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Excretion of biliary compounds during intrauterine life

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World journal of Gastroenterology 2009年第7期15卷 817-828页

作者： Rocio IR Macias jose jg marin maria A Serrano Laboratory of Experimental Hepatology and Drug Targeting CIBERehdUniversity of Salamanca

In adults,the hepatobiliary system,together with the kidney,constitute the main routes for the elimination of several endogenous and xenobiotic compounds into bile and urine,***,during intrauterine life the biliary route of excretion for cholephilic compounds,such as bile acids and biliary pigments,is very *** very early in pregnancy the fetal liver produces bile acids,bilirubin and biliverdin,these compounds cannot be efficiently eliminated by the fetal hepatobiliary system,owing to the immaturity of the excretory machinery in the fetal ***,the potentially harmful accumulation of cholephilic compounds in the fetus is prevented by their elimination across the *** to the presence of detoxifying enzymes and specifi c transport systems at different locations of the placental barrier,such as the endothe-lial cells of chorionic vessels and trophoblast cells,this organ plays an important role in the hepatobiliary-like function during intrauterine *** relevance of this excretory function in normal fetal physiology is evident in situations where high concentrations of biliary compounds are accumulated in the *** may result in oxidative stress and apoptosis,mainly in the placenta and fetal liver,which might affect normal fetal development and challenge the fate of the *** present article reviews current knowledge of the mechanisms underlying the hepatobiliary function of the fetal-placental unit and the repercussions of several pathological conditions on this tandem.

关键词： Bile acids Bilirubin Foetus Liver Placenta

Clinical relevance of the relationship between changes in gut microbiota and bile acid metabolism in patients with intrahepatic cholangiocarcinoma

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Hepatobiliary Surgery and Nutrition 2020年第2期9卷 211-214页

作者： Elisa Herraez Marta R.Romero Rocio I.R.Macias maria j.monte.jose j.G.marin Experimental Hepatology and Drug Targeting(HEVEFARM) IBSALUniversity of SalamancaSalamancaSpain National Institute for the Study of Liver and Gastrointestinal Diseases(CIBERehd) Carlos III National Health InstituteMadridSpain

Although only 10-15%of liver cancers are cholangiocarcinomas(CCAs),which derive from the epithelial cells of the biliary tree,these cancers constitute a serious and growing health problem *** rate of mortality due to this tumor is very high because CCA usually appears in aged people and very often,in more than 70%of cases,are diagnosed late because of:(I)their anatomical localization in a big organ like the liver;(II)the lack of specific symptoms during most time of their development;and(III)the absence of available accurate,specific and sensitive biomarkers(1).These characteristics reduce the rate of success of surgical resection,which is the only curative option for CCA patients,because the response of this aggressive cancer to the available pharmacological armamentarium is extremely feeble(2).This justifies the interest of many groups to identify non-invasive markers to achieve early diagnosis that also permit to distinguish CCA from non-malignant biliary diseases and from hepatocellular carcinoma(HCC),the most frequent liver cancer,which derives from hepatocytes(3).

关键词： metabolism patients diagnosis

AMP-activated kinase in human spermatozoa： identification, intracellular localization, and key function in the reRulation of sperm motility

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Asian journal of Andrology 2017年第6期19卷 707-714页

作者： Violeta Calle-Guisado Ana Hurtado de Llera David Martin-Hidalgo jose Mijares maria C Gil Ignacio S Alvarez maria j Bragado Luis j Garcia-marin Research Group of Intracellular Signalling and Technology of Reproduction (SINTREP) School of Veterinary Medicine University of Extremadura Caceres Spain Assisted Reproduction Unit at the-Minimally Invasive surgery Center jesos Uson (CCMIjU) Caceres Spain Norba Clinic Caceres Spain Research Group of Reproduction and Embryo Development (REDES) University of Extremadura Badajoz Spain Extremadura Institute of Assisted Reproduction (IERA) Badajoz Spain.

AMP-activated kinase （AMPK）, a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work＇s aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System （ISAS） in the presence or absence of the AMPK inhibitor compound C （CC）. AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed： percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

关键词： AMP-activated kinase human spermatozoa immunolocalization sperm motility sperm quality

Further understanding of mechanisms involved in liver cancer chemoresistance

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Hepatoma Research 2017年第1期3卷 22-26页

作者： Oscar Briz maria j.Perez jose j.G.marin Department of Physiology and Pharmacology University of Salamanca37007 SalamancaSpain

An important limitation for the success of chemotherapy in the treatment of primary liver cancer (hepatocellular carcinoma,hepatoblastoma and cholangiocarcinoma) is the marked efficacy of mechanisms of chemoresistance (MOC).These have been previously classified into five groups depending on whether they result in:a reduced drug uptake or enhanced drug export (MOC-1);poor intracellular activation of prodrugs or higher inactivation of active drugs (MOC-2);changes in the molecular targets that impairs the action of the drug by increasing the activity of the metabolic route to be inhibited or stimulating alternative routes (MOC-3);ability of tumor cells to repair drug-induced modifications in the target molecule,usually DNA (MOC-4);and the activation or inhibition of intracellular signaling pathways that lead to a change in the balance between proand anti-apoptotic factors favoring tumor cell survival (MOC-5).Nevertheless,novel information appeared over the last few years has recommended to consider two additional groups,MOC-6 and MOC-7,based on changes in tumor microenvironment,mainly hypoxia and acidity,and epithelial-mesenchymal transition,*** contribute to the defensive armamentaria developed or enhanced in liver cancer cells to resist the pharmacological attack,which accounts for a negligible beneficial effect of commonly used antitumor drugs and only a modest response to novel targeted therapies based on tyrosine kinase inhibitors,such as ***,further advances are urgently needed to better understand the molecular and cellular bases of the chemoresistant barrier and help scientists in this field to develop new tools able to overcome cancer cell defenses.

关键词： Chemotherapy cholangiocarcinoma hepatoblastoma hepatocellular carcinoma tumor environment epithelial-mesenchymal transition

Expanding the Therapeutic Spectrum of Artemisinin:Activity Against Infectious Diseases Beyond Malaria and Novel Pharmaceutical Developments

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World journal of Traditional Chinese Medicine 2016年第2期2卷 1-23页

作者： Thomas Efferth Marta R.Romero Anna Rita Bilia Ahmed Galal Osman Mahmoud ElSohly Michael Wink Rudolf Bauer Ikhlas Khan maria Camilla Bergonzi jose j.G.marin Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Experimental Hepatology and Drug Targeting (HEVEFARM) CIBERehd IBSAL University of SalamancaCampus Miguel de Unamuno Department of Chemistry "Ugo Schiff" University of Florence National Center for Natural Products Research School of Pharmacy University of Mississippi ElSohly Laboratories Inc. Department of Pharmaceutics University of Mississippi Institute of Pharmacy and Molecular Biotechnology Ruprecht-Karls University Institute of Pharmaceutical Sciences Department of Pharmacognosy University of Graz Devision of Pharmacognosy Department of Biomolecular Sciences University of Mississippi

The interest of Western medicine in Traditional Chinese Medicine(TCM) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCM over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCM. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been *** included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, ***-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in

关键词： Artemisinin derivatives Artemisia annua Asteraceae Antimalarial drugs Anti-pathogen activity Antiviral properties Artemisinin-loaded nanocarriers Traditional Chinese Medicine

Turbo-taxonomy to assemble a megadiverse lichen genus:seventy new species of Cora(Basidiomycota:Agaricales:Hygrophoraceae),honouring David Leslie Hawksworth’s seventieth birthday

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Fungal Diversity 2017年第3期84卷 139-207页

作者： Robert Lücking Manuela Dal Forno Bibiana Moncada Luis Fernando Coca Leidy Yasmín Vargas-Mendoza André Aptroot Laura juliana Arias Betty Besal Frank Bungartz Diego Mauricio Cabrera-Amaya Marcela E.S.Cáceres josé Luis Chaves Sionara Eliasaro Martha Cecilia Gutiérrez jesús E.Hernández marin María de los Ángeles Herrera-Campos María E.Holgado-Rojas Harald jonitz Martin Kukwa Fabiane Lucheta Santiago Madriñán Marcelo Pinto Marcelli Suzana maria de Azevedo Martins joel A.Mercado-Díaz jorge Alberto Molina Eduardo A.Morales Peter R.Nelson Freddy Nugra Francisco Ortega Telma Paredes Ayda Lucía Patiño Rouchi Nadine Peláez-Pulido Rosa Emilia Pérez Pérez Gary B.Perlmutter Eimy Rivas-Plata javier Robayo Camilo Rodríguez Diego Fernando Simijaca Edier Soto-Medina Adriano Afonso Spielmann Alejandra Suárez-Corredor jean-Marc Torres Carlos Alberto Vargas Alba Yánez-Ayabaca Gothamie Weerakoon Karina Wilk Marcela Celis Pacheco Mauricio Diazgranados Grischa Brokamp Thomas Borsch Patrick M.Gillevet Masoumeh Sikaroodi james D.Lawrey Botanical Garden and Botanical Museum Berlin KöniginLuise-Straße 6-814195 BerlinGermany Science Education The Field Museum1400 South Lake ShoreChicagoIL 60605USA Department of Botany Smithsonian InstitutionNational Museum of Natural History10th St Constitution Ave NWWashingtonDC 20560USA Department of Environmental Science and Policy George Mason UniversityFairfaxVA 22030-4444USA Licenciatura en Biologı´a Universidad Distrital Francisco Jose´de CaldasCra.4 No.26D-54Torre de LaboratoriosHerbarioBogota´D.C.Colombia Herbario Universidad de Caldas(FAUC) Edificio BicentenarioCalle 65No.26-10ManizalesA.A.275CaldasColombia ABL Herbarium G.v.d.Veenstraat 1073762 XK SoestThe Netherlands Biologı´a Universidad del Quindı´oCarrera 15 Calle 12 NorteArmeniaQuindı´oColombia 120 Chavis Avenue LexingtonVA 24450USA Charles Darwin Foundation Puerto AyoraSanta Cruz IslandGala´pagosEcuador Schedestraße 8 53113 BonnGermany jardı´n Bota´nico de Bogota´jose´Celestino Mutis Avenida Calle 63 No.68-95Bogota´D.C.Colombia Departamento de Biocieˆncias Universidade Federal de SergipeAvenida Vereador Olı´mpio Grandes/n.ItabaianaCEP:49.500-000 SergipeBrazil Laboratorio de Hongos Instituto Nacional de Biodiversidad(INBio)Apdo.22-3100Santo Domingo de HerediaCosta Rica Departamento de Botaˆnica Universidade Federal do Parana´Campus Polite´cnicoSetor de Cieˆncias Biolo´gicasAv.Cel.Francisco H.dos Santoss/nJardim das Ame´ricas81531-980 CuritibaPRBrazil Ingenierı´a Ambiental Universidad Distrital Francisco Jose´de CaldasCarrera 5 Este No.15-82Av.CircumvalarBogota´D.C.Colombia Instituto Experimental jardı´n Bota´nico Dr.Tobı´as Lasser Centro de Investigacio´n y DesarrolloUniversidad Central de VenezuelaAve.Salvador AllendeJardı´n Bota´nico de CaracasApartado#2156Caracas 1010-AVenezuela Departamento de Bota´nica Instituto de Biologı´aUniversidad Nacional Auto´noma de Me´xicoApartado Postal 70-36704510 Ciudad De Me´xicoMexico Facultad de Ciencias Escuela Profesional de Biologı´aUniv

Following a large-scale phylogenetic study of the lichenized genus Cora(Basidiomycota:Agaricales:Hygrophoraceae),we formally describe 70 new species,honouring the seventieth birthday of David Leslie Hawksworth,one of the preeminent figures in mycology and lichenology in the past 50 *** on an updated phylogeny using the ITS fungal barcoding locus,we now recognize 189 taxa in a genus that until recently was considered to represent a single species;including this contribution,92 of these are formally recognized,including five taxa based on historical names or collections that have not been *** of Cora can be recognized by a combination of morphological(size,colour,lobe configuration,surface hairs,hymenophore size and shape),anatomical(thallus thickness,cortex structure,photobiont type,hyphal papillae),and ecogeographical features(substrate,habitat,distribution),and a keytable allowing the identification of all accepted taxa is *** new species are:Cora accipiter Moncada,Madrin˜a´n&Lücking ***.,*** Moncada,Soto-Medina&Lücking ***.,*** Moncada,Dal Forno&Lücking ***.,*** Dal Forno,Chaves&Lücking ***.,*** Moncada,***ı´guez&Lücking ***.,*** Lücking,Moncada&*** ***.,*** Moncada,Ya´nez-Ayabaca&Lücking ***.,*** Moncada,Patin˜o&Lücking ***.,*** Lücking,***&Dal Forno ***.,*** Holgado,Rivas Plata&Perlmutter ***.,*** Dal Forno,Eliasaro&Spielmann ***.,*** Nugra,Dal Forno&Lücking ***.,*** Lücking,Martins&Lucheta ***.,*** Moncada,R.-***´rez&Lücking ***.,*** Moncada,***.&Lücking ***.,*** Moncada,CabreraAmaya&Lücking ***.,*** Moncada,R.-***´rez&***.,*** Lücking,***&Dal Forno ***.,*** Moncada,***´rez-Corredor&Lücking ***.,*** Moncada,***&Lücking ***.,***

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