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1.
Mediators Inflamm ; 2022: 5985255, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35586367

RESUMEN

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.


Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular , Angelica sinensis , Cumarinas , Factor 3 Regulador del Interferón , FN-kappa B , Proteínas Adaptadoras del Transporte Vesicular/antagonistas & inhibidores , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Angelica sinensis/química , Animales , Antiinflamatorios/farmacología , Cumarinas/farmacología , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Factor 3 Regulador del Interferón/antagonistas & inhibidores , Factor 3 Regulador del Interferón/metabolismo , Lipopolisacáridos/farmacología , Ratones , MicroARNs/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Ratas , Transducción de Señal/efectos de los fármacos
2.
Int J Mol Sci ; 23(11)2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35682567

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Biflavonoides , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Biflavonoides/farmacología , Humanos , Ratones , Neuronas/metabolismo
3.
J Nat Prod ; 78(12): 2983-93, 2015 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-26595875

RESUMEN

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.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Dioxinas/aislamiento & purificación , Dioxinas/farmacología , Phytolacca americana/química , Animales , Antineoplásicos Fitogénicos/química , Apoptosis , Proteína Quinasa CDC2/metabolismo , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Quinasa de Punto de Control 2/metabolismo , Neoplasias del Colon , Dioxinas/química , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células HCT116 , Humanos , Ratones , Ratones Desnudos , Estructura Molecular , Proteínas Quinasas/metabolismo , Semillas/química , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo
4.
Int J Mol Sci ; 16(1): 1482-3, 2015 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-25580538

RESUMEN

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.[...].

5.
J Nat Prod ; 77(2): 370-6, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24547878

RESUMEN

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.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Saponinas/farmacología , Ziziphus/química , Animales , Antracenos/farmacología , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Células HCT116 , Humanos , Macrólidos/farmacología , Ratones , Saponinas/química , Semillas/química
6.
J Nat Prod ; 77(4): 917-24, 2014 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-24689881

RESUMEN

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.


Asunto(s)
Antiinflamatorios/farmacología , Chrysanthemum/química , Citocinas/metabolismo , Proteínas I-kappa B/metabolismo , FN-kappa B/efectos de los fármacos , Terpenos/farmacología , Animales , Antiinflamatorios/química , Ciclooxigenasa 2 , Dinoprostona/metabolismo , Regulación hacia Abajo , Edema/inducido químicamente , Edema/tratamiento farmacológico , Proteínas I-kappa B/efectos de los fármacos , Interleucina-1beta/efectos de los fármacos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Modelos Animales , Estructura Molecular , Inhibidor NF-kappaB alfa , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fitoterapia , Transducción de Señal/efectos de los fármacos , Terpenos/química , Factor de Necrosis Tumoral alfa/efectos de los fármacos
7.
Bioengineering (Basel) ; 11(6)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38927812

RESUMEN

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.

8.
Ann Surg Oncol ; 20 Suppl 3: S716-24, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23982257

RESUMEN

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.


Asunto(s)
Anticonvulsivantes/farmacología , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Ácido Valproico/farmacología , Biomarcadores de Tumor/metabolismo , Western Blotting , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Técnicas para Inmunoenzimas , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides/metabolismo , Células Tumorales Cultivadas
9.
Bioorg Med Chem Lett ; 23(20): 5511-4, 2013 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-24018191

RESUMEN

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.


Asunto(s)
Antineoplásicos Fitogénicos/química , Flavonolignanos/química , Lignanos/química , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Proteína Axina/antagonistas & inhibidores , Proteína Axina/genética , Proteína Axina/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Flavonolignanos/aislamiento & purificación , Flavonolignanos/toxicidad , Humanos , Lonicera/química , Lonicera/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Vía de Señalización Wnt/efectos de los fármacos
10.
Phytother Res ; 27(6): 829-34, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22893618

RESUMEN

The seeds of Zizyphus jujuba (SZJ), a famous oriental traditional medicine, have been reported to exhibit diverse activities in biological systems including the cardiovascular system. However, little information is available on its antiplatelet activity. This study was undertaken to investigate the antiplatelet effects of the ethanolic extract of SZJ (ESZJ) and of its principal components jujuboside A and B. In the in vitro platelet aggregation study, ESZJ exhibited significant and concentration-dependent inhibitory effects on collagen-, thrombin-, and AA-induced platelet aggregation. In addition, ESZJ-treated mice showed significantly the prolongation of bleeding times and the protection against thromboembolic attack. A comparison of the effects of jujuboside A and B on platelet aggregation revealed that only jujuboside B had potent inhibitory effects on collagen-, thrombin-, AA-, and ADP-induced aggregation. Jujuboside B also exhibited superior protection on thromboembolic model. Furthermore, jujuboside B had a significant inhibitory effect on collagen-induced thromboxane A2 production in rat platelets. This study describes the antiplatelet effects of ESZJ and of its active component jujuboside B, and its findings suggest that these agents be considered as components of preventive and therapeutic herbal drugs targeting cardiovascular diseases associated with platelet hyperaggregation.


Asunto(s)
Extractos Vegetales/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Saponinas/farmacología , Ziziphus/química , Animales , Plaquetas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Embolia Pulmonar/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley
11.
Chem Pharm Bull (Tokyo) ; 61(9): 971-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23800854

RESUMEN

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.


Asunto(s)
Flavonoides/química , Glicósidos/química , Patrinia/química , Componentes Aéreos de las Plantas/química , Flavonoides/aislamiento & purificación , Glicósidos/aislamiento & purificación , Hidrólisis , Plantas Medicinales/química
12.
Phytochem Anal ; 24(2): 148-54, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22930642

RESUMEN

INTRODUCTION: The roots of Adenophorae species have been reported to exhibit anti-obese, anti-oxidant, anti-cancer, and anti-bacterial activities. However, there has been no single report regarding the preparative isolation and biological activities of the chemical components from Adenophora triphylla. OBJECTIVE: To develop an efficient method for the determination of the active fraction from the methanol extract from the roots of Adenophora triphylla and for the preparative isolation and purification of target compounds having cytotoxicity on carcinoma cells from the active fraction by high-speed counter-current chromatography (HSCCC). METHODS: The Plant (5 kg, dry weight) was extracted with methanol. Three hundred grams of the dried methanol extract (885 g) were fractionated by open-column chromatography with a stepwise gradient of water-methanol. Preparative isolation of bioactive components was performed by HSCCC with a two-phase solvent system composed of ethyl acetate-n-butanol-0.2% trifluoroacetic acid in water (5:5:10, v/v). The cytotoxicity of column fractions and isolated compounds was evaluated by 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. RESULTS: The 70% MeOH column fraction showed inhibitory effects against three human carcinoma cells A549, AGS and HepG2. Two saponins were separated from 400 mg of the active fraction by HSCCC. After further purification with solid phase extraction column, 25 mg of peak fraction 1 and 20 mg of peak fraction 2 were obtained. Their structures were identified by ¹H-NMR, ¹³C-NMR, Fourier transform infrared, fast atom bombardment-MS and electrospray ionisation-MS/MS. They exhibited strong cytotoxic effects against three cancer cells. CONCLUSION: Two cytotoxic saponins were isolated for the first time from the roots of Adenophora triphylla by HSCCC.


Asunto(s)
Campanulaceae/química , Distribución en Contracorriente/métodos , Raíces de Plantas/química , Saponinas/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Estructura Molecular , Saponinas/química , Saponinas/farmacología , Solventes/química
13.
Cell Biol Toxicol ; 28(6): 421-33, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23011636

RESUMEN

Oxidative stress caused by reactive oxygen species (ROS) induces DNA base modifications and DNA strand breaks. In this study, the protective effect of baicalein against H(2)O(2)-induced DNA damage was investigated in V79-4 Chinese hamster fibroblast cells. H(2)O(2) treatment increased the levels of intracellular ROS and DNA double-strand breaks (DSBs) and decreased the level of Ku70 protein and the phosphorylation (activation) of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), which are involved in the repair of DSBs by nonhomologous end joining. Baicalein effectively scavenged intracellular ROS induced by H(2)O(2), reduced DSBs, and rescued Ku70 protein level and phosphorylation of DNA-PKcs. In cellular response to DNA base damage, 8-oxoguanine DNA glycosylase 1 (OGG1) plays a vital role in the removal of 8-oxoguanine (8-OxoG), which is formed mainly by oxidative stress. Baicalein significantly decreased the levels of 8-OxoG induced by H(2)O(2), and this correlated with increases in OGG1 promoter activity and OGG1 mRNA and protein expression. The phosphorylated form of Akt kinase, which is a regulator of OGG1, was sharply decreased by H(2)O(2), but was prevented by baicalein. A specific Akt inhibitor abolished the cytoprotective effects of baicalein, suggesting that OGG1 induction by baicalein involves the Akt pathway. In conclusion, baicalein exerted protective effects against DNA damage induced by oxidative stress by activating DNA repair systems and scavenging ROS.


Asunto(s)
Daño del ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Flavanonas/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Antígenos Nucleares/biosíntesis , Línea Celular , Cricetinae , Roturas del ADN de Doble Cadena/efectos de los fármacos , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Proteína Quinasa Activada por ADN/metabolismo , Proteínas de Unión al ADN/biosíntesis , Guanina/análogos & derivados , Guanina/biosíntesis , Peróxido de Hidrógeno/farmacología , Autoantígeno Ku , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
14.
J Nat Prod ; 75(1): 67-71, 2012 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-22233348

RESUMEN

Phytochemical investigation of Leonurus japonicus has led to the isolation of a labdane diterpene derivative, 15,16-epoxy-3α-hydroxylabda-8,13(16),14-trien-7-one (1), which was tested for its in vitro anti-inflammatory effects. The results demonstrated that 1 exhibits an inhibitory effect on LPS-stimulated RAW 264.7 macrophages. The anti-inflammatory action shown by 1 suppressed LPS-induced NF-κB activation, resulting in the down-regulation of iNOS and COX-2 protein expression, attributable to the inhibitory action of LPS-induced NO and PGE(2) production. Compound 1 inhibited LPS-induced phosphorylation and the degradation of inhibitory kappa B (IκBα) and decreased the nuclear translocation of p50 and p65. In addition, 1 exhibited an inhibitory effect on LPS-induced NF-κB-DNA and AP-1-DNA binding activity, using an electrophoretic mobility shift assay with NF-κB- and AP-1-specific (32)P-labeled probes. The LPS-induced mitogen-activated protein kinases (p-JNK, p-p38, and p-ERK) and p-Akt were inhibited after 30 and 10 min of LPS stimulation, respectively. In addition, TNF-α production was suppressed by 1.


Asunto(s)
Antiinflamatorios/farmacología , Diterpenos/farmacología , Lamiaceae/química , Lipopolisacáridos/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/química , Antiinflamatorios/inmunología , Antiinflamatorios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Diterpenos/química , Diterpenos/inmunología , Diterpenos/aislamiento & purificación , Corea (Geográfico) , Macrófagos/efectos de los fármacos , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Estructura Molecular , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/análisis , Óxido Nítrico/biosíntesis , Raíces de Plantas/química , Factor de Transcripción AP-1/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
15.
Chem Pharm Bull (Tokyo) ; 60(3): 306-14, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22382409

RESUMEN

Six new germacranolides, zawadskinolides A-F (1-6), and a new eudesmane glucoside, chrysantiloboside (7) were isolated from the aerial parts of Dendranthema zawadskii var. latilobum, along with thirteen known constituents. Their structures were elucidated by means of spectroscopic evidence. Bioassay showed that flavonoids such as apigenin (9), (-)-eriodictyol (10) and nepetin (12), as well as the sesquiterpene lactone, zawadskinolide F (6), inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells with IC50 values of 66.15, 132.55, 35.44, and 91.32 µM, respectively.


Asunto(s)
Chrysanthemum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Animales , Células Cultivadas , Flavonoides/química , Flavonoides/farmacología , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/antagonistas & inhibidores , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacología , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacología , Análisis Espectral/métodos
16.
Br J Neurosurg ; 26(3): 355-60, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22103565

RESUMEN

We reviewed four surgical cases of purely third ventricle craniopharyngioma, focusing on surgical outcomes and adjuvant treatments. From 2002 to 2008, we performed surgical treatments, via a transcallosal transforaminal approach, on four patients. All were males, with a median age of 42 (36-45) years. Most patients complained of headaches, while two (50%) patients presented with visual disturbances, and one (25%) presented with an endocrinological disturbance. Patients' follow-up periods ranged from 1.6 to 8.6 years. We totally removed the tumor in each of the four patients. The tumors originated in the infundibulum of the third ventricular floor. The pituitary stalk was anatomically preserved. The histopathological findings showed the adamantinomatous type of craniopharyngioma in all patients. Postoperatively, two patients who had experienced visual disturbances showed improvement, and there was no aggravation. Two patients had intact pituitary functioning, while two needed complete hormone replacement. The patients experienced no surgery-related complications. Two patients experienced recurrences 4.5 and 1.6 years later. One patient received gamma knife surgery for the recurred lesion, which controlled the lesion well. Purely third ventricle craniopharyngioma showed good visual and endocrinological outcomes after surgery. Gamma knife surgery could be of help in the event of a recurred lesion.


Asunto(s)
Craneofaringioma/cirugía , Neoplasias Hipofisarias/cirugía , Tercer Ventrículo/cirugía , Adulto , Cuerpo Calloso , Craneofaringioma/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/etiología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias Hipofisarias/patología , Radiocirugia , Trastornos de la Visión/etiología
17.
Sci Rep ; 12(1): 20585, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36446924

RESUMEN

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.


Asunto(s)
Inteligencia Artificial , Tomografía Computarizada de Haz Cónico , Humanos , Niño , Cefalometría , Radiografía , Atención Odontológica
19.
J Neurooncol ; 103(1): 103-10, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20737192

RESUMEN

Oligodendroglial tumors sometimes show heterogeneous ring enhancement with a central necrotic portion. We aimed to reveal the prognosis of such tumors based on such radiologic findings and compare them to other prognostic factors. Participants were 32 patients with oligodendroglioma (17 oligodendrogliomas, 15 anaplastic oligodendrogliomas) who underwent surgery from 2004 to 2008. We investigated tumor radiologic findings, locations, calcification, whether localized or diffuse type, and enhancement patterns. Of other prognostic factors, we analyzed age, sex, pathology, extent of removal, adjuvant therapy, genetic change in 1p and 19q, and MGMT methylation status. We checked for genetic abnormality in 1p and 19q using the FISH method. To investigate MGMT methylation, we performed methylation-specific PCR (MSP). Mean follow-up duration was 3.2 years. Median age was 42.4 years, and the male:female ratio was 21:11. Out of 17 oligodendrogliomas, 14 (82.4%) showed combined 1p/19q deletion, and 14 (82.4%), methylated MGMT. Among 15 anaplastic oligodendrogliomas, there were 7 (46.6%) with combined 1p/19q deletion and 11 (73.3%) with methylated MGMT. The 4-year recurrence-free survival and overall survival were 77.6 and 100% in oligodendrogliomas and 59.1 and 71.6% in anaplastic oligodendrogliomas, respectively. On univariate analysis, radiologic variable of ring enhancement pattern was statistically significant related with recurrence-free survival (P = 0.003). Variables such as sex (P = 0.03), combined 1p/19q loss (P = 0.04), tumor location (P = 0.02), and anaplastic pathology (P = 0.04) were significantly correlated with overall survival. Cox's regression model revealed that ring enhancement pattern was associated with frequent recurrence (ring enhancement, hazard ratio = 8.281, P = 0.04), and these showed 1p deletion only. Anaplastic oligodendrogliomas with ring enhancement like glioblastomas and without combined 1p/19q loss should receive close follow-up after treatment because of frequent recurrences.


Asunto(s)
Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 1/genética , Oligodendroglioma/genética , Oligodendroglioma/patología , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Niño , Terapia Combinada , Metilación de ADN , ADN de Neoplasias/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mutación/genética , Necrosis , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , Oligodendroglioma/terapia , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de Supervivencia , Adulto Joven
20.
Neuropathology ; 31(1): 11-9, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20487307

RESUMEN

Nogo-A belongs to the reticulon protein family and is expressed in the inner and outer loops of myelin sheaths of oligodendrocytes. We analyzed the patterns of Nogo-A expression in human gliomas in an effort to identify a useful marker for the characterization of oligodendroglial tumors. We determined the expression of Nogo-A in a panel of 58 astrocytic and oligodendroglial tumors using immunohistochemistry and compared the expression of Nogo-A with Olig-2, a recently identified marker for oligodendrogliomas. To localize Nogo-A expression, immunofluorescent staining was performed using other glial markers (MAP-2 and GFAP). We also confirmed the overexpression of the Nogo-A protein in 53 astrocytic and oligodendroglial tumors using Western blot analysis. Based on immunohistochemical analysis, Nogo-A and Olig-2 had specificity in the detection of oligodendroglial tumors from astrocytic tumors (P=0.001). The level of Nogo-A staining was highly correlated with Olig-2 (P=0.001). The sensitivity and specificity of Nogo-A for oligodendroglial tumors was 86.9% and 57.1%, respectively. Nogo-A expression overlapped that of other oligodendroglial markers, but with different patterns of expression. Western blot analysis revealed that Nogo-A is predominantly expressed in 85.7% of oligodendroglioma cells and 93.7% of anaplastic oligodendroglioma cells. Like other oligodendroglial markers, Nogo-A is highly expressed in oligodendroglial tumors; however, it does not serve as a definite marker specific for oligodendroglial tumors.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/metabolismo , Proteínas de la Mielina/biosíntesis , Oligodendroglioma/metabolismo , Astrocitoma/metabolismo , Astrocitoma/patología , Western Blotting , Neoplasias Encefálicas/patología , Glioma/metabolismo , Glioma/patología , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Microscopía Fluorescente , Proteínas Nogo , Oligodendroglioma/patología , Sensibilidad y Especificidad
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