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This study assessed AI-processed low-dose cone-beam computed tomography (CBCT) images for single-tooth diagnosis. Human-equivalent phantoms were used to evaluate CBCT image quality with a focus on the right mandibular first molar. Two CBCT machines were used for evaluation. The first CBCT machine was used for the experimental group, in which images were acquired using four protocols and enhanced with AI processing to improve quality. The other machine was used for the control group, where images were taken in one protocol without AI processing. The dose-area product (DAP) was measured for each protocol. Subjective clinical image quality was assessed twice by five dentists, with a 2-month interval in between, using 11 parameters and a six-point rating scale. Agreement and statistical significance were assessed with Fleiss' kappa coefficient and intra-class correlation coefficient. The AI-processed protocols exhibited lower DAP/field of view values than non-processed protocols, while demonstrating subjective clinical evaluation results comparable to those of non-processed protocols. The Fleiss' kappa coefficient value revealed statistical significance and substantial agreement. The intra-class correlation coefficient showed statistical significance and almost perfect agreement. These findings highlight the importance of minimizing radiation exposure while maintaining diagnostic quality as the usage of CBCT increases in single-tooth diagnosis.
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Lateral cephalograms and related analysis constitute representative methods for orthodontic treatment. However, since conventional cephalometric radiographs display a three-dimensional structure on a two-dimensional plane, inaccuracies may be produced when quantitative evaluation is required. Cone-beam computed tomography (CBCT) has minimal image distortion, and important parts can be observed without overlapping. It provides a high-resolution three-dimensional image at a relatively low dose and cost, but still shows a higher dose than a lateral cephalogram. It is especially true for children who are more susceptible to radiation doses and often have difficult diagnoses. A conventional lateral cephalometric radiograph can be obtained by reconstructing the Digital Imaging and Communications in Medicine data obtained from CBCT. This study evaluated the applicability and consistency of lateral cephalograms generated by CBCT using an artificial intelligence analysis program. Group I comprised conventional lateral cephalometric radiographs, group II comprised lateral cephalometric radiographs generated from CBCT using OnDemand 3D, and group III comprised lateral cephalometric radiographs generated from CBCT using Invivo5. All measurements in the three groups showed non-significant results. Therefore, a CBCT scan and artificial intelligence programs are efficient means when performing orthodontic analysis on pediatric or orthodontic patients for orthodontic diagnosis and planning.
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Inteligência Artificial , Tomografia Computadorizada de Feixe Cônico , Humanos , Criança , Cefalometria , Radiografia , Assistência OdontológicaRESUMO
Deposition of fibrillar forms of amyloid ß-protein (Aß) is commonly found in patients with Alzheimer's disease (AD) associated with cognitive decline. Impaired clearance of Aß species is thought to be a major cause of late-onset sporadic AD. Aß secreted into the extracellular milieu can be cleared from the brain through multiple pathways, including cellular uptake in neuronal and non-neuronal cells. Recent studies have showed that the naturally-occurring polyphenol amentoflavone (AMF) exerts anti-amyloidogenic effects. However, its effects on metabolism and cellular clearance of Aß remain to be tested. In the present study, we demonstrated that AMF significantly increased the cellular uptake of both Aß1-40 and Aß1-42, but not inverted Aß42-1 in mouse neuronal N2a cells. Though AMF promoted internalization of cytotoxic Aß1-42, it significantly reduced cell death in our assay condition. Our data further revealed that the internalized Aß is translocated to lysosomes and undergoes enzymatic degradation. The saturable kinetic of Aß uptake and our pharmacologic experiments showed the involvement of receptor-mediated endocytosis, in part, through the class A scavenger receptors as a possible mechanism of action of AMF. Taken together, our findings indicate that AMF can lower the levels of extracellular Aß by increasing their cellular uptake and clearance, suggesting the therapeutic potential of AMF for the treatment of AD.
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Doença de Alzheimer , Biflavonoides , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Biflavonoides/farmacologia , Humanos , Camundongos , Neurônios/metabolismoRESUMO
The dried root of Angelica sinensis (A. sinensis) has been widely used in Chinese traditional medicine for various diseases such as inflammation, osteoarthritis, infections, mild anemia, fatigue, and high blood pressure. Searching for the secondary metabolites of A. sinensis has been mainly conducted. However, the bioactivity of coumarins in the plant remains unexplored. Therefore, this study was designed to evaluate the anti-inflammatory activity of glabralactone, a coumarin compound from A. sinensis, using in vitro and in vivo models, and to elucidate the underlying molecular mechanisms of action. Glabralactone effectively inhibited nitric oxide production in lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophage cells. The downregulation of LPS-induced mRNA and protein expression of iNOS, TNF-α, IL-1ß, and miR-155 was found by glabralactone. The activation of NF-κB and TRIF-dependent IRF-3 pathway was also effectively suppressed by glabralactone in LPS-stimulated macrophages. Glabralactone (5 and 10 mg/kg) exhibited an in vivo anti-inflammatory activity with the reduction of paw edema volume in carrageenan-induced rat model, and the expressions of iNOS and IL-1ß proteins were suppressed by glabralactone in the paw soft tissues of the animal model. Taken together, glabralactone exhibited an anti-inflammatory activity in in vitro and in vivo models. These findings reveal that glabralactone might be one of the potential components for the anti-inflammatory activity of A. sinensis and may be prioritized in the development of a chemotherapeutic agent for the treatment of inflammatory diseases.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Angelica sinensis , Cumarínicos , Fator Regulador 3 de Interferon , NF-kappa B , Proteínas Adaptadoras de Transporte Vesicular/antagonistas & inibidores , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Angelica sinensis/química , Animais , Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Fator Regulador 3 de Interferon/antagonistas & inibidores , Fator Regulador 3 de Interferon/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia. METHODS: We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears. RESULTS: We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro, in vivo, and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, -hyperlipidemic, -inflammatory, -mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM2.5 among high susceptible people with multiple underlying diseases. CONCLUSION: For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.
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Frutas/química , Alimento Funcional , Compostos Fitoquímicos/farmacologia , Pyrus/química , COVID-19 , Flavonoides , Humanos , Fenóis , TriterpenosRESUMO
BACKGROUND: Persimmon (Diospyros kaki Thunb.) is the most widely cultivated species of the genus Diospyros. In this study, genetic diversity and variations in persimmon genotypes were investigated using single nucleotide polymorphism (SNP) markers identified by genotyping-by-sequencing (GBS) analysis. RESULTS: Ninety-five persimmon accessions grown in the Pear Research Institute, National Institute Horticultural and Herbal Science, were sequenced using the Illumina Hiseq2500 platform and polymorphic SNPs were detected to develop molecular markers. These reliable SNPs were analyzed using the Kompetitive Allele Specific PCR (KASP) assay to discriminate among persimmon genotypes. GBS generated a total of 447,495,724 trimmed reads, of which 89.7% were raw reads. After demultiplexing and sequence quality trimming, 108,876,644 clean reads were mapped to the reference transcriptome. An average of 1,146,070 genotype reads were mapped. Filtering of raw SNPs in each sample led to selection of a total of 1,725,401 high-quality SNPs. The number of homozygous and heterozygous SNPs ranged from 1,933 to 6,834 and from 846 to 5,927, respectively. CONCLUSIONS: Of the 49 SNPs selected for development of an identification system for persimmons, 15 SNPs were used in the KASP assay to analyze 32 persimmon accessions. These KASP markers discriminated among all accessions.
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Reação em Cadeia da Polimerase/métodos , Diospyros/genética , Variação Genética , Marcadores Genéticos , Mapeamento Cromossômico , Polimorfismo de Nucleotídeo Único/genética , Alelos , Técnicas de Genotipagem , HomozigotoRESUMO
Alzheimer's disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals worldwide. Increased deposition of insoluble amyloid ß (Aß) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aß fibrils and/or destabilize ß-sheet-rich Aß fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aß amyloidogenesis utilizing an in vitro thioflavin T assay with Aß1-42 peptide which is prone to aggregate more rapidly to fibrils than Aß1-40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aß1-42 fibrillization (IC50: 0.26 µM), as well as on disassembling preformed Aß1-42 fibrils (EC50: 0.59 µM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aß1-42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aß1-42 fibrils, resulting in conversion of those fibrils to amorphous Aß1-42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aß1-42 fibrillization and disaggregation of preformed mature Aß1-42 fibrils.
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Mitochondria play a pivotal role in cancer bioenergetics and are considered a potential target for anticancer therapy. Considering the limited efficacy and toxicity of currently available mitochondria-targeting agents, it is necessary to develop effective mitochondria-targeting anticancer drugs. By screening a large chemical library consisting of natural products with diverse chemical entities, we identified gracillin, a steroidal saponin, as a mitochondria-targeting antitumor drug. Gracillin displayed broad-spectrum inhibitory effects on the viability of a large panel of human cancer cell lines, including those carrying acquired resistance to chemotherapy or EGFR-targeting drugs, by inducing apoptosis. We show that gracillin attenuates mitochondria-mediated cellular bioenergetics by suppressing ATP synthesis and by producing reactive oxygen species (ROS). Mechanistically, gracillin disrupts complex II (CII) function by abrogating succinate dehydrogenase (SDH) activity without affecting the succinate:ubiquinone reductase. The gracillin-induced cell death was potentiated by 3-nitropropionic acid (3-NPA) or thenoyltrifluoroacetone (TTFA), which inhibit CII by binding to the active site of SDHA or to the ubiquinone-binding site, respectively. Finally, we show that gracillin effectively suppressed the mutant-Kras-driven lung tumorigenesis and the growth of xenograft tumors derived from cell lines or patient tissues. Gracillin displayed no obvious pathophysiological features in mice. Collectively, gracillin has potential as a CII-targeting antitumor drug.
Assuntos
Carcinogênese/genética , Morte Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Espirostanos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Morte Celular/genética , Complexo II de Transporte de Elétrons/genética , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Nitrocompostos/metabolismo , Oxirredução , Propionatos/metabolismo , Espécies Reativas de Oxigênio , Tenoiltrifluoracetona/metabolismoAssuntos
Dioxinas/farmacologia , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Fator de Transcrição Associado à Microftalmia/metabolismo , Preparações Clareadoras de Pele/farmacologia , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Melanócitos/metabolismo , Camundongos , Monofenol Mono-Oxigenase/metabolismoRESUMO
The antiproliferative and antitumor activities of americanin A (1), a neolignan isolated from the seeds of Phytolacca americana, were investigated in human colon cancer cells. Compound 1 inhibited the proliferation of HCT116 human colon cancer cells both in vitro and in vivo. The induction of G2/M cell-cycle arrest by 1 was concomitant with regulation of the ataxia telangiectasia-mutated/ATM and Rad3-related (ATM/ATR) signaling pathway. Treatment with 1 activated ATM and ATR, initiating the subsequent signal transduction cascades that include checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2), and tumor suppressor p53. Another line of evidence underlined the significance of 1 in regulation of the S phase kinase-associated protein 2 (Skp2)-p27 axis. Compound 1 targeted selectively Skp2 for degradation and thereby stabilized p27. Therefore, compound 1 suppressed the activity of cyclin B1 and its partner cell division cycle 2 (cdc2) to prevent entry into mitosis. Furthermore, prolonged treatment with 1 induced apoptosis by producing excessive reactive oxygen species. The intraperitoneal administration of 1 inhibited the growth of HCT116 tumor xenografts in nude mice without any overt toxicity. Modulation of the ATM/ATR signaling pathway and the Skp2-p27 axis might be plausible mechanisms of action for the antiproliferative and antitumor activities of 1 in human colon cancer cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Dioxinas/isolamento & purificação , Dioxinas/farmacologia , Phytolacca americana/química , Animais , Antineoplásicos Fitogênicos/química , Apoptose , Proteína Quinase CDC2/metabolismo , Quinase 1 do Ponto de Checagem , Quinase do Ponto de Checagem 2/metabolismo , Neoplasias do Colo , Dioxinas/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Proteínas Quinases/metabolismo , Sementes/química , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismoRESUMO
The authors want to change Figure 1 of the paper published in IJMS [1]. In Figure 1, 5-position of OH was at 6-position. Therefore, Figure 1 is revised as follows. The authors would like to apologize for any inconvenience caused to the readers by this change.[...].
RESUMO
PURPOSE: To determine the effects of nonthermal plasma (NTP) induced by helium (He) alone or He plus oxygen (O2) on the generation of reactive oxygen species (ROS) and cell death in anaplastic thyroid cancer cells. MATERIALS AND METHODS: NTP was generated in He alone or He plus O2 blowing through a nozzle by applying a high alternating current voltage to the discharge electrodes. Optical emission spectroscopy was used to identify various excited plasma species. The apoptotic effect of NTP on the anaplastic thyroid cancer cell lines, such as HTH83, U-HTH 7, and SW1763, was verified with annexin V/propidium staining and TUNEL assay. ROS formation after NTP treatment was identified with fluorescence-activated cell sorting with DCFDA staining. The mitogen-activated protein kinase pathways and caspase cascade were investigated to evaluate the molecular mechanism involved and cellular targets of plasma. RESULTS: NTP induced significant apoptosis in all three cancer cell lines. The plasma using He and O2 generated more O2-related species, and increased apoptosis and intracellular ROS formation compared with the plasma using He alone. NTP treatment of SW1763 increased the expression of phosphor-JNK, phosphor-p38, and caspase-3, but not phosphor-ERK. Apoptosis of SW1763 as well as expressions of elevated phosphor-JNK, phosphor-p38, and caspase-3 induced by NTP were effectively inhibited by intracellular ROS scavengers. CONCLUSION: NTP using He plus O2 induced significant apoptosis in anaplastic cancer cell lines through intracellular ROS formation. This may represent a new promising treatment modality for this highly lethal disease.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Gases em Plasma/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Citometria de Fluxo , Humanos , Masculino , Espectrometria por Raios X , Carcinoma Anaplásico da TireoideRESUMO
The anti-inflammatory activity of handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) and the nuclear factor-κB (NF-κB) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE2 production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compound 1 also suppressed the induction of pro-inflammatory cytokines TNF-α and IL-1ß in LPS-stimulated RAW 264.7 cells. To further clarify the transcriptional regulatory pathway in the expression of iNOS and COX-2 by 1, the role of NF-κB was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-κB into the nuclear proteins. The transcriptional activity of NF-κB stimulated with LPS was also suppressed by 1, which coincided with the inhibition of IκB degradation. Compound 1 also suppressed the activation of mitogen-activated protein kinases, including ERK and JNK signaling. In addition, the LPS-stimulated upregulation of miRNA-155 expression was suppressed by 1. The oral administration of 1 inhibited acute inflammation in carrageenan-induced paw and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema models. The serum level of IL-1ß was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-κB activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of handelin.
Assuntos
Anti-Inflamatórios/farmacologia , Chrysanthemum/química , Citocinas/metabolismo , Proteínas I-kappa B/metabolismo , NF-kappa B/efeitos dos fármacos , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Ciclo-Oxigenase 2 , Dinoprostona/metabolismo , Regulação para Baixo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Proteínas I-kappa B/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Modelos Animais , Estrutura Molecular , Inibidor de NF-kappaB alfa , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Terpenos/química , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba var. spinosa. This study investigated the effect of spinosin on cholinergic blockade-induced memory impairment in mice. Behavioral tests were conducted using the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory-ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in these behavioral tasks with a prolonged latency time in the passive avoidance task, an increased percentage of spontaneous alternation in the Y-maze task and a lengthened swimming time in target quadrant in the Morris water maze task. In addition, a single administration of spinosin in normal naïve mice also enhanced the latency time in the passive avoidance task. To identify the mechanism of the memory-ameliorating effect of spinosin, receptor antagonism analysis and Western blotting were performed. The ameliorating effect of spinosin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor agonist. In addition, spinosin significantly increased the expression levels of phosphorylated extracellular signal-regulated kinases and cAMP response element-binding proteins in the hippocampus. Taken together, these results indicate that the memory-ameliorating effect of spinosin may be, in part, due to the serotonergic neurotransmitter system, and that spinosin may be useful for the treatment of cognitive dysfunction in diseases such as Alzheimer's disease.
Assuntos
Flavonoides/farmacologia , Hipnóticos e Sedativos/farmacologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Antagonistas Muscarínicos/toxicidade , Escopolamina/antagonistas & inibidores , Escopolamina/toxicidade , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Flavonoides/antagonistas & inibidores , Hipnóticos e Sedativos/antagonistas & inibidores , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacosRESUMO
Jujuboside B (1) is one of the saponins isolated from the seeds of Zizyphus jujuba var. spinosa, which are used as a well-known traditional medicine for the treatment of insomnia and anxiety in East Asian countries. This is the first study to investigate the antitumor mechanism of 1 in vivo and in vitro. The results showed that 1 induced apoptosis and autophagy in AGS and HCT 116 human cancer cells and also effectively suppressed tumor growth in a nude mouse xenograft model bearing HCT 116 cells. The apoptosis-inducing effect of 1 was characterized by annexin V/propidium iodide staining, sub-G1 phase increase, and caspase-3 activation. Mechanistic studies showed that 1-induced apoptosis is associated with the extrinsic pathway through an increase in FasL and caspase-8 activation. Moreover, 1 activated p38/c-Jun N-terminal kinase (JNK), and the extrinsic pathway-mediated apoptosis was attenuated by both SB202190 (a p38 inhibitor) and SP600125 (a JNK inhibitor). The autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF) decreased 1-induced cell viability and increased pp38, pJNK, FasL, caspase-8 activation, and caspase-3 activation. Taken together, these results demonstrate that 1 induced protective autophagy to retard extrinsic pathway-mediated apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Saponinas/farmacologia , Ziziphus/química , Animais , Antracenos/farmacologia , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Macrolídeos/farmacologia , Camundongos , Saponinas/química , Sementes/químicaRESUMO
A method based on HPLC with diode array detector (DAD) and electrospray ionisation mass spectrometry (ESI-MS) was established for the simultaneous determination of 5-HMF and its derivatives, including a new 5-HMF derivative, in Rehmanniae radix preparata. Validation parameters, such as linearity, limit of detection, limit of quantification, recovery, accuracy, and precision, were successfully obtained. In addition, the efficiencies of diverse extraction methods were compared for the development of a standard analytical method. The verified method was successfully applied to the quantitative determination of four representative metabolites in eighteen R. radix preparata samples from Korea and China. Additionally, the increase in the amount of 5-HMF derivatives was monitored during the processing of three dried R. radix samples. The results showed that a newly isolated diglycosylated 5-HMF derivative, 5-(α-D-galactopyranosyl-(1â6)-α-D-galactopyranosyloxymethyl)-2-furancarboxaldehyde, appeared in concentrations comparable to that of 5-HMF, suggesting its potential to serve as a marker compound in R. radix preparata.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Furaldeído/análise , Rehmannia/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Medicamentos de Ervas Chinesas/metabolismo , Furaldeído/metabolismo , Rehmannia/metabolismoRESUMO
In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naïve mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.
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Based on the Wnt inhibitors as potential targets in the development of anticancer agents, natural compounds were evaluated for ß-catenin-mediated transcriptional activity. A natural lignan hydnocarpin isolated from Lonicera japonica was considered a potential inhibitor for Wnt/ß-catenin signalings. The anti-proliferative activity of hydnocarpin was also found to be associated with the suppression of Wnt/ß-catenin-mediated signaling pathway in human colon cancer cells. These data suggest that hydnocarpin might be a novel Wnt inhibitor and has a potential of signaling regulator in ß-catenin-mediated signaling pathways.
Assuntos
Antineoplásicos Fitogênicos/química , Flavonolignanos/química , Lignanas/química , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Proteína Axina/antagonistas & inibidores , Proteína Axina/genética , Proteína Axina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Flavonolignanos/isolamento & purificação , Flavonolignanos/toxicidade , Humanos , Lonicera/química , Lonicera/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive human tumor associated with a median survival of 2-6 months. TRAIL, as a ligand of death receptors, is known to induce apoptotic cell death in several cancer cells. However, TRAIL treatment alone is not effective against TRAIL-resistant cancer cells. This study was designed to investigate whether valproic acid (VPA) enhances apoptotic cell death of TRAIL-resistant ATC cells and to identify the mechanism of cell death of ATC cells by combination treatment with VPA and TRAIL. METHODS: To evaluate the cytotoxic effect of TRAIL and/or VPA on ATC cells, we used the MTT assay. The effects of VPA and TRAIL on apoptosis were assessed using FACS analysis (Annexin-V/PI stain) and Western blotting. RESULTS: The combination of VPA with TRAIL significantly induced apoptotic cell death compared with 8505C and ARO cells treated with TRAIL alone. The protein levels of cleaved caspase-8, -3, and PARP were increased in VPA and TRAIL co-treated ARO cells. The combination induced the activation of JNK and the phosphorylation of FADD and c-Jun but not p38. However, pretreatment with caspase inhibitors reduced the expression of cleaved caspase-8, -3, and PARP in co-treated ARO cells. SP600125 remarkably reduced the expression of cleaved caspase-8, -3, and PARP and the phosphorylation of FADD and c-Jun, as well as apoptotic cell death. CONCLUSIONS: VPA sensitized TRAIL-resistant ATC cells to apoptotic cell death through involvement of the JNK pathway. Thus, the combination of VPA and TRAIL may be a promising therapy for ATC.
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Anticonvulsivantes/farmacologia , Apoptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Ácido Valproico/farmacologia , Biomarcadores Tumorais/metabolismo , Western Blotting , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Técnicas Imunoenzimáticas , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais CultivadasRESUMO
An investigation of the Korean medicinal plant Patrinia villosa (THUNB.) JUSS. (Valerianaceae) led to the isolation of two new flavonoid glycosides, patrivilosides 1 (1) and 2 (2), a new iridoid glycoside, patrinovalerosidate (3), and two new saponins, patrinovilosides A (4) and B (5), along with six known compounds including three flavonoid glycosides and three iridoid glycosides. The structures of the new compounds were elucidated based on analysis of their one dimensional (1D)- and 2D-NMR spectra along with their mass spectrometric data and the results of acid hydrolysis.