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1.
2.
EMBO Mol Med ; 15(12): e18199, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38037472

RESUMEN

Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors, and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.


Asunto(s)
Bancos de Muestras Biológicas , Neoplasias Encefálicas , Humanos , Niño , Xenoinjertos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Organoides/patología
3.
J Neural Eng ; 20(4)2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37437593

RESUMEN

Objective.Surface electromyography measurements of the Hoffmann (H-) reflex are essential in a wide range of neuroscientific and clinical applications. One promising emerging therapeutic application is H-reflex operant conditioning, whereby a person is trained to modulate the H-reflex, with generalized beneficial effects on sensorimotor function in chronic neuromuscular disorders. Both traditional diagnostic and novel realtime therapeutic applications rely on accurate definitions of the H-reflex and M-wave temporal bounds, which currently depend on expert case-by-case judgment. The current study automates such judgments.Approach.Our novel wavelet-based algorithm automatically determines temporal extent and amplitude of the human soleus H-reflex and M-wave. In each of 20 participants, the algorithm was trained on data from a preliminary 3 or 4 min recruitment-curve measurement. Output was evaluated on parametric fits to subsequent sessions' recruitment curves (92 curves across all participants) and on the conditioning protocol's subsequent baseline trials (∼1200 per participant) performed nearHmax. Results were compared against the original temporal bounds estimated at the time, and against retrospective estimates made by an expert 6 years later.Main results.Automatic bounds agreed well with manual estimates: 95% lay within ±2.5 ms. The resulting H-reflex magnitude estimates showed excellent agreement (97.5% average across participants) between automatic and retrospective bounds regarding which trials would be considered successful for operant conditioning. Recruitment-curve parameters also agreed well between automatic and manual methods: 95% of the automatic estimates of the current required to elicitHmaxfell within±1.4%of the retrospective estimate; for the 'threshold' current that produced an M-wave 10% of maximum, this value was±3.5%.Significance.Such dependable automation of M-wave and H-reflex definition should make both established and emerging H-reflex protocols considerably less vulnerable to inter-personnel variability and human error, increasing translational potential.


Asunto(s)
Reflejo H , Músculo Esquelético , Humanos , Estudios Retrospectivos , Electromiografía , Músculo Esquelético/fisiología , Reflejo H/fisiología , Nervios Periféricos , Estimulación Eléctrica
4.
Mater Today Bio ; 17: 100463, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36310541

RESUMEN

Recently nanotechnology has evolved as one of the most revolutionary technologies in the world. It has now become a multi-trillion-dollar business that covers the production of physical, chemical, and biological systems at scales ranging from atomic and molecular levels to a wide range of industrial applications, such as electronics, medicine, and cosmetics. Nanobiomaterials synthesis are promising approaches produced from various biological elements be it plants, bacteria, peptides, nucleic acids, etc. Owing to the better biocompatibility and biological approach of synthesis, they have gained immense attention in the biomedical field. Moreover, due to their scaled-down sized property, nanobiomaterials exhibit remarkable features which make them the potential candidate for different domains of tissue engineering, materials science, pharmacology, biosensors, etc. Miscellaneous characterization techniques have been utilized for the characterization of nanobiomaterials. Currently, the commercial transition of nanotechnology from the research level to the industrial level in the form of nano-scaffolds, implants, and biosensors is stimulating the whole biomedical field starting from bio-mimetic nacres to 3D printing, multiple nanofibers like silk fibers functionalizing as drug delivery systems and in cancer therapy. The contribution of single quantum dot nanoparticles in biological tagging typically in the discipline of genomics and proteomics is noteworthy. This review focuses on the diverse emerging applications of Nanobiomaterials and their mechanistic advancements owing to their physiochemical properties leading to the growth of industries on different biomedical measures. Alongside the implementation of such nanobiomaterials in several drug and gene delivery approaches, optical coding, photodynamic cancer therapy, and vapor sensing have been elaborately discussed in this review. Different parameters based on current challenges and future perspectives are also discussed here.

6.
Adv Exp Med Biol ; 1280: 97-113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33791977

RESUMEN

Most microbe-associated infectious diseases severely affect human health. However, clinical diagnosis of pathogenic diseases remains challenging due to the lack of specific and highly reliable methods. To better understand the diagnosis, pathogenesis, and treatment of these diseases, systems biology-driven metabolomics goes beyond the annotated phenotype and better targets the functions than conventional approaches. As a novel strategy for analysis of metabolomes in microbes, microbial metabolomics has been recently used to study many diseases, such as obesity, urinary tract infection (UTI), and hepatitis C. In this chapter, we attempt to introduce various microbial metabolomics methods to better interpret the microbial metabolism underlying a diversity of infectious diseases and inspire scientists to pay more attention to microbial metabolomics, enabling broadly and efficiently its translational applications to infectious diseases, from molecular diagnosis to therapeutic discovery.


Asunto(s)
Metabolómica , Infecciones Urinarias , Humanos , Metaboloma , Biología de Sistemas
7.
Adv Healthc Mater ; 9(6): e1901761, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31999081

RESUMEN

Over the past two decades, electrospun nanofibers have been actively explored for a range of applications, including those related to biomedicine, environmental science, energy harvesting, catalysis, photonics, and electronics. Regarding biomedical applications, one can readily produce nanofiber-based scaffolds with controlled compositions, structures, alignments, and functions by varying the material, design of collector, number of spinnerets, and electrospinning parameters. This report highlights both preclinical and translational applications of electrospun nanofibers and bioprinted constructs presented at the 2019 International Conference on Electrospinning, together with some perspectives on their future development.


Asunto(s)
Nanofibras , Ingeniería de Tejidos , Andamios del Tejido
8.
FEBS Lett ; 593(23): 3244-3252, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31691960

RESUMEN

Blood reprogramming, in which induced pluripotent stem cells (iPSCs) are derived from haematopoietic lineages, has rapidly advanced over the past decade. Since the first report using human blood, haematopoietic cell types from various sources, such as the peripheral bone marrow and cord blood, have been successfully reprogrammed. The volume of blood required has also decreased, from around tens of millilitres to a single finger-prick drop. Besides, while early studies were limited to reprogramming methods relying on viral integration, nonintegrating reprogramming systems for blood lineages have been subsequently established. Together, these improvements have made feasible the future clinical applications of blood-derived iPSCs. Here, we review the progress in blood reprogramming from various perspectives, including the starting materials and subsequent reprogramming strategies. We also discuss the downstream applications of blood-derived iPSCs, highlighting their clinical value in terms of disease modelling and therapeutic development.


Asunto(s)
Células Sanguíneas/metabolismo , Reprogramación Celular/genética , Células Madre Hematopoyéticas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células de la Médula Ósea/metabolismo , Diferenciación Celular/genética , Linaje de la Célula/genética , Sangre Fetal/citología , Sangre Fetal/metabolismo , Células Madre Hematopoyéticas/citología , Humanos
10.
J Vasc Surg ; 70(6): 2093-2097, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31147135

RESUMEN

Even though diabetes mellitus is a major risk for cardiovascular events and atherosclerosis-related diseases, it is negatively associated with abdominal aortic aneurysm. The understanding of the mechanisms underlying this negative association could bring new insights to identify prognostic and therapeutic targets. Here we summarize current knowledge of the relationship between glycemic parameters and clinical outcomes of patients with abdominal aortic aneurysm. Translational applications of glucose-targeted approaches as well as their potential interest for clinical practice are discussed in this context.


Asunto(s)
Aneurisma de la Aorta Abdominal/metabolismo , Glucemia/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Pronóstico , Medición de Riesgo , Factores de Riesgo
11.
Immunity ; 50(1): 37-50, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30650380

RESUMEN

Plasmacytoid dendritic cells (pDCs) are a unique sentinel cell type that can detect pathogen-derived nucleic acids and respond with rapid and massive production of type I interferon. This review summarizes our current understanding of pDC biology, including transcriptional regulation, heterogeneity, role in antiviral immune responses, and involvement in immune pathology, particularly in autoimmune diseases, immunodeficiency, and cancer. We also highlight the remaining gaps in our knowledge and important questions for the field, such as the molecular basis of unique interferon-producing capacity of pDCs. A better understanding of cell type-specific positive and negative control of pDC function should pave the way for translational applications focused on this immune cell type.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Diferenciación Celular , Células Dendríticas/fisiología , Neoplasias/inmunología , Virosis/inmunología , Animales , Regulación de la Expresión Génica , Humanos , Inmunidad Celular , Interferón Tipo I/metabolismo
12.
Mass Spectrom Rev ; 38(3): 239-252, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30035815

RESUMEN

Siderophores are chemically diverse small molecules produced by microorganisms for chelation of irons to maintain their survival and govern some important biological functions, especially those cause that infections in hosts. Still, siderophores can offer new insight into a better understanding of the diagnosis and treatments of infectious diseases from the siderophore biosynthesis and regulation perspective. Thus, this review aims to summarize the biomedical value and applicability of siderophores in pathogenic contexts by briefly reviewing mass spectrometry (MS)-based chemical biology and translational applications that involve diagnosis, pathogenesis, and therapeutic discovery for a variety of infectious conditions caused by different pathogens. We highlight the advantages and disadvantages of siderophore discovery and applications in pathogenic contexts. Finally, we propose a panel of new and promising strategy as precision-modification metabolomics method, to rapidly advance the discovery of and translational innovations pertaining to these value compounds in broad biomedical niches. © 2018 Wiley Periodicals, Inc. Mass Spec Rev XX:XX-XX, 2018.


Asunto(s)
Espectrometría de Masas/métodos , Metabolómica/métodos , Sideróforos/metabolismo , Animales , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Biomarcadores/análisis , Biomarcadores/metabolismo , Vías Biosintéticas , Humanos , Infecciones/diagnóstico , Infecciones/microbiología , Micosis/diagnóstico , Micosis/microbiología , Sideróforos/análisis , Investigación Biomédica Traslacional/métodos
13.
Crit Rev Clin Lab Sci ; 54(6): 414-432, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-29025326

RESUMEN

The overall goal of translational oncology is to identify molecular alterations indicative of cancer or of responsiveness to specific therapeutic regimens. While next-generation sequencing has played a pioneering role in this quest, the latest advances in proteomic technologies promise to provide a holistic approach to the further elucidation of tumor biology. Genetic information may be written in DNA and flow from DNA to RNA to protein, according to the central dogma of molecular biology, but the observed phenotype is dictated predominantly by the DNA protein coding region-derived proteotype. Proteomics holds the potential to bridge the gap between genotype and phenotype, because the powerful analytical tool of mass spectrometry has reached a point of maturity to serve this purpose effectively. This integration of "omics" data has given birth to the novel field of onco-proteogenomics, which has much to offer to precision medicine and personalized patient management. Here, we review briefly how each "omics" technology has individually contributed to cancer research, discuss technological and computational advances that have contributed to the realization of onco-proteogenomics, and summarize current and future translational applications.


Asunto(s)
Biomarcadores de Tumor , Neoplasias , Oncogenes/genética , Proteogenómica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Neoplasias/genética , Neoplasias/metabolismo
14.
J Physiol Paris ; 108(4-6): 323-33, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25218188

RESUMEN

The reconsolidation hypothesis posits that the presentation of a specific cue, previously associated with a life event, makes the stored memory pass from a stable to a reactivated state. In this state, memory is again labile and susceptible to different agents, which may either damage or improve the original memory. Such susceptibility decreases over time and leads to a re-stabilization phase known as reconsolidation process. This process has been assigned two biological roles: memory updating, which suggests that destabilization of the original memory allows the integration of new information into the background of the original memory; and memory strengthening, which postulates that the labilization-reconsolidation process strengthens the original memory. The aim of this review is to analyze the strengthening as an improvement obtained only by triggering such process without any other treatment. In our lab, we have demonstrated that when triggering the labilization-reconsolidation process at least once the original memory becomes strengthened and increases its persistence. We have also shown that repeated labilization-reconsolidation processes strengthened the original memory by enlarging its precision, and said reinforced memories were more resistant to interference. Finally, we have shown that the strengthening function is not operative in older memories. We present and discuss both our findings and those of others, trying to reveal the central role of reconsolidation in the modification of stored information.


Asunto(s)
Memoria/fisiología , Retención en Psicología/fisiología , Animales , Humanos , Recuerdo Mental , Factores de Tiempo
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