ABSTRACT
Bioactive peptides derived from plant sources have gained significant attention for their potential use in preventing and treating chronic degenerative diseases. However, the efficacy of these peptides depends on their bioaccessibility, bioavailability, and stability. Encapsulation is a promising strategy for improving the therapeutic use of these compounds. It enhances their stability, prolongs their shelf life, protects them from degradation during digestion, and enables better release control by improving their bioaccessibility and bioavailability. This review aims to analyze the impact of various factors related to peptide encapsulation on their stability and release to enhance their biological activity. To achieve this, it is necessary to determine the composition and physicochemical properties of the capsule, which are influenced by the wall materials, encapsulation technique, and operating conditions. Furthermore, for peptide encapsulation, their charge, size, and hydrophobicity must be considered. Recent research has focused on the advancement of novel encapsulation methodologies that permit the formation of uniform capsules in terms of size and shape. In addition, it explores novel wall materials, including polysaccharides derived from unconventional sources, that allow the precise regulation of the rate at which peptides are released into the intestine.
ABSTRACT
Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.
Subject(s)
Baccharis , Quercetin , Quinic Acid/analogs & derivatives , Chile , Tandem Mass Spectrometry , Phytochemicals/pharmacology , Flavonoids/pharmacology , Plant Extracts/pharmacologyABSTRACT
The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase, but exerts serine/threonine kinase activity. DLK has been implicated in many diseases, including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and, ultimately, MAPK. In addition, other mechanisms such as protein-protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide better insights into DLK action and, possibly, new targets to modulate DLK function.
Subject(s)
Leucine Zippers , MAP Kinase Kinase Kinases , MAP Kinase Kinase Kinases/metabolism , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Serine/metabolism , Threonine/metabolismABSTRACT
Attention deficit-hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. Magnetic resonance imaging (MRI) has revealed that neuroanatomical abnormalities such as the volume reduction in the neocortex and hippocampus are shared by several neuropsychiatric diseases such as schizophrenia, autism spectrum disorder and ADHD. Furthermore, the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability are well documented. Dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity that triggers intracellular cascades involving glutamate receptors, calcium influx and remodeling of the F-actin network. The long-term potentiation (LTP)-induced insertion of postsynaptic glutamate receptors is associated with the enlargement of spine heads and long-term depression (LTD) with spine shrinkage. Using a murine model of ADHD, a delay in dendritic spines' maturation in CA1 hippocampal neurons correlated with impaired working memory and hippocampal LTP has recently reported. The aim of this review is to summarize recent evidence that has emerged from studies focused on the neuroanatomical and genetic features found in ADHD patients as well as reports from animal models describing the molecular structure and remodeling of dendritic spines.
ABSTRACT
Advances in genomic technologies have significantly improved the management of colorectal cancer (CRC). Several biomarkers have been identified in CRC that enable personalization in the use of biologic agents that have shown to enhance the clinical outcomes of patients. However, technologies used for their determination generate massive amounts of information that can be difficult for the clinician to interpret and use adequately. Through several discussion meetings, a group of oncology experts from Spain and several Latin American countries reviewed the latest literature to provide practical recommendations on the determination of biomarkers in CRC based on their clinical experience. The article also describes the importance of looking for additional prognostic biomarkers and the use of histopathology to establish an adequate molecular classification. Present and future of immunotherapy biomarkers in CRC patients are also discussed, together with several techniques for marker determination, including liquid biopsy, next-generation sequencing (NGS), polymerase chain reaction (PCR), and fecal immunohistochemical tests. Finally, the role of Molecular Tumor Boards in the diagnosis and treatment of CRC is described. All of this information will allow us to highlight the importance of biomarker determination in CRC.
ABSTRACT
The conversion factor of nitrogen to proteins and isoflavones present in Glycine max was determined. For the determination of the conversion factor, we worked with solubilizing the proteins at alkaline pH and then extracting them with acidic pH. The proteins were identified by the Kjeldahl method. The antioxidant capacity was determined after extracting the isoflavones and their glycosides through the Soxhlet method, and then using the Brand Williams method (DPPH). The results indicate that the protein conversion factor was 5.85, the maximum concentration of total isoflavones was 33.33%, the antiradical efficiency of total isoflavones was 0.004 mL/ug min, the antiradical efficiency of gallic acid was 0.005 mL/ug min. and the antiradical efficiency of tannic acid was 0.0004 mL/ugmin. These results justify the consumption of Glycine max (Soya) as a food that has a high nutritional quality and provides an excellent source of antioxidants, which will prevent hormonal and carcinogenic diseases.
Se determinó el factor de conversión de nitrógeno a proteínas e isoflavonas presentes en Glycine max. Para la determinación del factor de conversión se trabajó con solubilizando las proteínas a pH alcalinos y luego extrayéndolas con pH ácidos. Las proteínas fueron identificadas por el método Kjeldahl. La capacidad antioxidante se determinó previa extracción de las isoflavonas y sus glicósidos a través del método de Soxhlet, y luego empleando el método de Brand Williams (DPPH).Los resultados indican que el factor de conversión proteica fue 5,85, la concentración máxima de isoflavonas totales fue 33,33 %, la eficiencia antirradicalaria de las isoflavonas totales fue 0,004 mL/ug min, la eficiencia antirradicalaria de ácido gálico fue 0,005 mL/ug min y la eficiencia antirradicalaria de ácido tánico fue 0,0004 mL/ug min. Estos resultados justifican el consumo de Glycine max (Soya) como un alimento que posee una alta calidad nutricional y proporciona una óptima fuente de antioxidantes, que permitirá prevenir enfermedades hormonales y cancerígenas.
Subject(s)
Plant Proteins/pharmacology , Protein Conformation , Glycine max/chemistry , Isoflavones/pharmacology , Plant Proteins/metabolism , Plants, Medicinal , Glycine max/metabolismABSTRACT
Medicinal plants have been used since prehistoric times and continue to treat several diseases as a fundamental part of the healing process. Inflammation is a condition characterized by redness, pain, and swelling. This process is a hard response by living tissue to any injury. Furthermore, inflammation is produced by various diseases such as rheumatic and immune-mediated conditions, cancer, cardiovascular diseases, obesity, and diabetes. Hence, anti-inflammatory-based treatments could emerge as a novel and exciting approach to treating these diseases. Medicinal plants and their secondary metabolites are known for their anti-inflammatory properties, and this review introduces various native Chilean plants whose anti-inflammatory effects have been evaluated in experimental studies. Fragaria chiloensis, Ugni molinae, Buddleja globosa, Aristotelia chilensis, Berberis microphylla, and Quillaja saponaria are some native species analyzed in this review. Since inflammation treatment is not a one-dimensional solution, this review seeks a multidimensional therapeutic approach to inflammation with plant extracts based on scientific and ancestral knowledge.
ABSTRACT
One of the main skills in internal medicine is clinical decision making. To make clinical decisions, physicians in training reorganize their knowledge in order to optimally perform their clinical functions (diagnosis, research methods and treatment), which are organized according to disease scripts. This ability develops with experience and is acquired during their academic training. The script concordance test has been described as an innovative evaluation tool, designed to evaluate clinical decision making (clinical reasoning) in addition to the degree of knowledge. The script theory, understood as the organization of knowledge, is the basis for decision making. Disease scripts play a key role in supporting and developing clinical reasoning skills, which should be acquired in order to produce differential diagnoses and interpret clinical data. (Acta Med Colomb 2022; 48. DOI:https://doi.org/10.36104/amc.2023.2569).
ABSTRACT
The dual leucine zipper kinase (DLK) and the ubiquitously expressed transcription factor c-FOS have important roles in beta-cell proliferation and function. Some studies in neuronal cells suggest that DLK can influence c-FOS expression. Given that c-FOS is mainly regulated at the transcriptional level, the effect of DLK on c-FOS promoter activity was investigated in the beta-cell line HIT. The methods used in this study are the following: Luciferase reporter gene assays, immunoblot analysis, CRISPR-Cas9-mediated genome editing, and real-time quantitative PCR. In the beta-cell line HIT, overexpressed DLK increased c-FOS promoter activity twofold. Using 5'-,3'-promoter deletions, the promoter regions from - 348 to - 339 base pairs (bp) and from a - 284 to - 53 bp conferred basal activity, whereas the promoter region from - 711 to - 348 bp and from - 53 to + 48 bp mediated DLK responsiveness. Mutation of the cAMP response element within the promoter prevented the stimulatory effect of DLK. Treatment of HIT cells with KCl and the adenylate cyclase activator forskolin increased c-FOS promoter transcriptional activity ninefold. Since the transcriptional activity of those promoter fragments activated by KCl and forskolin was decreased by DLK, DLK might interfere with KCl/forskolin-induced signaling. In a newly generated, genome-edited HIT cell line lacking catalytically active DLK, c-Fos mRNA levels were reduced by 80% compared to the wild-type cell line. DLK increased c-FOS promoter activity but decreased stimulated transcriptional activity, suggesting that DLK fine-tunes c-FOS promoter-dependent gene transcription. Moreover, at least in HIT cells, DLK is required for FOS mRNA expression.
Subject(s)
Leucine Zippers , MAP Kinase Kinase Kinases , Colforsin , MAP Kinase Kinase Kinases/metabolism , Cell Line , Promoter Regions, Genetic , Proto-Oncogene Proteins c-fos/genetics , Proto-Oncogene Proteins c-fos/metabolismABSTRACT
Introducción: el mixoma odontogénico es una neoplasia benigna, poco frecuente, de origen mesenquimal proveniente del órgano dentario, es localmente invasivo y no hace metástasis. Su localización más frecuente es a nivel de la mandíbula y poco frecuente en el maxilar. Objetivo: describir las características que presenta un mixoma odontogénico de larga data en el maxilar. Presentación del caso: paciente de sexo masculino de 23 años de edad, soltero, de profesión comerciante, acude a la Catedra de Patología Bucal de la Facultad de Odontología de la Universidad Nacional de Asunción por presentar una deformidad en la región facial del lado derecho, presente desde la infancia con crecimiento lento sin sintomatología dolorosa. Se realizó una biopsia incisional, tomando una muestra de más de 1 cm de la capsula tumoral para su estudio histopatológico; a partir de la cual se informa sobre un tumor odontogénico mesenquimal compatible con el mixoma odontogénico. Se realizó el tratamiento de una maxilectomía con márgenes de seguridad y el estudio anatomopatológico de todo el tumor extirpado confirmó el diagnóstico de Mixofibroma odontogénico de 2,5 cm de diámetro máximo. Conclusión: un diagnóstico precoz de tumores como los mixomas, que son de crecimiento lento e infiltrante, podría garantizar terapéuticas menos agresivas e invasivas como las del caso presentado, otorgando así mejor pronóstico como calidad de vida a los pacientes.
Introduction: Odontogenic myxoma is a rare benign neoplasm of mesenchymal origin originating from the dental organ, it is locally invasive and does not metastasize. Its most frequent location is at the level of the mandible and infrequently in the maxilla. Objective: To describe the characteristics of a long-standing odontogenic myxoma in the maxilla. Presentation of the case: Male patient, 23 years of age, single, businessman, came to the Department of Oral Pathology of the Faculty of Dentistry of the National University of Asuncion for presenting a deformity in the facial region on the right side, present since childhood with slow growth and no painful symptomatology. An incisional biopsy was performed, taking a sample of more than 1cm of the tumor capsule, for histopathological study; reporting a mesenchymal odontogenic tumor compatible with odontogenic myxoma. A maxillectomy treatment with safety margins performed and the anatomopathological study of the entire excised tumor confirmed the diagnosis of odontogenic myxofibroma with a maximum diameter of 2.5 cm. Conclusion: An early diagnosis of tumors such as myxomas, which are slow-growing and infiltrative, could guarantee less aggressive and invasive therapies such as those in the case presented, thus providing patients with a better prognosis and quality of life.
Subject(s)
Humans , Male , Young AdultABSTRACT
Calcium oxalate (CaOx) crystals in plants are formed in crystal idioblasts cells and have specific geometric shapes. Their proposed functions include calcium homeostasis and carbon source, among others. Amaranth is a plant that presents high tolerance to abiotic stresses and accumulates considerable amounts of CaOx crystals; however, few studies have focused on characterizing the crystals ultrastructure and none is related to identifying proteins bound to them. This information is of great interest to understand the mechanisms related to CaOx crystal formation and to support their proposed functions. Thus, this work aimed to characterize CaOx crystals in amaranth leaves. Crystals were purified and the proteins bound to them were isolated and identified by nLC-MS/MS. Leaf sections were analyzed by light and electron microscopy. The identified proteins were related to the chloroplast such as ATPb synthase, RuBisCO large subunit, and cell wall-related proteins, which were validated by immunohistochemistry and immunogold labeling. In addition, it was observed that CaOx crystal idioblasts were formed from parenchyma cells associated with mesophyll and veins, in which the thylakoid membranes of degraded chloroplasts turned into crystal chambers. These results significantly advance our understanding of the mechanisms of CaOx crystal formation and the potential function as an alternative carbon source in leaves.
Subject(s)
Calcium Oxalate , Calcium , Calcium Oxalate/chemistry , Carbon , Chloroplasts/metabolism , Crystallization , Ribulose-Bisphosphate Carboxylase , Tandem Mass SpectrometryABSTRACT
KCNQ1 (Kv7.1 or KvLQT1) is a voltage-gated potassium ion channel that is involved in the ventricular repolarization following an action potential in the heart. It forms a complex with KCNE1 in the heart and is the pore forming subunit of slow delayed rectifier potassium current (Iks). Mutations in KCNQ1, leading to a dysfunctional channel or loss of activity have been implicated in a cardiac disorder, long QT syndrome. In this study, we report the overexpression, purification, biochemical characterization of human KCNQ1100-370, and lipid bilayer dynamics upon interaction with KCNQ1100-370. The recombinant human KCNQ1 was expressed in Escherichia coli and purified into n-dodecylphosphocholine (DPC) micelles. The purified KCNQ1100-370 was biochemically characterized by SDS-PAGE electrophoresis, western blot and nano-LC-MS/MS to confirm the identity of the protein. Circular dichroism (CD) spectroscopy was utilized to confirm the secondary structure of purified protein in vesicles. Furthermore, 31P and 2H solid-state NMR spectroscopy in DPPC/POPC/POPG vesicles (MLVs) indicated a direct interaction between KCNQ100-370 and the phospholipid head groups. Finally, a visual inspection of KCNQ1100-370 incorporated into MLVs was confirmed by transmission electron microscopy (TEM). The findings of this study provide avenues for future structural studies of the human KCNQ1 ion channel to have an in depth understanding of its structure-function relationship.
Subject(s)
Long QT Syndrome , Potassium Channels, Voltage-Gated , Humans , KCNQ1 Potassium Channel/metabolism , Potassium/metabolism , Potassium Channels , Potassium Channels, Voltage-Gated/metabolism , Tandem Mass SpectrometryABSTRACT
Resumen La estomatitis aftosa recurrente (EAR) es una patología ulcerativa crónica idiopática, que, aunque no llega a comprometer la vida de los pacientes, si puede desmejorar su calidad de vida. Presenta una alta incidencia en la población con un alto porcentaje de recurrencia. Atendiendo a su importancia, el objetivo de esta revisión es brindar una actualización respecto a las terapias farmacológicas y con láser para el manejo de la estomatitis aftosa recurrente. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Science Direct, EBSCO HOST y LILACS desde enero de 2010 a octubre de 2020, identificando publicaciones en inglés y español. Los artículos que fueron incluidos debían estar relacionadas con la estomatitis aftosa y su tratamiento, enfocándose en el manejo farmacológico o con láser. La estrategia de búsqueda arrojó 4536 citas bibliográficas, de las cuales fueron incluidas 19 en esta presente revisión. La mayoría de los estudios fueron ensayos clínicos aleatorizados donde la población objeto fueron adultos que demostraron el uso de antiinflamatorios, inmunomoduladores, anticuerpos monoclonales, antisépticos, anestésicos, entre otros, para el manejo de la estomatitis aftosa recurrente. De los artículos analizados se pudo concluir que la terapia farmacológica debe ser instaurada de manera particular, de acuerdo a la clínica y antecedentes del paciente. Los fármacos de primera elección son de uso tópico, reservando los de uso sistémico para casos moderados o severos y para pacientes con tratamiento refractarios, asimismo, las recomendaciones coadyuvantes como alimentación e higiene pueden ayudar a la resolución de la enfermedad. La terapia láser surge como alternativa de tratamiento con bajo riesgo y buenos resultados para la EAR.
Abstract Recurrent Aphthous Stomatitis (RAS) is an idiopathic chronic ulcerative pathology. Although it does not compromise the life of the patients, it can impair their quality of life. It presents a high incidence in the population and a high percentage of recurrence. In view of its importance, the aim of this review is to provide an update on pharmacological and laser therapies that are being implemented for the management of RAS. A bibliographic search of literature that was published between January 2010 and October 2020 was performed in PubMed, Science Direct, EBSCOhost, and LILACS databases, identifying publications in English and Spanish languages. The articles that were included had to be related to aphthous stomatitis and its treatment, focusing on pharmacological or laser management. 4536 bibliographic citations were found and 19 of them were included in this review. Most of the studies were randomized clinical trials in which the target population were adults that reported the use of anti-inflammatory drugs, immunomodulators, monoclonal antibodies, antiseptics, anesthetics, among others for the treatment of recurrent aphthous stomatitis. From the articles analyzed, it was possible to conclude that pharmacological therapy should be established in a particular way according to the patient's symptoms and medical record. The first-choice drugs are of topical use, reserving those of systemic use for moderate or severe cases and for patients with refractory treatment. Likewise, adjuvant recommendations such as nutrition and hygiene can help in the resolution of the disease. Laser therapy emerges as an alternative treatment with low risk and positive results for recurrent aphthous stomatitis.
ABSTRACT
RESUMEN Introducción/objetivo: La medición del ambiente de aprendizaje en medicina es fundamental para evaluar la calidad de la educación médica. Existen múltiples instrumentos diseñados para este propósito, pero su contenido, fundamento teórico y utilidad práctica son variables. El objetivo de este estudio es sintetizar la validez de contenido y alcance de estos instrumentos. Métodos: Se realizó una revisión sistemática de la literatura de estudios originales en idioma inglés y español publicados desde 1990 hasta 2018 en las bases de datos de Pubmed, ERIC, British Nursing Index, Google Scholar, Science Direct, Cochrane, CINALH y Latindex, que contienen instrumentos para medir el ambiente de aprendizaje en medicina. Se analizaron los dominios, fundamentos teóricos y métodos para determinar la validez de contenido. Resultados: Se incluyeron treinta y ocho estudios que evaluaron doce instrumentos (uno disponible en español). Dos instrumentos identificados fueron específicos para el ambiente quirúrgico y uno para el comunitario. Únicamente tres instrumentos estuvieron respaldados por una teoría educativa. Los dominios más frecuentemente evaluados fueron la atmosfera del aprendizaje, la percepción social y percepción académica. La validez de contenido se estableció principalmente mediante un panel de expertos o método Delphi en el 83,3 % de los instrumentos. Conclusiones: Existen diversos instrumentos para evaluar un constructo complejo como el ambiente de aprendizaje en medicina. En general, estos instrumentos cuentan con validez de contenido respaldada por múltiples fuentes y metodologías, y pueden ser utilizados por los educadores médicos para evaluar de forma integral el ambiente de aprendizaje.
ABSTRACT Introduction/aim: The measurement of the learning environment in medicine is fundamental to assess the quality of medical education. Multiple instruments are available for this purpose, but their content, theoretical foundations and practical implications variate. Our aim is to synthesize the content validity and scope of these instruments. Methods: We conducted a systematic review of original studies designed to measure the learning environment in medicine, published in English and Spanish languages, from 1990 to 2018. We search for studies in Pubmed, ERIC, British Nursing Index, Google Scholar, Science Direct, Cochrane, CINALH and Latindex. We analyzed the main domains, theoretical foundations and methods to determine the content validity of each instrument. Results: Thirty-eight studies evaluating twelve instruments (one available in Spanish) were included. Two instruments were specific for the surgical environment and one for the community. Only three instruments were supported by an educational theory. The domains most frequently evaluated were the atmosphere, social perception and academic perception of learning. The content validity was established through expert panels or Delphi method in 83,3 % of the instruments. Conclusions: There are several instruments to evaluate a complex construct such as the learning environment in medicine. In general, these instruments have content validity supported by multiple sources and methodologies and they can be used by medical educators to assess the learning environment comprehensively.
ABSTRACT
Objective: Chronic hypoxia induces pulmonary and cardiovascular pathologies, including pulmonary hypertension (PH). L-arginine:glycine amidinotransferase (AGAT) is essential for homoarginine (hArg) and guanidinoacetate synthesis, the latter being converted to creatine by guanidinoacetate methyltransferase. Low hArg concentrations are associated with cardiovascular morbidity and predict mortality in patients with PH. We therefore aimed to investigate the survival and cardiac outcome of AGAT knockout (Agat -/-) mice under hypoxia and a possible rescue of the phenotype. Methods: Agat -/- mice and wild-type (WT) littermates were subjected to normoxia or normobaric hypoxia (10% oxygen) for 4 weeks. A subgroup of Agat -/- mice was supplemented with 1% creatine from weaning. Survival, hematocrit, blood lactate and glucose, heart weight-to-tibia length (HW/TL) ratio, hArg plasma concentration, and Agat and Gamt expression in lung, liver, and kidneys were evaluated. Results: After 6 h of hypoxia, blood lactate was lower in Agat -/--mice as compared to normoxia (p < 0.001). Agat -/- mice died within 2 days of hypoxia, whereas Agat -/- mice supplemented with creatine and WT mice survived until the end of the study. In WT mice, hematocrit (74 ± 4 vs. 55 ± 2%, mean ± SD, p < 0.001) and HW/TL (9.9 ± 1.3 vs. 7.3 ± 0.7 mg/mm, p < 0.01) were higher in hypoxia, while hArg plasma concentration (0.25 ± 0.06 vs. 0.38 ± 0.12 µmol/L, p < 0.01) was lower. Agat and Gamt expressions were differentially downregulated by hypoxia in lung, liver, and kidneys. Conclusion: Agat and Gamt are downregulated in hypoxia. Agat-/- mice are nonviable in hypoxia. Creatine rescues the lethal phenotype, but it does not reduce right ventricular hypertrophy of Agat-/- mice in hypoxia.
ABSTRACT
Amaranths are recognized by their high nutritive value and their natural tolerance to environmental stresses. In this study, physiological differences in response to water stress were compared between A. hybridus, a wild species considered as weed, and A. hypochondriacus, the most cultivated species for grain production, under the hypothesis that wild species have better adaptation to stress. In both species, photosynthetic parameters, pigments, and gene expression of selected genes were assessed. Biomass, effective quantum efficiency (ΦPSII), photochemical quenching (qP), and electron transport rate (ETR) values were reduced only in A. hybridus due to water deficit. Drought stress promoted proline accumulation by twice in A. hybridus but until three times in A. hypochondriacus. In both species, drought stress reduced net assimilation rate (A), transpiration rate (E), stomatal conductance (gs), and the expression of phosphoenol pyruvate carboxylase (PEPC). While, maximum quantum efficiency (Fv/Fm), chlorophyll, betacyanins, and the expression of ribulose1-5, bisphosphate carboxylase/oxygenase large subunit (LSU) did not change when plants were subjected to water stress. Likewise, both species accumulated total phenolic compounds and Oxalyl-CoA gene was up-regulated in response to drought. Our results have shown that A. hypochondriacus, the cultivated species, exhibited better tolerance to drought than A. hybridus, the wild species, probably due to an unconsciously selected trait during the domestication process.
Subject(s)
Amaranthus/metabolism , Biomass , Chlorophyll/metabolism , Droughts , Osmoregulation , Stress, Physiological , Acyl Coenzyme A/genetics , Amaranthus/genetics , Amaranthus/physiology , Down-Regulation , Fluorescence , Genes, Plant , Phosphoenolpyruvate Carboxykinase (ATP)/genetics , PhotosynthesisABSTRACT
Hypertension is a complex and multifactorial disorder caused by lifestyle and environmental factors, inflammation and disease-related genetic factors and is a risk factor for stroke, ischemic heart disease and renal failure. Although circulating monocytes and tissue macrophages contribute to the pathogenesis of hypertension, the underlying mechanisms are poorly understood. Cysteine rich protein 1 (CRIP1) is highly expressed in immune cells, and CRIP1 mRNA expression in monocytes associates with blood pressure (BP) and is up-regulated by proinflammatory modulation suggesting a link between CRIP1 and BP regulation through the immune system. To address this functional link, we studied CRIP1 expression in immune cells in relation to BP using a human cohort study and hypertensive mouse models. CRIP1 expression in splenic monocytes/macrophages and in circulating monocytes was significantly affected by angiotensin II (Ang II) in a BP-elevating dose (2 mg/kg/day). In the human cohort study, monocytic CRIP1 expression levels were associated with elevated BP, whereas upon differentiation of monocytes to macrophages this association along with the CRIP1 expression level was diminished. In conclusion, CRIP1-positive circulating and splenic monocytes seem to play an important role in hypertension related inflammatory processes through endogenous hormones such as Ang II. These findings suggest that CRIP1 may affect the interaction between the immune system, in particular monocytes, and the pathogenesis of hypertension.
Subject(s)
Carrier Proteins/metabolism , Hypertension/physiopathology , Monocytes/metabolism , Angiotensin II/administration & dosage , Animals , Blood Pressure , Carrier Proteins/genetics , Cell Differentiation , Cohort Studies , Disease Models, Animal , Humans , Hypertension/chemically induced , Hypertension/metabolism , Macrophages , Male , NG-Nitroarginine Methyl Ester/administration & dosage , Spleen , TranscriptomeABSTRACT
OBJECTIVES: We aimed to elucidate the correlation between expression patterns of aortic tissue microRNAs and the aortopathy formation in bicuspid aortic valve (BAV) disease. METHODS: All 65 patients who underwent elective aortic valve repair/replacement +/- proximal aortic replacement due to BAV disease with or without concomitant aortic aneurysm were identified from our BAV registry. Aortic tissue was collected intraoperatively from the ascending aorta at the greater and lesser curvature. Aortic tissue microRNAs analysis included 11 microRNAs (miR-1, miR-17, miR-18a, miR-19a, miR-20a, miR-21, miR-29b, miR-106a, miR-133a, miR-143 and miR-145). Furthermore, analysis of MMP2, TIMP1/2 mRNA and the protein expression was subsequently performed. The primary study endpoint was the correlation between microRNAs and MMP2, TIMP1/2 mRNA/protein expression. RESULTS: We found a significant association between miR-133a and TIMP1 mRNA (r = 0.870, p < 0.001), an inverse correlation between miR-143a and MMP2 protein expression (r= -0.614, p = 0.044) and a positive correlation between miR-133a and TIMP-2 protein expression (r = 0.583, p = 0.036) at the greater curvature. CONCLUSION: Our findings indicate that aortic tissue microRNAs may reflect remodelling processes of the proximal aorta in BAV aortopathy. Specific aortic tissue microRNAs may exert their regulatory effects on the aortopathy through their impact on MMPs/TIMPs homeostasis at the level of the greater curvature.
Subject(s)
Aorta/enzymology , Aortic Aneurysm/enzymology , Bicuspid Aortic Valve Disease/enzymology , Matrix Metalloproteinase 2/metabolism , MicroRNAs/metabolism , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/metabolism , Vascular Remodeling , Adult , Aged , Aorta/pathology , Aorta/surgery , Aortic Aneurysm/genetics , Aortic Aneurysm/pathology , Aortic Aneurysm/surgery , Bicuspid Aortic Valve Disease/genetics , Bicuspid Aortic Valve Disease/pathology , Bicuspid Aortic Valve Disease/surgery , Dilatation, Pathologic , Female , Humans , Male , Matrix Metalloproteinase 2/genetics , MicroRNAs/genetics , Middle Aged , Prospective Studies , Registries , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/geneticsABSTRACT
BACKGROUND: The presence of skin problems in patients using external lower limb prosthesis is recurrent. This has generated the need to develop interfaces for prosthesis with the ability to control microbial growth. Silver nanoparticles (AgNPs) have been implemented in the development of biomaterials because of their high antimicrobial activity. This article discusses the development of an AgNP-containing polymer composite with antimicrobial activity for developing prosthetic liners. METHODS: AgNPs were synthesized using a photochemical method and certain physicochemical properties were characterized. Furthermore, the antimicrobial activity of AgNPs against Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus (MRSA), was assessed on the basis of their minimum inhibitory concentrations (MICs). AgNPs were incorporated into a silicon elastomer to assess certain physicomechanical properties, antimicrobial activity and cytotoxic effect of the material. RESULTS: The maximum antimicrobial activity of the material against Staphylococcus aureus ATCC 25923 and MRSA was 41.58% ±2.97% at AgNP concentration of 32.98 µg/mL and 14.85% ±5.94% at AgNP concentration of 16.49 µg/mL, respectively. Additionally, the material exhibited tensile yield strength, rupture tensile strength, and tensile modulus of elasticity of 0.70 - 1.10 MPa, 0.71-1.06 MPa, and 0.20 - 0.30 MPa, respectively. The mechanical characteristics of the material were within the acceptable range for use in external lower limb prosthetic and orthotic interfaces. CONCLUSIONS: It was possible to incorporate the AgNPs in a silicone elastomer, finding that the composite developed presented antimicrobial activity against Staphylococcus aureus ATCC 25923 and MRSA when compared to non-AgNP material samples.
ABSTRACT
AIMS: Despite three decades of study, it is still challenging to discriminate acute apical variant stress cardiomyopathy (AVSCM) from acute left anterior descending-myocardial infarction (LAD-MI) at the time of presentation. A biomarker or practical imaging modality that can differentiate these two entities is highly desirable. Our objective was to characterize left ventricular (LV) mechanical deformation using 2-dimensional (2D) echocardiographic strain imaging in an attempt to discriminate AVSCM from LAD-MI at presentation. METHODS AND RESULTS: We studied 108 women (60 AVSCM, 48 ST segment elevation LAD-MI). All underwent echocardiography within 48 hours of presentation. 2D longitudinal strain (LS) from an 18-segment LV model was performed, with global LS (GLS) taken as the average of all 18 segments. GLS was abnormal, but did not differentiate AVSCM from LAD-MI. Mean LS of the basal and mid-anterior, basal, and mid-anteroseptum segments were significantly lower in LAD-MI vs AVSCM group (-14 ± 9% vs -20 ± 8%; -11 ± 7% vs -14 ± 6%; -9 ± 8% vs -14 ± 8%; -9 ± 7% vs -13 ± 5%, respectively, all P ≤ .05). Mean LS of the basal inferior and inferolateral segments was significantly higher in the LAD-MI vs. AVSCM group (-19 ± 9% vs -13 ± 7%; -23 ± 11% vs -18 ± 7%, respectively, all P ≤ .05). Using ROC curve analysis, segmental strain ratio of average basal inferior and inferolateral segments LS to average mid- and basal anterior and anteroseptum segments LS of ≥1.58 was 90% specific for LAD-MI [area under the curve (AUC) 0.87; P < .001]. CONCLUSION: Longitudinal strain patterns are useful in discriminating AVSCM from LAD-MI patients at presentation and may be valuable in stratifying patients for invasive evaluation.