RESUMEN
BACKGROUND: Gastric mucosal injury caused by ethanol is a common gastrointestinal disease. Quinoa (Chenopodium quinoa Willd.), as a nutrient-rich grain, plays a significant role in preventing and treating gastric mucosal damage. The present study aimed to explore the protective effect of quinoa on alcohol-induced gastric mucosal damage and its possible mechanism. RESULTS: The ethanol-induced gastric mucosal injury rat model was used for in vivo experiments and H2 O2 -induced GES-1 cells for in vitro experiments to elucidate the protective effect of quinoa. The results show that quinoa water extract can increase the superoxide dismutase level and decrease the malondialdehyde level in vitro and in vivo. Furthermore, quinoa also reduced the bleeding point and bleeding area in rats with ethanol-induced gastric mucosal injury and improved gastric histopathological changes. H2 O2 significantly increased the levels of inflammatory factors in GES-1 cells, which were markedly ameliorated by quinoa water extract. Likewise, quinoa water extract regulated the protein expression levels of Nrf2, Keap1, HO-1, p-IKK, and p-NF-κB through Nrf2 and nuclear factor-κB signaling pathways, reducing the production of oxidative stress and inflammation, thereby repairing the damaged gastric mucosa. CONCLUSION: The findings of this study demonstrated that quinoa shows protective effect against ethanol-induced gastric mucosal injury through its anti-inflammatory and anti-oxidant effects. We propose that our research will provide a reference for quinoa as a functional food. © 2022 Society of Chemical Industry.
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Chenopodium quinoa , Úlcera Gástrica , Ratas , Animales , Chenopodium quinoa/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Mucosa Gástrica/metabolismo , Etanol/metabolismo , Estrés Oxidativo , FN-kappa B/metabolismo , Agua/metabolismo , Úlcera Gástrica/inducido químicamenteRESUMEN
BACKGROUND: To illustrate the mechanism of miRNA and mRNA in coronary artery diseasen (CAD), differentially expressed microRNAs (DEmiRNAs) and genes (DEGs) were analyzed. METHODS: The mRNA transcription profiles of GSE20680 (including 87 blood samples of CAD and 52 blood samples of control), GSE20681 (including 99 blood samples of CAD and 99 blood samples of control) and GSE12288 (including 110 blood samples of CAD and 112 blood samples of control) and the miRNA transcription profiles of GSE59421 (including 33 blood samples of CAD and 37 blood samples of control), GSE49823 (including 12 blood samples of CAD and 12 blood samples of control) and GSE28858 (including 13 blood samples of CAD and 13 blood samples of control) were downloaded from Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/ ). Then, the homogenous expressed mRNAs and miRNAs across the three mRNA transcription profiles and three miRNA transcription profiles were screened using the Fishers exact test in MetaDE. ES package. The weighted gene co-expression network analysis (WGCNA) was used to analyze gene modules. Additionally, the integrated miRNAs-targets regulatory network using the DEmiRNA and their targets was constructed using Cytoscape. RESULTS: A total of 1201 homogenously statistically significant DEGs were identified including 879 up-regulated and 322 down-regulated DEGs, while a total of 47 homogenously statistically significant DEmiRNAs including 37 up-regulated and 10 down-regulated DEmiRNAs in CAD compared with the controls across the three mRNA transcription profiles and the three miRNA transcription profiles. A total of 5067 genes were clustered into 9 modules in the training dataset, among which, 8 modules were validated. In the miRNAs-targets network, there existed 267 interaction relationships among 5 miRNAs (hsa-miR-361-5p, hsa-miR-139-5p, hsa-miR-146b-5p, hsa-miR-502-5p and hsa-miR-501-5p) and 213 targets. CAV1 could be the target of hsa-miR-361-5 while HSF2 was the target of both hsa-miR-361-5p and hsa-miR-146b-5p. CAV1 was significantly enriched in the GO term of regulation of cell proliferation. CONCLUSION: hsa-miR-361-5p, has-miR-146b-5p, CAV1 and HSF2 could play an important role in CAD.
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Enfermedad de la Arteria Coronaria/genética , MicroARNs/genética , ARN Mensajero/genética , Transcriptoma , Adulto , Anciano , Estudios de Casos y Controles , Caveolina 1/genética , Caveolina 1/metabolismo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Estudios de Asociación Genética , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Temperature influences the physiological processes and ecology of both hosts and endophytes; however, it remains unclear how long noncoding RNAs (lncRNAs) modulate the consequences of temperature-dependent changes in host-pathogen interactions. To explore the role of lncRNAs in culm gall formation induced by the smut fungus Ustilago esculenta in Zizania latifolia, we employed RNA sequencing to identify lncRNAs and their potential cis-targets in Z. latifolia and U. esculenta under different temperatures. In Z. latifolia and U. esculenta, we identified 3194 and 173 lncRNAs as well as 126 and four potential target genes for differentially expressed lncRNAs, respectively. Further function and expression analysis revealed that lncRNA ZlMSTRG.11348 regulates amino acid metabolism in Z. latifolia and lncRNA UeMSTRG.02678 regulates amino acid transport in U. esculenta. The plant defence response was also found to be regulated by lncRNAs and suppressed in Z. latifolia infected with U. esculenta grown at 25 °C, which may result from the expression of effector genes in U. esculenta. Moreover, in Z. latifolia infected with U. esculenta, the expression of genes related to phytohormones was altered under different temperatures. Our results demonstrate that lncRNAs are important components of the regulatory networks in plant-microbe-environment interactions, and may play a part in regulating culm swelling in Z. latifolia plants.
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Enfermedades de las Plantas/genética , Poaceae/genética , ARN Largo no Codificante/genética , Transcriptoma/genética , Endófitos/genética , Endófitos/patogenicidad , Interacciones Huésped-Patógeno/genética , Enfermedades de las Plantas/parasitología , Poaceae/crecimiento & desarrollo , Análisis de Secuencia de ARN , Temperatura , Ustilago/genética , Ustilago/patogenicidadRESUMEN
Ralstonia solanacearum is the most destructive pathogen, causing bacterial wilt disease of eggplant. The present study aimed to develop green synthesis and characterization of silver chloride nanoparticles (AgCl-NPs) by using a native bacterial strain and subsequent evaluation of their antibacterial activity against R. solanacearum. Here, a total of 10 bacterial strains were selected for the biosynthesis of AgCl-NPs. Among them, the highest yield occurred in the synthesis of AgCl-NPs using a cell-free aqueous filtrate of strain IMA13. Ultrastructural observation revealed that the AgCl-NPs were spherical and oval with smooth surfaces and 5-35 nm sizes. XRD analysis studies revealed that these particles contained face-centered cubic crystallites of metallic Ag and AgCl. Moreover, FTIR analysis showed the presence of capping proteins, carbohydrates, lipids, and lipopeptide compounds and crystalline structure of AgCl-NPs. On the basis of phylogenetic analysis using a combination of six gene sequences (16S, gyrA, rpoB, purH, polC, and groEL), we identified strain IMA13 as Bacillus mojavensis. Three kinds of lipopeptide compounds, namely, bacillomycin D, iturin, and fengycin, forming cell-free supernatant produced by strain IAM13, were identified by MALDI-TOF mass spectrometry. Biogenic AgCl-NPs showed substantial antibacterial activity against R. solanacearum at a concentration of 20 µg/mL-1. Motility assays showed that the AgCl-NPs significantly inhibited the swarming and swimming motility (61.4 and 55.8%) against R. solanacearum. Moreover, SEM and TEM analysis showed that direct interaction of AgCl-NPs with bacterial cells caused rupture of cell wall and cytoplasmic membranes, as well as leakage of nucleic acid materials, which ultimately resulted in the death of R. solanacearum. Overall, these findings will help in developing a promising nanopesticide against phytopathogen plant disease management.
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Antibacterianos/biosíntesis , Antibacterianos/farmacología , Bacterias/metabolismo , Nanopartículas del Metal , Ralstonia solanacearum/efectos de los fármacos , Rizosfera , Compuestos de Plata/metabolismo , Antibiosis , Lipopéptidos/química , Lipopéptidos/farmacología , Nanopartículas del Metal/ultraestructura , Pruebas de Sensibilidad Microbiana , Enfermedades de las Plantas/microbiología , Ralstonia solanacearum/ultraestructura , Análisis EspectralRESUMEN
Myocardial ischemia/reperfusion injury (MIRI) is a clinically familiar disease, which possesses a great negative impact on human health. But, the effective treatment is still absent. MicroRNAs (miRNAs) have been testified to play a momentous role in MIRI. The purpose of the study aimed to probe the functions of miR-132 in oxygen and glucose deprivation (OGD)-evoked injury in H9c2 cells. miR-132 expression in H9c2 cells accompanied by OGD disposition was evaluated via real-time quantitative polymerase chain reaction. After miR-132 mimic and inhibitor transfections, the impacts of miR-132 on OGD-affected H9c2 cell viability, apoptosis, cell cycle, and the interrelated factors were appraised by exploiting cell counting kit-8, flow cytometry, and western blot analysis. FOXO3A expression was estimated in above-transfected cells, meanwhile, the correlation between miR-132 and FOXO3A was probed by dual-luciferase report assay. Ultimately, above mentioned cell processes were reassessed in H9c2 cells after preprocessing OGD administration and transfection with si-FOXO3A and si-NC plasmids. We got that OGD disposition obviously enhanced miR-132 expression in H9c2 cells. Overexpressed miR-132 evidently reversed OGD-evoked cell viability repression and apoptosis induction in H9c2 cells. In addition, overexpressed miR-132 mitigated OGD-evoked G0/G1 cell arrest by mediating p21, p27, and cyclin D1 expression. Repression of FOXO3A was observed in miR-132 mimic-transfected cells, which was also predicated as a direct gene of miR-132. We discovered that silenced FOXO3A alleviated OGD-evoked cell injury in H9c2 cells via facilitating cell viability, hindering apoptosis and restraining cell arrest at G0/G1 phase. In conclusion, these investigations corroborated that miR-132 exhibited the protective impacts on H9c2 cells against OGD-evoked injury via targeting FOXO3A.
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Proteína Forkhead Box O3/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/administración & dosificación , MicroARNs/metabolismo , Oxígeno/administración & dosificación , Animales , Apoptosis , Ciclo Celular/fisiología , Línea Celular , Proteína Forkhead Box O3/genética , Regulación de la Expresión Génica/fisiología , MicroARNs/genética , RatasRESUMEN
Ustilago esculenta, a smut fungus, can induce the formation of culm galls in Zizania latifolia, a vegetable consumed in many Asian countries. Specifically, the mycelia-teliospore (M-T) strain of U. esculenta induces the Jiaobai (JB) type of gall, while the teliospore (T) strain induces the Huijiao (HJ) type. The underlying molecular mechanism responsible for the formation of the two distinct types of gall remains unclear. Our results showed that most differentially expressed genes relevant to effector proteins were up-regulated in the T strain compared to those in the M-T strain during gall formation, and the expression of teliospore formation-related genes was higher in the T strain than the M-T strain. Melanin biosynthesis was also clearly induced in the T strain. The T strain exhibited stronger pathogenicity and greater teliospore production than the M-T strain. We evaluated the implications of the gene regulatory networks in the development of these two type of culm gall in Z. latifolia infected with U. esculenta and suggested potential targets for genetic manipulation to modify the gall type for this crop.
Asunto(s)
Basidiomycota/metabolismo , Expresión Génica , Tumores de Planta/microbiología , Poaceae/microbiología , Basidiomycota/genética , Basidiomycota/patogenicidad , Expresión Génica/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TranscriptomaRESUMEN
Oxaliplatin (OXL) is the first line treatment therapy for gastrointestinal (GI) cancers and often combines with other chemotherapy. However, few reports have studied on its GI toxicity. Magnolol (MG), one of the mainly active constituents in Magnolia, has been reported to treat digestive diseases. Therefore, the purpose of this study is to evaluate the intestinal protective effect of MG in OXL treatment group. OXL administration mice showed body weight loss, diarrhea, and intestinal damage characterized by the shortening of villi and destruction of intestinal crypts, as well as the colon length change. MG significantly reduced body weight loss, alleviated diarrhea, reversed histopathological changes, and prevented colon length reduction. Oxidative stress and inflammation were activated after OXL, and these responses were repressed by MG through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione, decreasing level of nuclear factor of kappa b and downregulating the following pro-inflammatory cytokines. Although the expression of tight junction protein occludin and numbers of proliferative crypt cells were reduced on ileum and colon after OXL, MG administration promoted these expressions. The fecal gut microbiota composition disturbed by OXL was significantly reversed by MG. Thus, MG could prevent the development and progression of mucositis induced by oxaliplatin through multipathway.
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Antineoplásicos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Flores/química , Mucosa Intestinal/lesiones , Lignanos/uso terapéutico , Oxaliplatino/efectos adversos , Animales , Antineoplásicos/farmacología , Compuestos de Bifenilo/farmacología , Lignanos/farmacología , Masculino , RatonesRESUMEN
BACKGROUND/AIMS: Astragaloside IV (AS-IV), a traditional Chinese medicine isolated from Astragalus membranaceus, has been shown to exert cardioprotective effect previously. This study aimed to reveal the effects of AS-IV on hypoxia-injured cardiomyocyte. METHODS: H9c2 cells were treated with various doses of AS-IV for 24 h upon hypoxia. CCK-8 assay, flow cytometry/Western blot, and qRT-PCR were respectively conducted to measure the changes in cell viability, apoptosis, and the expression of miR-23a and miR-92a. Sprague-Dawley rats were received coronary ligation, and were administrated by various doses of AS-IV for 14 days. The infarct volume and outcome of rats followed by ligation were tested by ultrasound, arteriopuncture and nitrotetrazolium blue chloride (NBT) staining. RESULTS: We found that 10 µg/ml of AS-IV exerted myocardioprotective effects against hypoxia-induced cell damage, as AS-IV significantly increased H9c2 cells viability and decreased apoptosis. Interestingly, the myocardioprotective effects of AS-IV were alleviated by miR-23a and/or miR-92a overexpression. Knockdown of miR-23a and miR-92a activated PI3K/AKT and MAPK/ ERK signaling pathways. Bcl-2 was a target gene for miR-23a, and BCL2L2 was a target gene for miR-92a. In the animal model of myocardial infarction (MI), AS-IV significantly reduced the infarct volume, ejection fraction (EF), shortening fraction (FS) and LV systolic pressure (LVSP), and significantly increased left ventricular end-diastolic internal diameter (LVEDd). And also, the elevated expression of miR-23a and miR-92a in MI rat was reduced by AS-IV. CONCLUSION: AS-IV protected cardiomyocytes against hypoxia-induced injury possibly via down-regulation of miR-23a and miR-92a, and via activation of PI3K/AKT and MAPK/ERK signaling pathways.
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Hipoxia de la Célula , Regulación hacia Abajo/efectos de los fármacos , MicroARNs/metabolismo , Sustancias Protectoras/farmacología , Saponinas/farmacología , Triterpenos/farmacología , Animales , Antagomirs/metabolismo , Apoptosis/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Línea Celular , Masculino , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/veterinaria , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
CONTEXT: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction. OBJECTIVE: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved. MATERIALS AND METHODS: In vivo, the study evaluated the effects of ALR (200-800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2-1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl2, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase). RESULTS: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p < 0.01, compared with neostigmine group 91.40 ± 7.81%), small intestinal transit (42.82 ± 3.82%, p < 0.01, compared with neostigmine group 85.53 ± 5.57%). In vitro, ALR concentration dependently decreased the contractions induced by ACh (10-5 M) and KCl (60 mM) with respective EC50 values of 0.35 and 0.32 mg/mL. The Ca2+ concentration-response curves were shifted by ALR to the right, similar to that caused by verapamil (the positive). The spasmolytic activity of ALR was inhibited by pre-incubation with l-NAME. DISCUSSION AND CONCLUSIONS: ALR played a spasmolytic role in GIM, which is probably mediated through inhibition of muscarinic receptors, blockade of Ca2+ influx and NO release. This is the first study presenting a comprehensive description of the effects of ALR on GIM.
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Bloqueadores de los Canales de Calcio/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Antagonistas Muscarínicos/farmacología , Óxido Nítrico/antagonistas & inhibidores , Parasimpatolíticos/farmacología , Extractos Vegetales/farmacología , Thymelaeaceae , Animales , Bloqueadores de los Canales de Calcio/aislamiento & purificación , Canales de Calcio/fisiología , Relación Dosis-Respuesta a Droga , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Motilidad Gastrointestinal/fisiología , Ratones , Antagonistas Muscarínicos/aislamiento & purificación , Óxido Nítrico/fisiología , Técnicas de Cultivo de Órganos , Parasimpatolíticos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Distribución Aleatoria , Ratas , Ratas Wistar , Receptores Muscarínicos/fisiologíaRESUMEN
KEY MESSAGE: We report a transcriptome assembly and expression profiles from RNA-Seq data and identify genes responsible for culm gall formation in Zizania latifolia induced by Ustilago esculenta. The smut fungus Ustilago esculenta can induce culm gall in Zizania latifolia, which is used as a vegetable in Asian countries. However, the underlying molecular mechanism of culm gall formation is still unclear. To characterize the processes underlying this host-fungus association, we performed transcriptomic and expression profiling analyses of culms from Z. latifolia infected by the fungus U. esculenta. Transcriptomic analysis detected U. esculenta induced differential expression of 19,033 and 17,669 genes in Jiaobai (JB) and Huijiao (HJ) type of gall, respectively. Additionally, to detect the potential gall inducing genes, expression profiles of infected culms collected at -7, 1 and 10 DAS of culm gall development were analyzed. Compared to control, we detected 8089 genes (4389 up-regulated, 3700 down-regulated) and 5251 genes (3121 up-regulated, 2130 down-regulated) were differentially expressed in JB and HJ, respectively. And we identified 376 host and 187 fungal candidate genes that showed stage-specific expression pattern, which are possibly responsible for gall formation at the initial and later phases, respectively. Our results indicated that cytokinins play more prominent roles in regulating gall formation than do auxins. Together, our work provides general implications for the understanding of gene regulatory networks for culm gall development in Z. latifolia, and potential targets for genetic manipulation to improve the future yield of this crop.
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Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/genética , Poaceae/genética , Poaceae/microbiología , Análisis de Secuencia de ARN/métodos , Ustilago/fisiología , Vías Biosintéticas/genética , Citocininas/biosíntesis , Regulación hacia Abajo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Genes Fúngicos , Interacciones Huésped-Patógeno/genética , Ácidos Indolacéticos/metabolismo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Tallos de la Planta/microbiología , Tumores de Planta/microbiología , Poaceae/crecimiento & desarrollo , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Transcriptoma/genética , Regulación hacia Arriba/genéticaRESUMEN
Cerebralcare granule(®) (CG) is a preparation of Traditional Chinese Medicine that widely used in China. It was approved by the China State Food and Drug Administration for treatment of headache and dizziness associated with cerebrovascular diseases. In the present study, we aimed to investigate whether CG had protective effect against D-galactose (gal)-induced memory impairment and to explore the mechanism of its action. D-gal was administered (100 mg/kg, subcutaneously) once daily for 8 weeks to induced memory deficit and neurotoxicity in the brain of aging mouse and CG (7.5, 15, and 30 g/kg) were simultaneously administered orally. The present study demonstrates that CG can alleviate aging in the mouse brain induced by D-gal through improving behavioral performance and reducing brain cell damage in the hippocampus. CG prevents aging mainly via suppression of oxidative stress response, such as decreasing NO and MDA levels, renewing activities of SOD, CAT, and GPx, as well as decreasing AChE activity in the brain of D-gal-treated mice. In addition, CG prevents aging through inhibiting NF-κB-mediated inflammatory response and caspase-3-medicated neurodegeneration in the brain of D-gal treated mice. Taken together, these data clearly demonstrates that subcutaneous injection of D-gal produced memory deficit, meanwhile CG can protect neuron from D-gal insults and improve memory ability.
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Medicamentos Herbarios Chinos/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Envejecimiento/efectos de los fármacos , Animales , Trastornos del Conocimiento/tratamiento farmacológico , Modelos Animales de Enfermedad , Galactosa/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
This study was conducted to determine the inhibitory effect of E-cinnamaldehyde (EC) against causal agent of storage carrot rot, Sclerotinia sclerotiorum, under in vivo and in vitro conditions. Based on the results, EC was able to completely inhibit mycelial growth of three isolates (P>0.05) in both volatile and contact phases after 6days at the concentrations 200µl and 1µl/ml, respectively. In addition, EC at concentrations 1 and 10µl/ml completely inhibited carpogenic germination of three isolates. The results of in vivo trials showed that EC at the concentration of 10µl/ml was able to control the disease caused by isolates 1 and 3. However the disease caused by isolate 2 was inhibited with the concentration of 20µl/ml. In enzyme analyses, the activity of polyphenoloxidase and peroxidase did not change in the inoculated carrots after application of EC. Furthermore, the level of phenylalanine ammonia lyase decreased. These results indicated that EC does not have any potential to be considered as resistance inducers against sclerotinia carrot rot.
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Acroleína/análogos & derivados , Ascomicetos/efectos de los fármacos , Daucus carota/microbiología , Acroleína/farmacología , Daucus carota/crecimiento & desarrollo , Germinación , Pruebas de Sensibilidad Microbiana , Enfermedades de las PlantasRESUMEN
Ferulic acid (FA) acts as a powerful antioxidant against various age-related diseases. To investigate the effect and underlying mechanism of FA against d-galactose(d-gal)-induced memory deficit, mice were injected with d-gal to induce memory impairment and simultaneously treated with FA and donepezil. The behavioral results revealed that chronic FA treatment reversed d-gal-induced memory impairment. Further, FA treatment inhibited d-gal-induced AChE activity and oxidative stress via increase of superoxide dismutase activity and reduced glutathione content, as well as decrease of malondialdehyde and nitric oxide levels. We also observed that FA significantly inhibits inflammation in the brain through reduction of NF-κB and IL-1ß by enzyme-linked immunosorbent assay. Additionally, FA treatment significantly reduces the caspase-3 level in the hippocampus of d-gal-treated mice. Hematoxylin and eosin and Nissl staining showed that FA prevents neurodegeneration induced by d-gal. These findings showed that FA inhibits d-gal-induced AChE activity, oxidative stress, neuroinflammation and neurodegeneration, and consequently ameliorates memory impairment.
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Envejecimiento/efectos de los fármacos , Ácidos Cumáricos/farmacología , Galactosa/toxicidad , Trastornos de la Memoria/tratamiento farmacológico , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Donepezilo , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Indanos/farmacología , Interleucina-1beta/metabolismo , Masculino , Malondialdehído/metabolismo , Trastornos de la Memoria/inducido químicamente , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piperidinas/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
Fusarium graminearum hypovirus 1 (FgHV1), which is phylogenetically related to Cryphonectria hypovirus 1 (CHV1), is a virus in the family Hypoviridae that infects the plant pathogenic fungus F. graminearum. Although hypovirus FgHV1 infection does not attenuate the virulence of the host (hypovirulence), it results in defects in mycelial growth and spore production. We now report that the vertical transmission rate of FgHV1 through asexual spores reached 100%. Using RNA deep sequencing, we performed genome-wide expression analysis to reveal phenotype-related genes with expression changes in response to FgHV1 infection. A total of 378 genes were differentially expressed, suggesting that hypovirus infection causes a significant alteration of fungal gene expression. Nearly two times as many genes were up-regulated as were down-regulated. A differentially expressed gene enrichment analysis identified a number of important pathways. Metabolic processes, the ubiquitination system, and especially cellular redox regulation were the most affected categories in F. graminearum challenged with FgHV1. The p20, encoded by FgHV1 could induce H2O2 accumulation and hypersensitive response in Nicotiana benthamiana leaves. Moreover, hypovirus FgHV1 may regulate transcription factors and trigger the RNA silencing pathway in F. graminearum.
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Virus Fúngicos/fisiología , Fusarium/metabolismo , Virus ARN/fisiología , Transcriptoma , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fusarium/genética , Fusarium/virología , Regulación Fúngica de la Expresión Génica , Ontología de Genes , Redes Reguladoras de Genes , Genes Fúngicos , Anotación de Secuencia Molecular , Análisis de Secuencia de ARN , Estrés FisiológicoRESUMEN
Two novel double-stranded RNA (dsRNA) mycoviruses, termed Fusarium poae dsRNA virus 2 (FpV2) and Fusarium poae dsRNA virus 3 (FpV3), were isolated from the plant pathogenic fungus, Fusarium poae strain SX63, and molecularly characterized. FpV2 and FpV3, with respective genome sequences of 9518 and 9419 base pairs (bps), are both predicted to contain two discontinuous open reading frames (ORFs), ORF1 and ORF2. A hypothetical polypeptide (P1) and a RNA-dependent RNA polymerase (RdRp) are encoded by ORF1 and ORF2, respectively. Phytoreo_S7 domain (pfam07236) homologs were detected downstream of the RdRp domain (RdRp_4; pfam02123) of the ORF2-coded proteins of both FpV2 and FpV3. The same shifty heptamers (GGAAAAC) were both found immediately before the stop codon UAG of ORF1 in FpV2 and FpV3, which could mediate programmed -1 ribosomal frameshifting (-1 PRF). Phylogenetic analysis based on RdRp sequences clearly place FpV2 and FpV3 in a taxonomically unassigned dsRNA mycovirus group. Together, with a comparison of genome organization, a new taxonomic family termed Fusagraviridae is proposed to be created to include FpV2- and FpV3-related dsRNA mycoviruses, within which FpV2 and FpV3 would represent two distinct virus species.
Asunto(s)
Virus Fúngicos/fisiología , Fusarium/virología , ARN Bicatenario/metabolismo , Secuencia de Aminoácidos , Virus Fúngicos/clasificación , Virus Fúngicos/genética , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Péptidos/genética , Filogenia , ARN Polimerasa Dependiente del ARN/genética , Alineación de Secuencia , Análisis de Secuencia de ARNRESUMEN
CONTEXT: Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders. OBJECTIVE: To examine the bronchodilatory activity of FE and the potential mechanisms involved. MATERIALS AND METHODS: The effects of ethyl acetate fraction of FE (EFE) (0.05-0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5-30 µg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors. RESULTS: With in vitro studies, the contractile response evoked by Ach or His (EC50 = 0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration-dependent relaxation precontracted by His (EC50 = 23.2 µg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 µM), NG-nitro-l-arginine methyl ester (l-NAME) (100 µM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 µM). EFE also inhibited the contraction in Ca2+-free medium and produced rightward parallel displacement of CaCl2 curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ. DISCUSSION AND CONCLUSION: These results suggest that bronchodilator activities of EFE were related to activation of ß-adrenoceptor and NO/cGMP pathway. Blockage of Ca2+ channels and inhibition of IP3R-mediated internal Ca2+ release were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway.
Asunto(s)
Broncodilatadores/farmacología , Eriobotrya , Extractos Vegetales/farmacología , Tráquea/efectos de los fármacos , Triterpenos/farmacología , Animales , Calcio/metabolismo , AMP Cíclico/fisiología , Eriobotrya/química , Cobayas , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/fisiología , Oxadiazoles/farmacología , Quinoxalinas/farmacología , Tráquea/fisiología , Ácido UrsólicoRESUMEN
To conduct multiple-reaction monitoring(MRM) quantitative analysis with high-performance liquid chromatography coupled with mass spectrometry method, establish the quantification method of magnolol and honokiol in blood sample under negative ion mode with ibuprofen as internal standard, investigate the pharmacokinetic process of lignans constituents after oral administration of Weichang'an pill(WCA) at different doses, and provide theoretical basis to further reveal the material basis of WCA's anti-diarrhea effect. In the plasma samples, the linear relationship was good over the concentration range of 5.25 to 1 344.00 µgâ¢L ⻹ for magnolol and 10.08 to 2 580.00 µgâ¢L ⻹ for honokiol. The results of precision, stability, and extraction recovery tests showed that the determination method of plasma concentration for such compositions was stable and reliable. Dose-dependence was shown for magnolol and honokiol in the plasma concentration-time profile. The results indicated that the time to reach the maximum plasma concentration(Tmax) for lignanoids was 0.55-1.42 h, when the maximum plasma concentration(Cmax) could reach 996.36-2 330.96,189.87-1 469.43 µgâ¢L ⻹ respectively for magnolol and honokiol. The lignanoids could be absorbed rapidly in the blood after oral administration of WAC pills, providing experimental basis to prove rapid and long-acting anti-diarrhea effect of WAC pills after oral administration.
Asunto(s)
Compuestos de Bifenilo/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Lignanos/farmacocinética , AnimalesRESUMEN
A HPLC-MS/MS multiple-reaction monitoring (MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide (Co) and dehydrocostuslactone (De) in blood samples in the positive ion mode, with diazepam as the internal standard substance, in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang'an pills, and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples, Co and De showed a good linearity within concentration ranges 0.700 0-769.7, 2.510-956.0 µg x L(-1), respectively. The results of precision, stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration, the concentrations of Co and De in plasma increased with the increase in dose, with T(max) between 10.65-12.98 h, indicating a long time to reach peak plasma concentrations; C(max) of costunolide and dehydrocostuslactone ranged between 3.750-5.450,15.34-44.52 µg x L(-1), respectively. The in vivo adsorption of Co and De conformed to the one-compartment model, with a longer time to attain the peak plasma concentrations. These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Lactonas/farmacocinética , Sesquiterpenos/farmacocinética , Administración Oral , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Lactonas/administración & dosificación , Lactonas/sangre , Masculino , Ratas , Ratas Wistar , Sesquiterpenos/administración & dosificación , Sesquiterpenos/sangre , Comprimidos/administración & dosificación , Comprimidos/química , Comprimidos/farmacocinéticaRESUMEN
Mitogen-activated protein (MAP) kinases play crucial roles in regulating fungal development, growth and pathogenicity, and in responses to the environment. In this study, we characterized a MAP kinase kinase FgMkk1 in Fusarium graminearum, the causal agent of wheat head blight. Phenotypic analyses of the FgMKK1 mutant (ΔFgMKK1) showed that FgMkk1 is involved in the regulation of hyphal growth, pigmentation, conidiation, deoxynivalenol biosynthesis and virulence of F. graminearum. ΔFgMKK1 also showed increased sensitivity to cell wall-damaging agents, and to osmotic and oxidative stresses, but exhibited decreased sensitivity to the fungicides iprodione and fludioxonil. In addition, the mutant revealed increased sensitivity to a biocontrol agent, Trichoderma atroviride. Western blot assays revealed that FgMkk1 positively regulates phosphorylation of the MAP kinases Mgv1 and FgOs-2, the key component in the cell wall integrity (CWI) and high-osmolarity glycerol (HOG) signalling pathway respectively. Yeast two-hybrid assay indicated that Mgv1 interacts with a transcription factor FgRlm1. The FgRLM1 mutant (ΔFgRLM1) showed increased sensitivity to cell wall-damaging agents and exhibited decreased virulence. Taken together, our data indicated that FgMkk1 is an upstream component of Mgv1, and regulates vegetative differentiation, multiple stress response and virulence via the CWI and HOG signalling pathways. FgRlm1 may be a downstream component of Mgv1 in the CWI pathway in F. graminearum.
Asunto(s)
Proteínas Fúngicas/genética , Fusarium/patogenicidad , Regulación Fúngica de la Expresión Génica , Hifa/patogenicidad , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Agentes de Control Biológico , Pared Celular/genética , Pared Celular/metabolismo , Proteínas Fúngicas/metabolismo , Fungicidas Industriales , Fusarium/efectos de los fármacos , Fusarium/genética , Fusarium/metabolismo , Eliminación de Gen , Glicerol/metabolismo , Hifa/efectos de los fármacos , Hifa/genética , Hifa/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/deficiencia , Concentración Osmolar , Presión Osmótica , Fosforilación , Enfermedades de las Plantas/microbiología , Transducción de Señal , Trichoderma/patogenicidad , Triticum/microbiología , VirulenciaRESUMEN
CONTEXT: Radix Aucklandiae, the dry rhizome of Aucklandia lappa Decne (Asteraceae), enjoyed traditional popularity for its antidiarrheal effects. Although there are many investigations on its chemical constituents and pharmacologic actions, few studies explaining its activity and mechanism in gastrointestinal disorders are available. OBJECTIVE: In this paper, we focused on the effects of the methanol extract of R. Aucklandiae (RA ext) on gastrointestinal tract, so as to assess some of the possible mechanisms involved in the clinical treatment. MATERIALS AND METHODS: In vivo, in neostigmine-induced mice and normal mice, after intragastric administration, RA ext (100, 200, 300, and 400 mg/kg) was studied on gastrointestinal transit including gastric emptying and small intestinal motility. Meanwhile, in vitro, the effect of it (0.1, 0.2, 0.3, and 0.4 mg/mL) on the isolated tissue preparations of rat jejunum was also investigated, as well as costunolide and dehydrocostuslactone which were the main constituents. RESULTS: In vivo, the gastric emptying increased and intestinal transit decreased after the administration of RA ext in normal mice. However, RA ext inhibited the gastric emptying and the intestinal transit throughout the concentrations in neostigmine-induced mice. In vitro, RA ext caused inhibitory effect on the spontaneous contraction of rat-isolated jejunum in a dose-dependent manner ranging from 0.1 to 0.4 mg/mL, and it also relaxed the acetylcholine chloride (Ach, 10(-5) M), 5-hydroxytryptamine (5-HT, 200 µM)-induced, and K(+) (60 mM)-induced contractions. RA ext shifted the Ca(2+) concentration-response curves to right, similar to that caused by verapamil (0.025 mM). The Ca(2+) concentration-response curves were shifted by costunolide (CO) (5.4, 8.1, and 10.8 µg/mL), dehydrocostuslactone (DE) (4.6, 6.9, and 9.2 µg/mL), costunolide-dehydrocostuslactone (CO-DE) (5.4-4.6, 8.1-6.9, and 10.8-9.2 µg/mL) to the right, similar to that caused by verapamil (0.01 mM). DISCUSSION AND CONCLUSION: These results indicate that RA ext played a spasmolytic role in gastrointestinal motility, which is probably mediated through the inhibition of muscarinic receptors, 5-HT receptors, and calcium influx. The presence of cholinergic and calcium antagonist constituents may be the compatibility of CO and DE. All these results provide a pharmacological basis for its clinical use in the gastrointestinal tract.