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BACKGROUND: It is broadly acknowledged that children with Developmental Language Disorder (DLD) show verb-related limitations. While most previous studies have focused on tense, the mastery of lexical aspect-particularly telicity-has not been the primary focus of much research. Lexical aspect refers to whether an action has a defined endpoint (telic verbs) or not (atelic verbs). OBJECTIVE: This study investigates the effect of telicity on verb recognition in Chilean children with DLD compared to their typically developing (TD) peers using the Event-Related Potential (ERP) technique. METHOD: The research design is a mixed factorial design with between-group factors of 2 (DLD/TD) and within-group factors of 2 (telic/atelic verbs) and 2 (coherent/incoherent sentences). The participants were 36 school-aged children (18 DLD, 18 TD) aged 7 to 7 years and 11 months. The task required subjects to listen to sentences that either matched or did not match an action in a video, with sentences including telic or atelic verbs. RESULTS: The study found notable differences between groups in how they processed verbs (N400 and post-N400 components) and direct objects (N400 and P600 components). CONCLUSIONS: Children with DLD struggled to differentiate telic and atelic verbs, potentially because they employed overgeneralization strategies consistent with the Event Structural Bootstrapping model.
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Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short-echo-time MRS data. In short-echo-time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long-echo-time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi-LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm-QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm-QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting.
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Algoritmos , Espectroscopía de Protones por Resonancia Magnética , Espectroscopía de Protones por Resonancia Magnética/métodos , Humanos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , ArtefactosRESUMEN
Animals adapt to the daily changes in their environmental conditions by means of genetically encoded circadian clocks. These clocks, found throughout the tree of life, regulate diverse biological functions, and allow periodical changes in physiology and behaviour. The molecular underpinnings of these clocks have been extensively studied across taxa, revealing a brain-based system that coordinates rhythmic activities through neuronal networks and signalling pathways. Entrainment, the alignment of internal rhythms with external cues or zeitgebers, is crucial for the adaptive value of these internal clocks. While the solar light-dark cycle is a primary zeitgeber for most animals, other relevant cues such as temperature, meal timing, predators, anxiety, fear, physical activity, and social interactions also play roles in entraining circadian clocks. The search of a detailed description of the circadian clocks is a goal for neurobiology and an area of growing societal interests. Moreover, as disruptions in circadian rhythms are implicated in various diseases, understanding the entrainment pathways contributes to developing interventions for improved wellbeing and health outcomes. This review focuses on socially relevant cues, examining their impact on animal physiology and behaviour, and explores the sensory pathways transmitting information to the central clock.
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Young children's linguistic and communicative abilities are foundational for their academic achievement and overall well-being. We present the positive outcomes of a brief tablet-based intervention aimed at teaching toddlers and preschoolers new word-object and letter-sound associations. We conducted two experiments, one involving toddlers ( ~ 24 months old, n = 101) and the other with preschoolers ( ~ 42 months old, n = 152). Using a pre-post equivalent group design, we measured the children's improvements in language and communication skills resulting from the intervention. Our results showed that the intervention benefited toddlers' verbal communication and preschoolers' speech comprehension. Additionally, it encouraged vocalizations in preschoolers and enhanced long-term memory for the associations taught in the study for all participants. In summary, our study demonstrates that the use of a ludic tablet-based intervention for teaching new vocabulary and pre-reading skills can improve young children's linguistic and communicative abilities, which are essential for future development.
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Until January 2023, Brazil recorded 37 million COVID-19 cases despite the decrease in mortality due to mass vaccination efforts against COVID-19. The infection continues to challenge researchers and health professionals with the persistent symptoms and onset manifestations after the acute phase of the disease, namely Post-Covid Condition (PCC). Being one of the countries with the highest infection rate, Brazil must prepare for a growing number of patients with chronic health consequences of COVID-19. Longitudinal studies that follow patients over extended periods are crucial in understanding the long-term impacts of COVID-19, including potential health consequences and the effects on quality of life. We describe the clinical profile of a cohort of COVID-19 patients infected during the first year of the pandemic in Brazil and a follow-up after two years to investigate the health impacts of SARS-CoV-2 infection. The first wave of SARS-CoV-2 infection in Brazil featured extensive drug misuse, notably the ineffective COVID kit comprised of ivermectin, antimalarials and azithromycin, and elevated in-hospital mortality. In the second phase of the study, Post-Covid Condition was reported by symptomatic COVID-19 subjects across different severity levels two years after infection. Long haulers are more likely to be women, previously hospitalized, and reported a range of symptoms from muscle pain to cognitive deficit. Our longitudinal study is essential to inform public health authorities to develop strategies and policies to control the spread of the virus and mitigate its impacts on society.
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COVID-19 , Síndrome Post Agudo de COVID-19 , Humanos , Femenino , Masculino , COVID-19/epidemiología , Brasil/epidemiología , Estudios de Seguimiento , Estudios Longitudinales , Calidad de Vida , SARS-CoV-2RESUMEN
Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals. Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction. Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction. Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.
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Chagas disease, African trypanosomiasis and Leishmaniasis are neglected parasitic diseases which affect millions of people worldwide. In a previous work, we report the antiprotozoal activity of the dichloromethane extract of Mikania periplocifolia Hook. & Arn. (Asteraceae). The aim of this work was to isolate and identify the bioactive compounds present in the extract. The fractionation of the dichloromethane extract has led to the isolation of the sesquiterpene lactone miscandenin and the flavonoid onopordin, together with the sesquiterpene lactones mikanolide, dihydromikanolide and deoxymikanolide, which have previously shown antiprotozoal activity. Miscandenin and onopordin were assayed in vitro against Trypanosoma cruzi, T. brucei and Leishmania braziliensis. Miscandenin was active against T. cruzi trypomastigotes and amastigotes with IC50 values of 9.1 and 7.7 µg/ml, respectively. This sesquiterpene lactone and the flavonoid onopordin showed activity against T. brucei trypomastigotes (IC50 = 0.16 and 0.37 µg/ml) and L. braziliensis promastigotes (IC50 = 0.6 and 1.2 µg/ml), respectively. The CC50 values on mammalian cells were 37.9 and 53.4 µg/ml for miscandenin and onopordin, respectively. Besides, the pharmacokinetic and physicochemical properties of miscandenin were assessed in silico, showing a good drug-likeness profile. Our results highlight this compound as a promising candidate for further preclinical studies in the search of new drugs for the treatment of trypanosomiasis and leishmaniasis.
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Antiprotozoarios , Asteraceae , Leishmaniasis , Mikania , Sesquiterpenos , Trypanosoma cruzi , Animales , Humanos , Asteraceae/química , Mikania/química , Cloruro de Metileno/uso terapéutico , Extractos Vegetales/química , Estructura Molecular , Antiprotozoarios/farmacología , Leishmaniasis/tratamiento farmacológico , Flavonoides/farmacología , Lactonas , MamíferosRESUMEN
Motivation for the study. There are few reports on intestinal parasites in children and domestic animals in urban areas in Argentina who live in homes with characteristics that favor the maintenance and transmission of parasites of zoonotic importance. Main findings. More than 50% of children and pets were parasitized, most of them with zoonotic pathogens. Implications. Our results showed the urgent need to improve sanitary control of children and animals, and to implement activities for the prevention of intestinal parasitosis in the homes analyzed.
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Parasitosis Intestinales , Parásitos , Niño , Animales , Humanos , Animales Domésticos , Argentina/epidemiología , Prevalencia , Heces/parasitología , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/veterinaria , Parasitosis Intestinales/parasitologíaRESUMEN
In this study, we present the results of a genome-wide scan for signatures of positive selection using data from four tribal groups (Kokana, Warli, Bhil, and Pawara) and two caste groups (Deshastha Brahmin and Kunbi Maratha) from West of the Maharashtra State In India, as well as two samples of South Asian ancestry from the 1KG project (Gujarati Indian from Houston, Texas and Indian Telugu from UK). We used an outlier approach based on different statistics, including PBS, xpEHH, iHS, CLR, Tajima's D, as well as two recently developed methods: Graph-aware Retrieval of Selective Sweeps (GRoSS) and Ascertained Sequentially Markovian Coalescent (ASMC). In order to minimize the risk of false positives, we selected regions that are outliers in all the samples included in the study using more than one method. We identified putative selection signals in 107 regions encompassing 434 genes. Many of the regions overlap with only one gene. The signals observed using microarray-based data are very consistent with our analyses using high-coverage sequencing data, as well as those identified with a novel coalescence-based method (ASMC). Importantly, at least 24 of these genomic regions have been identified in previous selection scans in South Asian populations or in other population groups. Our study highlights genomic regions that may have played a role in the adaptation of anatomically modern humans to novel environmental conditions after the out of Africa migration.
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Pueblo Asiatico , Selección Genética , Genética de Población , Genómica , Haplotipos , Humanos , India , Polimorfismo de Nucleótido Simple , TexasRESUMEN
Stem Cell based-therapy is an active area of research in regenerative medicine. Mesenchymal stem/stromal cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system, and secrete trophic factors to support the repair of damaged tissues. The use of MSCs for cell and regenerative purposes has garnered the attention of scientists and clinicians. However, one of the most important issues before use MSCs in clinical practice is to standardize a number of aspects related to the source of MSCs, culture conditions, pre-condition protocols before transplantation, administration route, doses, or treatment duration. In this chapter, we described two standard protocols to isolate MSCs from bone marrow and umbilical cord connective tissue. In addition, basic characterization including immunophenotyping by flow cytometry and differentiation capability is also described.
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Células Madre Mesenquimatosas , Adulto , Diferenciación Celular , Tratamiento Basado en Trasplante de Células y Tejidos , Células Cultivadas , Tejido Conectivo , Humanos , Medicina RegenerativaRESUMEN
In this paper, we propose a guiding operational definition and corresponding set of empirical steps to identify and study trapped populations. Trapped populations consist of actors who are highly vulnerable to climate and environmental stressors given limited resources (economic, social, etc.), which limit their ability to adapt to these stressors in-situ or by choosing to migrate. Informed by both insights and omissions from prior theoretical and empirical research, we propose a guiding operational definition of trapped populations that appreciates and incorporates actors' limited resources and their migration intentions against the backdrop of climate and environmental stressors. As it should, our operational definition points to a specific set of operations, or steps, which can be followed to empirically identify and study trapped populations. Using data from the Mexican Family Life Survey (MxFLS), we detail the steps permitting both retrospective and prospective identification of trapped populations. We conclude by discussing the strengths and weaknesses of our operational definition and empirical approach, as well as possible extensions.
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South America is home to more miniature fishes (<26 mm in standard length) than any other continent. Despite this diversity, the ecology of miniature fishes is poorly studied. To promote the study of miniature fish ecology, we investigated patterns in total richness, assemblage structure and environmental correlates for miniature fishes in the rio Jacundá drainage of the Lower Amazon River basin, Pará State. Based on multi-pass dip-netting of leaf litter at 20 locations distributed across two sites, we collected miniature species and used rarefaction to estimate 9 to 14 species might be present. The miniature fish assemblage at the upstream site was a nested subset of the downstream site, and water pH and canopy cover, two features known to be altered by deforestation, correlated most strongly with assemblage variation. Our work represents one of the first quantitative assessments of environmental correlates with miniature fish assemblages and highlights research topics that should be investigated further to promote conservation and preservation of the overlooked and understudied Amazonian diminutive freshwater fish fauna.(AU)
A América do Sul abriga o maior número de peixes miniaturas (<26 mm de comprimento padrão) do que qualquer outro continente. Apesar dessa diversidade, a ecologia dos peixes miniaturas é pouco estudada. Visando promover estudos de ecologia de peixes miniaturas, investigamos padrões de riqueza total, estrutura da assembleia e fatores ambientais correlacionados para peixes miniaturas no rio Jacundá, drenagem do baixo rio Amazonas, Pará. Com base em múltiplas passagens de redes no sedimento em 20 pontos distribuídos em dois locais, coletamos espécies miniaturas e usamos rarefação para estimar que 9 a 14 espécies podem estar presentes. A assembleia de peixes miniaturas no local à montante foi um subgrupo aninhado na assembleia no local à jusante, e pH da água e cobertura de copas, dois fatores sabidamente alterados por desmatamento, foram os mais correlacionados com a variação na assembleia. Nosso trabalho representa um dos primeiros estudos quantitativos de fatores ambientais correlacionados às assembleias de peixes miniaturas e ressalta um tópico de pesquisa que deveria ser melhor investigado para promover a conservação da pouco conhecida fauna de peixes diminutos da Amazônia.(AU)
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Animales , Biodiversidad , Ecología , Peces/anatomía & histología , BiotaRESUMEN
Genomic selection based on the single-step genomic best linear unbiased prediction (ssGBLUP) approach is becoming an important tool in forest tree breeding. The quality of the variance components and the predictive ability of the estimated breeding values (GEBV) depends on how well marker-based genomic relationships describe the actual genetic relationships at unobserved causal loci. We investigated the performance of GEBV obtained when fitting models with genomic covariance matrices based on two identity-by-descent (IBD) and two identity-by-state (IBS) relationship measures. Multiple-trait multiple-site ssGBLUP models were fitted to diameter and stem straightness in five open-pollinated progeny trials of Eucalyptus dunnii, genotyped using the EUChip60K. We also fitted the conventional ABLUP model with a pedigree-based covariance matrix. Estimated relationships from the IBD estimators displayed consistently lower standard deviations than those from the IBS approaches. Although ssGBLUP based in IBS estimators resulted in higher trait-site heritabilities, the gain in accuracy of the relationships using IBD estimators has resulted in higher predictive ability and lower bias of GEBV, especially for low-heritability trait-site. ssGBLUP based on IBS and IBD approaches performed considerably better than the traditional ABLUP. In summary, our results advocate the use of the ssGBLUP approach jointly with the IBD relationship matrix in open-pollinated forest tree evaluation.
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Eucalyptus , Eucalyptus/genética , Genoma , Genómica , Genotipo , Modelos Genéticos , Fenotipo , FitomejoramientoRESUMEN
We evaluated the performance of three PGx panels to estimate biogeographical ancestry: the DMET panel, and the VIP and Preemptive PGx panels described in the literature. Our analysis indicate that the three panels capture quite well the individual variation in admixture proportions observed in recently admixed populations throughout the Americas, with the Preemptive PGx and DMET panels performing better than the VIP panel. We show that these panels provide reliable information about biogeographic ancestry and can be used to guide the implementation of PGx clinical decision-support (CDS) tools. We also report that using these panels it is possible to control for the effects of population stratification in association studies in recently admixed populations, as exemplified with a warfarin dosing GWA study in a sample from Brazil.
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Genoma Humano/genética , Polimorfismo de Nucleótido Simple/genética , Américas , Brasil , Genética de Población/métodos , Estudio de Asociación del Genoma Completo/métodos , Humanos , Farmacogenética/métodosRESUMEN
OBJECTIVE: The RHO family of GTPases, particularly RAC1, has been linked with hepatocarcinogenesis, suggesting that their inhibition might be a rational therapeutic approach. We aimed to identify and target deregulated RHO family members in human hepatocellular carcinoma (HCC). DESIGN: We studied expression deregulation, clinical prognosis and transcription programmes relevant to HCC using public datasets. The therapeutic potential of RAC1 inhibitors in HCC was study in vitro and in vivo. RNA-Seq analysis and their correlation with the three different HCC datasets were used to characterise the underlying mechanism on RAC1 inhibition. The therapeutic effect of RAC1 inhibition on liver fibrosis was evaluated. RESULTS: Among the RHO family of GTPases we observed that RAC1 is upregulated, correlates with poor patient survival, and is strongly linked with a prooncogenic transcriptional programme. From a panel of novel RAC1 inhibitors studied, 1D-142 was able to induce apoptosis and cell cycle arrest in HCC cells, displaying a stronger effect in highly proliferative cells. Partial rescue of the RAC1-related oncogenic transcriptional programme was obtained on RAC1 inhibition by 1D-142 in HCC. Most importantly, the RAC1 inhibitor 1D-142 strongly reduce tumour growth and intrahepatic metastasis in HCC mice models. Additionally, 1D-142 decreases hepatic stellate cell activation and exerts an anti-fibrotic effect in vivo. CONCLUSIONS: The bioinformatics analysis of the HCC datasets, allows identifying RAC1 as a new therapeutic target for HCC. The targeted inhibition of RAC1 by 1D-142 resulted in a potent antitumoural effect in highly proliferative HCC established in fibrotic livers.
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Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Guanidinas/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Carcinogénesis/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/secundario , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Biología Computacional , Bases de Datos Genéticas , Inhibidores Enzimáticos/uso terapéutico , Guanidinas/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones , Terapia Molecular Dirigida , Trasplante de Neoplasias , Transcriptoma/efectos de los fármacos , Proteína de Unión al GTP rac1/genética , Proteínas de Unión al GTP rho/antagonistas & inhibidores , Proteínas de Unión al GTP rho/genéticaRESUMEN
The Rho GTPase Rac1 is involved in the control of cytoskeleton reorganization and other fundamental cellular functions. Aberrant activity of Rac1 and its regulators is common in human cancer. In particular, deregulated expression/activity of Rac GEFs, responsible for Rac1 activation, has been associated to a metastatic phenotype and drug resistance. Thus, the development of novel Rac1-GEF interaction inhibitors is a promising strategy for finding new preclinical candidates. Here, we studied structure-activity relationships within a new family of N,N'-disubstituted guanidine as Rac1 inhibitors. We found that compound 1D-142, presents superior antiproliferative activity in human cancer cell lines and higher potency as Rac1-GEF interaction inhibitor inâ vitro than parental compounds. In addition, 1D-142 reduces Rac1-mediated TNFα-induced NF-κB nuclear translocation during cell proliferation and migration in NSCLC. Notably, 1D-142 allowed us to show for the first time the application of a Rac1 inhibitor in a lung cancer animal model.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desarrollo de Medicamentos , Guanidina/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Proteína de Unión al GTP rac1/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Guanidina/síntesis química , Guanidina/química , Humanos , Hidroxilación , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Proteína de Unión al GTP rac1/metabolismoRESUMEN
Resumen La terapia celular y la medicina regenerativa son áreas en gran desarrollo en la investigación biomédica. En la mayoría de los tejidos existen mecanismos de auto-reparación llevados a cabo, principalmente, por células madre o progenitoras residentes con capacidad para diferenciarse y reemplazar a las células dañadas o para secretar factores tróficos que induzcan el proceso regenerativo. Dado que estos mecanismos de reparación no siempre son suficientes, se postula que la terapia celular puede contribuir a la regeneración de los tejidos sometidos a injuria. Las células madre/estromales mesenquimales (MSCs, del inglés Mesenchymal Stem/Stromal Cells) son un tipo de progenitor adulto multipotente, que tienen la capacidad de expandirse in vitro con facilidad cuando son aisladas de su nicho in vivo, migrar selectivamente a los tejidos lesionados, modular y evadir el sistema inmunológico, y secretar factores tróficos que ayudan a la reparación tisular. Asimismo, la fácil manipulación ex vivo permitiría también usarlas como vehículos de genes terapéuticos. Las principales fuentes de obtención son la médula ósea, el tejido adiposo y cordón umbilical. Los numerosos estudios pre-clínicos y clínicos han demostrado que las MSCs parecieran ser seguras tanto para uso autólogo como alogénico. En este trabajo se resumen las propiedades de las MSCs y su potencial terapéutico para una amplia gama de enfermedades, también presentamos los distintos ensayos clínicos avanzados que las posicionan en el ámbito biomédico como una herramienta interesante para la regeneración de tejidos y el tratamiento de enfermedades inflamatorias.
Abstract Cell therapy and regenerative medicine are currently active areas for biomedical research. In most tissues, there are self-repair mechanisms carried out mainly by resident stem cells that can differentiate and replace dead cells or secrete trophic factors that stimulate the regenerative process. These mechanisms often fail in degenerative diseases; thus it is postulated that exogenous cell therapy can contribute to tissue regeneration and repair. Mesenchymal stem cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system recognition, and secrete trophic factors to support tissue repair. Furthermore, MSCs could be engineered for the delivery of therapeutic genes. The main sources for MSCs are bone marrow, adipose tissue, and umbilical cord. A number of pre-clinical and clinical studies have shown that MSCs therapy is safe for both autologous and allogeneic uses. This review summarizes information about the properties of MSCs and their therapeutic potential for a broad spectrum of diseases. We also present here the last data about clinical trials that position the use of MSCs as an interesting tool for tissue regeneration and the treatment of inflammatory diseases.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ingeniería de Tejidos , Medicina RegenerativaRESUMEN
Cell therapy and regenerative medicine are currently active areas for biomedical research. In most tissues, there are self-repair mechanisms carried out mainly by resident stem cells that can differentiate and replace dead cells or secrete trophic factors that stimulate the regenerative process. These mechanisms often fail in degenerative diseases; thus it is postulated that exogenous cell therapy can contribute to tissue regeneration and repair. Mesenchymal stem cells (MSCs) are multipotent adult stem/progenitor cells, which could be easily expanded in vitro and have the ability to selectively migrate toward injured tissues, evade the immune system recognition, and secrete trophic factors to support tissue repair. Furthermore, MSCs could be engineered for the delivery of therapeutic genes. The main sources for MSCs are bone marrow, adipose tissue, and umbilical cord. A number of pre-clinical and clinical studies have shown that MSCs therapy is safe for both autologous and allogeneic uses. This review summarizes information about the properties of MSCs and their therapeutic potential for a broad spectrum of diseases. We also present here the last data about clinical trials that position the use of MSCs as an interesting tool for tissue regeneration and the treatment of inflammatory diseases.
La terapia celular y la medicina regenerativa son áreas en gran desarrollo en la investigación biomédica. En la mayoría de los tejidos existen mecanismos de auto-reparación llevados a cabo, principalmente, por células madre o progenitoras residentes con capacidad para diferenciarse y reemplazar a las células dañadas o para secretar factores tróficos que induzcan el proceso regenerativo. Dado que estos mecanismos de reparación no siempre son suficientes, se postula que la terapia celular puede contribuir a la regeneración de los tejidos sometidos a injuria. Las células madre/estromales mesenquimales (MSCs, del inglés Mesenchymal Stem/Stromal Cells) son un tipo de progenitor adulto multipotente, que tienen la capacidad de expandirse in vitro con facilidad cuando son aisladas de su nicho in vivo, migrar selectivamente a los tejidos lesionados, modular y evadir el sistema inmunológico, y secretar factores tróficos que ayudan a la reparación tisular. Asimismo, la fácil manipulación ex vivo permitiría también usarlas como vehículos de genes terapéuticos. Las principales fuentes de obtención son la médula ósea, el tejido adiposo y cordón umbilical. Los numerosos estudios pre-clínicos y clínicos han demostrado que las MSCs parecieran ser seguras tanto para uso autólogo como alogénico. En este trabajo se resumen las propiedades de las MSCs y su potencial terapéutico para una amplia gama de enfermedades, también presentamos los distintos ensayos clínicos avanzados que las posicionan en el ámbito biomédico como una herramienta interesante para la regeneración de tejidos y el tratamiento de enfermedades inflamatorias.
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Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Medicina Regenerativa , Ingeniería de TejidosRESUMEN
This extended paper presents the development and implementation at a prototype level of a wireless, low-cost system for the measurement of the electrical bioimpedance of the chest with two channels using the AD5933 in a bipolar electrode configuration to measure impedance pneumography. The measurement device works for impedance measurements ranging from 1 Ω to 1800 Ω. Fifteen volunteers were measured with the prototype. We found that the left hemithorax has higher impedance compared to the right hemithorax, and the acquired signal presents the phases of the respiratory cycle with variations between 1 Ω, in normal breathing, to 6 Ω in maximum inhalation events. The system can measure the respiratory cycle variations simultaneously in both hemithorax with a mean error of -0.18 ± 1.42 BPM (breaths per minute) in the right hemithorax and -0.52 ± 1.31 BPM for the left hemithorax, constituting a useful device for the breathing rate calculation and possible screening applications.