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Nodal-line semimetals, characterized by Dirac-like crossings along one dimensionalk-space lines, represent a unique class of topological materials. In this study, we investigate the intriguing properties of room-temperature antiferromagneticMnC4and its nodal-line features both with and without spin-orbit coupling (SOC). In the absence of SOC, we identify a doubly degenerate Dirac-nodal line, robustly protected by a combination of time-reversal, mirror, and partial-translation symmetries. Remarkably, this nodal line withstands various external perturbations, including isotropic and anisotropic strain, and torsional deformations, due to the ionic-like bonding between Mn atoms and C clusters. With the inclusion of SOC, we observe a distinctive quasi-Dirac-nodal line that emerges due to the interplay between antiferromagnetism and SOC-induced spin-rotation symmetry breaking. Finally, we observed a robust spin Hall conductivity that aligns with the energy range where the quasi-nodal line appears. This study presents a compelling example of a robust symmetry-protected Dirac-nodal line antiferromagnetic monolayer, which has potential for applications in next-generation spintronic devices.
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Data-independent acquisition (DIA) mass spectrometry methods provide systematic and comprehensive quantification of the proteome; yet, relatively few open-source tools are available to analyze DIA proteomics experiments. Fewer still are tools that can leverage gas phase fractionated (GPF) chromatogram libraries to enhance the detection and quantification of peptides in these experiments. Here, we present nf-encyclopedia, an open-source NextFlow pipeline that connects three open-source tools, MSConvert, EncyclopeDIA, and MSstats, to analyze DIA proteomics experiments with or without chromatogram libraries. We demonstrate that nf-encyclopedia is reproducible when run on either a cloud platform or a local workstation and provides robust peptide and protein quantification. Additionally, we found that MSstats enhances protein-level quantitative performance over EncyclopeDIA alone. Finally, we benchmarked the ability of nf-encyclopedia to scale to large experiments in the cloud by leveraging the parallelization of compute resources. The nf-encyclopedia pipeline is available under a permissive Apache 2.0 license; run it on your desktop, cluster, or in the cloud: https://github.com/TalusBio/nf-encyclopedia.
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Proteómica , Programas Informáticos , Proteómica/métodos , Flujo de Trabajo , Péptidos/análisis , Proteoma/análisisRESUMEN
Autoimmune (AI) diseases can affect many organs; however, the prostate has not been considered to be a primary target of these systemic inflammatory processes. Here, we utilize medical record data, patient samples, and in vivo models to evaluate the impact of inflammation, as seen in AI diseases, on prostate tissue. Human and mouse tissues are used to examine whether systemic targeting of inflammation limits prostatic inflammation and hyperplasia. Evaluation of 112,152 medical records indicates that benign prostatic hyperplasia (BPH) prevalence is significantly higher among patients with AI diseases. Furthermore, treating these patients with tumor necrosis factor (TNF)-antagonists significantly decreases BPH incidence. Single-cell RNA-seq and in vitro assays suggest that macrophage-derived TNF stimulates BPH-derived fibroblast proliferation. TNF blockade significantly reduces epithelial hyperplasia, NFκB activation, and macrophage-mediated inflammation within prostate tissues. Together, these studies show that patients with AI diseases have a heightened susceptibility to BPH and that reducing inflammation with a therapeutic agent can suppress BPH.
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Enfermedades Autoinmunes , Hiperplasia Prostática , Prostatitis , Animales , Enfermedades Autoinmunes/tratamiento farmacológico , Línea Celular , Humanos , Hiperplasia , Inflamación/tratamiento farmacológico , Masculino , Ratones , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/patologíaRESUMEN
The skin is a unique immune organ that constitutes a complex network of physical, chemical and microbiological barriers against external insults. Keratinocytes are the most abundant cell type in the epidermis. These cells form the physical skin barrier and represent the first line of the host defense system by sensing pathogens via innate immune receptors, initiating anti-microbial responses and producing various cytokines, chemokines and anti-microbial peptides, which are important events in immunity. A damaged epidermal barrier in atopic dermatitis allows the penetration of potential allergens and pathogens to activate keratinocytes. Among the dysregulation of immune responses in atopic dermatitis, activated keratinocytes play a role in several biological processes that contribute to the pathogenesis of atopic dermatitis. In this review, we summarize the current understanding of the innate immune functions of keratinocytes in the pathogenesis of atopic dermatitis, with a special emphasis on skin-derived anti-microbial peptides and atopic dermatitis-related cytokines and chemokines in keratinocytes. An improved understanding of the innate immunity mediated by keratinocytes can provide helpful insight into the pathophysiological processes of atopic dermatitis and support new therapeutic efforts.
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Dermatitis Atópica/inmunología , Inmunidad Innata/inmunología , Queratinocitos/inmunología , Alérgenos/inmunología , Quimiocinas/inmunología , Citocinas/inmunología , Epidermis/inmunología , Humanos , Piel/inmunologíaRESUMEN
Single-cell RNA sequencing (scRNA-seq) is now a commonly used technique to measure the transcriptome of populations of cells. Clustering heterogeneous cells based on these transcriptomes enables identification of cell populations (Butler, Hoffman, Smibert, Papalexi, & Satija, 2018; Trapnell et al., 2014). There are multiple methods available to identify "marker" genes that differ between these populations (Butler et al., 2018; Love, Huber, & Anders, 2014; Robinson, McCarthy, & Smyth, 2009). However, there are usually too many genes in these lists to directly suggest an experimental follow-up strategy for selecting them from a bulk population (e.g. via FACS (Tung et al., 2007)). Here we present scTree, a tool that aims to provide biologists using the R programming language and scRNA-seq analysis programs a minimal set of genes that can be used in downstream experiments. The package is free, open source and available though GitHub at github.com/jspaezp/sctree.
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Resumen: Los tumores neuroendocrinos primarios (NET) del mediastino son muy raros. Presentamos el caso de un tumor carcinoide atípico primario de timo. Un hombre de 52 años que fue a un examen médico porque se quejaba de tos no productiva sin hemoptisis. Se solicitó una radiografía de tórax donde se evidenció un mediastino notablemente ensanchado, con una tomografía de tórax que mostro una masa tumoral de 90 x 50 mm en el mediastino anterosuperior que comprime el arco aórtico y la arteria pulmonar sin un plano de clivaje adecuado. Debido a que el tumor era infiltrativo, se proporcionó escisión quirúrgica completa, quimioterapia y radioterapia al mediastino. El objetivo principal de nuestro estudio fue evaluar los hallazgos de CT y MRI con relación a la literatura mundial.
Abstract: Primary neuroendocrine tumors (NET) of the mediastinum are very rare. We present the case of a primary atypical carcinoid tumor of the thymus. A 52-year-old man who went to a medical examination because he complained of a non-productive cough without hemoptysis. A chest radiograph was requested where a markedly widened mediastinum was evidenced, with a thoracic tomography showing a tumor mass of 90 x 50 mm in the anterosuperior mediastinum that compresses the aortic arch and pulmonary artery without an adequate cleavage plane. Because the tumor was infiltrative, complete surgical excision, chemotherapy and radiotherapy were provided to the mediastinum. The main objective of our study was to evaluate the findings of CT and MRI in relation to universal literature.
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Humanos , Masculino , Persona de Mediana Edad , Neoplasias del Timo/diagnóstico por imagen , Tumor Carcinoide/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias del Timo/cirugía , Tumor Carcinoide/cirugía , Radiografía Torácica , Tomografía Computarizada por Rayos X , Tumores Neuroendocrinos/cirugía , Mediastino/patologíaRESUMEN
A shape-selective preparation method was used to obtain highly crystalline rod-, needle-, nut-, and doughnut-like ZnO morphologies with distinct particle sizes and surface areas. We study the nucleation and growth mechanism of those structures and the influence of physical-chemical parameters, such as the solvent and the pH of the solution, on the morphology, as well as the structural and optical properties. A clear correlation between the growth rate along the c-axis and surface defects was established. Our results suggest that the needle- and rod-like morphologies are formed due to the crystal growth orientation along the c-axis and the occurrence of crystalline defects, such as oxygen vacancies and interstitial Zn2+ located at the surface, whereas nuts and doughnuts are formed due to growth along all crystalline planes except those related to growth along the c-axis. Based on the experimental results, growth mechanisms for the formation of ZnO structures were proposed. We believe this synthetic route will be of guidance to prepare several materials whose shapes will depend on the desired applications.
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Mercury (Hg) is a toxic metal frequently used in illegal and artisanal extraction of gold and silver which makes it a cause of environmental poisoning. Since biosorption of other heavy metals has been reported for several Lysinibacillus sphaericus strains, this study investigates Hg removal. Three L. sphaericus strains previously reported as metal tolerant (CBAM5, Ot4b31, and III(3)7) were assessed with mercury chloride (HgCl2). Bacteria were characterized by scanning electron microscopy coupled with energy dispersive spectroscopy (EDS-SEM). Sorption was evaluated in live and dead bacterial biomass by free and immobilized cells assays. Hg quantification was achieved through spectrophotometry at 508 nm by reaction of Hg supernatants with dithizone prepared in Triton X-114 and by graphite furnace atomic absorption spectroscopy (GF-AAS). Bacteria grew up to 60 ppm of HgCl2. Non-immobilized dead cell mixture of strains III(3)7 and Ot4b31 showed a maximum sorption efficiency of 28.4 µg Hg/mg bacteria during the first 5 min of contact with HgCl2, removing over 95% of Hg. This process was escalated in a semi-batch bubbling fluidized bed reactor (BFB) using rice husk as the immobilization matrix leading to a similar level of efficiency. EDS-SEM analysis showed that all strains can adsorb Hg as particles of nanometric scale that can be related to the presence of S-layer metal binding proteins as shown in previous studies. These results suggest that L. sphaericus could be used as a novel biological method of mercury removal from polluted wastewater.
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In this work we compare the antifungal capacity of zinc oxide nanoparticles (ZnO-NPs) synthesized by a chemical route and a ZnO-based nanobiohybrid obtained by green synthesis in an extract of garlic (Allium sativum). To find out the characteristics of the materials synthesized, X-ray diffraction (XRD), IR spectroscopy and absorption in UV-Vis were used, as well as both scanning (SEM) and transmission (TEM) electron microscopy. The results showed that the samples obtained were of nanometric size (<100â¯nm), with a predominance of the wurtzite crystal phase of ZnO and little crystallization of the nanobiohybrids. Their antifungal capacity on two pathogenic fungi of coffee, Mycena citricolor (Berk and Curt) and Colletotrichum sp. was also evaluated. Both nanomaterials showed an efficient antifungal capacity, particularly the nanobiohybrids, with ~97% inhibition in growth of M. citricolor, and ~93% for Colletotrichum sp. The microstructural study with high resolution optical (HROM) and ultra-structural microscopy (using TEM) carried out on the fungi treated with the synthesized nanomaterials showed a strong nanofungicidal effect on the vegetative and reproductive structures and fungal cell wall, respectively. The inhibition of the growth of the fungi and micro and ultra-structural affectations were explained considering that the size of the nanomaterials allows them to pass easily through the cell membranes. This indicates that they can be absorbed easily by the fungi tested here, causing cellular dysfunction. Nanofungicide effects are also attributable to the unique properties of nanomaterials, such as the high surface-to-bulk ratio of atoms and their surface physicochemical characteristics that could directly or indirectly produce reactive oxygen species (ROS), which affect the proteins of the cell wall.
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Antifúngicos/farmacología , Basidiomycota/efectos de los fármacos , Café/microbiología , Colletotrichum/efectos de los fármacos , Nanopartículas/química , Óxido de Zinc/farmacología , Basidiomycota/crecimiento & desarrollo , Basidiomycota/ultraestructura , Colletotrichum/crecimiento & desarrollo , Colletotrichum/aislamiento & purificación , Colletotrichum/ultraestructura , Pruebas de Sensibilidad Microbiana , Nanopartículas/ultraestructura , Cebollas/química , Tamaño de la Partícula , Extractos Vegetales/química , Espectrofotometría Ultravioleta , Difracción de Rayos XRESUMEN
Glycoproteins comprise more than half of current FDA-approved protein cancer markers, but the development of new glycoproteins as disease biomarkers has been stagnant. Here we present a pipeline to develop glycoproteins from extracellular vesicles (EVs) through integrating quantitative glycoproteomics with a novel reverse phase glycoprotein array and then apply it to identify novel biomarkers for breast cancer. EV glycoproteomics show promise in circumventing the problems plaguing current serum/plasma glycoproteomics and allowed us to identify hundreds of glycoproteins that have not been identified in blood. We identified 1,453 unique glycopeptides representing 556 glycoproteins in EVs, among which 20 were verified significantly higher in individual breast cancer patients. We further applied a novel glyco-specific reverse phase protein array to quantify a subset of the candidates. Together, this study demonstrates the great potential of this integrated pipeline for biomarker discovery.
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Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico por imagen , Vesículas Extracelulares/química , Glicoproteínas/sangre , Cromatografía Liquida , Femenino , Humanos , Espectrometría de Masas en TándemRESUMEN
ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).
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Redes Neurales de la Computación , Pruebas de Toxicidad Aguda , Administración Oral , Alternativas a las Pruebas en Animales , Animales , Barrera Hematoencefálica/metabolismo , Línea Celular , Supervivencia Celular , Ensayo de Unidades Formadoras de Colonias , Simulación por Computador , Citocinas/metabolismo , Humanos , Absorción Intestinal , Dosificación Letal Mediana , Ratones , Estrés Oxidativo , Ratas , Medición de RiesgoRESUMEN
Studies on hexose consumption by Saccharomyces cerevisiae show that glucose is consumed faster than fructose when both are present (9:1 fructose to glucose) in the medium during the fermentation of Agave. The objective of this work was to select strains of S. cerevisiae that consume fructose equal to or faster than glucose at high fructose concentrations by analyzing the influence of different glucose concentrations on the fructose consumption rate. The optimal growth conditions were determined by a kinetics assay using high performance liquid chromatography (HPLC) using 50 g of glucose and 50 g of fructose per liter of synthetic medium containing peptone and yeast extract. Using the same substrate concentrations, strain ITD-00185 was shown to have a higher reaction rate for fructose over glucose. At 75 g of fructose and 25 g of glucose per liter, strain ITD-00185 had a productivity of 1.02 gL(-1) h(-1) after 40 h and a fructose rate constant of 0.071 h(-1). It was observed that glucose concentration positively influences fructose consumption when present in a 3:1 ratio of fructose to glucose. Therefore, adapted strains at high fructose concentrations could be used as an alternative to traditional fermentation processes.
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Agave/metabolismo , Agave/microbiología , Fructosa/metabolismo , Glucosa/metabolismo , Saccharomyces cerevisiae/aislamiento & purificación , Saccharomyces cerevisiae/metabolismo , Cromatografía Líquida de Alta Presión , Medios de Cultivo/química , Fermentación , Saccharomyces cerevisiae/crecimiento & desarrolloRESUMEN
BACKGROUND: The role of venous blood gases as an alternative to arterial blood gases in patients with severe acute heart failure has not been established. OBJECTIVE: To assess the correlation between arterial and peripheral venous blood gases together with pulse-oximetry (SpO2), as well as to estimate arterial values from venous samples in the first hours upon admission of patients with acute cardiogenic pulmonary oedema. METHODS: Simultaneous venous and arterial blood samples were extracted on admission and over the next 1, 2, 3, 4, and 10 hours. SpO2 was also registered at the same intervals. RESULTS: A total of 178 pairs of samples were obtained from 34 consecutive patients with acute cardiogenic pulmonary oedema. Arterial and venous blood gases followed a parallel course in the first hours, showing high correlation rates at all time intervals. Venous samples underestimated pH (mean difference -0.028) and overestimated CO2 (+5.1 mmHg) and bicarbonate (+1 mEq/l). Conversely, SpO2 tended to underestimate SaO2 (mean±SD: 93.1±9.1 vs. 94.2±8.4). Applying simple mathematical formulae based on these differences, arterial values were empirically calculated from venous samples, showing acceptable agreement in the Bland-Altman test. Likewise, a venous pH <7.32, pCO2 >51.3 mmHg, and bicarbonate <22.8 mEq/l could fairly identify arterial acidosis, either respiratory or metabolic, with a test accuracy of 92, 68, and 91%, respectively. CONCLUSIONS: In patients with cardiogenic pulmonary oedema, arterial blood gas disturbances may be estimated from peripheral venous samples. By monitoring SpO2 simultaneously, arterial punctures could often be avoided.
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The medium-term fatigue behaviour of calf pericardium (similar to the one used to manufacture cardiac bioprostheses valve leaflets) has been studied. 96 samples were tested under fatigue subjecting them to biaxial stress at 1 Hz frequency for 5000 cycles, in 4 series of 24 samples, at several supra-physiological mean pressures and pressure amplitudes. Short-term damage parameters such as the accumulated energy consumption in 10 cycles (E10) and medium-term ones after 5000 cycles like total energy consumption (Et) and maximum displacement of the membrane (Dt) have been evaluated. E10 showed exponential growing tendency with pressure and linear tendency with pressure amplitude when only one parameter curve was plotted. Similar results were found when analysing Et and Dt. Linear correlation models were established between E10 and Et and E10 and Dt. Similar results were achieved in the four series, with excellent determination coefficients. The results confirm that the fatigue behaviour from the very first cycles of the test can predict the medium-term behaviour of the tissue by means of measurement of suitable damage markers. The tendencies observed between the parameters seem to show that the results could have been the same ones if the test had been performed at physiological pressures and amplitudes. This work opens the door to a non-destructive test of the tissue prior to employ it to manufacture valve leaflets.
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Ensayo de Materiales , Fenómenos Mecánicos , Pericardio , Animales , Fenómenos Biomecánicos , Bovinos , Modelos Lineales , Presión , Factores de TiempoRESUMEN
This paper describes the design and development of a system for cardio rehabilitation of patients that suffered a myocardial infarction. The proposed solution focuses on exercise prescriptions and the encouragement of healthy behaviors. The innovative strategy of the design takes into account health promotion models to provide safe, assistive exercise training sessions, personalized feedbacks, and educational contents.
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Sistemas Especialistas , Monitoreo Ambulatorio/instrumentación , Infarto del Miocardio/rehabilitación , Modalidades de Fisioterapia/instrumentación , Autocuidado/instrumentación , Telemedicina/instrumentación , Terapia Asistida por Computador/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Interfaz Usuario-ComputadorAsunto(s)
Infección Hospitalaria/epidemiología , Neoplasias Hematológicas/complicaciones , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/enzimología , Trasplante , beta-Lactamasas/biosíntesis , Antibacterianos/farmacología , Brasil , Carbapenémicos/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , ADN Bacteriano/genética , Genotipo , Desinfección de las Manos/métodos , Humanos , Huésped Inmunocomprometido , Control de Infecciones/métodos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/aislamiento & purificación , Trasplante de Células Madre/efectos adversos , Resistencia betalactámicaRESUMEN
Un total de 712 alumnos de escolaridad primaria, de ambos sexos, fue estudiado en este monitoreo de bocio endémico en dos localidades de la provincia de La Rioja: Ciudad de La Rioja (442 niños) y Chilecito (270 niños). La edad de los escolares osciló entre 5 y 16 años. La palpación tiroidea fue hecha por el conjunto de los médicos participantes. Sin embargo, con la finalidad de aunar criterios con lo realizado previamente (1-24), se tomó como única referencia la palpación de H.N., que se llevó a cabo en la totalidad de los niños estudiados. La definición del grado de bocio fue similar a la utilizada en los otros relevamientos (1). Se determinó la yoduria en muestras casuales de orina emitidas por los niños una vez que fueron palpados (125 de La Rioja y 128 de Chilecito). Se recolectaron 251 muestras de sal de consumo hogareño de La Rioja y 141 de Chilecito, para medir su contenido en yodo. El examen palpatorio de los niños reveló la existencia de bocio grado 1 solamente. La prevalencia de bocio encontrada fue de 1,8% en La Rioja y de 2,6% en Chilecito. Los niveles de yoduria alcanzaron, en La Rioja, una media de 226 ± 181 (DS) μg/L y una mediana de 186μg/L, al tiempo que en Chilecito la media fue de 217 ± 161μg/L y la mediana de 185μg/L. El contenido de yodo de las sales, que aportaron los alumnos desde sus hogares, fue adecuado para casi todas las marcas. De esta manera, observamos que en la ciudad de La Rioja el promedio de yodo en la sal, tomada en conjunto, fue de 33,1 ± 12,5 mg/Kg, mientras que para Chilecito fue de 28,1 ± 8,2 mg/Kg. Al analizar las concentraciones de yodo <15mg/Kg, observamos que fue del 10,7% en La Rioja y del 9,5% en Chilecito. Teniendo en cuenta la línea de corte del 10% que fija el ICCIDD (25) como valor óptimo, podemos observar que la situación fue prácticamente satisfactoria en ambas poblaciones. Concluímos que en estas dos poblaciones de la provincia de La Rioja no existe, actualmente, bocio endémico por deficiencia de yodo. Estos resultados indican que la profilaxis con sal yodada fue óptima en esta provincia, dado que en el pasado solía ser una típica zona yodo-deficiente con un muy alto porcentaje de bocio endémico.
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Argentina , Deficiencia de Yodo/prevención & control , Bocio Endémico/epidemiología , Deficiencia de Yodo/diagnóstico , Cloruro de Sodio/análisis , Estudios Poblacionales en Salud Pública , Monitoreo Epidemiológico , Yodo/orinaRESUMEN
A neural model based on a numerical molecular representation using CODES program to predict oral absorption of any structure is described. This model predicts both high and low-absorbed compounds with a global accuracy level of 74%. CODES/ANN methodology shows promising utilities not only as a conventional in silico tool in high-throughput screening or improvement of absorption capabilities procedures but also the improvement of in vitro-in vivo correlation could be addressed.
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Modelos Químicos , Tecnología Farmacéutica , Administración Oral , Humanos , Redes Neurales de la Computación , Permeabilidad , Relación Estructura-Actividad CuantitativaRESUMEN
Chagas disease, also known as American trypanosomiasis, is caused by infection with the protozoan parasite Trypanosoma cruzi. The Pan American Health Organization (PAHO) estimates that currently 7.7 million of people have Trypanosoma cruzi infection in the 21 endemic countries from the southern and southwestern United States to central Argentina and Chile. The only approved therapeutics for the treatment of Chagas disease are two nitroheterocyclic compounds as a nitrofuran (nifurtimox; Lampit) and a nitroimidazole (benznidazole; Rochagan). However, the anti-Trypanosoma cruzi activities of these compounds were discovered empirically over three decades ago. The treatment of Chagas disease with nifurtimox or benznidazole is unsatisfactory because of their limited efficacy in the prevalent chronic stage of the disease and their toxic side effects. In this context, this article will review the current knowledge of the different aspects involved in this illness, such as Trypanosoma cruzi transmission, physiology and biochemistry of the etiological agent, epidemiological aspects and current treatments for American trypanosomiasis. An important section of this review will focus on the different strategies in drug discovery for Chagas disease, including methodology, in vitro screening studies against whole parasites, novel rationally developed approaches on the basis of the increasing knowledge of the biochemistry of Trypanosoma cruzi and the recent progress in the understanding and validation of several targets for the therapy of Chagas's disease. A summary of the most relevant drug targets such as sterol biosynthesis pathway, cysteine protease pathway, pyrophosphate metabolism and purine salvage pathway will be reviewed. Moreover, recent studies regarding other strategies currently under development including thiol-dependent redox metabolism, lysophospholipid analogues and DNA binders will also be discussed.
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Enfermedad de Chagas/etiología , Trypanosoma cruzi/efectos de los fármacos , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/epidemiología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Ergosterol/biosíntesis , Ergosterol/metabolismo , Glutatión/análogos & derivados , Glutatión/química , Glutatión/uso terapéutico , Humanos , Hipoxantina Fosforribosiltransferasa/metabolismo , Espermidina/análogos & derivados , Espermidina/química , Espermidina/uso terapéuticoRESUMEN
Alzheimer's disease is a chronic and progressive neurodegenerative disorder. The presence of functional cannabinoid CB2 receptors in central nervous system (CNS) has provoked that this receptor and its agonist ligands are now considered as promising pharmacological targets for neurological diseases. Herein, we review the evidences supporting the potential role of the ECS as a therapeutic target, focused on CB2 receptor and its ligands, for the treatment of Alzheimer's disease.