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Etiopathogenic role of ERK5 signaling in sarcoma: prognostic and therapeutic implications
Sánchez-Fdez Adrián,Matilla-Almazán Sofía,Del Carmen Sofía,Abad Mar,Arconada-Luque Elena,Jiménez-Suárez Jaime,Chinchilla-Tábora Luis Miguel,Ruíz-Hidalgo Mª José,Sánchez-Prieto Ricardo,Pandiella Atanas 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Sarcomas constitute a heterogeneous group of rare and difficult-to-treat tumors that can affect people of all ages, representing one of the most common forms of cancer in childhood and adolescence. Little is known about the molecular entities involved in sarcomagenesis. Therefore, the identification of processes that lead to the development of the disease may uncover novel therapeutic opportunities. Here, we show that the MEK5/ERK5 signaling pathway plays a critical role in the pathogenesis of sarcomas. By developing a mouse model engineered to express a constitutively active form of MEK5, we demonstrate that the exclusive activation of the MEK5/ERK5 pathway can promote sarcomagenesis. Histopathological analyses identified these tumors as undifferentiated pleomorphic sarcomas. Bioinformatic studies revealed that sarcomas are the tumors in which ERK5 is most frequently amplified and overexpressed. Moreover, analysis of the impact of ERK5 protein expression on overall survival in patients diagnosed with different sarcoma types in our local hospital showed a 5-fold decrease in median survival in patients with elevated ERK5 expression compared with those with low expression. Pharmacological and genetic studies revealed that targeting the MEK5/ERK5 pathway drastically affects the proliferation of human sarcoma cells and tumor growth. Interestingly, sarcoma cells with knockout of ERK5 or MEK5 were unable to form tumors when engrafted into mice. Taken together, our results reveal a role of the MEK5/ERK5 pathway in sarcomagenesis and open a new scenario to be considered in the treatment of patients with sarcoma in which the ERK5 pathway is pathophysiologically involved.
Claudia Concha,María Daniella Carretta,Pablo Alarcón,Ivan Conejeros,Diego Gallardo,Alejandra Isabel Hidalgo,Nestor Tadich,Dante Daniel Cáceres,María Angélica Hidalgo,Rafael Agustín Burgos 대한수의학회 2014 Journal of Veterinary Science Vol.15 No.2
Reactive oxygen species (ROS) production is one of the mainmechanisms used to kill microbes during innate immuneresponse. D-lactic acid, which is augmented during acuteruminal acidosis, reduces platelet activating factor(PAF)-induced ROS production and L-selectin shedding inbovine neutrophils in vitro. This study was conducted toinvestigate whether acute ruminal acidosis induced by acuteoligofructose overload in heifers interferes with ROSproduction and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugularvenipuncture, while ruminal samples were collected usingrumenocentesis. Lactic acid from plasma and ruminal sampleswas measured by HPLC. PAF-induced ROS production andL-selectin shedding were measured in vitro in bovineneutrophils by a luminol chemiluminescence assay and flowcytometry, respectively. A significant increase in ruminal andplasma lactic acid was recorded in these animals. Specifically,a decrease in PAF-induced ROS production was observed 8 hafter oligofructose overload, and this was sustained until 48 hpost oligofructose overload. A reduction in PAF-inducedL-selectin shedding was observed at 16 h and 32 h postoligofructose overload. Overall, the results indicated thatneutrophil PAF responses were altered in heifers with ruminalacidosis, suggesting a potential dysfunction of the innateimmune response.
César Hidalgo-García,José Miguel Tricás-Moreno,Orosia Lucha-López,Elena Estebanezde Miguel,Elena Bueno-Gracia,Silvia Pérez-Guillén,Pablo Fanlo-Mazas,Alazne Ruiz-de-Escudero,John Krauss 국제물리치료학회 2016 Journal of International Academy of Physical Ther Vol.7 No.1
The purpose of this study is to explore the effects of mobilization of C0-C1 and C7-T1 applied to asymptomatic individuals with reduced upper cervical rotation during the FRT. Design: parallel randomized controlled trial. 48 subjects(38.52 years±15.13) with C1-C2 rotation hypomobility in TFR joined the study and were randomized into three groups(C0, C7, control group). FRT in both directions was measured before and after the intervention. C0 intervention consisted of a dorsal translatoric mobilization of C0-C1 in the cervical neutral position. C7 intervention consisted of a ventral cranial translatoric mobilization of C7- T1 in neutral position and the control group maintained a supine position. C0 group experienced a FRT ROM to the restricted side increase of 17.64。(SD=4.55), that was significantly greater (P<0.001) than 5.95。 (SD=4.81) of the C7 group and 2.45。(SD=5.05) of the control group. The results showed that a dorsal translatoric mobilization of C0-C1 in neutral position restored the physiological FRT mobility in subjects with C1-C2 hypomobility and experienced statistical significant improvement in FRT as compared to a C7-T1 translatoric mobilization and a control group. (Level of evidence: 1b).
( Carol N. Flores-fernandez ),( Elizabeth Chavez-hidalgo ),( Marco Santos ),( Amparo I. Zavaleta ),( David R. Arahal ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 한국미생물·생명공학회지 Vol.47 No.3
All Idiomarina species are isolated from saline environments; microorganisms in such extreme habitats develop metabolic adaptations and can produce compounds such as proteases with an industrial potential. ARDRA and 16S rRNA gene sequencing are established methods for performing phylogenetic analysis and taxonomic identification. However, 16S-23S ITS is more variable than the 16S rRNA gene within a genus, and is therefore, used as a marker to achieve a more precise identification. In this study, ten protease producing Idiomarina strains isolated from the Peruvian salterns were characterized using biochemical and molecular methods to determine their bacterial diversity and industrial potential. In addition, comparison between the length and nucleotide sequences of a 16S-23S ITS region allowed us to assess the inter and intraspecies variability. Based on the 16S rRNA gene, two species of Idiomarina were identified (I. zobellii and I. fontislapidosi). However, biochemical tests revealed that there were differences between the strains of the same species. Moreover, it was found that the ITS contains two tRNA genes, tRNA<sup>Ile (GAT)</sup> and tRNA<sup>Ala (TGC)</sup>, which are separated by an ISR of a variable size between strains of I. zobellii. In one strain of I. zobellii (PM21), we found nonconserved nucleotides that were previously not reported in the tRNA<sup>Ala</sup> gene sequences of Idiomarina spp. Thus, based on the biochemical and molecular characteristics, we can conclude that protease producing Idiomarina strains have industrial potential; only two I. zobellii strains (PM48 and PM72) exhibited the same properties. The differences between the other strains could be explained by the presence of subspecies.
Balkys Quevedo-Hidalgo,Paulo César Narvaéz-Rincón,Aura Marina Pedroza-Rodríguez,Mario Enrique Velásquez-Lozano 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.5
In Colombia, a great amount of waste is generated during the cut-off and harvest stages in flowers culture. This study examines the possibility of degrading Chrysanthemum wastes by using Pleurotus ostreatus,Trametes versicolor, and Phanerochaete chrysosporium cultures; this has not been studied previously. The initial effect of fungi on the degradation of Chrysanthemum wastes were studied individually and in co-cultures. The highest degradation was by P. ostreatus. After that, the influence of pH and waste, copper, and manganese concentrations on reducing sugars concentration were determined in a submerged culture in 100 mL Erlenmeyer flasks. There was a significant effect of manganese and waste concentrations on sugar concentration, while the effect of copper concentration and pH were not significant. Following, the process was carried out in a 1.5 L reactor at the optimal values of the variables studied in Erlenmeyer flask but varying air injection from 0 to 2 vvm. The highest concentration of sugars was 21.2 g/L with 78% of glucose content at 6.3% w/v of waste, 7.5 mM of Mn and Cu and 2 vvm of air injection. Finally, laccase, Manganese peroxidase, endo-1,4-β-glucanase, exo-1,4-β-glucanase and 1,4-β-glucosidase were detected in the extract obtained under these conditions. The highest activities were obtained for laccase (4,694 U/L) and 1,4-β-glucosidase (9,513 U/L).
Flores-Fernandez, Carol N.,Chavez-Hidalgo, Elizabeth,Santos, Marco,Zavaleta, Amparo I.,Arahal, David R. The Korean Society for Microbiology and Biotechnol 2019 한국미생물·생명공학회지 Vol.47 No.3
All Idiomarina species are isolated from saline environments; microorganisms in such extreme habitats develop metabolic adaptations and can produce compounds such as proteases with an industrial potential. ARDRA and 16S rRNA gene sequencing are established methods for performing phylogenetic analysis and taxonomic identification. However, 16S-23S ITS is more variable than the 16S rRNA gene within a genus, and is therefore, used as a marker to achieve a more precise identification. In this study, ten protease producing Idiomarina strains isolated from the Peruvian salterns were characterized using biochemical and molecular methods to determine their bacterial diversity and industrial potential. In addition, comparison between the length and nucleotide sequences of a 16S-23S ITS region allowed us to assess the inter and intraspecies variability. Based on the 16S rRNA gene, two species of Idiomarina were identified (I. zobellii and I. fontislapidosi). However, biochemical tests revealed that there were differences between the strains of the same species. Moreover, it was found that the ITS contains two tRNA genes, $tRNA^{Ile(GAT)}$ and $tRNA^{Ala(TGC)}$, which are separated by an ISR of a variable size between strains of I. zobellii. In one strain of I. zobellii (PM21), we found nonconserved nucleotides that were previously not reported in the $tRNA^{Ala}$ gene sequences of Idiomarina spp. Thus, based on the biochemical and molecular characteristics, we can conclude that protease producing Idiomarina strains have industrial potential; only two I. zobellii strains (PM48 and PM72) exhibited the same properties. The differences between the other strains could be explained by the presence of subspecies.
Ovarian Stromal Hyperplasia: A Rare Cause of Postmenopausal Hyperandrogenism
Teresa Lozoya Araque,Isauro Rogelio Monfort Ortiz,José Enrique Martín González,Alenda Jiménez García,Inmaculada Navarro Hidalgo,Verónica Andrade Gamarra,Cecilia Parrell Soler,Fernando Gil Raga 대한폐경학회 2020 대한폐경학회지 Vol.26 No.1
Ovarian hyperthecosis and ovarian stromal hyperplasia (OSH) are two uncommon non-neoplastic causes of ovarian hyperandrogenism, whose etiology is still unknown. These conditions are characterized by obesity, hyperinsulinemia, acanthosis nigricans, and even virilization, mainly in postmenopausal women. Here we have reported the case of a 67-year-old patient with a diagnosis of OSH, which was resolved after bilateral laparoscopic oophorectomy. In this case report, we have discussed two different conditions posing a diagnostic challenge and requiring a high index of suspicion.
Hoyer, S.,Ló,pez-Morales, M.,Rojo, P.,Nascimbeni, V.,Hidalgo, S.,Astudillo-Defru, N.,Concha, F.,Contreras, Y.,Servajean, E.,Hinse, T. C. Oxford University Press 2013 Monthly notices of the Royal Astronomical Society Vol.434 No.1
<P>We report 12 new transit observations of the exoplanet WASP-4b from the Transit Monitoring in the South (TraMoS) project. These transits are combined with all previously published transit data for this planet to provide an improved radius measurement of R-p = 1.395 +/- 0.022R(jup) and improved transit ephemerides. In a new homogeneous analysis in search for transit timing variations (TTVs) we find no evidence of those with rms amplitudes larger than 20 s over a 4-yr time span. This lack of TTVs rules out the presence of additional planets in the system with masses larger than about 2.5, 2.0 and 1.0 M-circle plus around the 1:2, 5:3 and 2:1 orbital resonances. Our search for the variation of other parameters, such as orbital inclination and transit depth, also yields negative results over the total time span of the transit observations. Finally, we perform a simple study of stellar spots configurations of the system and conclude that the star rotational period is about 34 d.</P>
Fernando Gonzá,lez-Magañ,a,Hé,ctor Omar Malagó,n-Hidalgo,Eugenio Garcí,a-Cano,Roberto Vilchis-Ló,pez,Adriana Fentanes-Vera,Fernan-Alejandra Ayala-Ugalde 대한구강악안면외과학회 2018 대한구강악안면외과학회지 Vol.44 No.1
Objectives: Airway management in patients with panfacial trauma is complicated. In addition to involving facial lesions, such trauma compromises the airway, and the use of intermaxillary fixation makes it difficult to secure ventilation by usual approaches (nasotracheal or endotracheal intubation). Submental airway derivation is an alternative to tracheostomy and nasotracheal intubation, allowing a permeable airway with minimal complications in complex patients. Materials and Methods: This is a descriptive, retrospective study based on a review of medical records of all patients with facial trauma from January 2003 to May 2015. In total, 31 patients with complex factures requiring submental airway derivation were included. No complications such as bleeding, infection, vascular, glandular, or nervous lesions were presented in any of the patients. Results: The use of submental airway derivation is a simple, safe, and easy method to ensure airway management. Moreover, it allows an easier reconstruction. Conclusion: Based on these results, we concluded that, if the relevant steps are followed, the use of submental intubation in the treatment of patients with complex facial trauma is a safe and effective option.
Wendoline Rosiles-Alanis,Alejandro Zamilpa,Rebeca Garcı´a-Macedo,Miguel A. Zavala-Sa´nchez,Sergio Hidalgo-Figueroa,Beatriz Mora-Ramiro,Rube´n Roma´n-Ramos,Samuel E. Estrada-Soto,Julio C. Almanza-Perez 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.6
Insulin secretion and GLUT4 expression are two critical events in glucose regulation. The receptors G-protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor-gamma (PPARγ) modulate these processes, and they represent potential therapeutic targets for new antidiabetic agent's design. Cucurbita ficifolia fruit is used in traditional medicine for diabetes control. Previous studies demonstrated several effects: a hypoglycemic effect mediated by an insulin secretagogue action, antihyperglycemic effect, and promoting liver glycogen storage. Anti-inflammatory and antioxidant effects were also reported. Moreover, some of its phytochemicals have been described, including d-chiro-inositol. However, to understand these effects integrally, other active principles should be investigated. The aim was to perform a chemical fractionation guided by bioassay to isolate and identify other compounds from C. ficifolia fruit that explain its hypoglycemic action as insulin secretagogue, its antihyperglycemic effect by PPARγ activation, and on liver glycogen storage. Three different preparations of C. ficifolia were tested in vivo. Ethyl acetate fraction derived from aqueous extract showed antihyperglycemic effect in an oral glucose tolerance test and was further fractioned. The insulin secretagogue action was tested in RINm5F cells. For the PPARγ activation, C2C12 myocytes were treated with the fractions, and GLUT4 mRNA expression was measured. Chemical fractionation resulted in the isolation and identification of β-sitosterol and 4-hydroxybenzoic acid (4-HBA), which increased insulin secretion, GLUT4, PPARγ, and adiponectin mRNA expression, in addition to an increase in glycogen storage. 4-HBA exhibited an antihyperglycemic effect, while β-sitosterol showed hypoglycemic effect, confirming the wide antidiabetic related results we found in our in vitro models. An in silico study revealed that 4-HBA and β-sitosterol have potential as dual agonists on PPARγ and GPR40 receptors. Both compounds should be considered in the development of new antidiabetic drug development.