TGF-β dependent regulation of oxygen radicals during transdifferentiation of activated hepatic stellate cells to myofibroblastoid cells

Background: The activation of hepatic stellate cells (HSCs) plays a pivotal role during liver injury because the resulting myofibroblasts (MFBs) are mainly responsible for connective tissue re-assembly. MFBs represent therefore cellular targets for anti-fibrotic therapy. In this study, we employed activated HSCs, termed M1-4HSCs, whose transdifferentiation to myofibroblastoid cells (named M-HTs) depends on transforming growth factor (TGF)-β. We analyzed the oxidative stress induced by TGF-β and examined cellular defense mechanisms upon transdifferentiation of HSCs to M-HTs. Results: We found reactive oxygen species (ROS) significantly upregulated in M1-4HSCs within 72 hours of TGF-β administration. In contrast, M-HTs harbored lower intracellular ROS content than M1-4HSCs, despite of elevated NADPH oxidase activity. These observations indicated an upregulation of cellular defense mechanisms in order to protect cells from harmful consequences caused by oxidative stress. In line with this hypothesis, superoxide dismutase activation provided the resistance to augmented radical production in M-HTs, and glutathione rather than catalase was responsible for intracellular hydrogen peroxide removal. Finally, the TGF-β/NADPH oxidase mediated ROS production correlated with the upregulation of AP-1 as well as platelet-derived growth factor receptor subunits, which points to important contributions in establishing antioxidant defense. Conclusion: The data provide evidence that TGF-β induces NADPH oxidase activity which causes radical production upon the transdifferentiation of activated HSCs to M-HTs. Myofibroblastoid cells are equipped with high levels of superoxide dismutase activity as well as glutathione to counterbalance NADPH oxidase dependent oxidative stress and to avoid cellular damage.

NADPH oxidase NOX4 mediates stellate cell activation and hepatocyte cell death during liver fibrosis development.

A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but the implication of NOX4 is poorly understood yet. The aim of this work was to study the functional role of NOX4 in different cell populations implicated in liver fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) and hepatocytes. Two different mice models that develop spontaneous fibrosis (Mdr2−/−/p19ARF−/−, Stat3Δhc/Mdr2−/−) and a model of experimental induced fibrosis (CCl4) were used. In addition, gene expression in biopsies from chronic hepatitis C virus (HCV) patients or non-fibrotic liver samples was analyzed. Results have indicated that NOX4 expression was increased in the livers of all animal models, concomitantly with fibrosis development and TGF-β pathway activation. In vitro TGF-β-treated HSC increased NOX4 expression correlating with transdifferentiation to MFBs. Knockdown experiments revealed that NOX4 downstream TGF-β is necessary for HSC activation as well as for the maintenance of the MFB phenotype. NOX4 was not necessary for TGF-β-induced epithelial-mesenchymal transition (EMT), but was required for TGF-β-induced apoptosis in hepatocytes. Finally, NOX4 expression was elevated in patients with hepatitis C virus (HCV)-derived fibrosis, increasing along the fibrosis degree. In summary, fibrosis progression both in vitro and in vivo (animal models and patients) is accompanied by increased NOX4 expression, which mediates acquisition and maintenance of the MFB phenotype, as well as TGF-β-induced death of hepatocytes.

Carme Serrallonga, el plaer de traduir

Carme Serrallonga (Barcelona, 1909-1997) començà a traduir als anys seixanta, en moments de represa de consciència ideològica i literària. Bona coneixedora de diversos idiomes, especialment l’alemany, l’anglès, el francès i l’italià, girà al català unes vint obres del teatre universal dels grans autors. Serrallonga explicava que havia començat a aprendre alemany per poder conèixer a fons l’obra de Brecht, del qual el 1966 traduí La bona persona de Sezuan, a proposta de Ricard Salvat, i cinc obres més. De l’alemany també portà al català autors com Georg Büchner, Heinrich Böll, Friedrich Dürrenmatt, Peter Handke, György Lukács, Goethe, Mozart o Alfred Döblin. A més de l’alta literatura alemanya, Serrallonga féu petites incursions en la literatura anglesa i nord-americana, la italiana i, fins i tot, la sud-africana. El 1983 l’editorial La Galera li encarregà la traducció d’En Jim Botó i en Lluc el maquinista de Michael Ende. En sis anys traduí més de trenta títols de literatura infantil. Ja jubilada, a vuitanta-quatre anys, es posà a estudiar rus pel plaer de poder llegir Anna Akhmàtova i Txèkhov en la seva llengua originària. Abans de morir, treballava en la traducció d’un llibre de poemes de l’autora russa.

Biosynthesis of panaxynol and panaxydol in Panax ginseng

The natural formation of the bioactive C17-polyacetylenes (−)-(R)-panaxynol and panaxydol was analyzed by 13C-labeling experiments. For this purpose, plants of Panax ginseng were supplied with 13CO2 under field conditions or, alternatively, sterile root cultures of P. ginseng were supplemented with [U-13C6]glucose. The polyynes were isolated from the labeled roots or hairy root cultures, respectively, and analyzed by quantitative NMR spectroscopy. The same mixtures of eight doubly 13C-labeled isotopologues and one single labeled isotopologue were observed in the C17-polyacetylenes obtained from the two experiments. The polyketide-type labeling pattern is in line with the biosynthetic origin of the compounds via decarboxylation of fatty acids, probably of crepenynic acid. The 13C-study now provides experimental evidence for the biosynthesis of panaxynol and related polyacetylenes in P. ginseng under in planta conditions as well as in root cultures. The data also show that 13CO2 experiments under field conditions are useful to elucidate the biosynthetic pathways of metabolites, including those from roots.

Cálculo independente de dose para tratamentos de arco dinâmico com colimador micromultilâminas

OBJETIVO: Em técnicas de tratamento como o arco dinâmico, a verificação manual dos cálculos do sistema de planejamento é muito difícil. Assim, a utilização de ferramentas computacionais é de utilidade e torna-se componente essencial do programa de controle de qualidade. MATERIAIS E MÉTODOS: Foi criado um programa computacional de tipo planilha eletrônica para realizar cálculo independente da dose, ou equivalente das unidades monitoras, nos tratamentos realizados pela técnica de arco dinâmico com micromultilâminas. Os valores de dose calculados, por arco e por tratamento completo, foram comparados aos valores obtidos do sistema de planejamento BrainScan v5.3. O programa desenvolvido foi testado com 229 campos de arco dinâmico que representam 42 tratamentos de crânio. Desses, 109 campos foram calculados em reconstrução tridimensional feita a partir das imagens de tomografia dos pacientes, 109 na reconstrução de um objeto simulador de polimetilmetacrilato e 21 na de um objeto simulador sólido equivalente à água. RESULTADOS: A diferença média de doses totais encontrada nos 42 tratamentos (compostos de um ou mais arcos dinâmicos), entre o programa de verificação e o sistema de planejamento, foi de +1,73%, com desvio-padrão de 0,76%. A diferença máxima encontrada foi de 3,32% e a mínima, de -0,20%. No caso dos 229 arcos testados um a um, a diferença média encontrada foi de 1,61%, com desvio-padrão de 1,04%. Os valores máximos e mínimos das diferenças foram de 4,01% e -2,04%, respectivamente. Em 80,35% dos arcos testados, as doses calculadas acham-se na faixa de ± 2,5% de diferença com relação às doses geradas pelo sistema de planejamento. CONCLUSÃO: O programa apresentado é recomendado para a verificação da dose pontual dos planos de tratamento, como parte do procedimento de garantia de qualidade em radioterapia e radiocirurgia estereotáxica quando se utiliza a técnica de arco dinâmico por meio de um colimador micromultilâminas, nos quais um cálculo manual é muito difícil ou inviável, pela complexidade da técnica.

Kuljetuslajin yhteys kannattavuuteen etelä- ja itäsuomalaisissa kuljetusyrityksissä

Tämä Pro-Gradu –tutkielma tarkastelee etelä- ja itäsuomalaisia kuljetusyrityksiä kannattavuuden, vakavaraisuuden ja maksuvalmiuden näkökulmasta kuljetuslajeittain. Tutkielman pyrkimyksenä on valottaa Etelä- ja Itä-Suomen läänien kilpailuympäristöä numeeristen tunnuslukujen ja tilinpäätöserien perusteella. Päätavoitteena on osoittaa, onko kuljetuslajien välillä kannattavuuseroja. Tutkielma koostuu teoriaosasta sekä empiirisestä osasta, jonka aineisto koostuu etelä- ja itäsuomalaisten kuljetusyritysten tilinpäätöstiedoista ja tunnusluvuista. Tutkimuksen empiirinen aineisto on kerätty haulla Amadeus–tietokannasta ja postikyselynä haun tuottamilta yrityksiltä. Aineistoa on analysoitu kvantitatiivisilla menetelmillä SPSS–ohjelmistolla. Tuloksista selviää, että kuljetuslajilla on yhteys kannattavuuteen ROCE–tunnusluvulla mitattuna. Kannattavuuden osa-alueita, kuten tuottoja, kustannuksia ja sidottua pääomaa analysoitiin erikseen, mutta kannattavuuseroille ei silti löydetty selitystä.

Omistusrakenne ja kannattavuus – empiirinen tutkimus neljällä toimialalla

Metsäteollisuudessa on aika ajoin esitetty ajatus, että perheyritykset menestyvät alalla paremmin kuin muut toimijat. Tämän tutkimuksen tavoitteena oli selvittää, onko omistusrakenteen ja kannattavuuden välillä yhteyttä. Omistusrakennetta tarkasteltiin kahdesta näkökulmasta: omistuksen keskittyneisyys ts. omistajan valvonta operatiiviseen johtoon nähden ja omistajatyyppi (perhe, rahoitusyhtiö, ei-rahoitusyhtiö, valtio). Näiden molempien suhdetta kannattavuuteen (ROA tai EBITDA) analysoitiin kvantitatiivisesti kovarianssianalyysilla. Teoreettisena lähtökohtana käytettiin agenttiteoriaa. Tutkimuskohteeksi valittiin pääomavaltaiset alat: metsäteollisuus, kemianteollisuus, konepajateollisuus ja energiateollisuus. Aineisto koottiin eurooppalaisten yritysten tilinpäätöstiedoista Amadeus-tietokannasta. Tutkimuksen tuloksena todettiin, ettei omistuksen keskittyneisyydellä eikä omistajatyypillä ts. omistusrakenteella ole tilastollisesti merkitsevää yhteyttä kannattavuuteen millään tutkituista toimialoista.

Avaliação quantitativa de cardenolídeos no cultivar experimental de Digitalis lanata do maciço do itatiaia e perspectivas de seu emprego industrial

The content of digoxin and lanatoside C (jointly quantified), lanatoside A, lanatoside B, glucoevatromonoside, odorobioside G, glucogitoroside, glucoverodoxine, glucodigifucoside and digitalinum verum was determined by HPLC in Digitalis lanata harvested in Brazil, as well as in clones industrially employed for the production of cardenolides. The Brazilian plants presented greater variation in the contents of cardenolides than the analyzed clones. Lanatoside C and digoxin concentrations were higher in the clones (6120±640 nmol/g dry leaf) than in the Brazilian plants (1820±900 nmol/g dry leaf). The concentrations of these glycosides were found to be within the range described for native species and also were similar to an European cultivar, what makes possible its industrial use for the cardenolides production.

O uso de cálculos teóricos como ferramenta para a detecção de moléculas no meio interestelar: o caso dos carbenos CnNH (n=1, 3 e 5)

This work reviews some applications of ab initio molecular orbital calculations to the elucidation of structures of interstellar molecules. The case of the CnNH (n=1, 3 and 5 ) carbenes is extensively analyzed and discussed. Theoretical conformational analysis and predicted values for the rotational constants and dipole moments of the singlet state of C5NH are reported for the first time and a comparison is performed with results previously obtained for C3NH and CNH.

A química na região nordeste: o papel da SBQ

In the opportunity of the 20th year of foundation of the Brazilian Chemical Society, the role of this organization in behalf of the development of Science, in particular of Chemistry, is analysed by the way it is observed by someone that has been working in the Northeast of this Country.

Spectroscopic characterization of phases formed by high-dose carbon ion implantation in silicon

High-dose carbon-ion-implanted Si samples have been analyzed by infrared spectroscopy, Raman scattering, and x-ray photoelectron spectroscopy (XPS) correlated with transmission electron microscopy. Samples were implanted at room temperature and 500°C with doses between 1017 and 1018 C+/cm2. Some of the samples were implanted at room temperature with the surface covered by a capping oxide layer. Implanting at room temperature leads to the formation of a surface carbon-rich amorphous layer, in addition to the buried implanted layer. The dependence of this layer on the capping oxide suggests this layer to be determined by carbon migration toward the surface, rather than surface contamination. Implanting at 500°C, no carbon-rich surface layer is observed and the SiC buried layer is formed by crystalline ßSiC precipitates aligned with the Si matrix. The concentration of SiC in this region as measured by XPS is higher than for the room-temperature implantation.