Smartphone-Based Diagnosis of Parasitic Infections With Colorimetric Assays in Centrifuge Tubes

A smartphone-based platform for the diagnosis of parasitic infections has been developed, tested and validated. The system is capable of making automatic and accurate analysis of millimetric colorimetric arrays in centrifuge collection tubes, which are well established tools used in clinical analysis. To that end, an Android-based software application has been developed, making use of the smartphone rear camera, enabling precise image processing of the colorimetric spot arrays. A low-cost plastic accessory has been developed using 3D-printing to provide controlled illumination, xed sample positioning and cell phone attachment. The platform was then tested repeatedly for its size detection, edge blurriness and colour detection capabilities. A minimum spot radius of 175 m is detectable when using the developed app, with a tolerance of 15%, corresponding to 0.25%of the area where the spot array is printed. Spot edge de nition has been studied up to 40% of blurriness, resulting in a low average percentage error of 1.24%. Colour detection follows the well-known Gamma correction function. Finally, the whole platform was tested and validated using real DNA to analyse for accurate discrimination of Trypanosomatid species, which are responsible for devastating diseases in humans and livestock. The smartphone-based platform can be further extended to other clinical analysis. Its simplicity and reliable performance mean it can be used in remote, limited-resource settings by relatively unskilled technicians/nurses, where diagnostic laboratories are sparsely distributed. The results can however be sent easily via the smartphone to medical experts as well as government health agencies.This work was supported in part by the Spanish Ministry of Economics and Competitivity under Project CTQ2016-78754-C2-1-R, in part by the European Regional Development Fund (ERDF), and in part by the DestiNA Genomica SL provided reagents, samples and Spin-Tube devices. The work of P. Escobedo was supported by the Spanish Ministry of Education, Culture and Sport (MECD), under Grant (FPU13/05032)

Novel bead-based platform for direct detection of unlabelled nucleic acids through Single Nucleobase Labelling

Over the last decade, circulating microRNAs have received attention as diagnostic and prognostic biomarkers. In particular, microRNA122 has been demonstrated to be an early and more sensitive indicator of drug-induced liver injury than the widely used biomarkers such as alanine aminotransferase and aspartate aminotransferase. Recently, microRNA122 has been used in vitro to assess the cellular toxicity of new drugs and as a biomarker for the development of a rapid test for drug overdose/liver damage. In this proof-of-concept study, we report a PCR-free and label-free detection method that has a limit of detection (3 standard deviations) of 15 fmoles of microRNA122, by integrating a dynamic chemical approach for "Single Nucleobase Labelling" with a bead-based platform (Luminex®) thereby, in principle, demonstrating the exciting prospect of rapid and accurate profiling of any microRNAs related to diseases and toxicology

Diseño y síntesis de derivados del ácido hidroxámico como nuevos inhibidores de las histonas desacetilasas con actividad antitumoral

Tesis Univ. Granada. Departamento de Química Farmacéutica y Orgánica. Leída el 10 de julio de 200

Derivados de benzo[d]isotiazoles como inhibidores de las histonas desacetilasas

Número de publicación: 2 288 803 Número de solicitud: 200601946Derivados de benzo[d]isotiazoles como inhibidores de las histonas desacetilasas, seleccionados de entre los compuestos de fórmula general (Ia) y (Ib) o una de sus sales, en particular una de sus sales farmacéuticamente aceptables, o uno de sus solvatos correspondientes. Estos compuestos son inhibidores de las enzimas histonas desacetilasas y son adecuados como agentes farmacológicamente activos en un medicamento para el tratamiento y/o profilaxis de trastornos o enfermedades asociados a las histonas desacetilasas. La invención describe asimismo un procedimiento de obtención de los citados compuestos y las composiciones farmacéuticas que los contienen.Universidad de Granad

Nuevos derivados de ftalimida como inhibidores de las histonas desacetilasas

Número de publicación: 2 288 802 Número de solicitud: 200601945Nuevos derivados de ftalimida como inhibidores de las histonas desacetilasas, de fórmula general o una de sus sales, en particular una de sus sales farmacéuticamente aceptables, o uno de sus solvatos correspondientes. Estos compuestos son inhibidores de las enzimas histonas desacetilasas y son adecuados como agentes farmacológicamente activos en un medicamento para el tratamiento y/o profilaxis de trastornos o enfermedades asociados a las histonas desacetilasas. La invención describe asimismo un procedimiento de obtención de los citados compuestos y las composiciones farmacéuticas que los contienen.Universidad de Granad

Synthesis and evaluation of new HDAC inhibitors

La acetilación de residuos de lisina en las histonas está mediada por las enzimas denominadas histona acetiltransferasas (HAT). Los grupos acetilo son eliminados de las e-N-acetil-lisinas por la actividad de las histonas desacetilasas (HDAC). El balance entre las actividades opuestas de las HAT y las HDAC regula el estado de acetilación de las histonas. Este tipo de modificaciones regulan en la célula procesos fundamentales clave en respuesta a señales extracelulares. En general, altos niveles de acetilación (hiperacetilación) se asocian a un incremento de la actividad transcripcional, mientras que bajos niveles de acetilación (hipoacetilación) se asocian a la represión de la expresión genética. Actualmente se conocen diversos tipos de inhibidores de las HDAC que pueden reactivar la expresión genética e inhibir el crecimiento de las células tumorales, por lo que se investiga su uso en el tratamiento frente al cáncer. Sería deseable identificar nuevos inhibidores de las enzimas HDAC para su utilización en el tratamiento o profilaxis de enfermedades en las que la inhibición de dichas enzimas HDAC está implicada. Se han obtenido 10 nuevos inhibidores de las HDAC y se ha evaluado su actividad frente a HDAC aislada. Se discute la importancia de las modificaciones realizadas en el espaciador.Lysine residues acetylation on histones is mediated by histone acetyltransferase (HAT). The acetyl groups are removed from e-N-acetyl-lysine by the histone deacetylase (HDAC) activity. The balance between the HATs and HDACs activities regulates the histone acetylation status. Such changes regulate key processes in the cell in response to extracellular signals. Mostly, high levels of acetylation (hyperacetylation) are associated with increased transcriptional activity. Low levels of acetylation (hypoacetylation) are associated with repression of gene expression. Currently, different types of HDAC inhibitors are known to reactivate gene expression and inhibit tumor cell growth. We aim at identifying novel HDAC inhibitors for the treatment or prophylaxis of cancer diseases. Ten new HDAC inhibitors have been obtained and their potency as HDAC inhibitors has been evaluated. A structure-activity relationship discussion has been focused on the structural changes made in the spacer

Simultaneous Detection of Drug-Induced Liver Injury Protein and microRNA Biomarkers Using Dynamic Chemical Labelling on a Luminex MAGPIX System

Drug-induced liver injury (DILI) is a potentially fatal adverse event and a leading cause for pre- and post-marketing drug withdrawal. Several multinational DILI initiatives have now recommended a panel of protein and microRNA (miRNA) biomarkers that can detect early liver injury and inform about mechanistic basis. This manuscript describes the development of seqCOMBO, a unique combo-multiplexed assay which combines the dynamic chemical labelling approach and an antibody-dependant method on the Luminex MAGPIX system. SeqCOMBO enables a versatile multiplexing platform to perform qualitative and quantitative analysis of proteins and miRNAs in patient serum samples simultaneously. To the best of our knowledge, this is the first method to profile protein and miRNA biomarkers to diagnose DILI in a single-step assay

Compuesto con actividad antileishmania

Número de publicación: ES2402252 B1. Número de solicitud: 201101074.La presente invención se refiere a compuestos de fórmula general (I), procedimiento de síntesis de los mismos y composiciones que comprenden dichos compuestos y para el tratamiento de enfermedades causadas por parásitos de género Leishmania.Universidad de Granad

Dataset from article 'A New Horizon in Multiplexed micro-RNA Biomarker Detection: Bridging Lifetime Filtering Imaging and Dynamic Chemistry Labeling'

MicroRNAs (miRs) have emerged as promising biomarkers for early disease diagnosis and personalised treatment monitoring. However, but their clinical utility has been hampered by technical limitations. Dynamic chemical labelling (DCL) based on capturing abasic PNA probes and reactive nucleobases, so-called SMART bases, is a PCR-free approach that has proven very useful for the direct interrogation of circulating miRs. In this work, we expand the palette of available tools for DCL miR detection methods with a newly synthesised SMART nucleobase, SMART-C-Eu. This nucleobase contains a stable lanthanide cryptate. Using this SMART-C-Eu base and time-gated (TG) luminescence imaging, we successfully detect and quantify miR-122-5p in human serum samples. miR-122-5p is a well-known biomarker for drug-induced liver injury. A bead-counting analysis approach improved statistical robustness and allowed the detection of miR-122-5p concentrations in the nanomolar range. Furthermore, we extend this approach to multiplexed detection of three different miRs (miR-371a-3p, miR-451a-5p, and miR-122-5p) using spectral and temporal filtering. Consistent results were obtained using machine learning algorithms for automatic bead classification. Although this technique requires further sensitivity improvements to detect miRs at lower concentrations, it represents a significant advancement in miR analysis. It offers multiplexing capabilities and the potential for automation, paving the way for more accurate and robust clinical applications in the future.European Union through the H2020 diaRNAgnosis project, under grant agreement No. 101007934Agencia Estatal de Investigación (Spain) through grant PID2020-114256RB-I00 AEI/10.13039/501100011033Agencia Estatal de Investigación (Spain) through grant CTQ2017-85658-R AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa”