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1.
Artículo en Inglés | MEDLINE | ID: mdl-37907061

RESUMEN

Fibromuscular dysplasia (FMD) is a noninflammatory arterial diseases that affects predominantly women. Multiple studies have demonstrated an increased prevalence of FMD in patients who experience carotid or vertebral artery dissection (VAD). This case report presents a 57-year-old female who presented with a headache and was diagnosed with partially thrombosed giant aneurysm of vertebral artery. This aneurysm was successfully treated with flow-diverter and coil, but new onset rupture of vertebral artery was detected two weeks later, leading to internal trapping. This case report underscores the need for awareness and understanding of treatment of dissection and aneurysm in patient who is suspected FMD.

2.
J Cerebrovasc Endovasc Neurosurg ; 25(4): 403-410, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37828744

RESUMEN

OBJECTIVE: While patients with medically intractable acute cerebellar infarction typically undergo suboccipital craniectomy and removal of the infarcted tissue, this procedure is associated with long operating times and postoperative complications. This study aimed to investigate the effectiveness of minimally invasive navigationguided burr hole aspiration surgery for the treatment of acute cerebellar infarction. METHODS: Between January 2015 and December 2021, 14 patients with acute cerebellar infarction, who underwent navigation-guided burr hole aspiration surgery, were enrolled in this study. RESULTS: The preoperative mean Glasgow Coma Scale (GCS) score was 12.7, and the postoperative mean GCS score was 14.3. The mean infarction volume was 34.3 cc at admission and 23.5 cc immediately following surgery. Seven days after surgery, the mean infarction volume was 15.6 cc. There were no surgery-related complications during the 6-month follow-up period and no evidence of clinical deterioration. The mean operation time from skin incision to catheter insertion was 28 min, with approximately an additional 13 min for extra-ventricular drainage. The mean Glasgow Outcome Scale score after 6 months was 4.8. CONCLUSIONS: Navigation-guided burr hole aspiration surgery is less time-consuming and invasive than conventional craniectomy, and is a safe and effective treatment option for acute cerebellar infarction in selected cases, with no surgery-related complication.

3.
Opt Express ; 31(9): 13798-13805, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37157258

RESUMEN

This paper presents a single-photon avalanche diode (SPAD) in 55 nm bipolar-CMOS-DMOS (BCD) technology. In order to realize a SPAD having sub-20 V breakdown voltage for mobile applications while preventing high tunneling noise, a high-voltage N-well available in BCD is utilized to implement the avalanche multiplication region. The resulting SPAD has a breakdown voltage of 18.4 V while achieving an excellent dark count rate of 4.4 cps/µm2 at the excess bias voltage of 7 V in spite of the advanced technology node. At the same time, the device achieves a high peak photon detection probability (PDP) of 70.1% at 450 nm thanks to the high and uniform E-field. Its PDP values at 850 and 940 nm, wavelengths of interest for 3D ranging applications reach 7.2 and 3.1%, respectively, with the use of deep N-well. The timing jitter of the SPAD, full width at half maximum (FWHM), is 91 ps at 850 nm. It is expected that the presented SPAD enables cost-effective time-of-flight and LiDAR sensors with the advanced standard technology for many mobile applications.

4.
Toxicol Res ; 39(2): 317-331, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37008697

RESUMEN

The migratory locust, Locusta migratoria (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of L. migratoria had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of L. migratoria (fdLM) and identify allergic components in ELISA and PCR techniques. In this subchronic study, fdLM was administered once daily by oral gavage at the doses of 750, 1500, and 3000 mg/kg/day. No toxicological changes were observed in both sexes of rats for 13 weeks in accordance with the OECD guidelines and GLP conditions. In addition, fdLM did not induced increases of serum immunoglobulin E and 21 homologous proteins were not detected under our present conditions. In conclusion, the NOAEL (no-observed-adverse-effect level) was 3000 mg/kg/day and no target organ was identified in both sexes. In conclusion, we found that fdLM is safe with no adverse effects and offers the potential of its use as an edible ingredient or other biological uses.

5.
Sensors (Basel) ; 22(22)2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36433302

RESUMEN

Strawberry (Fragaria × ananassa Duch) plants are vulnerable to climatic change. The strawberry plants suffer from heat and water stress eventually, and the effects are reflected in the development and yields. In this investigation, potential chlorophyll-fluorescence-based indices were selected to detect the early heat and water stress in strawberry plants. The hyperspectral images were used to capture the fluorescence reflectance in the range of 500 nm-900 nm. From the hyperspectral cube, the region of interest (leaves) was identified, followed by the extraction of eight chlorophyll-fluorescence indices from the region of interest (leaves). These eight chlorophyll-fluorescence indices were analyzed deeply to identify the best indicators for our objective. The indices were used to develop machine-learning models to assess the performance of the indicators by accuracy assessment. The overall procedure is proposed as a new workflow for determining strawberry plants' early heat and water stress. The proposed workflow suggests that by including all eight indices, the random-forest classifier performs well, with an accuracy of 94%. With this combination of the potential indices, namely the red-edge vegetation stress index (RVSI), chlorophyll B (Chl-b), pigment-specific simple ratio for chlorophyll B (PSSRb), and the red-edge chlorophyll index (CIREDEDGE), the gradient-boosting classifier performs well, with an accuracy of 91%. The proposed workflow works well with a limited number of training samples which is an added advantage.


Asunto(s)
Deshidratación , Fragaria , Calor , Fluorescencia , Clorofila
6.
Opt Express ; 30(9): 14958-14965, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35473228

RESUMEN

This paper presents the effect of shallow trench isolation (STI) on the dark count rate (DCR) and after-pulsing probability (APP) of deep-junction-based single-photon avalanche diodes (SPADs). Two different SPADs were fabricated in 110 nm CMOS image sensor technology, one with STI and the other without STI between its anode and cathode. With TCAD simulations and measurements, we have clearly demonstrated that the SPAD without STI enables a dramatic decrease in DCR by more than three orders of magnitude without suffering from the lateral leakage current between the anode and cathode. By excluding the STI from the device, the proposed SPAD also achieves a negligible APP while the SPAD with STI shows a very high APP of 92%. Thanks to the low-noise performance, the proposed SPAD becomes operable with higher excess bias voltage so that it achieves good photon detection probability, 58.3% at 500 nm and 3% at 940 nm, and timing jitter, 71 ps full width at half maximum at 670 nm, when the reverse bias voltage is 17 V.

7.
Toxicol Rep ; 9: 499-504, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35345861

RESUMEN

Local lymph node assay (LLNA) is a predictive in vivo method to provide estimates of relative potency and to contribute to risk assessment/risk management regarding skin sensitizing potency of chemicals and formulations as a stand-alone alternative test. In addition, LLNA is relatively rapid and cost-effective compared to the Buehler method (Guinea pig test), and confers important animal welfare benefits. CBA/J and BALB/c strains are widely commercially available and have been evaluated by formal LLNA validation studies. However, the LLNA method using BrdU with ELISA, unlike other LLNA methods (OECD TG 429, 442 A, 442B), has not been previously validated. Therefore, in this study a validation method was performed to evaluate if the LLNA:BrdU-ELISA method could also be used to identify sensitizers among chemicals listed in OECD TG 429 using CBA/J and BALB/c strains. Here, we newly found that the LLNA:BrdU-ELISA validation method correctly identified 12 of 13 sensitizers in the BALB/c, 11 of 13 sensitizers in the CBA/J, and 3 of 5 non-sensitizers were identified in the two strains. Collectively, we found that the results of LLNA:BrdU-ELISA method provide a similar level of performance for accuracy and sensitivity in two mouse strains BALB/c and CBA/J.

8.
Sensors (Basel) ; 20(23)2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33255997

RESUMEN

In this study, conventional machine learning and deep leaning approaches were evaluated using X-ray imaging techniques for investigating the internal parameters (endosperm and air space) of three cultivars of watermelon seed. In the conventional machine learning, six types of image features were extracted after applying different types of image preprocessing, such as image intensity and contrast enhancement, and noise reduction. The sequential forward selection (SFS) method and Fisher objective function were used as the search strategy and feature optimization. Three classifiers were tested (linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and k-nearest neighbors algorithm (KNN)) to find the best performer. On the other hand, in the transfer learning (deep learning) approaches, simple ConvNet, AlexNet, VGG-19, ResNet-50, and ResNet-101 were used to train the dataset and class prediction of the seed. For the supervised model development (both conventional machine learning and deep learning), the germination test results of the samples were used where the seeds were divided into two classes: (1) normal viable seeds and (2) nonviable and abnormal viable seeds. In the conventional classification, 83.6% accuracy was obtained by LDA using 48 features. ResNet-50 performed better than other transfer learning architectures, with an 87.3% accuracy which was the highest accuracy in all classification models. The findings of this study manifested that transfer learning is a constructive strategy for classifying seeds by analyzing their morphology, where X-ray imaging can be adopted as a potential imaging technique.


Asunto(s)
Citrullus , Aprendizaje Profundo , Algoritmos , Aprendizaje Automático , Semillas/anatomía & histología , Rayos X
9.
J Cerebrovasc Endovasc Neurosurg ; 22(3): 134-140, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32971572

RESUMEN

OBJECTIVE: Cerebral vasospasm and delayed cerebral ischemia (DCI) are considered complications after aneurysmal subarachnoid hemorrhage (aSAH). Several hypotheses involving platelet activation have been asserted in the pathophysiology of cerebral vasospasm and DCI. This study aimed to investigate the effect of dual antiplatelet treatment (DAPT) on symptomatic vasospasm and DCI in patients with aSAH. METHODS: A retrospective study was conducted on patients with aSAH from 2009 to 2018. The patients are divided into 2 groups according to the treatment method such as simple or balloon-assisted coil embolization group (SB coiling), and stent-assisted coil embolization group. Patients treated by SB coiling without DAPT were classified as the control group. Patients who required dual antiplatelet treatment due to stent-assisted coil embolization were classified as DAPT group. The incidence of symptomatic vasospasm and DCI was compared between the two groups. RESULTS: Of 743 patients with aSAH, 563 patients were treated with clipping, 115 patients treated with SB coiling, and 65 patients receive stent-assisted coiling. Among 115 patients underwent SB coiling, 14 patients were excluded by the exclusion criteria. Total number of control group (SB coiling) was 101, DAPT group (stent-assisted coiling) was 65. Depending on whether or not taking DAPT, the incidence of symptomatic vasospasm was lower in the DAPT group (p=0.010). DCI incidence was also lower in the DAPT group, which was statistically significant (p=0.029). CONCLUSIONS: DAPT reduces the frequency of symptomatic vasospasm and DCI in patients with aSAH in our single-center study. To warranting this topic, further, larger prospective and randomized studies should be needed.

10.
Foods ; 9(8)2020 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-32722267

RESUMEN

Zophobas atratus (Coleoptera: Tenebrionidae), the giant mealworm beetle, is known as an edible insect containing a high protein content which may serve as new sources of human food and animal feed. However, potential toxicity and food safety analyses of Z. atratus have not been previously investigated. Therefore, in this study, we aimed to evaluate toxicity of freeze-dried skimmed powder of Z. atratus larvae (frpfdZAL), known as the super mealworm. Toxicological assessments were performed at the doses of 1250, 2500, and 5000 mg/kg/day in a 2- and a 13-week oral repeated-dose toxicity study of frpfdZAL in male and female Sprague-Dawley (SD) rats in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines and the principles of Good Laboratory Practice (GLP). No toxicological changes in clinical signs, body weights, water and food consumption, urinalysis, hematology, clinical biochemistry, gross findings, and histopathological examinations were observed. In conclusion, the no-observed-adverse-effect level (NOAEL) of frpfdZAL was 5000 mg/kg/day and target organ was not identified in both sexes of rats. In addition, frpfdZAL did not induce increases of serum ImmunoglobulinE (IgE), an identifier of allergic reactions in rats. Collectively, these results suggest that frpfdZAL is safe with no adverse effects, and able to be applied as an edible ingredient or other biological uses.

11.
J Phys Condens Matter ; 30(16): 165401, 2018 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-29528301

RESUMEN

Low-dimensional electronic systems with confined electronic wave functions have attracted interest due to their propensity toward novel quantum phases and their use in wide range of nanotechnologies. The newly discovered chalcogenide Nb2PdS5 possesses a quasi-one-dimensional electronic structure and becomes superconducting. Here, we report spectroscopic evidence for two-band superconductivity, where soft point-contact spectroscopic measurements in the superconducting (SC) state reveal Andreev reflection in the differential conductance G. Multiple peaks in G are observed at 1.8 K and explained by the two-band Blonder-Tinkham-Klapwijk model with two gaps Δ1 = 0.61 meV and Δ2 = 1.20 meV. The progressive evolution of G with temperature and magnetic field corroborates the multiple nature of the SC gaps.

12.
J Cerebrovasc Endovasc Neurosurg ; 19(3): 155-161, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29159148

RESUMEN

OBJECTIVE: The cause of severe clinical vasospasm after aneurysmal subarachnoid hemorrhage remains unknown, despite extensive research over the past 30 years. However, the intra-arterial administration of vasodilating agents and balloon angioplasty have been successfully used in severe refractory cerebral vasospasm. MATERIALS AND METHODS: We retrospectively analyzed the data of 233 patients admitted to our institute with aneurysmal subarachnoid hemorrhage (SAH) over the past 3 years. RESULTS: Of these, 27 (10.6%) developed severe symptomatic vasospasm, requiring endovascular therapy. Vasospasm occurred at an average of 5.3 days after SAH. A total of 46 endovascular procedures were performed in 27 patients. Endovascular therapy was performed once in 18 (66.7%) patients, 2 times in 4 (14.8%) patients, 3 or more times in 5 (18.5%) patients. Intra-arterial vasodilating agents were used in 44 procedures (27 with nimodipine infusion, 17 with nicardipine infusion). Balloon angioplasty was performed in only 2 (7.4%) patients. The Average nimodipine infusion volume was 2.47 mg, and nicardipine was 3.78 mg. Most patients recovered after the initial emergency room visit. Two patients (7.4%) worsened, but there were no deaths. CONCLUSION: With advances in endovascular techniques, administration of vasodilating agents and balloon angioplasty reduces the morbidity and mortality of vasospasm after aneurysmal SAH.

13.
J Biomed Res ; 2017 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-28866658

RESUMEN

Peripheral nerve injury often causes neuropathic pain and is associated with changes in the expression of numerous proteins in the dorsal horn of the spinal cord. To date, proteomic analysis method has been used to simultaneously analyze hundreds or thousands of proteins differentially expressed in the dorsal horn of the spinal cord in rats or dorsal root ganglion of rats with certain type of peripheral nerve injury. However, a proteomic study using a mouse model of neuropathic pain could be attempted because of abundant protein database and the availability of transgenic mice. In this study, whole proteins were extracted from the ipsilateral dorsal half of the 4th-6th lumbar spinal cord in a mouse model of spared nerve injury (SNI)-induced neuropathic pain. In-gel digests of the proteins size-separated on a polyacrylamide gel were subjected to reverse-phase liquid-chromatography coupled with electrospray ionization ion trap tandem mass spectrometry (MS/MS). After identifying proteins, the data were analyzed with subtractive proteomics using ProtAn, an in-house analytic program. Consequently, 15 downregulated and 35 upregulated proteins were identified in SNI mice. The identified proteins may contribute to the maintenance of neuropathic pain, and may provide new or valuable information in the discovery of new therapeutic targets for neuropathic pain.

14.
Neurosci Lett ; 656: 9-14, 2017 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-28720382

RESUMEN

Activated leukocyte cell adhesion molecule (ALCAM), a member of type I transmembrane immunoglobulin superfamily of cell adhesion molecule, is expressed in the surface membrane of various cell types including neurons. In the spinal cord dorsal horn (DH), the first gate for the sensory and pain transmission to the brain, the expression and function of ALCAM have not been known yet. Therefore, we here investigate the synaptic function of ALCAM in the substantia gelatinosa (lamina II) of the spinal DH, as well as its expression in the DH. Bath-application of ALCAM/Fc or CD6/Fc, the recombinant human IgG1-Fc chimeric proteins, specifically potentiated C-fiber-mediated excitatory synaptic transmission and predominantly increased spontaneous release of glutamate. In addition, the development of long-term potentiation, a form of synaptic plasticity, at excitatory synapses was significantly inhibited in the presence of the recombinant proteins. The functional roles of ALCAM in the spinal DH were further supported by immunohistochemical analysis; it showed that ALCAM intensely expressed through laminae I/II with the exception of lateral portion of the dorsal part of inner lamina II and distinctly co-localized with molecular markers of C-fibers, such as peptidergic calcitonin gene-related protein and transient receptor potential vanilloid type 1 and non-peptidergic isolectin B4. This study, for the first time, suggests the modulatory roles of ALCAM in the excitatory synaptic transmission and plasticity in the rat spinal DH.


Asunto(s)
Molécula de Adhesión Celular del Leucocito Activado/metabolismo , Plasticidad Neuronal , Asta Dorsal de la Médula Espinal/metabolismo , Transmisión Sináptica , Molécula de Adhesión Celular del Leucocito Activado/genética , Animales , Antígenos CD/genética , Antígenos de Diferenciación de Linfocitos T/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Humanos , Lectinas/metabolismo , Masculino , Ratones , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/farmacología , Células Receptoras Sensoriales/metabolismo , Sinapsis/fisiología , Canales Catiónicos TRPV/metabolismo
15.
Sci Rep ; 5: 16385, 2015 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-26548444

RESUMEN

We investigate the relation of the critical current density (Jc) and the remarkably increased superconducting transition temperature (Tc) for the FeSe single crystals under pressures up to 2.43 GPa, where the Tc is increased by ~8 K/GPa. The critical current density corresponding to the free flux flow is monotonically enhanced by pressure which is due to the increase in Tc, whereas the depinning critical current density at which the vortex starts to move is more influenced by the pressure-induced magnetic state compared to the increase of Tc. Unlike other high-Tc superconductors, FeSe is not magnetic, but superconducting at ambient pressure. Above a critical pressure where magnetic state is induced and coexists with superconductivity, the depinning Jc abruptly increases even though the increase of the zero-resistivity Tc is negligible, directly indicating that the flux pinning property compared to the Tc enhancement is a more crucial factor for an achievement of a large Jc. In addition, the sharp increase in Jc in the coexisting superconducting phase of FeSe demonstrates that vortices can be effectively trapped by the competing antiferromagnetic order, even though its antagonistic nature against superconductivity is well documented. These results provide new guidance toward technological applications of high-temperature superconductors.

16.
Proteins ; 83(6): 1054-67, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25820699

RESUMEN

Many proteins undergo large-scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non-overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter-domain bending motion. The performance of the algorithm is demonstrated on several proteins.


Asunto(s)
Biología Computacional/métodos , Estructura Terciaria de Proteína , Proteínas/química , Análisis de Secuencia de Proteína/métodos , Algoritmos , Simulación de Dinámica Molecular , Programas Informáticos
17.
Artículo en Inglés | MEDLINE | ID: mdl-23606882

RESUMEN

The primo vascular structures comprising primo nodes and vessels (originally called Bonghan corpuscles and ducts, resp.) have recently been suggested to be the anatomical correlate of acupuncture, a therapeutic technique used in oriental medicine. Although the primo vascular structures have been observed in many parts of animals, including the nervous system, using anatomical methodologies, its physiological functions are still unclear. This paper summarizes the reports on the primo vascular structures, particularly in the nervous system and its surroundings, as well as the electrophysiological properties of cells in the primo nodes. In addition, recent reports examining the potential roles of the primo vascular structures in acupuncture are discussed. This review raises some fundamental questions and, at the same time, highlights the potential physiological roles of the primo vascular structures in acupuncture.

18.
Connect Tissue Res ; 54(2): 94-100, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23186263

RESUMEN

Novel threadlike structures (NTSs) on the surfaces of mammalian abdominal organs have recently attracted interests regarding their ability to transport fluid, enable cell migration, and possibly facilitate cancer metastasis. Nevertheless, histological studies of NTSs have been sporadic and often have inconsistent interpretations of the NTS internal structure. In this article, we provide a synthetic and consistent view of the NTS internal structure: the NTS is a loose bundle of fibrous stroma that forms interstitial channels and microsinusoids infiltrated with inflammatory cells. The fibroblasts are embedded in the stroma and mostly aligned along the major axis of the NTS. The sinusoids, which are in inconsecutive cross sections, have boundaries more or less delineated by extracellular fibers, partly surrounded by endothelial-like cells, or both. We compare these morphological features to other well-known connective tissues (i.e., trabecular meshwork and lymphatic capillary) and discuss the biomechanical and biological functions of NTSs based on their structural characteristics.


Asunto(s)
Cavidad Abdominal/anatomía & histología , Fibroblastos/citología , Inflamación/patología , Mamíferos/anatomía & histología , Animales , Fibroblastos/ultraestructura , Membranas/ultraestructura , Especificidad de Órganos , Conejos , Células del Estroma/citología , Células del Estroma/ultraestructura
19.
Mol Cells ; 30(5): 461-6, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20848228

RESUMEN

Fos, a protein product of immediate early gene c-fos, has been used as a marker for activation of nociceptive neurons in central nervous system including spinal trigeminal nucleus (Vsp). By noxious stimulation applied to orofacial area, the expression of Fos occurred in the Vsp pars oralis (Vo), the subnucleus receiving inputs from trigeminal primary afferents that predominantly innervate intraoral receptive fields. The present study demonstrates that the in vitro activation of group I metabotropic glutamate receptors (mGluRs; mGluR1 and 5) by bath-application of their well-known agonist (S)-3,5-dihydroxyphenylglycine (DHPG) increased the number of Fos-expressing neurons in the Vo area. In addition, bath application of DHPG caused inward currents, a parameter of neuronal excitation, in the Vo neurons held at -70 mV in voltage-clamp mode of whole-cell recordings. In further experiments characterizing two phenomena, the increased Fos expression in the Vo was mediated by an additive activation of both mGluR1 and mGluR5, which required the activation of N-methyl-D-aspartate (NMDA) receptors, protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). In contrast, the inward currents were mediated only by mGluR1, but not by others. The data resulting from this in vitro study indicate that the DHPG-induced membrane depolarisation or neuronal excitation may be upstream to, or skip, the NMDA receptor, PKC and ERK pathways for the DHPG-induced Fos expression.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteína Quinasa C/metabolismo , Proteínas Proto-Oncogénicas c-fos/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Núcleo Espinal del Trigémino/metabolismo , Animales , Benzoatos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Femenino , Flavonoides/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Indoles/farmacología , Masculino , Maleimidas/farmacología , Neuronas/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Receptor del Glutamato Metabotropico 5 , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inhibidores , Resorcinoles/farmacología , Núcleo Espinal del Trigémino/citología
20.
Mol Cancer ; 9: 97, 2010 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-20433747

RESUMEN

BACKGROUND: Myc is a well known driver of lymphomagenesis, and Myc-activating chromosomal translocation is the recognized hallmark of Burkitt lymphoma, an aggressive form of non-Hodgkin's lymphoma. We developed a model that mimics this translocation event by inserting a mouse Myc cDNA gene into the immunoglobulin heavy chain locus, just upstream of the intronic Emu enhancer. These mice, designated iMyc E mu, readily develop B-cell lymphoma. To study the mechanism of Myc-induced lymphoma, we analyzed signaling pathways in lymphoblastic B-cell lymphomas (LBLs) from iMyc E mu mice, and an LBL-derived cell line, iMyc E mu-1. RESULTS: Nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) were constitutively activated in iMyc E mu mice, not only in LBLs but also in the splenic B-lymphocytes of young animals months before tumors developed. Moreover, inhibition of either transcription factor in iMyc E mu-1 cells suppressed growth and caused apoptosis, and the abrogation of NF-kappaB activity reduced DNA binding by both STAT3 and Myc, as well as Myc expression. Inhibition of STAT3 signaling eliminated the activity of both NF-kappaB and Myc, and resulted in a corresponding decrease in the level of Myc. Thus, in iMyc E mu-1 cells NF-kappaB and STAT3 are co-dependent and can both regulate Myc. Consistent with this, NF-kappaB and phosphorylated STAT3 were physically associated with one another. In addition, LBLs and iMyc E mu-1 cells also showed constitutive AKT phosphorylation. Blocking AKT activation by inhibiting PI3K reduced iMyc E mu-1 cell proliferation and caused apoptosis, via downregulation of NF-kappaB and STAT3 activity and a reduction of Myc levels. Co-treatment with NF-kappaB, STAT3 or/and PI3K inhibitors led to additive inhibition of iMyc E mu-1 cell proliferation, suggesting that these signaling pathways converge. CONCLUSIONS: Our findings support the notion that constitutive activation of NF-kappaB and STAT3 depends on upstream signaling through PI3K, and that this activation is important for cell survival and proliferation, as well as for maintaining the level of Myc. Together, these data implicate crosstalk among NF-kappaB, STAT3 and PI3K in the development of iMyc E mu B-cell lymphomas.


Asunto(s)
Linfoma de Células B/metabolismo , FN-kappa B/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor Cross-Talk/fisiología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/genética , Animales , Apoptosis/fisiología , Western Blotting , Línea Celular Tumoral , Fragmentación del ADN , Modelos Animales de Enfermedad , Ensayo de Cambio de Movilidad Electroforética , Elementos de Facilitación Genéticos , Activación Enzimática/fisiología , Ensayo de Inmunoadsorción Enzimática , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Genes myc , Inmunoprecipitación , Linfoma de Células B/genética , Ratones , FN-kappa B/genética , Fosfatidilinositol 3-Quinasas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética
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