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Sleep deprivation (SD) is prevalent throughout the world, which has negative effects on cognitive abilities, and causing mood alterations. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in Lamiophlomis rotata (L. rotata) Kudo, possesses potent neuroprotective properties and analgesic effects. Here, we evaluated the alleviative effects of 8-OaS on memory impairment and anxiety in mice subjected to SD (for 72-h). Our results demonstrated that 8-OaS (0.2, 2, 20 mg/kg) administration dose-dependently ameliorated behavioral abnormalities in SD mice, accompanied with restored synaptic plasticity and reduced shrinkage and loss of hippocampal neurons. 8-OaS reduced the inflammatory response and oxidative stress injury in hippocampus caused by SD, which may be related to inhibition of NLRP3 inflammasome-mediated inflammatory process and activation of the Nrf2/HO-1 pathway. SD also led to increases in the expressions of TLR-4/MyD88, active NF-κB, pro-IL-1ß, TNFα and MDA, as well as a decrease in the level of SOD in mice hippocampus, which were reversed by 8-OaS administration. Moreover, our molecular docking analyses showed that 8-OaS also has good affinity for NLRP3 and Nrf2 signaling pathways. These results suggested that 8-OaS could be used as a novel herbal medicine for the treatment of sleep loss and for use as a structural base for developing new drugs.
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Proteína con Dominio Pirina 3 de la Familia NLR , Privación de Sueño , Animales , Ratones , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Cognición , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Privación de Sueño/complicaciones , Privación de Sueño/tratamiento farmacológicoRESUMEN
The Compound Cheqian Tablets are derived from Cheqian Power in Comprehensive Recording of Divine Assistance, and they are made by modern technology with the combination of Plantago asiatica and Coptis chinensis. To investigate the material basis of Compound Cheqian Tablets in the treatment of diabetic nephropathy, in this study, the chemical components of Compound Cheqian Tablets were characterized and analyzed by UPLC-Q-TOF-MS/MS, and a total of 48 chemical components were identified. The identified chemical compounds were analyzed by network pharmacology. By validating with previous literature, six bioactive compounds including acteoside, isoacteoside, coptisine, magnoflorine, palmatine, and berberine were confirmed as the index components for qua-lity evaluation. Furthermore, the content of the six components in the Compound Cheqian Tablets was determined by the "double external standards" quantitative analysis of multi-components by single marker(QAMS), and the relative correction factor of isoacteoside was calculated as 1.118 by using acteoside as the control; the relative correction factors of magnoflorine, palmatine, and berberine were calculated as 0.729, 1.065, and 1.126, respectively, by using coptisine as the control, indicating that the established method had excellent stability under different conditions. The results obtained by the "double external standards" QAMS approximated those obtained by the external standard method. This study qualitatively characterized the chemical components in the Compound Cheqian Tablets by applying UPLC-Q-TOF-MS/MS and screened the pharmacodynamic substance basis for the treatment of diabetic nephropathy via network pharmacology, and primary pharmacodynamic substance groups were quantitatively analyzed by the "double external stan-dards" QAMS method, which provided a scientific basis for clarifying the pharmacodynamic substance basis and quality control of Compound Cheqian Tablets.
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Berberina , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Humanos , Espectrometría de Masas en Tándem , Berberina/farmacología , Cromatografía Líquida de Alta Presión/métodos , Farmacología en Red , Medicamentos Herbarios Chinos/química , Control de Calidad , ComprimidosRESUMEN
In our continuous search for antibacterial agents against Pseudomonas syringae pv. actinidiae (Psa) from kiwi-associated fungi, two pairs of epimeric cytochalasins, zopfiellasins A-D (1-4), were characterized from the fungus Zopfiella sp. The structures were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1 and 3 exhibited antibacterial activity against Psa with MIC values of 25 and 50 µg/mL, respectively. This is the first report of anti-Psa activity of cytochalasin derivatives.
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Actinidia/microbiología , Antibacterianos/química , Antibacterianos/farmacología , Citocalasinas/química , Citocalasinas/farmacología , Sordariales/química , Antibacterianos/aislamiento & purificación , Citocalasinas/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Pseudomonas syringae/efectos de los fármacos , Estereoisomerismo , Difracción de Rayos XRESUMEN
The adverse reaction to irinotecan is related to the single nucleotide polymorphism (SNP) of UGT1A1*6 genotype. The current SNP detection methods have various disadvantages, including time-consuming procedures, high- risk cross-contamination, and cumbersome operation. Hence, it is necessary to establish a new method suitable for clinical application, which is easy and simple to detect SNP with minimal risk for cross-contamination. In this study, a cascade invader assay-based real-time PCR, for UGT1A1*6 genotyping has been established by optimizing reaction conditions with DNA samples of three genotypes. The sensitivity and accuracy of the method were evaluated with DNAs derived from oral swab samples. The results showed that the method could detect the UGT1A1*6 genotypes from the oral swab samples with a detection limit of 6 ng genomic DNA with 100% accuracy. Due to its convenient and non-invasive sampling, single close-tube operation, and minimal risk for cross-contamination, the method has the potential in clinical application for individualized detection of drug-related UGT1A1*6 polymorphism and reaction to irinotecan.
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Glucuronosiltransferasa/genética , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Saliva/química , Genotipo , HumanosRESUMEN
To evaluate the effect of Tongxie Yaofang on cardiac endogenous metabolism in irritable bowel syndrome(IBS) rats by using metabolomics method, find its potential biomarkers, analyze the metabolic pathways, and explore the pharmacological effects, mechanisms of action and syndrome essence of syndrome model. Forty Wistar rats were used to establish IBS models, and then randomly divided into four groupsï¼ model control group and Tongxie Yaofang treatment groups (high, medium, low dose). Another 10 rats were used as normal group. The rats in Tongxie Yaofang-treated(low, medium and high dose) groups were orally administrated with Tongxie Yaofang extracts once a day for 2 weeks, respondingly with the doses of 0.203,0.406,0.812 gâ¢mL⻹. The rats in normal group and model control group were given with equal volume of saline once a day for 2 weeks. On the 0 and 15th days, serum was collected and each sample extract was analyzed by UPLC-Q-TOF-MS. Eight potential biomarkers were identified and 8 major metabolic pathways were found to be related with IBS diseases neurotransmitter metabolism, inflammatory immunity, brain function and energy metabolism, etc. Tongxie Yaofang had certain pharmacological effects on IBS, and its mechanism may be related to serotonergic synapse, tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and so on, which might be the biological basis of IBS liver-spleen deficiency syndrome.
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Medicamentos Herbarios Chinos/farmacología , Síndrome del Colon Irritable/sangre , Metabolómica , Animales , Biomarcadores/sangre , Modelos Animales de Enfermedad , Síndrome del Colon Irritable/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
Without extra addition of sulfinate salt, allylic sulfones were synthesized by palladium-catalyzed cross-coupling of aryl iodide with N-tosylhydrazone. In this transformation, not only the diazo compound but also the sulfinate salt, which were both generated in situ from base-mediated decomposition of the N-tosylhydrazone, was used as nucleophilic partner.
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Compuestos Alílicos/síntesis química , Hidrazonas/química , Paladio/química , Sulfonas/síntesis química , Compuestos de Tosilo/química , Compuestos Alílicos/química , Catálisis , Sulfonas/químicaRESUMEN
The increasing incidence of vulvovaginal candidiasis (VVC) and the emergence of fluconazole resistance are an indisputable fact. However, little information is available regarding the correlation between fluconazole resistance in vaginal Candida albicans and the expression of drug efflux pump genes. In this study, we investigated the species distribution, fluconazole susceptibility profiles and the mechanisms of fluconazole resistance in Candida strains. In total, 785 clinical Candida isolates were collected from patients with VVC. C. albicans was the most frequently isolated species(n = 529) followed by C. glabrata (n = 164) and C. krusei (n = 57). Of all Candida isolates, 4.7% were resistant to fluconazole. We randomly selected 18 fluconazole resistant isolates of C. albicans to evaluate the expression of CDR1, CDR2, MDR1 and FLU1 genes. Compared with fluconazole-susceptible C. albicans isolates, CDR1 gene expression displayed 3.16-fold relative increase, which was statistically significant. CDR2, MDR1 and FLU1 overexpression was observed in several fluconazole-resistant C. albicans isolates, but statistical significance was not achieved. These results demonstrate a high frequency of non-albicans species (32.6%); however, C. albicans is the most common Candida species implicated in vaginitis, and this strain displays considerable fluconazole resistance. Meanwhile, our study further indicates that fluconazole resistance in C. albicans may correlate with CDR1 gene overexpression.
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Transportadoras de Casetes de Unión a ATP/genética , Antifúngicos/farmacología , Candida/aislamiento & purificación , Candidiasis Vulvovaginal/microbiología , Farmacorresistencia Fúngica , Fluconazol/farmacología , Proteínas Fúngicas/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Candida/clasificación , Candida/efectos de los fármacos , Candida/genética , Candidiasis Vulvovaginal/tratamiento farmacológico , Femenino , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , HumanosRESUMEN
BACKGROUND: Rhododendron nivale subsp. boreale Philipson et M. N. Philipson is an alpine woody species with ornamental qualities that serve as the predominant species in mountainous scrub habitats found at an altitude of â¼4,200 m. As a high-altitude woody polyploid, this species may serve as a model to understand how plants adapt to alpine environments. Despite its ecological significance, the lack of genomic resources has hindered a comprehensive understanding of its evolutionary and adaptive characteristics in high-altitude mountainous environments. FINDINGS: We sequenced and assembled the genome of R. nivale subsp. boreale, an assembly of the first subgenus Rhododendron and the first high-altitude woody flowering tetraploid, contributing an important genomic resource for alpine woody flora. The assembly included 52 pseudochromosomes (scaffold N50 = 42.93 Mb; BUSCO = 98.8%; QV = 45.51; S-AQI = 98.69), which belonged to 4 haplotypes, harboring 127,810 predicted protein-coding genes. Conjoint k-mer analysis, collinearity assessment, and phylogenetic investigation corroborated autotetraploid identity. Comparative genomic analysis revealed that R. nivale subsp. boreale originated as a neopolyploid of R. nivale and underwent 2 rounds of ancient polyploidy events. Transcriptional expression analysis showed that differences in expression between alleles were common and randomly distributed in the genome. We identified extended gene families and signatures of positive selection that are involved not only in adaptation to the mountaintop ecosystem (response to stress and developmental regulation) but also in autotetraploid reproduction (meiotic stabilization). Additionally, the expression levels of the (group VII ethylene response factor transcription factors) ERF VIIs were significantly higher than the mean global gene expression. We suspect that these changes have enabled the success of this species at high altitudes. CONCLUSIONS: We assembled the first high-altitude autopolyploid genome and achieved chromosome-level assembly within the subgenus Rhododendron. In addition, a high-altitude adaptation strategy of R. nivale subsp. boreale was reasonably speculated. This study provides valuable data for the exploration of alpine mountaintop adaptations and the correlation between extreme environments and species polyploidization.
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Altitud , Genoma de Planta , Haplotipos , Filogenia , Rhododendron , Tetraploidía , Rhododendron/genética , Adaptación Fisiológica/genética , Anotación de Secuencia Molecular , Poliploidía , Regulación de la Expresión Génica de las PlantasRESUMEN
Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.
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RNA interference (RNAi) is a powerful tool that post-transcriptionally silences target genes in eukaryotic cells. However, silencing efficacy varies greatly among different insect species. Recently, we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA injection. The disappearance of double-stranded RNA (dsRNA) could be a potential factor that restricts RNAi efficiency. Here, we found that dsRNA can be degraded in midgut fluids, and a dsRNase of A. lucorum (AldsRNase) was identified and characterized. Sequence alignment indicated that its 6 key amino acid residues and the Mg2+ -binding site were similar to those of other insects' dsRNases. The signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali dsRNase. AldsRNase showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle, with peaks at the 4th instar ecdysis in the whole body. The purified AldsRNase protein obtained by heterologously expressed can rapidly degrade dsRNA. When comparing the substrate specificity of AldsRNase, 3 specific substrates (dsRNA, small interfering RNA, and dsDNA) were all degraded, and the most efficient degradation is dsRNA. Subsequently, immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut cells. Through cloning and functional study of AldsRNase, the enzyme activity and substrate specificity of the recombinant protein, as well as the subcellular localization of nuclease, the reason for the disappearance of dsRNA was explained, which was useful in improving RNAi efficiency in A. lucorum and related species.
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Heterópteros , ARN Bicatenario , Animales , ARN Bicatenario/genética , Alineación de Secuencia , Interferencia de ARN , Insectos/genética , Clonación Molecular , Heterópteros/genéticaRESUMEN
Nucleotide-binding oligomerization domain-2 (NOD2, also designated CARD15), a member of the NOD-leucine-rich repeat (LRR) protein family (also called the CATERPILLAR family), is upregulated in atheroma lesions and has an important role in regulating the intracellular recognition of bacterial components by immune cells. However, the effect of NOD2 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of NOD2 deficiency on cardiac hypertrophy induced by aortic banding (AB) in mice. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. NOD2 expression was upregulated in cardiomyocytes after aortic banding surgery in wild-type (WT) mice. NOD2 deficiency promoted cardiac hypertrophy and fibrosis 4 weeks after AB. Further, the enhanced activation of TLR4 and the MAPKs, NF-κB and TGF-ß/Smad pathways were found in NOD2-knockout (KO) mice compared with WT mice. Our results suggest that NOD2 attenuates cardiac hypertrophy and fibrosis via regulation of multiple pathways.
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Cardiomegalia/metabolismo , Modelos Animales de Enfermedad , Hipertensión/fisiopatología , Miocardio/metabolismo , Proteína Adaptadora de Señalización NOD2/metabolismo , Animales , Cardiomegalia/etiología , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Núcleo Celular , Progresión de la Enfermedad , Fibrosis , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/patología , Proteína Adaptadora de Señalización NOD2/biosíntesis , Proteína Adaptadora de Señalización NOD2/genética , Fosforilación , Procesamiento Proteico-Postraduccional , Transporte de Proteínas , Distribución Aleatoria , Proteínas Smad/metabolismo , Receptor Toll-Like 4/metabolismo , Factor de Transcripción ReIA/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: To explore the pathogenesis of tumors by blocking the normal differentiation process of stem cells. METHODS: Bone marrow mesenchymal stem cells (BMSCs) from rats were isolated, cultured and purified by whole bone marrow adherence method. The rat BMSCs were induced to differentiate into adipocytes with dexamethasone, insulin and indomethacin. Blockage of the differentiation process was induced by 3-methylcholanthrene (3-MC). RESULTS: The differentiation experiment showed that at 30 days after the induction, oil red O staining-positive cells occurred with increased intracytolasmic lipid droplets, characteristic for adipocytes. The differentiation blockage experiment showed that at 30 days after induction, the deposits of oil red O staining-cytoplasmic lipid droplets was significantly reduced, indicating that the blocked cells were adipocytes, but not fully differentiated. Morphological identification showed that cell contact inhibition disappeared, abnormal cell nuclei, increased number of micronucleus aberration and karyotype abnormalities, indicating that malignant transformation of the stem cells occurred after the differentiation blockage. CONCLUSIONS: The results of this study show a blockage of the differentiation of that stem cells at the intermediate phase, and a tendency of malignant transformation of the stem cells. The results of our study provide new evidence that cancer stem cells may be originated by suppression of stem cell differentiation.
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Adipocitos/citología , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Metilcolantreno/farmacología , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Transformación Celular Neoplásica , Células Cultivadas , Dexametasona/farmacología , Combinación de Medicamentos , Femenino , Indometacina/farmacología , Insulina/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The titanium (Ti) and its alloys have been widely used for dental and orthopedic implants. However, the Ti-based implants may suffer from bacterial infection, which would result in insufficient healing, implant failure and repeated surgical intervention. It is of great interest to inhibit the bacterial adhesion and colonization on the Ti-based implants by introducing proper surface coatings. In this work, a simple method was employed to synthesize the water-soluble catechol-containing chitosan (CACS). The CACS coatings can be deposited onto various substrate surfaces and exhibit substrate-independent behavior. The CACS-coated Ti surfaces were further deposited with silver nanoparticles (Ag NPs) via in-situ reduction of Ag+ ions using catechol moieties as the reducing agents. The resulting AgNPs/CACS-coated Ti surfaces exhibit antibacterial properties and can prevent the surface adhesion of bacterial cells, as evidenced by the inhibition zone test, live/dead bacterial staining assay and spread plate method. In addition, they show negligible cytotoxicity to L929 mouse fibroblast cells.
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Antibacterianos/química , Catecoles/química , Quitosano/química , Nanopartículas del Metal/química , Plata/química , Titanio/químicaRESUMEN
Chemical reduction of graphene oxide (GO) is a simple and inexpensive method for the large-scale production of graphene-based materials. A suitable reducing agent, especially a green reductant, is in high demand for the production of reduced GO (RGO). Vancomycin, a glycopeptide antibiotic used to treat a variety of Gram-positive bacterial infections, was used to chemically reduce GO at a weak alkaline pH. As far as we know, this is the first report of reduction of GO by a glycopeptide antibiotic. The resulting vancomycin-decorated RGO (RGO-Van) was characterized by UV-visible adsorption and Raman spectroscopies, X-ray diffraction pattern and atomic force microscopy (AFM). The antibacterial effect of the RGO-Van suspension was investigated by the bacterial growth curves. The RGO-Van sheet can be fabricated into paper-like film through vacuum filtration. The antibacterial property of the as-obtained RGO-Van film was assessed by the inhibition zone test, and the bacterial adhesion assay. The antibacterial efficacy of the RGO-Van film was also verified by treatment of wound infection caused by Staphylococcus aureus (S. aureus) in a rat infection model.
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Antibacterianos/farmacología , Grafito/farmacología , Óxidos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/efectos de los fármacos , Vancomicina/farmacología , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Grafito/química , Masculino , Pruebas de Sensibilidad Microbiana , Óxidos/química , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie , Vancomicina/síntesis química , Vancomicina/químicaRESUMEN
Bullous pemphigoid is a common autoimmune blistering disease of the elderly associated with autoantibody-mediated complement activation, and complement dysregulation is critical for its pathogenesis. As a crucial regulator of the complement system, CD55 has been widely studied in autoimmune diseases. Here, we investigated the involvement of CD55 in bullous pemphigoid, as little is known regarding its role in this disease. We found that CD55 levels were significantly lower in the lesions of patients with bullous pemphigoid (n = 8) compared to those in skin samples from healthy controls (n = 6). Interestingly, CD55 depletion in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Moreover, complement activation was blocked by exogenous recombinant CD55 protein in both skin sections and keratinocytes exposed to pathogenic antibodies from patients with bullous pemphigoid. Notably, a significant increase in the expression of TNF-α and IFN-γ, administration of which downregulated CD55 levels in HaCaT cells, was observed in the sera of patients with bullous pemphigoid (n = 38) compared to that in healthy controls (n = 19). We found that ERK1/2 is involved in both TNF-α- and IFN-γ-induced CD55 downregulation. Thus, CD55 deficiency is a crucial factor in bullous pemphigoid pathogenesis, suggesting that increasing CD55 levels may exert a therapeutic effect.
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BACKGROUND AND AIM: Trefoil factor family 3 (TFF3) is expressed by intestinal epithelial cells and it mainly functions to protect the mucosa from injury. Expression of TFF3 has been correlated with a poor prognosis in patients with cancer, but little is known about whether TFF3 directly contributes to the malignant behavior of cancer cells. The present study was conducted to determine whether TFF3 expression contributes to the malignant behavior of cancer cells in vitro and in vivo. METHODS: Two subclones of a metastatic rat colorectal cancer cell line, demonstrated previously to manifest aggressive (LN cells) and non-aggressive (LP cells) growth in vivo, were analyzed for expression of TFF3 and tested in assays of cancer cell migration, invasion, and apoptosis in vitro, and mortality in vivo. RESULTS: The aggressive LN cell line endogenously expressed TFF3 and supported the transcription of a TFF3 promoter-driven reporter construct, whereas the non-aggressive LP cell line did not express TFF3. LN cells demonstrated enhanced migration, invasion, and less apoptosis compared to LP cells. Transfecting TFF3 into LP cells enhanced their ability to migrate, invade, block apoptosis, and behave more aggressively in vivo, thereby resembling the phenotype of LN cells. CONCLUSIONS: In rat colon cancer cells, both endogenous and constitutive expression of TFF3 correlates with an aggressive phenotype. These data provide direct evidence that TFF3 contributes to the malignant behavior of cancer cells.
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Neoplasias del Colon/patología , Perfilación de la Expresión Génica , Invasividad Neoplásica , Neuropéptidos/biosíntesis , Neuropéptidos/fisiología , Animales , Apoptosis , Movimiento Celular , Neoplasias del Colon/veterinaria , Neuropéptidos/genética , Fenotipo , Pronóstico , Ratas , Factor Trefoil-3 , Células Tumorales CultivadasRESUMEN
In order to find out the optimal composition of novel Nd-Mg-Ni alloys for hydrogen storage, the isothermal section of Nd-Mg-Ni system at 400 °C is established by examining the equilibrated alloys. A new ternary compound Nd4Mg80Ni8 is discovered in the Mg-rich corner. It has the crystal structure of space group I41/amd with lattice parameters of a = b = 11.2743(1) Å and c = 15.9170(2) Å, characterized by the synchrotron powder X-ray diffraction (SR-PXRD). High-resolution transmission electron microscopy (HR-TEM) is used to investigate the microstructure of Nd4Mg80Ni8 and its hydrogen-induced microstructure evolution. The hydrogenation leads to Nd4Mg80Ni8 decomposing into NdH2.61-MgH2-Mg2NiH0.3 nanocomposites, where the high density phase boundaries provide a great deal of hydrogen atoms diffusion channels and nucleation sites of hydrides, which greatly enhances the hydriding/dehydriding (H/D) properties. The Nd4Mg80Ni8 exhibits a good cycle ability. The kinetic mechanisms of H/D reactions are studied by Real Physical Picture (RPP) model. The rate controlling steps are diffusion for hydriding reaction in the temperature range of 100 ~ 350 °C and surface penetration for dehydriding reaction at 291 ~ 347 °C. In-situ SR-PXRD results reveal the phase transformations of Mg to MgH2 and Mg2Ni to Mg2NiH4 as functions of hydrogen pressure and hydriding time.
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3,3'-Diindolylmethane (DIM) is the major product of the acid-catalyzed condensation of indole-3-carbinol (I3C), a component of extracts of Brassica food plants. Numerous studies have suggested that DIM has several beneficial biological activities, including elimination of free radicals, antioxidant and anti-angiogenic effects and activation of apoptosis of various tumor cells. In the present study, an in vitro model was established, using 1 µM angiotensin II (Ang II) in cultured rat cardiac H9c2 cells, to observe the effects of DIM on cardiac hypertrophy. Following 24 h stimulation with DIM (1, 5, and 10 µM) with or without Ang II, cells were characterized by immunoï¬uorescence to analyze cardiac α-actinin expression. Cardiomyocyte hypertrophy and molecular markers of cardiac hypertrophy were assessed by quantitative polymerase chain reaction. Atrial natriuretic peptide, brain natriuretic peptide and myosin heavy chain ß mRNA expression were induced by Ang II in H9c2 cells treated with the optimal concentration of DIM for 6, 12, and 24 h. The levels of phosphorylated and total proteins of the 5' AMP-activated protein kinase α (AMPKα)/mitogen-activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling pathways in H9c2 cells treated with DIM for 0, 15, 30, and 60 min induced by Ang II were determined by western blot analysis. The results showed that DIM attenuated cellular hypertrophy in vitro, enhanced the phosphorylation of AMPKα and inhibited the MAPKmTOR signaling pathway in response to hypertrophic stimuli.
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Proteínas Quinasas Activadas por AMP/genética , Cardiotónicos/farmacología , Indoles/farmacología , Miocitos Cardíacos/efectos de los fármacos , Serina-Treonina Quinasas TOR/genética , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/metabolismo , Angiotensina II/farmacología , Animales , Factor Natriurético Atrial/genética , Factor Natriurético Atrial/metabolismo , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/prevención & control , Línea Celular , Regulación de la Expresión Génica , Modelos Biológicos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Péptido Natriurético Encefálico/genética , Péptido Natriurético Encefálico/metabolismo , Fosforilación/efectos de los fármacos , Ratas , Transducción de Señal , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo , Vasoconstrictores/antagonistas & inhibidores , Vasoconstrictores/farmacologíaRESUMEN
Cardiac remodeling is a key determinant in the clinical course and outcome of heart failure and characterized by cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis and inflammation. The anti-inflammatory, anti-apoptotic and anti-fibrotic effects of paeoniflorin have been identified in various types of tissue and cells. However, the role of paeoniflorin in cardiac remodeling remains unclear. We performed aortic banding (AB) in mice to induce a cardiac remodeling model in response to pressure overload. Paeoniflorin (20 mg/kg) was administered by daily intraperitoneal (i.p.) injection. Paeoniflorin treatment promoted the survival rate and improved cardiac function of mice at 8 weeks post surgery. AB-induced cardiac hypertrophy, as assessed by heart weight, gross heart, HE and WGA staining, cross-sectional area of cardiomyocyte and mRNA expresssion of hypertrophic makers, was attenuated by paeoniflorin. Paeoniflorin also inhibited collagen deposition, expression of TGFß, CTGF, collagen Iα and collagen IIIα, and phosphorylation of Smad2 and Smad3 in the heart exposed to pressure overload. Cardiomyocyte apoptosis and induction of Bax and cleaved caspase3 in response to AB were suppressed by paeoniflorin. Furthermore, paeoniflorin decreased the quantity of CD68+ cells, protein levels of TNF-α and IL-1ß, and phosphorylation of IκBα and NFκB-p65 in the heart after AB. In conclusion, paeoniflorin attenuated cardiac hypertrophy, fibrosis, apoptosis and inflammation, and improved left ventricular function in pressure overloaded mice. The cardioprotective effect of paeoniflorin is associated with the inhibition of TGFß/Smads and NF-κB pathways.
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Benzoatos/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Glucósidos/farmacología , Corazón/efectos de los fármacos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Smad/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Remodelación Ventricular/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatología , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Fibrosis/fisiopatología , Corazón/fisiopatología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Monoterpenos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
PURPOSE: 3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. It has strong antioxidant and anti-angiogenic effects and promotes the apoptosis of a variety of tumor cells. However, little is known about the critical role of DIM on cardiac hypertrophy. In the present study, we investigated the effects of DIM on cardiac hypertrophy. METHODS: Multiple molecular techniques such as Western blot analysis, real-time PCR to determine RNA expression levels of hypertrophic, fibrotic and oxidative stress markers, and histological analysis including H&E for histopathology, PSR for collagen deposition, WGA for myocyte cross-sectional area, and immunohistochemical staining for protein expression were used. RESULTS: In pre-treatment and reverse experiments, C57/BL6 mouse chow containing 0.05% DIM (dose 100 mg/kg/d DIM) was administered one week prior to surgery or one week after surgery, respectively, and continued for 8 weeks after surgery. In both experiments, DIM reduced to cardiac hypertrophy and fibrosis induced by aortic banding through the activation of 5'-adenosine monophosphate-activated protein kinase-α2 (AMPKα2) and inhibition of mammalian target of the rapamycin (mTOR) signaling pathway. Furthermore, DIM protected against cardiac oxidative stress by regulating expression of estrogen-related receptor-alpha (ERRα) and NRF2 etc. The cardioprotective effects of DIM were ablated in mice lacking functional AMPKα2. CONCLUSION: DIM significantly improves left ventricular function via the activation of AMPKα2 in a murine model of cardiac hypertrophy.