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Iron homeostasis and H63D mutations in alcoholics with and without liver disease

World Journal of Gastroenterology 2009年第1期15卷 106-111页

作者： Mariana Verdelho Machado Paula Ravasco Alexandra Martins Maria Rosário Almeida Maria Ermelinda Camilo helena Cortez-Pinto Unidade de Nutrio e Metabolismo Instituto de Medicina Molecular Faculdade de Medicina da Universidade de Lisboa1649-035 Departamento de Gastrenterologia do Hospital de Santa Maria 1649-035 Lisboa Portugal Genomed Instituto de Medicina Molecular1649-035 Portugal

MM： To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease. METHODS： One hundred and fifty-three heavy drinkers （defined as alcohol consumption 〉 80 g/d for at least 5 years） were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics （LDA）] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics （NLDA）], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area. RESULTS： Gender ratio was similar in both study groups. LDA patients were older than NLDA patients （52 ± 10 years vs 48 ± 11 years, P = 0.03）. One third and one fifth of the study population had serum transferrin saturation （TS） greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS （51 ± 27 vs 36 ± 13, P 〈 0.001） and ferritin levels （559 ± 607 ng/mL vs 159 ± 122 ng/mL, P 〈 0.001）, and lower total iron binding capacity （TIBC）（241 ± 88 μg/dL vs 279 ± 40 μg/dL, P = 0.001）. The odds ratio for having liver disease with TS greater than 45% was 2.20 （95% confidence interval （CI）： 1.37-3.54）. There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients （0.25 vs 0.16, P = 0.03）. LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients （49.5% vs 31.6%, P = 0.02）. The odds ratio for LDA in patients with H63D mutation was 1.57 （95% CI： 1.02-2.40）. CONCLUSION： The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with liver disease,

关键词： Alcoholic liver disease Iron lIFE gene H63D Hemochromatosis

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Hormonal modulation of reproduction and fertility signaling in polistine wasps

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Current Zoology 2021年第5期67卷 519-530页

作者： Cintia Akemi OI Rafael Carvalho DA SILVA Ian STEVENS helena Mendes FERREIRA Fabio Santos NASCIMENTO Tom WENSELEERS Laboratory of Socioecology and Social Evolution KU LeuvenLeuven 3000Belgium Faculdade de Filosofia Ciencias e Letras de Ribeirao PretoDepartamento de BiologiaUniversidade de Sao Paulo—USPRibeirao PretoSP 14040-901Brazil

In social insects,it has been suggested that reproduction and the production of particular fertilitylinked cuticular hydrocarbons(CHC)may be under shared juvenile hormone(JH)control,and this could have been key in predisposing such cues to later evolve into full-fledged queen pheromone ***,to date,only few studies have experimentally tested this“hormonal pleiotropy”***,we formally test this hypothesis using data from four species of Polistine wasps,Polistes dominula,Polistes satan,Mischocyttarus metathoracicus,and Mischocyttarus cassununga,and experimental treatments with JH using the JH analogue methoprene and the anti-JH *** line with reproduction being under JH control,our results show that across these four species,precocene significantly decreased ovary development when compared with both the acetone solvent-only control and the methoprene *** with the hormonal pleiotropy hypothesis,these effects on reproduction were further matched by subtle shifts in the CHC profiles,with univariate analyses showing that in *** and *** the abundance of particular linear alkanes and mono-methylated alkanes were affected by ovary development and our hormonal *** results indicate that in primitively eusocial wasps,and particularly in Polistes,reproduction and the production of some CHC cues are under joint JH *** suggest that pleiotropic links between reproduction and the production of such hydrocarbon cues have been key enablers for the origin of true fertility and queen signals in more derived,advanced eusocial insects.

关键词： Polistinae wasps fertility cues queen pheromones cuticular hydrocarbons juvenile hormone

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Biologging is suspect to cause corneal opacity in two populations of wild living Northern Bald Ibises (Geronticus eremita)

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Avian Research 2020年第4期11卷 412-420页

作者： Johannes Fritz Barbara Eberhard Corinna Esterer Bernhard Goenner Daniela Trobe Markus Unsoeld Bernhard Voelkl helena Wehner Alexandra Scope Waldrappteam LIFE Northern Bald Ibis6162 MuttersAustria Department of Behavioural and Cognitive Biology University of ViennaViennaAustria Veterinary University Vienna ViennaAustria University of Bern Vetsuisse FacultyBernSwitzerland Bavarian State Collection of Zoology MunichGermany

Background:In this paper,we present evidence that biologging is strongly correlated with eye irritation,with sometimes severely impairing effects.A migratory population of the Northern Bald Ibis(Geronticus eremita,NBI)is reintroduced in Europe,in course of a LIFE+*** 2014,all individuals have been equipped with *** monitoring allows the implementation of focussed measures against major mortality ***:Initially all birds carried battery-powered devices,fixed on the lower back of the *** 2016 an increasing amount of birds has been equipped with solar-powered devices,fixed on the upper back,the more sunexposed *** 2016,we observed opacity in the cornea of one eye(unilateral corneal opacity;UCO)during a regular health monitoring for the first ***:By 2018,a total of 25 birds were affected by UCO,with varying intensity up to *** examination of the birds revealed no clear cause for the ***,only birds carrying a device on the upper back were affected(2017 up to 70%of this group).In contrast,none of the birds carrying devices on the lower back ever showed UCO *** unexpected relationship between tagging and UCO was discovered in *** we took countermeasures by removing the device or repositioning it on the lower back,we observed an immediate reduction of the incidence rate without any new cases reported since January *** roost with their head on the back,one eye closely placed to the device if it was positioned on the upper ***,we conclude that the most parsimonious explanation for the symptomatology is either a repetitive slight temperature rise in the corneal tissue due to electromagnetic radiation by the GSM module of the device or a repetitive slight mechanical irritation of the corneal *** evidence is missing so ***,cases of UCO were found in another NBI ***:Our observations indicate that further research in the fast-

关键词： Blindness Electromagnetic radiation Endangered bird species Eye opacity GPS-devices Mechanical irritation Reintroduction Solar-powered

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Ultraviolet light exposure and its penetrance through the eye in a porcine model

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International Journal of Ophthalmology(English edition) 2023年第2期16卷 172-177页

作者： Hideki Fukuoka helena E.Gali Jennifer J.Bu Ruti Sella Natalie A.Afshari Shiley Eye Institute Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCA 92093USA

AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact ***:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye *** light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye *** the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the ***,UVprotective contact lenses were placed over the structures,and UV light penetrance was *** of UV light exposure were taken outdoors at various locations and ***:Cornea absorbed 63.56%of UV light that reached the *** and lens absorbed 99.34%of UV *** eye absorbed 99.77%of UV *** UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,*** light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a ***:Cornea absorbs the majority of UV light that reaches the eye in this ***-protective contact lenses reduce UV exposure to the *** with high albedo expose the eye to higher levels of UV light.

关键词： ultraviolet light penetrance contact lens cornea lens

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Tumors due to chronic exposure to benzene and biomarkers of exposure

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 412-421页

作者： Gilda Alves Rodolfo AcatauassúNunes Karina Melo Maria helena Faria Ornellas Circulating Biomarkers Laboratory Pathology DepartmentMedical Sciences FacultyState University of Rio de Janeiro(UERJ)Rio de Janeiro 20550-170Brazil General Surgery Department State University of Rio de Janeiro(UERJ)Rio de Janeiro 20551-030Brazil Hemotherapy and Hematology Service State University of Rio de Janeiro(UERJ)Rio de Janeiro 20551-030Brazil

Due to occupational activities,many people are exposed to carcinogenic airborne pollutants,such as ***,benzene is also present in cigarette *** main cancers associated with benzene,toluene,ethylbenzene,and xylenes(BTEX)are lung cancer and malignancies of the *** initial stages,lung cancer is often asymptomatic,but progression into metastasis is a huge clinical *** performed a review on possible biomarkers for monitoring increased genome instability and downregulation of the immune system in connection with overexposure to BTEX in a subgroup of workers being exposed to BTEX at Brazilian gas *** workers are subject to routine blood exams every semester;however,early genomic assessment is not *** evaluated available tests to be applied,including measuring benzene-derived metabolites in urine,determination of oxidative and inflammatory markers in blood,immunophenotypical profiling,micronucleus test,comet(single-cell gel electrophoresis)assay,(molecular)cytogenetics,chromosomal microarray,epigenetic-changes oriented tests,determination of mitochondrial(mt)DNA copy numbers,and studies on ***,no consensus was reached about their application and which test combination might be suited best.

关键词： Benzene BTEX lung cancer blood biomarker

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From regenerative strategies to pharmacological approaches:can we fine-tune treatment for Parkinson's disease?

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Neural Regeneration Research 2022年第5期17卷 933-936页

作者： Rita Caridade Silva helena Sofia Domingues António J.Salgado Fábio G.Teixeira Life and Health Sciences Research Institute(ICVS) School of MedicineUniversity of MinhoBragaPortugal ICVS/3B’s Associate Lab PT Government Associated LabBraga/GuimarãesPortugal

Parkinson's disease is the second most prevalent neurodegenerative disorder ***,it is characterized by severe motor complications caused by progressive degeneration of dopaminergic *** treatment is focused on mitigating the symptoms through the administration of levodopa,rather than on preventing dopaminergic neuronal ***,the use and development of neuroprotective/disease-modifying strategies is an absolute need that can lead to promising gains on translational research of Parkinson's *** instance,N-acetylcysteine,a natural compound with strong antioxidant effects,has been shown to modulate oxidative stress,preventing dopamine-induced cell *** the evidence of neuroprotective and modulatory effects of this drug,as far as we know,it does not induce per se any regenerative ***,it would be of interest to combine the latter with innovative therapies that induce dopaminergic neurons repair or even differentiation,as stem cell-based *** cells secretome has been proposed as a promising therapeutic approach for Parkinson's disease,given its ability to modulate cell viability/preservation of dopaminergic *** approach represents a shift in the paradigm,showing that cell-transplantation free therapies based on the use of stem cells secretome may represent a potential alternative for regenerative medicine of Parkinson's ***,in this review,we address the current understanding of the potential combination of stem cell free-based strategies and neuroprotective/disease-modifying strategies as a new paradigm for the treatment of central nervous system neurodegenerative diseases,like Parkinson's disease.

关键词： disease-modifying strategies mesenchymal stem cells N-acetylcysteine neuroprotection Parkinson's disease stem cells secretome

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Low-grade mucinous appendiceal neoplasm mimicking an ovarian lesion: A case report and review of literature

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World Journal of Clinical Cases 2021年第10期9卷 2334-2343页

作者： André Luís Borges Catarina Reis-de-Carvalho Martinha Chorão helena Pereira Dusan Djokovic Department of Obstetrics and Gynecology Hospital de São Francisco Xavier-Centro Hospitalar Lisboa OcidentalLisbon 1449-005Portugal Faculdade de Ciências da Saúde Universidade da Beira InteriorCovilhã6201-001Portugal Department of Obstetrics Gynecology and Reproductive MedicineHospital de Santa Maria-Centro Hospitalar Universitário Lisboa NorteLisbon 1649-028Portugal Department of Pathology Hospital Egas MonizCentro Hospitalar Lisboa OcidentalLisbon 1349-019Portugal Department of Obstetrics and Gynecology Maternidade Dr.Alfredo da Costa-Centro Hospitalar Universitário de Lisboa CentralLisbon 2890-495Portugal Faculdade de Ciências Médicas Nova Medical SchoolLisbon 1169-056Portugal

BACKGROUND Appendiceal tumors are rare lesions that may not be easily differentiated from primary ovarian lesions preoperatively,despite the use of advanced diagnostic methods by experienced *** SUMMARY A 59-year-old G2P2 woman,with chronic pelvic pain,underwent a pelvic ultrasound that revealed an adnexal mass measuring 58 mm×34 mm×36 mm,with irregular borders,heterogeneous echogenicity,no color Doppler vascularization and without acoustic *** ovarian tissue was visualized in contact with the lesion,and it was impossible to separate the lesion from the ovary by applying pressure with the ultrasound ***,peritoneal metastases or other alterations were not *** the international ovarian tumor analysis ADNEX model,the lesion was classified as a malignant tumor(the risk of malignancy was 27.1%,corresponding to Ovarian-Adnexal Reporting Data System category 4).Magnetic resonance imaging confirmed the presence of a right adnexal mass,apparently an ovarian tumor measuring 65 mm×35 mm,without signs of invasive or metastatic *** explorative laparotomy,normal morphology of the internal reproductive organs was noted.A solid mobile lesion involved the entire *** was *** of the abdominal cavity revealed no signs of malignant ***,the appendiceal lesion corresponded to a completely resected low-grade mucinous appendiceal neoplasm(LAMN).CONCLUSION The appropriate treatment and team of specialists who should provide health care to patients with seemingly adnexal lesions depend on the nature(benign vs malignant)and origin(gynecological vs nongynecological)of the ***,gynecologists and other pelvic surgeons should be familiar with the imaging signs of LAMN whose clinical presentation is silent or *** assistance of a consultant specializing in intestinal tumors is important support that gynecological surgeons can receive during the operation

关键词： Adnexal mass Appendiceal neoplasm Diagnostic imaging Pelvic neoplasm Adnexal diseases Pelvic neoplasm Case report

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Degradation of duloxetine: Identification of transformation products by UHPLC-ESI(+)-HRMS/MS,in silico toxicity and wastewater analysis

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Journal of Environmental Sciences 2019年第8期31卷 113-123页

作者： Rodrigo A.Osawa Ana P.Carvalho Olinda C.Monteiro M.Conceicao Oliveira M.helena Florêncio Centro de Química e Bioquímica Faculdade de Ciências Universidade de Lisboa Laboratório de FTICR e Espectrometria de Massa Estrutural Faculdade de Ciências Universidade de Lisboa Centro de Química Estrutural Instituto Superior Técnico Universidade de Lisboa

Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.

关键词： High resolution mass spectrometry Duloxetine Degradation processes Transformation products Wastewater analysis In silico toxicity

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Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

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World Journal of Hepatology 2016年第22期8卷 924-932页

作者： Katriina Nemes Fredrik Aberg helena Gylling helena Isoniemi University of Helsinki and Helsinki University Central Hospital Trans-plantation and Liver Surgery ClinicMeilahti Hospital University of Helsinki and Helsinki University Central Hospital Internal MedicineBiomedicum Helsinki C 422

The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

关键词： Cholesterol metabolism Cholestasis Liver transplantation Non-cholesterol sterols Cholestanol Donor Low density lipoprotein receptor mutation Apolipoprotein B-100 Lipoprotein-X

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The ULT1 and ULT2 trxG Genes Play Overlapping Roles in Arabidopsis Development and Gene Regulation

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Molecular Plant 2013年第5期6卷 1564-1579页

作者： Mona M. Monfared Cristel C. Caries Pascale Rossignol helena R. Pires Jennifer C. Fletcher Plant Gene Expression Center USDA-ARS/UC Berkeley 800 Buchanan Street. Albany CA 94710 USA Department of Plant and Microbial Biology University of California Berkeley 111 Koshland Hall Berkeley CA 94720 USA CNRS UMR5168 F-38054 Grenoble France Universite Grenoble Alpes UMR5168 F-38041 Grenoble France CEA iRTSV Laboratoire Physiologie Cellulaire et Vegetale F-38054 Grenoble France INRA F-38054 Grenoble France Department of Molecular Cellular and Developmental Biology Yale University New Haven CT 06520 USA Faculdade de Ciencias da Universidade do Porto Porto Portugal

The epigenetic regulation of gene expression is critical for ensuring the proper deployment and stability of defined genome transcription programs at specific developmental stages. The cellular memory of stable gene expression states during animal and plant development is mediated by the opposing activities of Polycomb group （PcG） factors and trithorax group （trxG） factors. Yet, despite their importance, only a few trxG factors have been characterized in plants and their rotes in regulating plant development are poorly defined. In this work, we report that the closely related Arabidopsis trxG genes ULTRAPETALA1 （ULT1） and ULT2 have overlapping functions in regulating shoot and floral stem cell accumula- tion, with ULT1 playing a major role but ULT2 also making a minor contribution. The two genes also have a novel, redun- dant activity in establishing the apical-basal polarity axis of the gynoecium, indicating that they function in differentiating tissues. Like ULT1 proteins, ULT2 proteins have a dual nuclear and cytoplasmic localization, and the two proteins physically associate in planta. Finally, we demonstrate that ULT1 and ULT2 have very similar overexpression phenotypes and regulate a common set of key development target genes, including floral MADS-box genes and class I KNOX genes. Our results reveal that chromatin remodeling mediated by the ULT1 and ULT2 proteins is necessary to control the development of mer- istems and reproductive organs. They also suggest that, like their animal counterparts, plant trxG proteins may function in multi-protein complexes to up-regulate the expression of key stage- and tissue-specific developmental regulatory genes.

关键词： trxG factor epigenetics stem cells Arabidopsis polarity ULTRAPETALA.

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