RESUMEN
Plants allocate a substantial amount of C belowground for root exudates and for the construction and adjustment of root morphological and architectural traits. What relationships exist between root exudates and other root traits and these relationships change with growing season, however, remain unclear. We quantified the root exudation rate and root morphological traits, including total root length (RL), total root surface area (RS), root diameter (RD), specific root length (SRL), specific root area (SRA) and root tissue density (RTD), and architectural traits, such as branching intensity (BI), and investigated their associations during the rapidly growing season (April and August) and the slowly growing season (December) of three common native tree species, Liquidambar formosana, Michelia maudiae and Schima superba, in subtropical China. We found that the linkages of RD, SRL, SRA, RTD and BI did not change with the growing season, reflecting their highly conservative relationships. The root exudation rate varied significantly with growing season (P < 0.05) and produced various associations with other root traits at different growing seasons. During the rapidly growing season (i.e., April), the exudation rate was the highest and was positively correlated with RL. The exudation rate was the lowest during the slowly growing season (i.e., December) and was negatively associated with RL, RS and RTD. Our findings demonstrate the seasonality of the linkages of root exudation rate with other root traits, which highlights the highly plastic and complex associations of belowground root traits. These findings help to deepen our understanding of plant nutrient acquisition strategies.
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Raíces de Plantas , Suelo , Estaciones del Año , Raíces de Plantas/anatomía & histología , Plantas , ÁrbolesRESUMEN
INTRODUCTION: A combination of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. METHOD: An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. RESULTS: In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P < 0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P < 0.05); the relative weights of the liver, kidney, spleen and brain increased (P < 0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The haemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P < 0.05). The total protein, albumin, cholesterol and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P < 0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P < 0.05). CONCLUSION: The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.
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Fármacos Anti-VIH , Infecciones por VIH , Femenino , Masculino , Animales , Ratones , Ratas , Lamivudine/toxicidad , Zidovudina/toxicidad , Zidovudina/uso terapéutico , Lopinavir/toxicidad , Ritonavir , Fármacos Anti-VIH/toxicidad , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , MamíferosRESUMEN
Aluminum oxide nanoparticles (Al2O3NPs) are one class of widely used nanomaterials. However, the teratogenicity toxicity of Al2O3NPs in mammal remains poorly understood. This study was aimed to evaluate the teratogenicity of Al2O3NPs in Sprague Dawley (SD) rats by gavage and to compare the effects of Al2O3NPs to those of equivalent dose of microscale aluminum oxide (bulk Al2O3). Sixty pregnant rats were randomly divided into 5 groups and treated with 100 and 200 mg/kg body weight (bw) Al2O3NPs (30 nm), 200 mg/kg bulk Al2O3, deionized water (as the negative control), and 300 mg/kg aspirin (as the positive control). Rats were exposed daily by oral gavage from the 7th day of gestation for 10 consecutive days and sacrificed on the 20th day of gestation. Results of the study showed that there were no significant effects of Al2O3NPs on pregnant rats (clinical signs, body weight, food consumption, ovary and uterus weight, number of corpora lutea) and fetuses (body weight, sex, body length, tail length, skeletal and visceral development). Under the experimental conditions of the present study, 10 consecutive days of repeated oral administration of Al2O3NPs at doses of up to 200 mg/kg/day did not induce any treatment-related teratogenicity in SD rats. Accordingly, the NOAEL was determined to be 200 mg/kg Al2O3NPs (106 mg Al/kg bw/day) in rats. The teratogenic effects of Al2O3NPs in rats were comparable to those of the bulk Al2O3 of same doses (200 mg/kg).
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Óxido de Aluminio , Nanopartículas , Óxido de Aluminio/toxicidad , Animales , Peso Corporal , Femenino , Feto , Mamíferos , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
Xylan is the second most abundant polysaccharide group in plants and has a wide variety of food and pharmaceutical applications. However, little information on the safety assessment of extracted xylan as dietary supplement is available. As part of a comprehensive toxicological assessment, this study examined the potential toxicity of xylan extracted from sugarcane bagasse by three genotoxicity studies (Ames test, in vivo mice bone marrow micronucleus test, and mice sperm abnormality test) and a teratogenicity study in rats. In the Ames test, xylan showed no mutagenic activity on histidine dependent strains of Salmonella typhimurium at concentrations up to 5000 µg/plate; results of the in vivo mice bone marrow micronucleus test and mice sperm abnormality test indicated no significant effect on sperm morphology and micronucleus rate of polychromatic erythrocytes in mice at doses up to 5 g/kg body weight. In the teratogenicity study, a total of 60 pregnant rats were exposed to 10, 5, and 2.5% xylan in diet, from gestation days 7 to 16, and the no-observed-adverse-effect levels (NOAEL) of xylan was determined to be 9.8 g/kg body weight. The safe dose of xylan for human was estimated to be 98 mg/kg/day (i.e., 6.86 g/day for a 70-kg person), using a 100-fold safety factor. Taken together, results of this study indicated that xylan is practically nontoxic in terms of potential dietary consumption by humans in food or as a dietary supplement.
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Saccharum , Xilanos , Animales , Celulosa , Femenino , Masculino , Ratones , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Nivel sin Efectos Adversos Observados , Embarazo , Ratas , Xilanos/toxicidadRESUMEN
Previously, we have identified ZFAS1 as a potential new long non-coding RNA (lncRNA) biomarker of acute myocardial infarction (MI) and as a sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) inhibitor, causing intracellular Ca2+ overload and contractile dysfunction in a mouse model of MI. In the current study, we aimed to evaluate the effects of ZFAS1 on the apoptosis of cardiomyocytes in the MI mouse model. Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA or siZFAS1 partially abrogated the ischemia-induced apoptosis of cardiomyocytes. Overexpression of ZFAS1 in normal cardiomyocytes reduced the cell viability, similar to that observed in hypoxia-treated cardiomyocytes. Moreover, ZFAS1 cardiac-specific knock-in mice showed impaired cardiac function, adversely altered Ca2+ homeostasis, repressed expression and activities of SERCA2a, and increased apoptosis. At the subcellular level, ZFAS1 induced mitochondrial swelling and showed a pronounced decrease in mitochondrial membrane potential. At the molecular level, ZFAS1 activated the mitochondria apoptosis pathway, which could be nearly abolished by a calcium chelator. The effects of ZFAS1 were readily reversible upon knockdown of this lncRNA. Notably, ZFAS1-FD (only functional domain) mimicked the effects of full-length ZFAS1 in regulation of cardiomyocyte apoptosis. In conclusion, our study shows that ZFAS1, an endogenous SERCA2a inhibitor, induces mitochondria-mediated apoptosis via cytosolic Ca2+ overload. Therefore, anti-ZFAS1 might be considered a new therapeutic strategy for protecting cardiomyocytes from MI-induced apoptosis.
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Apoptosis/genética , Calcio/metabolismo , Citosol/metabolismo , Mitocondrias/metabolismo , Infarto del Miocardio/metabolismo , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/metabolismo , Factores Generales de Transcripción/metabolismo , Animales , Hipoxia de la Célula , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Técnicas de Sustitución del Gen , Técnicas de Silenciamiento del Gen , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , ARN Largo no Codificante/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/antagonistas & inhibidores , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , TransfecciónRESUMEN
The chemical constituents from the fruiting bodies of Tremella sanguinea were separated and purified by column chromatography on silica gel,ODS,Sephadex LH-20,and RP-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic data analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the fruiting bodies of T. sanguinea,which were identified as( 22 E)-5α,8α-epidioxy-24-methyl-cholesta-6,9( 11),22-trien-3ß-ol( 1),( 22 E)-5α,8α-epidioxyergosta-6,22-dien-3ß-ol( 2),cerevisterol( 3),ergosta-7-ene-3ß,5α,6ß-triol( 4),( 22 E)-6ß-methoxyergosta-7,22-diene-3ß,5α-diol( 5),ergosta-7-en-3ß-ol( 6),4-hydroxy-methylincisterol( 7),2-pyrrolidone( 8),nicotinamide( 9),1-( 3-indolyl)-3-dihydroxypropan-1-one( 10),yangambin( 11),linoleic acid( 12),( 9 Z,12 Z,15 Z)-2,3-dihydroxypropyl octadeca-trienoate( 13),( 9 Z,12 Z)-2,3-dihydroxypropyl-octadeca-dienoate( 14),crypticin B( 15)and 3-phenyllactic acid( 16). All compounds were isolated from T. sanguinea for the first time. Except for compounds 6,9 and 12,the remained compounds were isolated from the genus Tremella for the first time.
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Basidiomycota/química , Cuerpos Fructíferos de los Hongos/química , Estructura MolecularRESUMEN
BACKGROUND/AIMS: Cardiac fibrosis is an important cardiac remodeling event that can ultimately lead to the development of severe arrhythmia and heart failure. MicroRNAs (miRNAs) are involved in the pathogenesis of many cardiovascular diseases. Here, we aimed to investigate the effects of caveolin-3 (Cav3) on the pathogenesis of cardiac fibrosis and the underlying molecular mechanisms. METHODS: Cav3 expression was decreased in cardiac fibrosis in vivo and in vitro model. To investigate the role of Cav3 in cardiac fibrosis, we transfected cardiac fibroblasts (CFs) with the siRNA of Cav3 and Cav3-overexpressing plasmid. The collagen content and proliferation of CFs were detected by qRT-PCR, western blot, MTT, and immunofluorescence. A luciferase reporter gene assay and gain/loss of function were used to detect the relationship between miR-22 and Cav3. RESULTS: Cav3 depletion in CFs induced an increase in collagen content, cell proliferation, and phenotypic conversion of fibroblasts to myofibroblasts. Conversely, Cav3 overexpression in CFs was shown to inhibit angiotensin II-mediated excessive collagen deposition through protein kinase C (PKC)ε inactivation. Cav3 was experimentally confirmed as a direct target of miR-22, containing two seed binding sites in its 3'-untranslated region, and miR-22 was demonstrated to be significantly upregulated in the ischemic border zone in mice after myocardial infarction and in neonatal rat CFs pretreated with angiotensin II. miR-22 overexpression increased CFs proliferation, and collagen and α-smooth muscle actin levels in CFs, while the knockdown of endogenous miR-22 decreased CFs numbers. CONCLUSIONS: Our findings demonstrate that miR-22 accelerates cardiac fibrosis through the miR-22-Cav3-PKCε pathway, which, therefore, may represent a new therapeutic target for treatment of excessive fibrosis-associated cardiac diseases.
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Caveolina 3/metabolismo , MicroARNs/metabolismo , Infarto del Miocardio/patología , Actinas/metabolismo , Angiotensina II/farmacología , Animales , Secuencia de Bases , Caveolina 3/antagonistas & inhibidores , Caveolina 3/genética , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibrosis , Masculino , Ratones , MicroARNs/genética , Infarto del Miocardio/metabolismo , Miocardio/citología , Miocardio/metabolismo , Proteína Quinasa C-epsilon/metabolismo , Interferencia de ARN , Ratas , Ratas Sprague-DawleyRESUMEN
RATIONALE: Ca2+ homeostasis-a critical determinant of cardiac contractile function-is critically regulated by SERCA2a (sarcoplasmic reticulum Ca2+-ATPase 2a). Our previous study has identified ZFAS1 as a new lncRNA biomarker of acute myocardial infarction (MI). OBJECTIVE: To evaluate the effects of ZFAS1 on SERCA2a and the associated Ca2+ homeostasis and cardiac contractile function in the setting of MI. METHODS AND RESULTS: ZFAS1 expression was robustly increased in cytoplasm and sarcoplasmic reticulum in a mouse model of MI and a cellular model of hypoxia. Knockdown of endogenous ZFAS1 by virus-mediated silencing shRNA partially abrogated the ischemia-induced contractile dysfunction. Overexpression of ZFAS1 in otherwise normal mice created similar impairment of cardiac function as that observed in MI mice. Moreover, at the cellular level, ZFAS1 overexpression weakened the contractility of cardiac muscles. At the subcellular level, ZFAS1 deleteriously altered the Ca2+ transient leading to intracellular Ca2+ overload in cardiomyocytes. At the molecular level, ZFAS1 was found to directly bind SERCA2a protein and to limit its activity, as well as to repress its expression. The effects of ZFAS1 were readily reversible on knockdown of this lncRNA. Notably, a sequence domain of ZFAS1 gene that is conserved across species mimicked the effects of the full-length ZFAS1. Mutation of this domain or application of an antisense fragment to this conserved region efficiently canceled out the deleterious actions of ZFAS1. ZFAS1 had no significant effects on other Ca2+-handling regulatory proteins. CONCLUSIONS: ZFAS1 is an endogenous SERCA2a inhibitor, acting by binding to SERCA2a protein to limit its intracellular level and inhibit its activity, and a contributor to the impairment of cardiac contractile function in MI. Therefore, anti-ZFAS1 might be considered as a new therapeutic strategy for preserving SERCA2a activity and cardiac function under pathological conditions of the heart.
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Calcio/metabolismo , Infarto del Miocardio/genética , ARN Largo no Codificante/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/antagonistas & inhibidores , Animales , Señalización del Calcio , Hipoxia de la Célula , Secuencia Conservada , Citoplasma/metabolismo , Inducción Enzimática , Humanos , Ratones , Ratones Endogámicos C57BL , Mutación , Contracción Miocárdica , Infarto del Miocardio/etiología , Infarto del Miocardio/metabolismo , Isquemia Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Factores de Transcripción NFATC/metabolismo , Oligonucleótidos Antisentido/genética , Interferencia de ARN , ARN Largo no Codificante/biosíntesis , ARN Interferente Pequeño/genética , Retículo Sarcoplasmático/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/fisiología , Activación TranscripcionalRESUMEN
Cistanche deserticola (C. deserticola), a holoparasitic plant widely distributed in arid or semi-arid areas in Eurasia and North Africa, has been used as an important tonic in traditional Eastern medicine for centuries. However, little information on the systemic toxicity and safety evaluation of it is available. The purpose of this study was to investigate the potential toxicity of powdered C. deserticola as a novel food ingredient by use of a subchronic toxicity study in Sprague-Dawley (SD) rats. A total of 80 male and female rats were fed with diets containing 8, 4, 2 and 0% (control) powdered C. deserticola for 90 days. A toxicological assessment was performed including mortality, body and organ weight, food consumption, blood biochemistry, hematology, gross necropsy and histopathological examinations. There were no signs of toxicity and treatment-related changes in rats treated with powdered C. deserticola. The no-observed-adverse-effect level (NOAEL) of powdered C. deserticola was 7.8 g kg-1 body weight for males and 8.0 g kg-1 body weight for females of rats under the experimental conditions of this study.
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Cistanche/química , Suplementos Dietéticos/efectos adversos , Fármacos para la Fertilidad Femenina/efectos adversos , Fármacos para la Fertilidad Masculina/efectos adversos , Ingredientes Alimentarios/efectos adversos , Tallos de la Planta/química , Animales , China , Cistanche/crecimiento & desarrollo , Ingestión de Energía , Etnobotánica , Femenino , Fármacos para la Fertilidad Femenina/administración & dosificación , Fármacos para la Fertilidad Masculina/administración & dosificación , Masculino , Medicina Tradicional China , Nivel sin Efectos Adversos Observados , Tamaño de los Órganos , Tallos de la Planta/crecimiento & desarrollo , Distribución Aleatoria , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Pruebas de Toxicidad Subcrónica , Aumento de PesoRESUMEN
MicroRNAs are important posttranscriptional regulators of gene expression in animals and plants. A sensitive and specific detection method is urgently needed for intensive studies on differential expression and regulatory roles of microRNA. Here we present a simple and reliable method for the quantification of microRNA. The hybridization products of target microRNA with capture probe and gold nanoparticle probe are immobilized onto the surface of a streptavidin-coated microplate, and the signal is amplified by silver enhancement. Distribution of miR-122a/miR-128 in mouse brain and liver tissue was detected by this method, and synthetic miRNA122a was quantified. This method allowed a lower detect limit of 10 fM with a linear dynamic range from 10 pM to 10 fM and a high specificity to discriminate one single oligonucleotide mismatch of the target microRNA.