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1.
Nat Commun ; 14(1): 6139, 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37783680

RESUMEN

The climate effects of atmospheric aerosol particles serving as cloud condensation nuclei (CCN) depend on chemical composition and hygroscopicity, which are highly variable on spatial and temporal scales. Here we present global CCN measurements, covering diverse environments from pristine to highly polluted conditions. We show that the effective aerosol hygroscopicity, κ, can be derived accurately from the fine aerosol mass fractions of organic particulate matter (ϵorg) and inorganic ions (ϵinorg) through a linear combination, κ = ϵorg ⋅ κorg + ϵinorg ⋅ κinorg. In spite of the chemical complexity of organic matter, its hygroscopicity is well captured and represented by a global average value of κorg = 0.12 ± 0.02 with κinorg = 0.63 ± 0.01 as the corresponding value for inorganic ions. By showing that the sensitivity of global climate forcing to changes in κorg and κinorg is small, we constrain a critically important aspect of global climate modelling.

2.
Angiol. (Barcelona) ; 75(5): 330-334, Sept-Oct, 2023. ilus
Artículo en Español | IBECS | ID: ibc-226590

RESUMEN

Introducción: en el contexto del trauma vascular, la ligadura de estructuras venosas periféricas es una prácticahabitual en su manejo, pero no está exenta de complicaciones y de secuelas; además, algunos estudios realizadosen las últimas guerras y en centros de trauma civil muestran los beneficios de realizar una reparación venosa. Casos clínicos: se presentan dos casos de traumas inciso-contusos en accidentes de tráfico en población pediátrica, uno de ellos con compromiso de la vena femoral común de forma aislada y un segundo caso con lesión de laarteria femoral superfi cial y de la vena femoral, ambos casos llevados a reconstrucción venosa con una evoluciónsatisfactoria. Discusión: aunque el manejo clásico de las lesiones venosas es la ligadura de la estructura, la literatura médica escontradictoria, ya que la evidencia actual sugiere una tendencia a favorecer la reconstrucción venosa. en pacienteshemodinámicamente inestables debe realizarse una ligadura o shunt de las grandes estructuras venosas; en lospacientes estables con lesiones en miembros inferiores, en especial los que presentan lesiones arteriales concomitantes, debe intentarse la reparación de la lesión venosa para disminuir el riesgo de amputación y las complicaciones secundarias a la hipertensión venosa.(AU)


Introduction: in the context of vascular trauma, the ligation of peripheral venous structures is a common practicein management, it is not exempt from complications and sequelae, in addition, some studies carried out in recentwars and in civilian trauma centers show benefits of performing a venous repair. Cases reports: two cases of blunt force trauma in traffic accidents in the pediatric population are presented, oneof them with isolated involvement of the common femoral vein and a second case with injury to the superficialfemoral artery and femoral vein, both cases led to venous reconstruction with an adequate outcome.Discussion: the classic management of venous injuries is the ligation of the structure, however, the current evidence has shown a tendency to favor venous reconstruction, but the current information is controversial. in hemodynamically unstable patients, a ligation or shunt of the large venous structures should be performed. in stablepatients with injuries to the lower limbs, especially those with concomitant arterial injuries, repair of the venous injury should be attempted to reduce the risk of amputation and complications secondary to venous hypertension.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Vena Femoral , Vena Femoral/lesiones , Anastomosis Quirúrgica , Accidentes de Tránsito , Pacientes Internos , Examen Físico , Evaluación de Síntomas
3.
Rev. colomb. cir ; 38(4): 735-740, 20230906. fig
Artículo en Español | LILACS | ID: biblio-1511131

RESUMEN

Introducción. La ingesta de cáusticos continúa siendo un problema de salud pública en los países en vía de desarrollo, por lo que a veces es necesario realizar un reemplazo esofágico en estos pacientes. Aún no existe una técnica estandarizada para este procedimiento. Caso clínico. Masculino de 10 años con estenosis esofágica por ingesta de cáusticos, quien no mejoró con las dilataciones endoscópicas. Se realizó un ascenso gástrico transhiatal por vía ortotópica mediante cirugía mínimamente invasiva como manejo quirúrgico definitivo .Discusión. Actualmente existen varios tipos de injertos usados en el reemplazo esofágico. La interposición colónica y gástrica son las que cuentan con mayores estudios, mostrando resultados similares. Conclusiones. La elección del tipo y posición del injerto debe ser individualizada, tomando en cuenta las características de las lesiones y la anatomía de cada paciente para aumentar la tasa de éxito.


Introduction. The ingestion of caustics continues to be a public health problem in developing countries, which is why sometimes is necessary to perform an esophageal replacement in these patients. There is still no standardized technique for this procedure. Clinical case. A 10-year-old male with esophageal stricture due to caustic ingestion, who did not improve with endoscopic dilations. A laparoscopic transhiatal gastric lift was performed orthotopically as definitive surgical management using minimally invasive surgery. Discussion. Currently there are several types of grafts used in esophageal replacement. Colonic and gastric interposition are the ones that have the most studies, showing similar results. Conclusions. Choice of type and position of the graft must be individualized, taking into account the characteristics of the lesions and anatomy of each patient, in order to increase the success rate.


Asunto(s)
Humanos , Pediatría , Cáusticos , Esofagectomía , Enfermedades del Esófago , Estenosis Esofágica , Esófago
4.
Angiol. (Barcelona) ; 75(4): 228-241, Juli-Agos. 2023. ilus, tab
Artículo en Español | IBECS | ID: ibc-223703

RESUMEN

La disección aórtica representa una afección relativamente poco común pero potencialmente mortal que se debe a un desgarro en la capa íntima de la arteria aorta o sangrado dentro de su pared, lo que da como resultado una separación de las capas de esta. Se han identificado varios factores de riesgo y comparten los mismos que para otras enfermedades cardiovasculares, como la edad, la hipertensión arterial, la dislipidemia y los trastornos genéticos del tejido conectivo. Es muy importante que el clínico pueda realizar un diagnóstico oportuno y un tratamiento adecuado en los pacientes afectados. El tipo de tratamiento depende de la extensión y de la localización de la disección. La reparación quirúrgica abierta suele ser la más usada para aquellas en las que están involucradas la aorta ascendente y el arco aórtico; por otro lado, la intervención endovascular está recomendada para las disecciones de la aorta descendente, que suelen ser complicadas. En este trabajo se revisará la epidemiología, la fisiopatología, las manifestaciones clínicas y finalmente el manejo de la disección aórtica.(AU)


Aortic dissection represents a relatively rare but highly fatal condition that is due to a tear in the intimal layer ofthe aortic artery or bleeding within its wall, resulting in a separation of its layers. Several risk factors have beenidentifi ed and share the same as for other cardiovascular diseases such as age, high blood pressure, dyslipidemiaand genetic disorders of connective tissue.It is very important that the clinician can make a timely diagnosis and appropriate treatment in patients affectedby it; the type of treatment depends on the extent and location of the dissection. open surgical repair is usuallythe most used for those that involve the ascending aorta and the aortic arch, on the other hand, endovascularintervention is recommended for dissections of the descending aorta that are usually complicated.In this work, the epidemiology, pathophysiology, clinical manifestations and finally the management of aorticdissection will be reviewed.(AU)


Asunto(s)
Humanos , Disección Aórtica/diagnóstico , Disección Aórtica/terapia , Disección Aórtica/cirugía , Aorta/lesiones , Disección Aórtica/epidemiología , Disección Aórtica/fisiopatología
5.
Commun Biol ; 6(1): 255, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36899051

RESUMEN

SETD2 is a tumor suppressor that is frequently inactivated in several cancer types. The mechanisms through which SETD2 inactivation promotes cancer are unclear, and whether targetable vulnerabilities exist in these tumors is unknown. Here we identify heightened mTORC1-associated gene expression programs and functionally higher levels of oxidative metabolism and protein synthesis as prominent consequences of Setd2 inactivation in KRAS-driven mouse models of lung adenocarcinoma. Blocking oxidative respiration and mTORC1 signaling abrogates the high rates of tumor cell proliferation and tumor growth specifically in SETD2-deficient tumors. Our data nominate SETD2 deficiency as a functional marker of sensitivity to clinically actionable therapeutics targeting oxidative respiration and mTORC1 signaling.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Animales , Ratones , Adenocarcinoma del Pulmón/genética , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Estrés Oxidativo , N-Metiltransferasa de Histona-Lisina/genética
6.
Pharmaceutics ; 15(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36986642

RESUMEN

Fungal infections are a growing public health concern worldwide and the emergence of antifungal resistance has limited the number of therapeutic options. Therefore, developing novel strategies for identifying and developing new antifungal compounds is an active area of research in the pharmaceutical industry. In this study, we purified and characterized a trypsin protease inhibitor obtained from Yellow Bell Pepper (Capsicum annuum L.) seeds. The inhibitor not only showed potent and specific activity against the pathogenic fungus Candida albicans, but was also found to be non-toxic against human cells. Furthermore, this inhibitor is unique in that it also inhibits α-1,4-glucosidase, positioning it as one of the first plant-derived protease inhibitors with dual biological activity. This exciting discovery opens new avenues for the development of this inhibitor as a promising antifungal agent and highlights the potential of plant-derived protease inhibitors as a rich source for the discovery of novel multifunctional bioactive molecules.

7.
J Am Heart Assoc ; 12(8): e026974, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-36942628

RESUMEN

Background Diagnosis of shockable rhythms leading to defibrillation remains integral to improving out-of-hospital cardiac arrest outcomes. New machine learning techniques have emerged to diagnose arrhythmias on ECGs. In out-of-hospital cardiac arrest, an algorithm within an automated external defibrillator is the major determinant to deliver defibrillation. This study developed and validated the performance of a convolution neural network (CNN) to diagnose shockable arrhythmias within a novel, miniaturized automated external defibrillator. Methods and Results There were 26 464 single-lead ECGs that comprised the study data set. ECGs of 7-s duration were retrospectively adjudicated by 3 physician readers (N=18 total readers). After exclusions (N=1582), ECGs were divided into training (N=23 156), validation (N=721), and test data sets (N=1005). CNN performance to diagnose shockable and nonshockable rhythms was reported with area under the receiver operating characteristic curve analysis, F1, and sensitivity and specificity calculations. The duration for the CNN to output was reported with the algorithm running within the automated external defibrillator. Internal and external validation analyses included CNN performance among arrhythmias, often mistaken for shockable rhythms, and performance among ECGs modified with noise to mimic artifacts. The CNN algorithm achieved an area under the receiver operating characteristic curve of 0.995 (95% CI, 0.990-1.0), sensitivity of 98%, and specificity of 100% to diagnose shockable rhythms. The F1 scores were 0.990 and 0.995 for shockable and nonshockable rhythms, respectively. After input of a 7-s ECG, the CNN generated an output in 383±29 ms (total time of 7.383 s). The CNN outperformed adjudicators in classifying atrial arrhythmias as nonshockable (specificity of 99.3%-98.1%) and was robust against noise artifacts (area under the receiver operating characteristic curve range, 0.871-0.999). Conclusions We demonstrate high diagnostic performance of a CNN algorithm for shockable and nonshockable rhythm arrhythmia classifications within a digitally connected automated external defibrillator. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03662802; Unique identifier: NCT03662802.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/terapia , Estudios Retrospectivos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Desfibriladores , Algoritmos , Electrocardiografía , Redes Neurales de la Computación , Reanimación Cardiopulmonar/métodos
8.
Annu Rev Entomol ; 68: 69-88, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36170643

RESUMEN

Mites are masters at attaching to larger animals, often insects, in a temporary symbiosis called phoresy that allows these tiny animals to exploit patchy resources. In this article, we examine phoresy in the Acari, including those that feed on their carriers in transit, from a broad perspective. From a phylogenetic perspective, phoresy has evolved several times from free-living ancestors but also has been lost frequently. Rotting logs appear to be the first patchy resource exploited by phoretic mites, but the evolution of rapid life cycles later permitted exploitation of short-lived resources. As phoresy is a temporary symbiosis, most species have off-host interactions with their carrier. These relationships can be highly complex and context dependent but often are exploitative of the carrier's resources or progeny. Transitions from phoresy to parasitism seem widespread, but evidence for transitions from obligate phoretic parasitism to permanent parasitism is weak.


Asunto(s)
Ácaros , Animales , Filogenia , Estadios del Ciclo de Vida , Simbiosis
9.
Diabetes Metab Syndr Obes ; 15: 1865-1876, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35757193

RESUMEN

Background: Chronic hyperinsulinemia is a hallmark of insulin resistance that affects a diversity of cells, including leukocytes modifying the expression of some genes involved in insulin signaling. Purpose: The aim of this study was to evaluate how hyperinsulinemia affects the expression of genes involved in the proximal insulin signaling pathway in leukocytes from 45 young individuals grouped: normal weight with not insulin resistance (NIR), with insulin resistance (IR) and with obesity (OB-IR). Methods: qPCR was performed to analyze the expression of insulin receptor (INSR), insulin receptor substrate 1 and 2 (IRS-1 and IRS-2), neutrophil elastase (NE), alpha 1 antitrypsin (A1AT), glucose transporters 1, 3 and 4 (GLUT-1, GLUT-3 and GLUT-4) by the 2-ΔCt method, and the correlation between the genes was determined by Spearman's test. Results: The mRNA expression analysis of all genes between NIR and IR individuals revealed no differences. However, when comparing NIR and IR individuals with OB-IR, an increase in NE and A1AT expression and a clear trend towards a decrease in IRS-2 expression was observed, whereas the comparison of IR and OB-IR showed a decrease in GLUT-3 expression. Overall, the correlation analysis showed that in the IR group there was a positive correlation only between NE with IRS-1 (r = 0.72, p = 0.003), while in the OB-IR group, there was a positive correlation between the NE and A1AT with INSR (r = 0.62, p = 0.01 and r = 0.74, p = 0.002, respectively) and with IRS-2 (r = 0.74, p = 0.002 and r = 0.76, p = 0.001, respectively). Conclusion: These results suggest that hyperinsulinemia and obesity are associated with changes in the expression of genes in leukocytes involved in the insulin pathway that are related to NE and A1AT.

10.
Glob Chang Biol ; 28(2): 588-611, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34562049

RESUMEN

High-quality atmospheric CO2  measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2 . In this study, we present the first 6 years (2014-2019) of continuous, high-precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1°S, 58.9°W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal ( ΔCO2obs ) that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter-annual scales, we find differences in phase between ΔCO2obs and the local eddy covariance net ecosystem exchange (EC-NEE), which is interpreted as an indicator of a decoupling between local and non-local drivers of ΔCO2obs . In addition, we present how the 2015-2016 El Niño-induced drought was captured by our atmospheric record as a positive 2σ anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter-annual variability of ΔCO2obs together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non-optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data-driven non-optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.


Asunto(s)
Dióxido de Carbono , Ecosistema , Ciclo del Carbono , Ríos , Estaciones del Año
11.
J Leukoc Biol ; 111(1): 197-208, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-33724523

RESUMEN

Insulin is the hormone responsible for maintaining glucose homeostasis in the body, in addition to participating in lipid metabolism, protein synthesis, and the inhibition of gluconeogenesis. These functions are well characterized in the classic organ target cells that are responsible for general energy regulation: the liver, skeletal muscle, and adipose tissue. However, these actions are not restricted to these tissues because insulin has been shown to affect most cells in the body. This review describes the role of insulin in leukocyte signaling pathways, metabolism and functions, and how insulin resistance could affect this signaling and deteriorate leukocyte metabolism and function, in addition to showing evidence that suggests leukocytes may substantially contribute to the development of systemic insulin resistance.


Asunto(s)
Metabolismo Energético , Insulina/metabolismo , Leucocitos/metabolismo , Animales , Glucosa/metabolismo , Humanos , Resistencia a la Insulina , Leucocitos/citología , Metabolismo de los Lípidos , Transducción de Señal
12.
Rev. colomb. cir ; 37(2): 245-250, 20220316. tab, fig
Artículo en Español | LILACS | ID: biblio-1362958

RESUMEN

Introducción. Los linfangiomas son anormalidades benignas del sistema linfático, que corresponden a dilataciones quísticas de estos vasos y se localizan especialmente en el cuello. Solo el 10 % de todas estas malformaciones se encuentran en el abdomen y presentan síntomas variables de acuerdo al tamaño y su ubicación especifica, siendo el dolor abdominal el principal síntoma. Métodos. Se presentan cinco pacientes pediátricos con malformaciones linfáticas abdominales. Se describen su cuadro clínico, localización, tratamiento y la experiencia en el manejo de dicha patología en un hospital de referencia. Resultados. Los métodos más apropiados para hacer una aproximación diagnóstica son la ecografía, la tomografía computarizada y la resonancia nuclear magnética. Dentro de las opciones descritas para el tratamiento están la farmacológica, la escleroterapia y la resección quirúrgica, tanto por vía abierta como por laparoscopia. Conclusión. Existe una variedad de métodos para realizar la resección de los linfangiomas abdominales, pero la cirugía sigue siendo la más efectiva, especialmente cuando se cuenta con la laparoscopia como una herramienta terapéutica.


Introduction. Lymphangiomas are benign abnormalities of the lymphatic system, which correspond to cystic dilations of these vessels and are located especially in the neck. Only 10% of all these malformations are found in the abdomen and present variable symptoms according to size and their specific location, with abdominal pain being the main symptom. Methods. Five pediatric patients with abdominal lymphatic malformations are presented. Their clinical presentation, location, treatment and experience in the management of this pathology in a referral hospital are described. Results. The most appropriate methods to make a diagnostic approach are ultrasound, computed tomography and magnetic resonance imaging. Among the options described for treatment are pharmacological, sclerotherapy and surgical resection, both open and laparoscopic. Conclusion. There are a variety of methods for resecting abdominal lymphangiomas, but surgery remains the most effective, especially when laparoscopy is used as a therapeutic tool.


Asunto(s)
Humanos , Linfangioma , Enfermedades Linfáticas , Escleroterapia , Laparoscopía , Sistema Linfático
13.
PLoS Genet ; 17(12): e1009941, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34879057

RESUMEN

The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation in vivo. In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to Rb knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function in vivo.


Asunto(s)
Neoplasias Hipofisarias/genética , Proteínas de Unión a Retinoblastoma/genética , Neoplasias de la Tiroides/genética , Animales , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Modelos Animales de Enfermedad , Factores de Transcripción E2F/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Ratones Transgénicos , Células 3T3 NIH , Neoplasias Hipofisarias/patología , ARN Interferente Pequeño/metabolismo , Neoplasias de la Tiroides/patología
14.
Int J Biol Macromol ; 192: 931-938, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34656538

RESUMEN

In recent years, many attempts have been made to find new plant proteases to make artisan cheeses. The global increase in cheese consumption, together with a lower supply and increasing cost of calf rennet, religious factors (Islam and Judaism) and food choices (vegetarianism) have led to the search for suitable rennet substitutes for milk clotting. This study describes the milk-clotting and hydrolytic activities of an aspartic protease from Salpichroa origanifolia fruits (SoAP) on individual caseins to explore its potential use as an alternative to animal rennet. The milk-clotting index obtained for SoAP was 8.4 times lower than that obtained for chymosin. SoAP showed a higher degree of hydrolysis on α-casein than on the other fractions under the proposed conditions. RP-HPLC, mass spectrometry analyses and sequencing of the hydrolysates allowed identifying five peptides from α-casein, one peptide from ß-casein, and three peptides from k-casein. In silico analysis showed that the peptides identified may display a wide variety of potential biological activities. These results demonstrate the possibility of using SoAP for the manufacture of new types or artisan cheeses, with the simultaneous added value of the potential health-promoting benefits of the bioactive peptides generated during the hydrolysis.


Asunto(s)
Proteasas de Ácido Aspártico/química , Caseínas/química , Frutas/enzimología , Leche/química , Solanaceae/enzimología , Animales , Proteasas de Ácido Aspártico/aislamiento & purificación , Queso/análisis , Fenómenos Químicos , Activación Enzimática , Frutas/química , Hidrólisis , Cinética , Extractos Vegetales , Solanaceae/química , Relación Estructura-Actividad
15.
Nat Commun ; 12(1): 4800, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34417450

RESUMEN

Histone lysine methylations have primarily been linked to selective recruitment of reader or effector proteins that subsequently modify chromatin regions and mediate genome functions. Here, we describe a divergent role for histone H4 lysine 20 mono-methylation (H4K20me1) and demonstrate that it directly facilitates chromatin openness and accessibility by disrupting chromatin folding. Thus, accumulation of H4K20me1 demarcates highly accessible chromatin at genes, and this is maintained throughout the cell cycle. In vitro, H4K20me1-containing nucleosomal arrays with nucleosome repeat lengths (NRL) of 187 and 197 are less compact than unmethylated (H4K20me0) or trimethylated (H4K20me3) arrays. Concordantly, and in contrast to trimethylated and unmethylated tails, solid-state NMR data shows that H4K20 mono-methylation changes the H4 conformational state and leads to more dynamic histone H4-tails. Notably, the increased chromatin accessibility mediated by H4K20me1 facilitates gene expression, particularly of housekeeping genes. Altogether, we show how the methylation state of a single histone H4 residue operates as a focal point in chromatin structure control. While H4K20me1 directly promotes chromatin openness at highly transcribed genes, it also serves as a stepping-stone for H4K20me3-dependent chromatin compaction.


Asunto(s)
Cromatina/metabolismo , Genes Esenciales , Histonas/metabolismo , Lisina/metabolismo , Transcripción Genética , Secuencia de Aminoácidos , Animales , Ciclo Celular/genética , Línea Celular , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/química , Humanos , Espectroscopía de Resonancia Magnética , Metilación , Ratones , Modelos Biológicos , Nucleosomas/metabolismo , Conformación Proteica
16.
Pharmaceutics ; 13(8)2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34452114

RESUMEN

Geoffroea decorticans is a xerophilous deciduous tree present in most arid forests of southern South America, which is commonly used in traditional medicine. The seeds of this tree have been previously investigated for their singular chemical composition, but their protein content has been poorly investigated. Herein, we report the isolation, purification, and characterization of a set of thermostable peptides derived from Geoffroea decorticans seeds (GdAPs) with strong antioxidant and anticoagulant activities. The most potent antioxidant peptides showed a half maximal inhibitory concentration (IC50) of 35.5 ± 0.3 µg/mL determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH). They also caused a dose-dependent prolongation of the aPTT clotting time with an IC50 value of ~82 µg/mL. Interestingly, MALDI-TOF/MS analysis showed the presence of three major peptides with low molecular weights of 2257.199 Da, 2717.165 Da, and 5422.002 Da. The derived amino-acid sequence of GdAPs revealed their unique structural features, exhibiting homology with various proteins present in the genome of Arachis hypogaea. All in all, our data suggest a direct applicability of GdAPs for pharmaceutical purposes.

17.
Pharmaceutics ; 13(4)2021 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-33917878

RESUMEN

Plant cystatins (or phytocystatins) comprise a large superfamily of natural bioactive small proteins that typically act as protein inhibitors of papain-like cysteine proteases. In this report, we present the purification and characterization of the first phytocystatin isolated from Moringa oleifera (MoPI). MoPI has a molecular mass of 19 kDa and showed an extraordinary physicochemical stability against acidic pHs and high temperatures. Our findings also revealed that MoPI is one of the most potent cysteine protease inhibitors reported to date, with Ki and IC50 values of 2.1 nM and 5.7 nM, respectively. More interestingly, MoPI presents a strong antimicrobial activity against human pathogens such as Enterococcus faecalis and Staphylococcus aureus. In addition, MoPI also showed important anticoagulant activity, which is an unprecedented property for this family of protease inhibitors. These results highlight the pharmaceutical potential of this plant and its derived bioactive molecules.

18.
Cancer Res ; 81(12): 3241-3254, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33619116

RESUMEN

Fusion genes including NPM-ALK can promote T-cell transformation, but the signals required to drive a healthy T cell to become malignant remain undefined. In this study, we introduce NPM-ALK into primary human T cells and demonstrate induction of the epithelial-to-mesenchymal transition (EMT) program, attenuation of most T-cell effector programs, reemergence of an immature epigenomic profile, and dynamic regulation of c-Myc, E2F, and PI3K/mTOR signaling pathways early during transformation. A mutant of NPM-ALK failed to bind several signaling complexes including GRB2/SOS, SHC1, SHC4, and UBASH3B and was unable to transform T cells. Finally, T-cell receptor (TCR)-generated signals were required to achieve T-cell transformation, explaining how healthy individuals can harbor T cells with NPM-ALK translocations. These findings describe the fundamental mechanisms of NPM-ALK-mediated oncogenesis and may serve as a model to better understand factors that regulate tumor formation. SIGNIFICANCE: This investigation into malignant transformation of T cells uncovers a requirement for TCR triggering, elucidates integral signaling complexes nucleated by NPM-ALK, and delineates dynamic transcriptional changes as a T cell transforms.See related commentary by Spasevska and Myklebust, p. 3160.


Asunto(s)
Desdiferenciación Celular , Transformación Celular Neoplásica/patología , Reprogramación Celular , Linfoma Anaplásico de Células Grandes/patología , Proteínas Tirosina Quinasas/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/inmunología , Apoptosis , Proliferación Celular , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/metabolismo , Humanos , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/inmunología , Linfoma Anaplásico de Células Grandes/metabolismo , Fosforilación , Proteínas Tirosina Quinasas/genética , Receptores de Antígenos de Linfocitos T/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Células Tumorales Cultivadas
19.
BMJ Qual Saf ; 30(3): 216-227, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32350128

RESUMEN

BACKGROUND: Understanding adverse events among children treated in the emergency department (ED) offers an opportunity to improve patient safety by providing evidence of where to focus efforts in a resource-restricted environment. OBJECTIVE: To estimate the risk of adverse events, their type, preventability and severity, for children seen in a paediatric ED. METHODS: This prospective cohort study examined outcomes of patients presenting to a paediatric ED over a 1-year period. The primary outcome was the proportion of patients with an adverse event (harm to patient related to healthcare received) related to ED care within 3 weeks of their visit. We conducted structured telephone interviews with all patients and families over a 3-week period following their visit to identify flagged outcomes (such as repeat ED visits, worsening symptoms) and screened admitted patients' health records with a validated trigger tool. For patients with flagged outcomes or triggers, three ED physicians independently determined whether an adverse event occurred. RESULTS: Of 1567 eligible patients, 1367 (87.2%) were enrolled and 1319 (96.5%) reached in follow-up. Median patient age was 4.34 years (IQR 1.5 to 10.57 years) and most (n=1281; 93.7%) were discharged. Among those with follow-up, 33 (2.5%, 95% CI 1.8% to 3.5%) suffered an adverse event related to ED care. None experienced more than one event. Twenty-nine adverse events (87.9%, 95% CI 72.7% to 95.2%) were deemed preventable. The most common types of adverse events (not mutually exclusive) were management issues (51.5%), diagnostic issues (45.5%) and suboptimal follow-up (15.2%). CONCLUSION: One in 40 children suffered adverse events related to ED care. A high proportion of events were preventable. Management and diagnostic issues warrant further study.


Asunto(s)
Servicio de Urgencia en Hospital , Médicos , Niño , Preescolar , Humanos , Lactante , Alta del Paciente , Seguridad del Paciente , Estudios Prospectivos
20.
BMJ Case Rep ; 13(8)2020 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-32847890

RESUMEN

The mediastinum is a rare site for occurrence of a primary synovial sarcoma (SS) with very few cases reported in the literature. The diagnosis so far has been achieved mainly via open surgery, with only three reported cases diagnosed via endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), however, none of those were located at the posterior mediastinum, without showing any oesophageal or endobronchial involvement. To our knowledge, this is the first reported case of a monophasic primary pleural mediastinal SS purely involving the posterior mediastinum without oesophageal or endobronchial component, diagnosed via EBUS-TBNA.


Asunto(s)
Neoplasias del Mediastino/patología , Neoplasias Pleurales/patología , Sarcoma Sinovial/patología , Anciano , Broncoscopía , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Humanos , Masculino
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