المؤلفون: Irene García Toledo, Juan Miguel Godoy Corchuelo, Zeinab Ali, Jesús Jimenez-Rodriguez, Irene Jimenez-Coca, Anna Fernández-Bernal, Mariona Jové, Èlia Obis, Jorge Matias-Guiu, Thommas Cunningham, Manuel Portero-Otin, Reinald Pamplona, Estela Area-Gomez, Silvia Corrochano

المصدر: IBRO Neuroscience Reports, Vol 15, Iss , Pp S409- (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2667242123008436Test; https://doaj.org/toc/2667-2421Test

الوصول الحر: https://doaj.org/article/f70be57aa2d54e7bbf8ffee89f5dfa42Test

المؤلفون: Manuel Portero-Otin, M. Pia de la Maza, Jaime Uribarri

المصدر: Cells, Vol 12, Iss 13, p 1684 (2023)

مصطلحات موضوعية: insulin resistance, glycation, oxidative stress, inflammation, ultraprocessed foods, Cytology, QH573-671

الوصف: Insulin resistance (IR) is commonly observed during aging and is at the root of many of the chronic nontransmissible diseases experienced as people grow older. Many factors may play a role in causing IR, but diet is undoubtedly an important one. Whether it is total caloric intake or specific components of the diet, the factors responsible remain to be confirmed. Of the many dietary influences that may play a role in aging-related decreased insulin sensitivity, advanced glycation end products (AGEs) appear particularly important. Herein, we have reviewed in detail in vitro, animal, and human evidence linking dietary AGEs contributing to the bodily burden of AGEs with the development of IR. We conclude that numerous small clinical trials assessing the effect of dietary AGE intake in combination with strong evidence in many animal studies strongly suggest that reducing dietary AGE intake is associated with improved IR in a variety of disease conditions. Reducing AGE content of common foods by simple changes in culinary techniques is a feasible, safe, and easily applicable intervention in both health and disease. Large-scale clinical trials are still needed to provide broader evidence for the deleterious role of dietary AGEs in chronic disease.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4409/12/13/1684Test; https://doaj.org/toc/2073-4409Test

الوصول الحر: https://doaj.org/article/3317616a883647d19156ba057ceac0a5Test

المؤلفون: Mariona Jové, Natàlia Mota-Martorell, Èlia Obis, Joaquim Sol, Meritxell Martín-Garí, Isidre Ferrer, Manuel Portero-Otin, Reinald Pamplona

المصدر: Antioxidants, Vol 12, Iss 2, p 293 (2023)

مصطلحات موضوعية: antioxidants, lipidomics, lipid oxidation, human brain, neurodegeneration, plasmalogens, Therapeutics. Pharmacology, RM1-950

الوصف: One of the richest tissues in lipid content and diversity of the human body is the brain. The human brain is constitutively highly vulnerable to oxidative stress. This oxidative stress is a determinant in brain aging, as well as in the onset and progression of sporadic (late-onset) Alzheimer’s disease (sAD). Glycerophospholipids are the main lipid category widely distributed in neural cell membranes, with a very significant presence for the ether lipid subclass. Ether lipids have played a key role in the evolution of the human brain compositional specificity and functionality. Ether lipids determine the neural membrane structural and functional properties, membrane trafficking, cell signaling and antioxidant defense mechanisms. Here, we explore the idea that ether lipids actively participate in the pathogenesis of sAD. Firstly, we evaluate the quantitative relevance of ether lipids in the human brain composition, as well as their role in the human brain evolution. Then, we analyze the implications of ether lipids in neural cell physiology, highlighting their inherent antioxidant properties. Finally, we discuss changes in ether lipid content associated with sAD and their physiopathological implications, and propose a mechanism that, as a vicious cycle, explains the potential significance of ether lipids in sAD.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2076-3921/12/2/293Test; https://doaj.org/toc/2076-3921Test

الوصول الحر: https://doaj.org/article/a383516e892f45008dfc4fed86ba6b68Test

المؤلفون: María Arnoriaga-Rodríguez, Jordi Mayneris-Perxachs, Aurelijus Burokas, Vicente Pérez-Brocal, Andrés Moya, Manuel Portero-Otin, Wifredo Ricart, Rafael Maldonado, José-Manuel Fernández-Real

المصدر: Microbiome, Vol 8, Iss 1, Pp 1-10 (2020)

مصطلحات موضوعية: Microbiome, Bacterial gene function, Body weight regulation, Obesity, Microbial ecology, QR100-130

الوصف: Abstract Background The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans. Results Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10−2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor’s body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10−7), Rikenellaceae (r = 0.702, p = 3.9 × 10−4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = − 0.445, p = 0.038) and Prevotellaceae RA (r = − 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice’ weight gain and positively with gut bacterial ClpB-like gene function. Conclusions In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice. Video Abstract

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s40168-020-00837-6Test; https://doaj.org/toc/2049-2618Test

الوصول الحر: https://doaj.org/article/9743bb5719b149bea9b8999d1331a269Test

المؤلفون: Luis Servià, Mariona Jové, Joaquim Sol, Reinald Pamplona, Mariona Badia, Neus Montserrat, Manuel Portero-Otin, Javier Trujillano

المصدر: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, Vol 27, Iss 1, Pp 1-10 (2019)

مصطلحات موضوعية: Metabolome, Mortality, Traumatic brain injury, Biomarker, Multiple traumatism, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9

الوصف: Abstract Background We wanted to define metabolomic patterns in plasma to predict a negative outcome in severe trauma patients. Methods A prospective pilot study was designed to evaluate plasma metabolomic patterns, established by liquid chromatography coupled to mass spectrometry, in patients allocated to an intensive care unit (in the University Hospital Arnau de Vilanova, Lleida, Spain) in the first hours after a severe trauma (n = 48). Univariate and multivariate statistics were employed to establish potential predictors of mortality. Results Plasma of patients non surviving to trauma (n = 5) exhibited a discriminating metabolomic pattern, involving basically metabolites belonging to fatty acid and catecholamine synthesis as well as tryptophan degradation pathways. Thus, concentration of several metabolites exhibited an area under the receiver operating curve (ROC) higher than 0.84, including 3-indolelactic acid, hydroxyisovaleric acid, phenylethanolamine, cortisol, epinephrine and myristic acid. Multivariate binary regression logistic revealed that patients with higher myristic acid concentrations had a non-survival odds ratio of 2.1 (CI 95% 1.1–3.9). Conclusions Specific fatty acids, catecholamine synthesis and tryptophan degradation pathways could be implicated in a negative outcome after trauma. The metabolomic study of severe trauma patients could be helpful for biomarker proposal.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13049-019-0631-5Test; https://doaj.org/toc/1757-7241Test

الوصول الحر: https://doaj.org/article/de4d873658f34ec2b4d6f39e7332a4f0Test

المؤلفون: José María Moreno-Navarrete, Laura Liñares-Pose, Mònica Sabater, Eva Rial-Pensado, Ferran Comas, Mariona Jové, Jèssica Latorre, Francisco Ortega, Wifredo Ricart, Manuel Portero-Otin, Miguel López, José Manuel Fernández-Real

المصدر: Cellular Physiology and Biochemistry, Vol 51, Iss 1, Pp 142-153 (2018)

مصطلحات موضوعية: Thyroid-stimulating hormone, Euthyroidism, Hypothyroidism, Adipose tissue, Cellular senescence, Physiology, QP1-981, Biochemistry, QD415-436

الوصف: Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. Conclusion: These data point to a possible role of TSH in AT cellular senescence.

وصف الملف: electronic resource

العلاقة: https://www.karger.com/Article/FullText/495170Test; https://doaj.org/toc/1015-8987Test; https://doaj.org/toc/1421-9778Test

الوصول الحر: https://doaj.org/article/e95060e6d42949f0af24b6b840fffba1Test

المؤلفون: Francisco Purroy, Gloria Arque, Gerard Mauri, Cristina García-Vázquez, Mikel Vicente-Pascual, Cristina Pereira, Daniel Vazquez-Justes, Coral Torres-Querol, Ana Vena, Sònia Abilleira, Pere Cardona, Carles Forné, Xavier Jiménez-Fàbrega, Jorge Pagola, Manuel Portero-Otin, Ana Rodríguez-Campello, Àlex Rovira, Joan Martí-Fàbregas

المصدر: Frontiers in Neurology, Vol 11 (2020)

مصطلحات موضوعية: ischemic stroke, remote ischemic perconditioning (rPerC), neuroprotection, infarct size (IS), metabolomics (OMICS), Neurology. Diseases of the nervous system, RC346-429

الوصف: Rationale: Remote ischemic perconditioning during cerebral ischemia (RIPerC) refers to the application of brief episodes of transient limb ischemia commonly to a limb, it represents a new safe, simple and low-cost paradigm in neuroprotection.Aim and/or Hypothesis: To evaluate the effects of RIPerC on acute ischemic stroke (AIS) patients, applied in the ambulance, to improve functional outcomes compared with standard of care.Sample Size Estimates: A sample size of 286 patients in each arm achieves 80% power to detect treatment differences of 14% in the outcome, using a two-sided binomial test at significance level of 0.05, assuming that 40% of the control patients will experience good outcome and an initial misdiagnosis rate of 29%.Methods and Design: We aim to conduct a multicentre study of pre-hospital RIPerC application in AIS patients. A total of 572 adult patients diagnosed of suspected clinical stroke within 8 h of symptom onset and clinical deficit >0 according to prehospital rapid arterial occlusion evaluation (RACE) scale score will be randomized, in blocks of size 4, to RIPerC or sham. Patients will be stratified by RACE score scale. RIPerC will be started in the ambulance before hospital admission and continued in the hospital if necessary. It will consist of five cycles of electronic tourniquet inflation and deflation (5 min each). The cuff pressure for RIPerC will be 200 mmHg during inflation. Sham will only simulate vibration of the device.Study Outcome(s): The primary outcome will be the difference in the proportion of patients with good outcomes as defined by a mRS score of 2 or less at 90 days. Secondary outcomes to be monitored will include early neurological improvement rate, treatment related serious adverse event rates, size of the infarct volume, symptomatic intracranial hemorrhage, metabolomic and lipidomic response to RIPerC and Neuropsychological evaluation at 90 days.Discussion: Neuroprotective therapies could not only increase the benefits of available reperfusion therapies among AIS patients but also provide an option for patients who are not candidates for these treatments. REMOTE-CAT will investigate the clinical benefit of RIC as a new neuroprotective strategy in AIS.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03375762.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fneur.2020.569696/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/364aefab01c14f929d764e40e390b00bTest

المؤلفون: Xiaoyan Yin, Christine M. Willinger, Joshua Keefe, Jun Liu, Antonio Fernández-Ortiz, Borja Ibáñez, José Peñalvo, Aram Adourian, George Chen, Dolores Corella, Reinald Pamplona, Manuel Portero-Otin, Mariona Jove, Paul Courchesne, Cornelia M. van Duijn, Valentín Fuster, José M. Ordovás, Ayşe Demirkan, Martin G. Larson, Daniel Levy

المصدر: EBioMedicine, Vol 51, Iss , Pp - (2020)

مصطلحات موضوعية: Medicine, Medicine (General), R5-920

الوصف: Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were associated with obesity and eight with dysglycemia in the FHS. Of 32 lipids that were available for replication for obesity and six for dyslipidemia, 28 (88%) replicated for obesity and five (83%) for dysglycemia. Four lipids were associated with longitudinal changes in body mass index and four were associated with changes in fasting blood glucose in the FHS. Conclusions: We identified and replicated several novel lipid biomarkers of key metabolic traits. The lipid moieties identified in this study are involved in biological pathways of metabolic risk and can be explored for prognostic and therapeutic utility. Keywords: Metabolic risk, Metabolic syndrome, Cardiovascular disease, Dysglycemia, Dyslipidemia, Biomarker

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396419307169Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/98fd106f80924dd290aeb5b37959b3bbTest

المؤلفون: Hugo Gonzalo, Lara Nogueras, Anna Gil-Sánchez, José Vicente Hervás, Petya Valcheva, Cristina González-Mingot, Meritxell Martin-Gari, Marc Canudes, Silvia Peralta, Maria José Solana, Reinald Pamplona, Manuel Portero-Otin, Jordi Boada, Jose Carlos Enrique Serrano, Luis Brieva

المصدر: Frontiers in Neuroscience, Vol 13 (2019)

مصطلحات موضوعية: multiple sclerosis, oxidative stress, mitochondria, superoxide anion, mitochondrial complexes, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Literature suggests that oxidative stress (OS) may be involved in the pathogenesis of multiple sclerosis (MS), in which the immune system is known to play a key role. However, to date, the OS in peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted [n = 58: 34 MS and 24 healthy subjects (control group)]. We have measured superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041, respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative protein content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044, and p = 0.051, respectively), which was maintained for complexes I, III, and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend toward increased plasma lactate concentration was detected [8.04 mg lactate/dL (5.25, 9.49) in the control group, 11.36 mg lactate/dL (5.41, 14.81) in MS patients] that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for the first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fnins.2019.00938/fullTest; https://doaj.org/toc/1662-453XTest

الوصول الحر: https://doaj.org/article/87a481ffa83347c588d29ab65f5304a2Test

المؤلفون: Chiara Rossi, Anna Fernàndez, Pascual Torres, Omar Ramirez-Nuñez, Ana Belén Granado-Serrano, Laia Fontdevila, Mònica Povedano, Reinald Pamplona, Isidro Ferrer, Manuel Portero-Otin

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 16, p 8853 (2021)

مصطلحات موضوعية: TDP-43, Jun, REST, ERK, mitochondria, cell stress, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/22/16/8853Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/b90f9e6eebfa4e61bed124b6f1e5717cTest