Taurine inhibits serum deprivation-induced osteoblast apoptosis via the taurine transporter/ERK signaling pathway

Taurine has positive effects on bone metabolism. However, the effects of taurine on osteoblast apoptosis in vitro have not been reported. The aim of this study was to investigate the activity of taurine on apoptosis of mouse osteoblastic MC3T3-E1 cells. The data showed that 1, 5, 10, or 20 mM taurine resulted in 16.7, 34.2, 66.9, or 63.75% reduction of MC3T3-E1 cell apoptosis induced by the serum deprivation (serum-free α-MEM), respectively. Taurine (1, 5, or 10 mM) also reduced cytochrome c release and inhibited activation of caspase-3 and -9, which were measured using fluorogenic substrates for caspase-3/caspase-9, in serum-deprived MC3T3-E1 cells. Furthermore, taurine (10 mM) induced extracellular signal-regulated kinase (ERK) phosphorylation in MC3T3-E1 cells. Knockdown of the taurine transporter (TAUT) or treatment with the ERK-specific inhibitor PD98059 (10 μM) blocked the activation of ERK induced by taurine (10 mM) and abolished the anti-apoptotic effect of taurine (10 mM) in MC3T3-E1 cells. The present results demonstrate for the first time that taurine inhibits serum deprivation-induced osteoblast apoptosis via the TAUT/ERK signaling pathway.

Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells

Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h) compared to 5.1% in control cells (P < 0.05). Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia groupvs control group) at 3 h in MKN28 cells, respectively (P < 0.05). We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM) decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4%) treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8%) of cells treated with hyperthermia alone (P < 0.05). Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.

De veritate occulta, Psalm. LI. 8

Invokaatio: I.N.J.

Screening of iron-enriched fungus from natural environment and evaluation of organically bound iron bioavailability in rats

Iron is an essential element for nearly all living organisms, and its deficiency is the most common form of malnutrition in the world. The organic forms of trace elements are considered more bioavailable than the inorganic forms. Although Saccharomyces cerevisiae can enrich metal elements and convert inorganic iron to organic species, its tolerability and transforming capacity are limited. The aim of this study was to screen higher biomass and other iron-enriched fungi strains besides Saccharomyces cerevisiae from the natural environment. A PDA medium containing 800 μg/mL iron was used for initial screening. Fifty strains that tolerated high iron concentration were isolated from the natural environment, and only one strain, No.BY1109, grew well at Fe (II) concentration of 10,000μg/ml. According to morphological characterization, 18S rDNA sequence analysis, and biophysical and biochemical characterization, the strain No.BY1109 was identified as Rhodotorula. The iron content of No.BY1109 (10 mg Fe/g dry cell) was determined using atomic absorption spectrometry. The results of distribution of iron in the cells showed that iron ion was mainly chelated in the cell walls and vacuoles. The bioavailability in rats confirmed that strain No.BY1109 had higher absorption efficiency than that of ferrous sulfate after single dose oral administration. The present study introduces new iron supplements, and it is a basis for finding new iron supplements from natural environment.

As definições teóricas de direitos humanos de Jürgen Habermas: o princípio legal e as correções morais[ign] [title language="en"]The theoretical definitions of human rights of Jürgen Habermas[ign]: [subtitle]legal principle and moral corrections

No entendimento de Habermas, "direito", na expressão "direitos humanos", é um conceito jurídico, donde direitos humanos, para ele, serem direitos jurídicos, normas legais declaradas em atos de fundações do Estado ou anunciadas em convenções do direito internacional e/ou constituições estatais. Ao conceber assim os direitos e tematizar os direitos humanos numa abordagem tríplice (focando-os entre moral, direito e política), ele fornece diferentes definições teóricas dos direitos humanos. O texto apresenta uma exposição sistemática dessas definições e focaliza os diferentes problemas que motivaram Habermas a alterar e ampliar suas concepções de direitos humanos.

Razão e democracia: uso público da razão e política deliberativa em Habermas[ign] [title language="en"]Reason and democracy[ign]: [subtitle]Public use of reason and deliberative politics in Habermas

O objetivo do artigo é examinar como Habermas, orientado pela intuição normativa do uso público da razão, reconstrói uma concepção procedimental de democracia deliberativa, que, sem desconsiderar da dimensão estratégica e instrumental da esfera pública e da política, reformula a dimensão epistêmica da democracia: a aceitabilidade racional dos acordos políticos. Inicialmente, apresento brevemente a análise sociológica e histórica do conceito de esfera pública crítica, realizada em Mudança Estrutural da Esfera Pública (1962), para, em seguida, expor duas linhas de argumentação sobre o conceito de esfera pública e de política deliberativa, em Direito e Democracia (1992): a que se refere ao princípio de legitimação baseado na razão pública como uma reconstrução intersubjetiva e política do conceito kantiano de autonomia; e a que concerne aos aspectos essenciais da teoria crítica da sociedade fundada na distinção entre mundo da vida e sistema e a "tradução" sociológica e institucional do uso público da razão, nos conceitos de sociedade civil e esfera pública.

« Li Livre dou Bret », ou Le Roman de Tristan [de LUCE DU GAST].

Commençant par : «... voluntez d'Elinde et landemain quant il fut ajornez... » et finissant par : «... et plairai tant com li mondes durrai, li quex est apelez li Livres dou Bret. Explicit li Livres dou Bret. Amen » . D'après l'épilogue, « HELYE DE BERRON » aurait remanié le travail de LUCE DU GAST, qu'il a divisé en trois livres. Voir l'introduction au livre III, fol. 264. Manque le premier feuillet de chaque livre.

« Li rommans de Godefroy de Buillon et de Salehadin et de tous lez autres roys qui ont esté outre mer jusques a saint Loys qui darrenierement y fu ».

Début : « Si povés vous savoir les sains leus de la terre... — Fin : «... Adonc estoient l'an de l'incarnation Nostre Seigneur mil CCLXI. Explicit les Feiz d'Outremer. Ce livre ci fu complet d'escripture l'an de l'incarnation Nostre Seigneur mil trois cens et trante et VII, le jeudi devant la feste mon seigneur saint Thomas l'apostre devant Noël. » — Nombreuses miniatures. — Au fol. 1, on lit : « Au duc d'Arschot en 1584 ».

Li queste del S. Graal [La quête du Saint-Graal]

Commencement : « A la veille de la Pentecouste quant li compaignon de la Table reonde furent venu a Chamahelot... » — Fin : « ...Et quand Boors ot conté les aventures del S. Graal, teles com il les avoit veu, si furent mises en escript et gardées moult chierement, dont mestres Gautiers Map le traist a faire sen livre del Graal pour l'amour del roy Henri son signour, qui fist l'hystoire translater de latin en franchois. Si s'en taist atant li contes que plus n'en dist des aventures del S. Graal. Amen. — Chius livres fu parescrips le nuit Nostre Dame en mi aoust l'a[n] mil trois cens et LI : si l'escripst Pierars dou Tielt, et enlumina et loia. — Explicit li queste del S. Graal. » Fol. 95 : Annales depuis le commencement du monde jusqu'en 1281. Commencement : « Chi conmencent li an dés le conmencement del monde tres chi qu'en nos temps... » — Fin : « M. CC. LXXIX. Margerite contesse de Flandres et de Hainau moru. Guis ses fieus fu quens. — MCCLXXX. Nicolas pape morut. — MCCLXXXI. Martins fu pape. »

Guiron le Courtois, translaté de latin en françois par Luce du Châtel du Gat. « Cy commence li seconds livres de Guiron le Courtois »

Commencement : « Or dist li contes que li rois Melyadus demoura ou chastel... » — Fin : « ...et encore est communement son nom par toute Engleterre. — Cy fine le tiers et derrenier livre de Guiron le Courtois. »

Le prince Yi Hou [i. e. Yi Un] et la princesse Masako après leur mariage : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60269

Un groupe de demoiselles d'honneur au mariage du prince Yi Hou [i. e. Yi Un] et la princesse Masako : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60268