Ex vivo models for the noninvasive study of myelin-related diseases represent an essential tool to understand the mechanisms of diseases and develop therapies against them. Herein, we assessed the potential of multimodal imaging traceable... more
Ex vivo models for the noninvasive study of myelin-related diseases represent an essential tool to understand the mechanisms of diseases and develop therapies against them. Herein, we assessed the potential of multimodal imaging traceable myelin-targeting liposomes to quantify myelin in organotypic cultures. Methods: MRI testing was used to image mouse cerebellar tissue sections and organotypic cultures. Demyelination was induced by lysolecithin treatment. Myelin-targeting liposomes were synthetized and characterized, and their capacity to quantify myelin was tested by fluorescence imaging. Results: Imaging of freshly excised tissue sections ranging from 300 µm to 1 mm in thickness was achieved with good contrast between white (WM) and gray matter (GM) using T2w MRI. The typical loss of stiffness, WM structures, and thickness of organotypic cultures required the use of diffusion-weighted methods. Designed myelin-targeting liposomes allowed for semiquantitative detection by fluoresce...
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Multiple sclerosis (MS) is a complex and demyelinating disease of the central nervous system. One of the challenges of the post-genome-wide association studies (GWAS) era is to understand the molecular basis of statistical associations to... more
Multiple sclerosis (MS) is a complex and demyelinating disease of the central nervous system. One of the challenges of the post-genome-wide association studies (GWAS) era is to understand the molecular basis of statistical associations to reveal gene networks and potential therapeutic targets. The L3MBTL3 locus has been associated with MS risk by GWAS. To identify the causal variant of the locus, we performed fine mapping in a cohort of 3440 MS patients and 1688 healthy controls. The variant that best explained the association was rs6569648 (P = 4.13E-10, odds ratio = 0.71, 95% confidence interval (CI) = 0.64–0.79), which tagged rs7740107, located in intron 7 of L3MBTL3. The rs7740107 (A/T) variant has been reported to be the best expression and splice quantitative trait locus (eQTL and sQTL) of the region in up to 35 human genotype-tissue expression (GTEx) tissues. By sequencing RNA from blood of 17 MS patients and quantification by digital qPCR, we determined that this eQTL/sQTL o...
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Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore,... more
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (...
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COVID-19 pandemic has put the protocols and the capacity of our Hospitals to the test. The management of severe patients admitted to the Intensive Care Units has been a challenge for all health systems. To assist in this challenge,... more
COVID-19 pandemic has put the protocols and the capacity of our Hospitals to the test. The management of severe patients admitted to the Intensive Care Units has been a challenge for all health systems. To assist in this challenge, various models have been proposed to predict mortality and severity, however, there is no clear consensus for their use. In this work, we took advantage of data obtained from routine blood tests performed on all individuals on the first day of hospitalization. The test has been done by standardized cost-effective technique available in all the hospitals. We have analyzed the results of 1082 patients with COVID19 and using artificial intelligence we have generated a predictive model based on data from the first days of admission that predicts the risk of developing severe disease with an AUC = 0.78. Our results show the importance of immature granulocytes and their ratio with Lymphocytes in the disease and present an algorithm based on 5 parameters to iden...
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Morphine binding to opioid receptors, mainly to μ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed... more
Morphine binding to opioid receptors, mainly to μ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4R/MOR interactions. To shed light on the molecular mechanisms implicated, we evaluated the transcriptome alterations following acute administration of morphine and/or PD168,077 (D4R agonist) using whole-genome microarrays and a linear regression-based differential expression analysis. The results highlight the development of a unique transcriptional signature following the co-administration of both drugs that reflects a countereffect of PD168,077 on morphine effects. A KEGG...
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Cognitive impairment and the presence of depressive symptoms, which are commonly found in patients with multiple sclerosis, affect the patients' quality of life. AIM. To describe the quality of life, cognitive compromise and levels of... more
Cognitive impairment and the presence of depressive symptoms, which are commonly found in patients with multiple sclerosis, affect the patients' quality of life. AIM. To describe the quality of life, cognitive compromise and levels of depression, in relation to other clinical variables, in patients with multiple sclerosis in the province of Gipuzkoa. A total of 114 patients were submitted to neuropsychological evaluation. The MSQoL-54 and Beck's Depression Inventory were applied to evaluate the quality of life and levels of depression. Three main analyses were performed: a comparison of cognitive performance among subtypes, an analysis of the correlation among clinical, neuro-psychological and quality of life variables, and an analysis of the effects of gender on cognitive performance. A neuropsychological pattern is found in multiple sclerosis that is characterised by a slowing of the processing of information and attentional difficulties. Quality of life is related with de...
Research Interests: Multiple sclerosis, Depression, Quality of life, Speech Disorders, Medicine, and 15 moreSpain, Humans, Female, Male, Depressive Disorder, Aged, Middle Aged, Adult, Sex Factors, Intelligence tests, Memory Disorders, Cognition disorders, Socioeconomic Factors, Severity of Illness Index, and Neuropsychological Tests
Aim: To evaluate whether circulating microparticles (MPs) derived from three cell subtypes (platelets, total leukocytes or monocytes) obtained from multiple sclerosis (MS) patients were modulated depending on the clinical status and to... more
Aim: To evaluate whether circulating microparticles (MPs) derived from three cell subtypes (platelets, total leukocytes or monocytes) obtained from multiple sclerosis (MS) patients were modulated depending on the clinical status and to investigate the effect of treatments on MP levels. Patients & methods: The MP counts were assessed with flow cytometry. Results: The platelet-derived MP level was higher in untreated MS patients than controls. Relapsing–remitting patients showed the highest levels in the three subtypes of MP while secondary progressive patients presented similar levels to those of healthy controls. Treatments had significant effects increasing the three subtypes of MP counts. Conclusion: We suggest that MPs play a role in MS pathogenesis, reflecting disease status with an increment of their shedding during inflammatory periods and turning to baseline during chronic progressive degeneration.
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Summary Rat serum or plasma creatine kinase (CK) activity is widely used to evaluate myopathic processes, to test the myotoxicity of different drugs, or to analyse the benefits of emerging gene therapies in some neuromuscular disorders.... more
Summary Rat serum or plasma creatine kinase (CK) activity is widely used to evaluate myopathic processes, to test the myotoxicity of different drugs, or to analyse the benefits of emerging gene therapies in some neuromuscular disorders. However, great variability is found in this determination. The aim of this study has been to control some factors of variation in order to reduce variability and increase the reproducibility of analytical data. 8–10-week-old Wistar-Han rats were used. The study consisted of four sequential phases. Phase I aimed to analyse the effect of ether and isoflurane as anaesthetic drugs. The objective of Phase II was to evaluate bleeding rats via retro-orbital sinus vs. tail vein. Phases III and IV were designed as two separate, repeated measure experiments on two factors: habituation to laboratory handling procedures in Phase III and gender in Phase IV. The repeated factor was the storage temperature of blood sample prior to centrifugation. Ether did not sign...
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Research Interests: Genetics, Computational Biology, Biology, Humans, Genetic Testing, and 15 moreHaplotypes, Female, Genotype, Adult, Genetic Association, Genetic Predisposition, Case Control Study, Allele, Genetic Markers, Haplotype, Extracellular Matrix Proteins, Case Control Studies, DNA mutational analysis, Gene frequency, and Genetic predisposition to disease
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letter (FAS) and semantic (fruits, animals) verbal fluency tests, Digit Span Test, Stroop Color-Word Interference Test, Boston Naming Test, Rule shift cards of BADS, DEX and VOSP. The genetic study consisted of three SNPs in PICALM... more
letter (FAS) and semantic (fruits, animals) verbal fluency tests, Digit Span Test, Stroop Color-Word Interference Test, Boston Naming Test, Rule shift cards of BADS, DEX and VOSP. The genetic study consisted of three SNPs in PICALM (rs3851179), CLU (rs11136000) and CR1 (rs3818361) gene. Genotypingwas performed through Taqman 5 ’ nuclease Assays.Results: Several associations were found between these genes and cognitive tasks. In the PICALM analysis, those carrying the GG combination (vs AA+AG) performed worse on FAS-F (GG: 7.664.6; AA+AG: 9.364; p1⁄40.027) and FAS-A (GG: 7 64.5; AA+AG: 8.664.3; p1⁄40.05). For the CLU polymorphism, patients who carried the protective TT genotype (vs CC+CT) showed a better performance on TMT-B time (TT: 168.6691; CC+CT: 244.66112.7; p1⁄40.023), on FAS-A (TT: 1165.1; CC+CT: 7.564.3; p1⁄40.012) and on backwards digit span (TT: 5.361.8; CC+CT: 3.961.3; p1⁄40.021). Finally, for the CR1 gene, MCI subjects who carried the TT genotype (VS CC+CT) got lower scores in the semantic fluency task, both in fruits (TT: 764.2; CC+CT: 10.463.1; p1⁄40.029) and animals (TT: 11.560.6; CC+CT: 13.164.3; p1⁄40.023) sections. Conclusions: There is a gene-cognitive endophenotype association between PICALM, CLU and CR1 genes in patients with MCI, being PICAL and CLU associated with prefrontal dysfunction (executive functioning) and CR1 with frontotemporal lobe dysfunction (executive functioning and semantic memory).
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Multiple Sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression... more
Multiple Sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice.Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a "sponge system" and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in serum or other biofluids makes them seemingly good candidates as biomarkers.Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypot...
Research Interests: MicroRNA, Biomarkers, Biology, Medicine, Gene expression, and 15 moreBiological Sciences, Humans, Female, Male, Human Molecular Genetics, Alternative splicing, Gene, Immune system, Adult, Alternative Splicing, circular RNA, Gene Expression Regulation, Gene expression profiling, Case Control Studies, and Medical and Health Sciences
The improvement of life quality and medical advances has resulted in increased life expectancy. Despite this, health status commonly worsens in the last years of life. Frailty is an intermediate and reversible state that often precedes... more
The improvement of life quality and medical advances has resulted in increased life expectancy. Despite this, health status commonly worsens in the last years of life. Frailty is an intermediate and reversible state that often precedes dependency and therefore, its identification may be essential to prevent dependency. However, there is no consensus on the best tools to identify frailty. In this sense, diverse molecules have been proposed as potential biomarkers. Some investigations pointed to an increased chronic inflammation or inflammaging with frailty, while others did not report such differences. In this work, we evaluated the circulating concentration of the inflammaging markers in adults and older adults (aged over 70 years) by ELISA and Luminex techniques. The Barthel Index was applied for the evaluation of dependency and Timed up-and-go, Gait Speed, Short Physical Performance Battery, Tilburg Frailty Indicator and Gerontopole Frailty Screening Tool were used for the identif...
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Background Extracellular vesicles (EVs) are released by almost all cell types and are implicated in a number of biological and pathological processes including autoimmune diseases such as multiple sclerosis (MS). Differences in the number... more
Background Extracellular vesicles (EVs) are released by almost all cell types and are implicated in a number of biological and pathological processes including autoimmune diseases such as multiple sclerosis (MS). Differences in the number and cargo of plasma derived EVs have been described in MS. In this work, we attempt to characterise the EV RNA cargo of MS patients with particular attention to a recently discovered non coding RNA type, circular RNAs (circRNAs), which have been shown to play important roles in physiology and disease and hold a great biomarker potential. Methods Plasma was collected from 20 MS patients and 8 healthy controls (HC) and total RNA was isolated from plasma-derived extracellular vesicles isolated by differential centrifugation. Samples were pooled in disease status, sex and age paired groups and RNA-Sequenced with Illumina HiSeq X Ten after rRNA depletion. CircRNAs were detected by both find_circ and CIRI2 and their quantification was based on BSJ-spanni...
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Extracellular vesicles (EVs) are important players for intercellular communication. EVs are secreted by almost all cell types; they can transfer information between nearby or distant cells, and they are highly abundant in body fluids. In... more
Extracellular vesicles (EVs) are important players for intercellular communication. EVs are secreted by almost all cell types; they can transfer information between nearby or distant cells, and they are highly abundant in body fluids. In this review, we describe the general characteristics of EVs, as well as isolation and characterization approaches. Then, we focus on one of the most relevant sources of EVs: the blood. Indeed, apart from EVs secreted by blood cells, EVs of diverse origins travel in the bloodstream. We present the numerous types of EVs that have been found in circulation. Besides, the implications of blood-derived EVs in both physiological and pathological processes are summarized, highlighting their potential as biomarkers for the diagnosis, treatment monitoring, and prognosis of several diseases, and also as indicators of physiological modifications. Finally, the applications of EVs introduced in the circulatory system are discussed. We describe the use of EVs from...
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The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and... more
The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and the environment. Diet could be assumed to be one of the most prominent factors influencing the microbiota composition. Nevertheless, and in spite of numerous strategies proposed to modulate the human microbiota through dietary means, guidelines to achieve this goal have yet to be established. This review assesses the correlation between social and dietary changes over the course of human evolution and the adaptation of the human microbiota to those changes. In addition, it discusses the main dietary strategies for modulating the microbiota and the difficulties of putting them properly into practice.
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Genome-wide association studies and meta-analysis have contributed to the identification of more than 200 loci associated with multiple sclerosis (MS). However, a proportion of MS heritability remains unknown. We aimed to uncover new... more
Genome-wide association studies and meta-analysis have contributed to the identification of more than 200 loci associated with multiple sclerosis (MS). However, a proportion of MS heritability remains unknown. We aimed to uncover new genetic variants associated with MS and determine their functional effects. For this, we resequenced the exons and regulatory sequences of 14 MS risk genes in a cohort of MS patients and healthy individuals (n = 1070) and attempted to validate a selection of signals through genotyping in an independent cohort (n = 5138). We identified three new MS-associated variants at C-X-C motif chemokine receptor 5 (CXCR5), Ts translation elongation factor, mitochondrial (TSFM) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). Rs10892307 resulted in a new signal at the CXCR5 region that explains one of the associations with MS within the locus. This polymorphism and three others in high linkage disequilibrium mapped within regulatory regions. Of them, rs...
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Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination... more
Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use ...
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The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding... more
The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10−4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ul...
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Research Interests: Genetics, RNA, Computational Biology, Biology, Medicine, and 3 moreJournal Article, Genome, and circular RNA
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Extracellular vesicles (EVs) are membrane-bound particles involved in intercellular communication. They carry proteins, lipids, and nucleotides such as microRNAs (miRNAs) from the secreting cell that can modulate target cells. We and... more
Extracellular vesicles (EVs) are membrane-bound particles involved in intercellular communication. They carry proteins, lipids, and nucleotides such as microRNAs (miRNAs) from the secreting cell that can modulate target cells. We and others have previously described the presence of EVs in peripheral blood of multiple sclerosis (MS) patients and postulated them as novel biomarkers. However, their immune function in MS pathogenesis and the effect during the onset of new immunomodulatory therapies on EVs remain elusive. Here, we isolated plasma EVs from fingolimod-treated MS patients in order to assess whether EVs are affected by the first dose of the treatment. We quantified EVs, analyzed their miRNA cargo, and checked their immune regulatory function. Results showed an elevated EV concentration with a dramatic change in their miRNA cargo 5 h after the first dose of fingolimod. Besides, EVs obtained prior to fingolimod treatment showed an increased immune regulatory activity compared ...
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Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes... more
Multiple sclerosis (MS) is a common inflammatory and degenerative disease that causes neurological disability. It affects young adults and its prevalence is higher in women. The most common form is manifested as a series of acute episodes of neurological disability (relapses) followed by a recovery phase (remission). Recently, non-coding RNAs have emerged as new players in transcriptome regulation, and in turn, they could have a significant role in MS pathogenesis. In this context, our aim was to investigate the involvement of microRNAs and snoRNAs in the relapse-remission dynamics of MS in peripheral blood leucocytes, to shed light on the molecular and regulatory mechanisms that underlie this complex process. With this approach, we found that a subset of small non-coding RNAs (sncRNA) is altered in relapse and remission, revealing unexpected opposite changes that are sex dependent. Furthermore, we found that a relapse-related miRNA signature regulated general metabolism processes i...
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The gold standard for cancer diagnosis remains the histological examination of affected tissue, obtained either by surgical excision, or radiologically guided biopsy. Such procedures however are expensive, not without risk to the patient,... more
The gold standard for cancer diagnosis remains the histological examination of affected tissue, obtained either by surgical excision, or radiologically guided biopsy. Such procedures however are expensive, not without risk to the patient, and require consistent evaluation by expert pathologists. Consequently, the search for non‐invasive tools for the diagnosis and management of cancer has led to great interest in the field of circulating nucleic acids in plasma and serum. An additional benefit of blood‐based testing is the ability to carry out screening and repeat sampling on patients undergoing therapy, or monitoring disease progression allowing for the development of a personalized approach to cancer patient management. Despite having been discovered over 60 years ago, the clear clinical potential of circulating nucleic acids, with the notable exception of prenatal diagnostic testing, has yet to translate into the clinic. The recent discovery of non‐coding (nc) RNA (in particular ...
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The research in extracellular vesicles (EVs) has been rising during the last decade. However, there is no clear consensus on the most accurate protocol to isolate and analyze them. Besides, most of the current protocols are difficult to... more
The research in extracellular vesicles (EVs) has been rising during the last decade. However, there is no clear consensus on the most accurate protocol to isolate and analyze them. Besides, most of the current protocols are difficult to implement in a hospital setting due to being very time-consuming or to requirements of specific infrastructure. Thus, our aim is to compare five different protocols (comprising two different medium-speed differential centrifugation protocols; commercially polymeric precipitation - exoquick - acid precipitation; and ultracentrifugation) for blood and urine samples to determine the most suitable one for the isolation of EVs. Nanoparticle tracking analysis, flow cytometry, western blot (WB), electronic microscopy, and spectrophotometry were used to characterize basic aspects of EVs such as concentration, size distribution, cell-origin and transmembrane markers, and RNA concentration. The highest EV concentrations were obtained using the exoquick protoco...
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Research Interests: Genetics, Genomics, Biology, Infectious Diseases, B cells, and 15 moreBiological Sciences, Clinical immunology, Humans, Autoimmune diseases, Female, Gene networks, Gene, Gene Regulatory Networks, Aged, Adult, Disease Progression, B Lymphocytes, Gene expression profiling, gender specific, and Immune cells
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Research Interests: Genetics, Immunology, Biology, DNA replication, Disease susceptibility, and 15 moreHumans, Female, Central Nervous System, Inflammatory disease, Adult, Genetic Association, Allele, Genetic Markers, Confidence Interval, Case Control Studies, Cohort Studies, alleles, Human leucocyte antigen, Gene frequency, and Human leukocyte antigen
Research Interests: Genetics, Immunology, Multiple sclerosis, Polymorphism, Biology, and 15 moreRheumatoid Arthritis, Medicine, Humans, Autoimmune Disease, Autoimmune diseases, Disease, Proteins, Gene, Genes, Kinesin, Odds ratio, European Continental Ancestry Group, Risk Factors, Confidence Interval, and Case Control Studies
The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal... more
The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in peripheral blood mononuclear cells (PBMCs) from patients with lipid-specific oligoclonal IgM band characterization. We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (I...
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ABO blood groups have recently been related to COVID19 infection. In the present work, we performed this analysis using data from 412 COVID19 patients and 17796 blood donors, all of them from Gipuzkoa, a region in Northern Spain. The... more
ABO blood groups have recently been related to COVID19 infection. In the present work, we performed this analysis using data from 412 COVID19 patients and 17796 blood donors, all of them from Gipuzkoa, a region in Northern Spain. The results obtained confirmed this relation, in addition to showing a clear importance of group O as a protective factor in COVID19 disease, with an OR = 0.59 (CI95% 0.481–0.7177, p<0.0001) while A, B and AB are risk factors. ABO blood groups are slightly differently distributed in the populations and therefore these results should be replicated in the specific areas with a proper control population.
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Multiple sclerosis (MS) is a chronic and neurodegenerative disease of the central nervous system (CNS) characterized by the immune mediated attack on axons and the subsequent demyelination. There is growing evidence that the gut... more
Multiple sclerosis (MS) is a chronic and neurodegenerative disease of the central nervous system (CNS) characterized by the immune mediated attack on axons and the subsequent demyelination. There is growing evidence that the gut microbiota of MS patients is altered; however, the connection between demyelination events and changes in the gut microbiota has not been determined. The objective of the current work was to characterize the microbial dysbiosis in two murine demyelinating models and to study the correlation between them. Concurrently, their suitability as predictors of microbial changes in MS patients was assessed. To this purpose, experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models were induced in C57BL/6 mice that were monitored for 4 and 9 weeks, respectively. Fecal samples were collected during disease progression. Motor skill performance was evaluated by EAE scale measurement in EAE mice and demyelination by magnetic resonance imaging (MRI) in CPZ ones. EAE and CPZ mice revealed drastic microbial changes according to disease progression, adding a new layer of complexity to the understanding of demyelination and remyelination processes. Besides, the reported microbial changes replicate most of the characteristics that define the potential dysbiosis in MS patients. The controlled environment and stable diet that animals have in research centers offer an exceptional scenario to modify animal's microbiota and provide opportunities to study host microbiota interplay with restrained conditions not achievable in human studies. Nevertheless the slight differences from murine model's and patient's microbiota should be considered in the design of studies aiming to modulate the microbiota.
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Frailty represents a state of vulnerability and increases the risk of negative health outcomes, which is becoming an important public health problem. Over recent years, multiple independent studies have attempted to identify biomarkers... more
Frailty represents a state of vulnerability and increases the risk of negative health outcomes, which is becoming an important public health problem. Over recent years, multiple independent studies have attempted to identify biomarkers that can predict, diagnose, and monitor frailty at the biological level. Among them, several promising candidates have been associated with frailty status including antioxidants and free radicals, and also inflammatory response biomarkers. In this review, we will summarize the more recent advances in this field. Moreover, the identification of scales and measurements to detect and quantify frailty in aged mice, as well as the generation of mouse models, have started to unravel the underlying biological and molecular mechanisms of frailty. We will discuss them here with an emphasis on murine models with overexpression of glucose-6-phosphate dehydrogenase and loss of function of superoxide dismutase and interleukin 10, which reveal that altered oxidative stress and inflammation pathways are involved in the physiopathology of frailty. In summary, we provide the current available evidence, from both human cohorts and experimental animal models, that highlights oxidative damage and inflammation as relevant biomarkers and drivers of frailty.