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Glutathione metabolism is essential for self-renewal and chemoresistance of pancreatic cancer stem cells

World Journal of Stem Cells 2020年第11期12卷 1410-1428页

作者： Petra Jagust sonia Alcala Bruno Sainz Jr Christopher Heeschen Patricia Sancho Molecular Pathology Programme Spanish National Cancer Research Centre(CNIO)Madrid 28029Spain Department of Biochemistry Autónoma University of MadridInstituto de Investigaciones Biomédicas"Alberto Sols"CSIC-UAMMadrid 28029Spain Center for Single-Cell Omics&Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai Jiao Tong University School of MedicineShanghai 200025China Hospital Universitario Miguel Servet IIS AragonZaragoza 50009Spain

BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing *** suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative *** glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS *** To investigate the role of glutathione metabolism in pancreatic *** Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in ***-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following *** TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver *** glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow *** inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched *** with propidium iodide(cell cycle),Annexin-V(apoptosis)and CD133(CSC content)were determined by flow ***-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for *** Analysis of our previously published RNAseq dataset E-MTAB-

关键词： Pancreatic cancer Cancer stem cells Glutathione Self-renewal Chemoresistance Redox

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To explore patients’ perceptions about motivators and barriers of adherence to highly active antiretroviral therapy among people living with HIV: A qualitative study

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Journal of Integrative Nursing 2023年第4期5卷 256-265页

作者： sonia GULATI Hariprasath PANDURANGAN Pulin Kumar GUPTA Department of Health and Allied Sciences Amity College of NursingAmity UniversityGurugramHaryanaIndia Department of Medicine Atal Bihari Vajpayee Institute of Medical Sciences and Dr.Ram Manohar Lohia HospitalNew DelhiIndia

Objective:For people living with HIV(PLHIV),strict adherence to highly active antiretroviral therapy(HAART)is the key to effective treatment and retention in human immunodeficiency virus(HIV)*** are many factors which promote or halt the antiretroviral therapy(ART)adherence ***,the present study aimed to examine the HAART adherence levels and to explore patients’views about barriers and facilitators to HIV treatment ***:Semi-structured interviews were conducted among 15 PLHIV at the ART clinic of *** Manohar Lohia Hospital,New *** were audio-recorded in the local Hindi language,and bilingual experts(English and Hindi)transcribed *** data were coded for themes and subthemes and analyzed using a phenomenological approach as per thematic content ***:Feeling of hopelessness,delayed ART initiation,difficult initial phase of ART,forget to take ART on time,fear of disclosure of HIV diagnosis,lack of privacy and negative social support,and impact of lockdown due to COVID-19 were revealed as significant barriers to ART *** the same time,commitment to raise and educate children,ART to increase life span,maintain oneself to be physically fit and healthy,only a single pill per day,very supportive counselors and health-care professionals,and hope to give birth to a healthy child were identified as facilitators of HIV ***:Understanding patient’s perception about ART adherence,its motivational and barrier factors which are directly affecting ART adherence and retention of PLHIV in HIV treatment and follow-ups are of utmost importance to improve ART adherence during HIV patient care services.

关键词： Adherence barriers highly active antiretroviral therapy human immunodeficiency virus motivators perceptions

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Surveillance and diagnosis of hepatocellular carcinoma: A systematic review

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World Journal of Clinical Cases 2019年第16期7卷 2269-2286页

作者： sonia Pascual Cayetano Miralles Juan M Bernabé Javier Irurzun Mariana Planells Liver Unit Hospital General Universitario de AlicanteAlicante 03010Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHDAlicante 03010Spain Radiology Department Hospital General Universitario de AlicanteAlicante 03010Spain

BACKGROUND Hepatocellular carcinoma (HCC) appears in most of cases in patients with advanced liver disease and is currently the primary cause of death in this *** of HCC has been proposed and recommended in clinical guidelines to obtain earlier diagnosis,but it is still controversial and is not accepted *** To review the actual evidence to support the surveillance programs in patients with cirrhosis as well as the diagnosis *** Systematic review of recent literature of surveillance (tools,interval,cost-benefit,target population) and the role of imaging diagnosis (radiological non-invasive diagnosis,optimal modality and agents) of *** The benefits of surveillance of HCC,mainly with ultrasonography,have been assessed in several prospective and retrospective analysis,although the percentage of patients diagnosed in surveillance programs is still *** of HCC permits diagnosis in early stages allows better access to curative treatment and increases life expectancy in patients with *** is a tumor with special radiological characteristics in computed tomography and magnetic resonance imaging,which allows highly accurate diagnosis without routine biopsy *** actual recommendation is to perform biopsy only in indeterminate *** The evidence supports the recommendation of performing surveillance of HCC in patients with cirrhosis susceptible of treatment,using ultrasonography every 6 *** diagnosis evaluation of HCC can be established based on noninvasive imaging criteria in patients with cirrhosis.

关键词： Surveillance Hepatocellular carcinoma Ultrasonography Cirrhosis Imaging diagnosis

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New advances in hepatocellular carcinoma

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World Journal of Hepatology 2016年第9期8卷 421-438页

作者： sonia Pascual Iván Herrera Javier Irurzun Liver Unit Gastroenterology Department Interventional Radiological Unit Hospital General Universitario de Alicante03010 AlicanteSpain

AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarke

关键词： DNA methylation Epigenetics Hepatitis B virus Hepatocellular carcinoma White blood cell DNA

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Adolescent mothers' experiences of the transition to motherhood: An integrative review

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International Journal of Nursing Sciences 2019年第2期6卷 221-228页

作者： Erfina Erfina Widyawati Widyawati Lisa McKenna sonia Reisenhofer Djauhar Ismail Doctoral Program Faculty of MedicineHealth Sciences and NursingGadjah Mada UniversityIndonesia Faculty of Nursing Hasanuddin UniversityIndonesia School of Nursing and Midwifery La Trobe UniversityAustralia School of Nursing Faculty of MedicineHealth Sciences and NursingGadjah Mada UniversityIndonesia Department of Child Health Faculty of MedicineHealth Sciences and NursingGadjah Mada UniversityIndonesia

A woman experiences heightened vulnerability and faces tremendous challenges when transitioning to *** is exacerbated for young mothers and studies have shown that adolescent mothers experience an increased burden of responsibility during the transition to *** research addressing the experiences of adolescent mothers has ***,the current literature on this topic is still *** aim of this study was to conduct an integrative review of the literature to explore adolescent mothers' experiences of transition to motherhood and identify associated *** literature was searched using electronic databases: Medline,Cumulative index to Nursing and Allied Health Literature (CINAHL),ProQuest,Scopus and *** articles published in English from February 2005 to 2018 were *** articles were included in the *** on this review,factors influencing a successful to transition to motherhood for adolescents included physical problems related to birth and breastfeeding,psychological well-being,ability to care for their baby,social support,education and economic strain and the provision of *** literature indicated a relationship between social supports and the development of positive maternal identity in the transition period for adolescent *** healthcare interventions for adolescent mothers during the transitional period should aim to provide social support and the increase ability of adolescent mothers to manage the physical and psychological challenges of young motherhood,and enhance new mothers' knowledge about caring for babies.

关键词： Adolescent Motherhood Role Social support

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Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

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World Journal of Gastroenterology 2008年第29期14卷 4694-4696页

作者： sonia Nemolato Daniela Fanni Antonio Giuseppe Naccarato Alberto Ravarino Generso Bevilacqua Gavino Faa Department of Cytomorphology Section of Pathology Univeristy of Cagliari Cagliari 09124 Italy Depart-ment of Oncology Section of Pathology University of Pisa56126 Pisa Italy

Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcino-mas. Here a rare case of lymphoepithelioma-like hepa-tocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonogra-phy revealed a liver nodule, 2.2 cm in diameter, local-ized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nod-ule was hypoechogenic. The patient underwent sur-gery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a promi-nent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic sup-pressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-edge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carci-noma. The association between the lack of EBV infec-tion, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.

关键词： Liver Hepatocellular carcinoma Tumorinfiltrating lymphocytes Primary liver tumors Liverlymphoepithelioma

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Progress towards reduced-crude protein diets for broiler chickens and sustainable chicken-meat production

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Journal of Animal Science and Biotechnology 2021年第3期12卷 828-840页

作者： sonia Yun Liu Shemil P.Macelline Peter V.Chrystal Peter H.Selle Poultry Research Foundation within The University of Sydney Camden Campus425 Werombi RoadCamdenNSW 2570Australia School of Life and Environmental Sciences The University of SydneyCamperdownNSW 2006Australia Baiada Poultry Pty Limited Pendle HillNSW 2145Australia Sydney School of Veterinary Science The University of SydneySydneyNSW 2006Australia

The prime purpose of this review is to explore the pathways whereby progress towards reduced-crude protein(CP)diets and sustainable chicken-meat production may be best ***-CP broiler diets have the potential to attenuate environmental pollution from nitrogen and ammonia emissions;moreover,they have the capacity to diminish the global chicken-meat industry’s dependence on soybean meal to tangible *** variable impacts of reduced-CP broiler diets on apparent amino acid digestibility coefficients are *** more accurate identification of amino acid requirements for broiler chickens offered reduced-CP diets is essential as this would diminish amino acid imbalances and the deamination of surplus amino *** of amino acids increases the synthesis and excretion of uric acid for which there is a requirement for glycine,this emphasises the value of so-called“non-essential”amino *** digestive dynamics and their possible impact of glucose on pancreatic secretions of insulin are discussed,although the functions of insulin in avian species require *** is probably a superior feed grain to wheat as the basis of reduced-CP diets;if so,the identification of the underlying reasons for this difference should be *** increases in starch concentrations and condensing dietary starch:protein ratios in reduced-CP diets may prove to be advantageous as expanding ratios appear to be aligned to inferior broiler *** is specifically examined because elevated free threonine plasma concentrations in birds offered reduced-CP diets may be indicative of compromised *** progress in these directions can be realised,then the prospects of reduced-CP diets contributing to sustainable chicken-meat production are promising.

关键词： Amino acids Broiler chickens Glucose Insulin Protein Starch Threonine

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Dose-Dependent AGO1-Mediated Inhibition of the miRNA165/166 Pathway Modulates Stem Cell Maintenance in Arabidopsis Shoot Apical Meristem

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Plant Communications 2020年第1期1卷 179-189页

作者： Fei Du Wen Gong sonia Bosca Matthew Tucker Herve Vaucheret Thomas Laux Signalling Research Centres BIOSS and CIBSS Faculty of BiologyUniversity of FreiburgSchanzlestrasse 179104 FreiburgGermany Institut Jean-Pierre Bourgin INRAAgroParisTechCNRSUniversite Paris-Saclay78000 VersaillesFrance Sino-German Joint Research Center on Agricultural Biology Shandong Agricultural UniversityTai’anShandongChina State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China School of Agriculture Food and WineUniversity of AdelaideWaite CampusUrrbraeSAAustralia

Pluripotent stem cells localized in proliferating growth centers, the meristems, are the origin of life-long organ formation and growth in higher plants. In the shoot apical meristem of Arabidopsis thaliana, the closelyrelated ARGONAUTE proteins AGO1 and ZLL/AGO10 bind miR165/166 species to regulate mRNAs of HDZIP III transcription factors that are essential to maintaining stem cells. Several genetic studies showed thatAGO1 and ZLL/AGO10 act redundantly to maintain stem cells. By contrast, the reported biochemical datasuggested antagonistic functions: AGO1 utilizes miR165/166 to slice HD-ZIP III mRNAs, whereas ZLL/AGO10 promotes degradation of miR165/166 and thus stabilizes HD-ZIP III mRNAs. How these differentfunctions are balanced in stem cell regulation has remained enigmatic. Here, we show that autorepressionof AGO1 through miR168-mediated slicing of its own RNA is required to maintain the ability of AGO1 to suppress HD-ZIP III mRNAs. Increased AGO1 expression, either in the miR168a-2 mutant or by transgenicexpression, inhibits this ability despite the presence of high levels of miR165/166, effectively uncouplingHD-ZIP III and miR165/166 expression. AGO1 activity can be restored, however, by increasing the levelsof chaperones SQN and HSP90, which promote assembly of RNA-induced silencing complex (RISC). Thissuggests that cellular abundance of SQN and HSP chaperones limits AGO1-mediated RNA interferencein shoot meristem stem cell regulation. Localized misexpression of AGO1 indicates that the cells surrounding the shoot meristem primordium play a crucial role in stem cell development. Taken together, our studyprovides a framework that reconciles biochemical and genetic data, showing that restriction of AGO1 levelsby miR168-mediated autorepression is key to RISC homeostasis and the function of AGO1 in stem cellregulation.

关键词： Arabidopsis ARGONAUTE1 ZWILLE(ARGONAUTE10) HD-ZIP III stem cell shoot meristem

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Neuromuscular fatigue and recovery profiles in individuals with intellectual disability

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Journal of Sport and Health Science 2019年第3期8卷 242-248页

作者： Rihab Borji Firas Zghal Nidhal Zarrouk Vincent Martin sonia Sahli Haithem Rebai Research Unit Education Motor Skills Sports and Health (EM2S UR15JS01) Higher Institute of Sport and Physical Education of SfaxUniversity of Sfax Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions Blaise Pascal University

Purpose: This study aimed to explore neuromuscular fatigue and recovery profiles im individuals with intellectual disability(ID) after exhausting submaximal ***: Ten men with ID were compared to 10 men without ID. The evaluation of neuromuscular function consisted in brief(3 s) isometric maximal voluntary contraction(IMVC) of the knee extension superimposed with electrical nerve stimulation before, immediately after, and during33 min after an exhausting submaximal isometric task at 15% of the IMVC. Force, voluntary activation level(VAL), potentiated twitch(Ptw), and electromyography(EMG) signals were measured during IMVC and then ***: Individuals with ID developed lower baseline IMVC, VAL, Ptw; and RMS/M_(max) ratio(root-mean-square value normalized to the maximal peak-to-peak amplitude of the M-wave) than controls(p < 0.05). Nevertheless, the time to task failure was significantly longer in ID vs. controls(p < 0.05). The 2 groups presented similar IMVC decline and recovery kinetics after the fatiguing exercise. However. individuals with ID presented higher VAL and RMS/M_(max) ratio declines but lower Ptw decline compared to those without ID. Moreover, individuals with ID demonstrated a persistent central fatigue but faster recovery from peripheral ***: These differences in neuromuscular fatigue profiles and recovery kinetics should be acknowledged when prescribing training programs for individuals with ID.

关键词： Central fatigue Intellectual disability Neuromuscular fatigue Peripheral fatigue Sustained sub-maximal exercise Twitch interpolation technique

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On the Base Point Locus of Surface Parametrizations:Formulas and Consequences

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Communications in Mathematics and Statistics 2022年第4期10卷 757-783页

作者： David A.Cox sonia Pérez-Díaz J.Rafael Sendra Department of Mathematics and Statistics Amherst CollegeAmherstMA 01002USA Universidad de Alcalá Dpto.de Física y Matemáticas28871 MadridSpain

This paper shows that the multiplicity of the base point locus of a projective rational surface parametrization can be expressed as the degree of the content of a univariate *** a consequence,we get a new proof of the degree formula relating the degree of the surface,the degree of the parametrization,the base point multiplicity and the degree of the rational map induced by the *** addition,we extend both formulas to the case of dominant rational maps of the projective plane and describe how the base point loci of a parametrization and its reparametrizations are *** an application of these results,we explore how the degree of a surface reparametrization is affected by the presence of base points.

关键词： Base point Hilbert-Samuel multiplicity Surface parametrization Reparametrization Parametrization degree Surface degree

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