) has already approved some of them. In this review, we will focus on the recent advances and latest discoveries of innovative strategies in the development and applications of compounds that demonstrate inhibitory or degradation activity against HDACs, such as PROteolysis-TArgeting Chimeras (PROTACs), tumor-targeted HDACis (e.g., folate conjugates and nanoparticles), and imaging probes (positron emission tomography (PET) and fluorescent ligands).


Asunto(s)
Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Histona Desacetilasas/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos
7.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34576138

RESUMEN

Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1' heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells.


Asunto(s)
Diseño de Fármacos , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Osteosarcoma/patología , Agua/química , Línea Celular Tumoral , Química Clic , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Metaloproteinasa 13 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/síntesis química , Inhibidores de la Metaloproteinasa de la Matriz/química , Modelos Moleculares , Solubilidad
8.
Molecules ; 26(18)2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34577077

RESUMEN

Protein degradation by the Ubiquitin-Proteasome System is one of the main mechanisms of the regulation of cellular proteostasis, and the E3 ligases are the key effectors for the protein recognition and degradation. Many E3 ligases have key roles in cell cycle regulation, acting as checkpoints and checkpoint regulators. One of the many important proteins involved in the regulation of the cell cycle are the members of the Histone Deacetylase (HDAC) family. The importance of zinc dependent HDACs in the regulation of chromatin packing and, therefore, gene expression, has made them targets for the design and synthesis of HDAC inhibitors. However, achieving potency and selectivity has proven to be a challenge due to the homology between the zinc dependent HDACs. PROteolysis TArgeting Chimaera (PROTAC) design has been demonstrated to be a useful strategy to inhibit and selectively degrade protein targets. In this review, we attempt to summarize the E3 ligases that naturally ubiquitinate HDACs, analyze their structure, and list the known ligands that can bind to these E3 ligases and be used for PROTAC design, as well as the already described HDAC-targeted PROTACs.


Asunto(s)
Histona Desacetilasas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Humanos , Complejo de la Endopetidasa Proteasomal/efectos de los fármacos , Zinc/metabolismo
9.
Molecules ; 26(11)2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34071973

RESUMEN

Recommendations towards increased consumption of fresh fruit and vegetables are well supported by epidemiological and clinical trials. However, in some specific cases, it is difficult to follow these recommendations and the use of nutraceuticals or, in the present work, a freeze-dried fruits mixture can be recommended in order to afford the optimal consumption of dietary polyphenols naturally present in fruits and vegetables. In this work we have carefully characterized a red-berry mixture in terms of polyphenol composition, encountering mainly anthocyanins, which account for a total of 2.8 mg/g as cyanidin-3-glucoside equivalents. Additionally, we have assayed the red-berry blend in a cell model of neurological damage by differentiating the cells and measuring the effect of red-berry polyphenols on cell viability and redox state by flow cytometry. The berry-fruit extract showed an inhibitory effect on differentiated SH-SY5Y ROS formation at a concentration as low as 250 µg/mL (33% inhibition). The results show the potential of this berry-fruit blend for its nutraceutical use in the prevention of the neurodegeneration associated with age or environmental agents.


Asunto(s)
Suplementos Dietéticos , Frutas/química , Neuronas/metabolismo , Aminoácidos/análisis , Animales , Antocianinas/metabolismo , Antioxidantes/farmacología , Línea Celular Tumoral , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Flavonoles/química , Humanos , Espectrometría de Masas , Neuronas/efectos de los fármacos , Estrés Oxidativo , Extractos Vegetales/farmacología , Polifenoles/análisis , Especies Reactivas de Oxígeno
10.
Alcohol Clin Exp Res ; 44(5): 1037-1045, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32154588

RESUMEN

BACKGROUND: Pleiotrophin (PTN) and midkine (MK) are cytokines that are up-regulated in the prefrontal cortex (PFC) after alcohol administration and have been shown to reduce alcohol intake and reward. Both cytokines are endogenous inhibitors of receptor protein tyrosine phosphatase (RPTP) ß/ζ (a.k.a. PTPRZ1). Recently, a new compound named MY10 was designed with the aim of mimicking the activity of PTN and MK. MY10 has already shown promising results regulating alcohol-related behaviors in mice. METHODS: We have now tested the effects of MY10 on alcohol operant self-administration and Drinking In the Dark-Multiple Scheduled Access (DID-MSA) paradigms in rats. Gene expression of relevant genes in the PTN/MK signaling pathway in the PFC was analyzed by real-time PCR. RESULTS: MY10, at the highest dose tested (100 mg/kg), reduced alcohol consumption in the alcohol operant self-administration paradigm (p = 0.040). In the DID-MSA paradigm, rats drank significantly less alcohol (p = 0.019) and showed a significant decrease in alcohol preference (p = 0.002). We observed that the longer the exposure to alcohol, the greater the suppressing effects of MY10 on alcohol consumption. It was demonstrated that the effects of MY10 were specific to alcohol since saccharin intake was not affected by MY10 (p = 0.804). MY10 prevented the alcohol-induced down-regulation of Ptprz1 (p = 0.004) and anaplastic lymphoma kinase (Alk; p = 0.013) expression. CONCLUSIONS: Our results support and provide further evidence regarding the efficacy of MY10 on alcohol-related behaviors and suggest the consideration of the blockade of RPTPß/ζ as a target for reducing excessive alcohol consumption.


Asunto(s)
Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Inhibidores Enzimáticos/administración & dosificación , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/antagonistas & inhibidores , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/farmacología , Citocinas/genética , Citocinas/farmacología , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Masculino , Midkina/genética , Midkina/farmacología , Ratas , Ratas Wistar , Proteínas Tirosina Fosfatasas Clase 5 Similares a Receptores/genética , Transducción de Señal/genética
11.
Molecules ; 25(7)2020 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-32218358

RESUMEN

The design of multitarget drugs (MTDs) has become an innovative approach for the search of effective treatments in complex diseases such as cancer. In this work, we communicate our efforts in the design of multi-targeting histone deacetylase (HDAC) and protein kinase CK2 inhibitors as a novel therapeutic strategy against cancer. Using tetrabromobenzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole (DMAT) as scaffolds for CK2 inhibition, and a hydroxamate to coordinate the zinc atom present in the active site of HDAC (zinc binding group, ZBG), new multitarget inhibitors have been designed and synthesized. According to the in vitro assays, N-Hydroxy-6-(4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)hexanamide (11b) is the most interesting compound, with IC50 values of 0.66; 1.46 and 3.67 µM. for HDAC6; HDAC1 and CK2; respectively. Cellular assays on different cancer cell lines rendered promising results for N-Hydroxy-8-(4,5,6,7-tetrabromo-2-(dimethylamino)-1H-benzo[d]imidazol-1-yl)octanamide (11d). This inhibitor presented the highest cytotoxic activity, proapoptotic capability, and the best mitochondria-targeting and multidrug-circumventing properties, thus being the most promising drug candidate for further in vivo studies.


Asunto(s)
Antineoplásicos/farmacología , Quinasa de la Caseína II/análisis , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Apoptosis/efectos de los fármacos , Quinasa de la Caseína II/antagonistas & inhibidores , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Especies Reactivas de Oxígeno/metabolismo
12.
J Clin Biochem Nutr ; 66(1): 24-35, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32001953

RESUMEN

To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity.

13.
Org Biomol Chem ; 17(4): 916-929, 2019 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-30629065

RESUMEN

In this article, we describe our efforts in the search of MMP2/CK2 dual targeting inhibitors. We have followed a rational drug design approach based on our experience in the selective inhibition of these two enzymes. We have successfully obtained highly active MMP2 (10, IC50 = 70 nM; 11, IC50 = 100 nM) and CK2 (16a, IC50 = 500 nM) inhibitors. However, structural fine tuning of these small molecules to simultaneously target both enzymes turned out to be an unattainable goal. Unexpectedly, we were lucky to identify new and selective MMP13 inhibitors (10, IC50 = 3.7 nM and 11, IC50 = 5.6 nM) with a novel TBB-derived scaffold. These compounds constitute an interesting starting point for further optimization.


Asunto(s)
Quinasa de la Caseína II/antagonistas & inhibidores , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinasa de la Caseína II/metabolismo , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad
14.
Clin Rehabil ; 33(4): 631-641, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30607986

RESUMEN

OBJECTIVE:: To compare the effectiveness of a precast adjustable compression system with that of multilayered compression bandages in the treatment of breast cancer-related lymphoedema. DESIGN:: Multicenter, randomized, single-blind parallel-group clinical trial. SETTING:: The rehabilitation services of four general university hospitals. SUBJECTS:: Patients with upper limb breast cancer-related lymphoedema. INTERVENTIONS:: All the patients received manual lymphatic drainage, followed by a precast adjustable compression system or multilayered compression bandages, according to the group allocation. The treatment included 10 consecutive sessions over a two-week period from Monday to Friday, followed by some sessions on three alternate days per week, until the patient received a tailored compression garment. PRIMARY MEASUREMENTS:: The patients were evaluated just before the treatment, after 10 sessions and at three months posttreatment. The primary outcome was the change in excess lymphoedema volume. Secondary outcomes were changes in the symptoms of pain, heaviness, tightness and hardness. Analyses were performed using an intention-to-treat approach. RESULTS:: In all, 42 patients were included; there were 22 in the precast adjustable compression system group and 20 in the multilayered compression bandages group. Both groups exhibited significant decreases in excess volume and symptoms after 10 sessions and at three months. There were no significant differences regarding excess volume or symptoms between the precast adjustable compression system and multilayered compression bandages groups after 10 sessions and at the three-month follow-up exam. CONCLUSION:: The precast adjustable compression system and the multilayered compression bandages have similar efficacy for the reduction of excess lymphoedema volume or symptoms.


Asunto(s)
Neoplasias de la Mama/fisiopatología , Vendajes de Compresión , Linfedema/terapia , Extremidad Superior/fisiopatología , Drenaje , Femenino , Humanos , Linfedema/fisiopatología , Persona de Mediana Edad , Método Simple Ciego
15.
Phytother Res ; 33(4): 1142-1149, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30729593

RESUMEN

Lung carcinoma is one of the most common cancers and has a high mortality. Recently, we showed that it produces neurological paraneoplastic syndrome, with Ilex paraguariensis (IP) extract exerting palliative effects due to its content of phenolic compounds. It is possible, therefore, that these diet agents can arrive at the brain and exert neuroprotection, after the oral intake of IP. Here, the aim was to investigate the protective role of bioavailable IP compounds on the telencephalon and diencephalon in lung adenocarcinoma-bearing BALB/cJ males. Mice aged 2 months were treated for 3 weeks with 0-100 IP mg·kg-1 ·day-1 . HPLC-UV revealed the presence of chlorogenic acid and quercetin in brain regions, liver, and tumour, in an IP dose-dependent manner. Brain was also evaluated histologically, and interleukin-6 was measured by ELISA. Chlorogenic acid was the major compound found in brain, whereas quercetin was observed at the diencephalon to a lesser extent. Both compounds were involved in IP dose-dependent diencephalic interleukin-6 reduction. Histology suggested cellular protection with less apoptosis in chlorogenic-exposed areas. Taken together, chlorogenic acid and quercetin from dietary IP were bioavailable and bioactive in brain, thereby attenuating lung cancer-related neuroinflammation and damage. These findings support plant-based strategies to improve prognosis.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Cromatografía Líquida de Alta Presión/métodos , Ilex paraguariensis/química , Interleucina-6/uso terapéutico , Fenoles/uso terapéutico , Extractos Vegetales/química , Adenocarcinoma del Pulmón/patología , Animales , Interleucina-6/farmacología , Masculino , Ratones , Fenoles/farmacología
16.
Molecules ; 24(16)2019 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-31426440

RESUMEN

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPIs) have been developed as novel therapeutics, and some of them have entered clinical trials. However, so far, only one MMPI (doxycycline) has been approved by the FDA. Therefore, the evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPIs labeled imaging agents have emerged. This article begins by providing an overview of the MMP subfamily and its structure and function. The latest advances in the design of subtype selective MMPIs and their biological evaluation are then summarized. Subsequently, the potential use of MMPI-labeled diagnostic agents in clinical imaging techniques are discussed, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, this article concludes with future perspectives and clinical utility.


Asunto(s)
Aterosclerosis/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Inhibidores de la Metaloproteinasa de la Matriz/farmacocinética , Metaloproteinasas de la Matriz/química , Sondas Moleculares/farmacocinética , Neoplasias/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Dominio Catalítico/genética , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/diagnóstico por imagen , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Humanos , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/patología , Inhibidores de la Metaloproteinasa de la Matriz/síntesis química , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Imagen Molecular/métodos , Sondas Moleculares/síntesis química , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Neoplasias/metabolismo , Neoplasias/patología , Osteoartritis/metabolismo , Osteoartritis/patología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos
17.
Biochim Biophys Acta Mol Basis Dis ; 1864(1): 69-78, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28986308

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD.


Asunto(s)
Citoprotección/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Flavonoides/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Animales , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Hígado Graso/patología , Hígado Graso/prevención & control , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL
18.
Mar Drugs ; 16(10)2018 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-30309000

RESUMEN

To sustainably produce marine fish with a high lipid quality rich in omega-3 fatty acids, alternative sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are being identified. Moreover, the use of bioactive compounds that would stimulate the in vivo fatty acid synthesis, such as resveratrol (RV), would reduce the dependence on fish oil in aquafeeds. Gilthead sea bream (Sparus aurata) were fed four experimental diets combining two fish oil levels (6% dry matter (DM); 2% DM) with or without 0.15% DM resveratrol supplementation (F6, F2, F6 + RV, F2 + RV) for two months. Additionally, the fish were challenged either at 19 °C or 23 °C. A higher water temperature promoted their feed intake and growth, resulting in an increased crude lipid content irrespective of dietary treatment. The fatty acid composition of different tissues was significantly affected by the holding temperature and dietary fish oil level. The dietary RV significantly affected the hepatic EPA and DHA content of fish held at 19 °C. The observed effect of RV may be partly explained by alterations of the mRNA steady-state levels of ∆6-desaturase and ß-oxidation-related genes. Besides the relevant results concerning RV-mediated regulation of fatty acid synthesis in marine fish, further studies need to be conducted to clarify the potential value of RV to enhance fillet lipid quality.


Asunto(s)
Ácidos Grasos/genética , Ácidos Grasos/metabolismo , Aceites de Pescado/farmacología , Expresión Génica/efectos de los fármacos , Resveratrol/farmacología , Dorada/metabolismo , Alimentación Animal , Animales , Dieta/métodos , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos Omega-3/metabolismo , Expresión Génica/genética , Dorada/genética , Temperatura
19.
Int J Mol Sci ; 19(3)2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29495642

RESUMEN

Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.


Asunto(s)
Antocianinas/química , Antocianinas/farmacología , Biomarcadores , Dieta , Metabolismo Energético/efectos de los fármacos , Alimentos , Taninos Hidrolizables/química , Taninos Hidrolizables/farmacología , Miocardio/metabolismo , Antocianinas/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Fenómenos Fisiológicos Cardiovasculares/efectos de los fármacos , Sistema Cardiovascular/efectos de los fármacos , Suplementos Dietéticos , Humanos , Taninos Hidrolizables/efectos adversos , Factores de Riesgo
20.
Molecules ; 23(4)2018 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-29642422

RESUMEN

Red wine polyphenols are known for their implications for human health protection, although they suffer from high instability. For this reason, a red wine powder was prepared by freeze-drying encapsulation in maltodextrin/arabic gum matrix, and its composition was determined by means of high-performance liquid chromatography coupled quadrupole time-of-flight mass spectrometry (HPLC-MS-QTOF). More than thirty polyphenols, including anthocyanins, flavanols, flavonols, phenolic acids and stilbenoids, were identified. Some of the main quantified polyphenols were: malvidin-3-O-glucoside, malvidin 3-O-(6″-acetyl-glucose), petunidin-3-O-glucoside, quercetin-3-O-glucuronide, syringenin-3-O-glucoside, epicatechin, gallic acid and syringic acid. The biological activity of this de-alcoholized and encapsulated red wine on human neuroblastoma SH-SY5Y cells was studied. The results showed that the encapsulated red wine powder has active redox properties, as verified by performing reactive oxygen species (ROS) analysis utilizing a neuronal model. This could help explain its action against the neurotoxicity induced by 6-hydroxydopamine (6-OHDA).


Asunto(s)
Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Polifenoles/farmacología , Vino/análisis , Cápsulas , Línea Celular , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Goma Arábiga/química , Humanos , Espectrometría de Masas , Modelos Biológicos , Neuronas/citología , Neuronas/metabolismo , Fármacos Neuroprotectores/química , Oxidopamina/efectos adversos , Polifenoles/química , Polisacáridos/química , Polvos , Especies Reactivas de Oxígeno/metabolismo
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