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Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

World Journal of Gastroenterology 2016年第44期22卷 9744-9751页

作者： ángel Hernández-Bartolomé Rosario López-Rodríguez María Jesús Borque Leticia González-Moreno Yolanda Real-Martínez Luisa García-Buey Ricardo Moreno-Otero paloma sanz-cameno Gastroenterology Service Instituto Investigación Sanitaria Princesa Molecular Biology Unit Instituto Investigación Sanitaria Princesa CIBERehd

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system.Groups were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.

关键词： Chronic hepatitis C Area under the curve of receiver operator characteristics Liver fibrosis Cirrhosis Angiopoietin-2 Angiopoietin-1 Biomarker Angiogenesis

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Dysregulated microRNAs in type 2 diabetes and breast cancer:Potential associated molecular mechanisms

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World Journal of Diabetes 2024年第6期15卷 1187-1198页

作者： Alex Cleber Improta-Caria Filipe Ferrari João Lucas Penteado Gomes paloma Brasilio Villalta Úrsula Paula RenóSoci Ricardo Stein Edilamar M Oliveira Laboratory of Biochemistry and Molecular Biology of the Exercise Physical Education and Sport SchoolUniversity of São PauloSão Paulo 05508-030Brazil Graduate Program in Cardiology and Cardiovascular Sciences Federal University of Rio Grande do SulHospital de Clínicas de Porto AlegrePorto Alegre 90035003Brazil Laboratory of Metabolic Disorders(Labdime) School of Applied SciencesUniversity of Campinas-UNICAMPCampinas 13484-350Brazil Departments of Internal Medicine Molecular Pharmacology and PhysiologyCenter for Regenerative MedicineUSF Health Heart InstituteMorsani College of MedicineUniversity of South FloridaTampaFL 33602United States

Type 2 diabetes(T2D)is a multifaceted and heterogeneous syndrome associated with complications such as hypertension,coronary artery disease,and notably,breast cancer(BC).The connection between T2D and BC is established through processes that involve insulin resistance,inflammation and other factors.Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC,especially through microRNAs(miRNAs),remain elusive.miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes.However,the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated.This review aims to identify dysregulated miRNAs in both T2D and BC,exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

关键词： Type 2 diabetes Breast cancer MicroRNAs Molecular mechanisms

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星星西班牙丝绸亭

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室内设计与装修 2024年第1期 138-139页

作者： [捷克]paloma Ca'izares Office coco(编译) Josema Cutillas(摄影) Asier Rua(摄影) paloma Ca?izares Office

丝绸亭是paloma Ca'izares Office对编织物进行研究的初步成果,旨在深入挖掘硬质织物的结构潜力。项目于2023年春在洛格罗尼奥(西班牙)国际建筑与设计节(Concentrico)期间展出,地点包括位于洛格罗尼奥的拉里奥哈官方建筑学院和马德里城... 详细信息

丝绸亭是paloma Ca'izares Office对编织物进行研究的初步成果,旨在深入挖掘硬质织物的结构潜力。项目于2023年春在洛格罗尼奥(西班牙)国际建筑与设计节(Concentrico)期间展出,地点包括位于洛格罗尼奥的拉里奥哈官方建筑学院和马德里城市议程部。

关键词：编织物丝绸西班牙马德里初步成果

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Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

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World Journal of Gastroenterology 2017年第20期23卷 3572-3580页

作者： paloma Martín-sanz Marta Casado Lisardo Boscá Department of Metabolism and Cell Signaling Institute of Biomedical Research Alberto Sols Biomedical Network Center for the Study of Hepatic and Digestive Disease and Cardiovascular Diseases Metabolic Experimental Pathology Unit Biomedical Institute of ValenciaJaume Roig 11

The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically.Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.

关键词： Cyclooxygenase-2 NAS 前列腺素非酒精的 steatohepatitis Hepatocellular 癌

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COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?

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World Journal of Gastroenterology 2010年第12期16卷 1430-1435页

作者： paloma Martín-sanz Rafael Mayoral Marta Casado Lisardo Boscá Biomedical Network Center for the Study of Hepatic and Digestive Diseases(CIBERehd) Department of Metabolism and Cell Signaling Institute of Biomedical Research "Alberto Sols"(CSIC-UAM) Department of Pathology and Molecular and Cellular Therapy Institute of Biomedicine of Valencia(IBV-CSIC)

The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function.However,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene function.Here we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the hepatocyte.Upon challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the injury.In addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.

关键词： Cyclooxygenase 2 Prostaglandins Liver diseases Apoptosis Inflammation Animal models

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PANoptosis:new insights in regulated cell death in ischemia/reperfusion models

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Neural Regeneration Research 2023年第2期18卷 342-343页

作者： paloma González-Rodríguez Arsenio Fernández-López Área de Biología Celular Instituto de BiomedicinaUniversidad de LeónSpain

See related article,pp 357-363The first study describing the cell death and destruction of tissues,organs,and organ systems as programmed events during the development of multicellular organisms was performed by JW Saunders Jr in 1966.The term apoptosis was introduced by Kerr,Wyllie,and Currie in 1972 to describe a programmed phenomenon opposite to mitosis in the regulation of animal cell populations.Later,a description of ectodermal cell lineages as programmed cell death in the worm Caenorhabditis elegans was publishedby JE Sulston and HR Horvitz in 1976.

关键词： organs insight opposite

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Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

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World Journal of Gastroenterology 2018年第48期24卷 5454-5461页

作者： Rafael I Jaén Patricia Prieto Marta Casado paloma Martín-sanz Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Department of Biomedicine Instituto de Biomedicina de Valencia (CSIC) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares y Hepáticas y DigestivasISCⅢ Unidad Asociada IIBMULPGC Universidad de las Palmas de Gran Canaria (ULPGC)

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

关键词： Prostaglandins Prostaglandin-endoperoxide synthase 2 Post-translational modifications Glycosylation Colorectal cancer Inflammation

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Short and long term corneal biomechanical analysis after overnight orthokeratology

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International Journal of Ophthalmology(English edition) 2022年第7期15卷 1128-1134页

作者： Amelia Nieto-Bona paloma Porras-Ángel Adela Elena Ayllón-Gordillo Gonzalo Carracedo David P Piñero Department of Optometry&Vision Optics and Optometry FacultyComplutense University of MadridMadrid 28037Spain Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicante 03690Spain

AIM: To investigate the short and long term corneal biomechanical changes after overnight orthokeratology(OK) and compare them with those occurring in subjects not wearing contact lenses.METHODS: Retrospective case control study enrolling 54 subjects that were divided into three groups 18 subjects each: control group(CG), short term(15 nights) OK(STOK) group, and long term(more than 1 y of OK wear) OK(LTOK) group. Corneal biomechanics were characterized using the Cor Vis? ST system(Oculus), recording parameters such as time [first/second applanation time(AT1, AT2)], speed [velocity of corneal apex at the first/second applanation time(AV1, AV2)], and amplitude of deformation(AD1, AD2) in the first and second corneal flattening, corneal stiffness(SPA1), biomechanically corrected intraocular pressure(b IOP) and corneal(CBI) and tomographic biomechanical indices(TBI).RESULTS: Significantly lower AD1 and standard deviate on of Ambrosio’s relational average thickness related to the horizontal profile(ARTh) values were found in the OK groups compared to CG(P<0.05). Likewise, significantly higher values of CBI were found in STOK and LTOK groups compared to CG(P<0.01). No significant differences between groups were found in integrated radius index(P=0.24), strain stress index(P=0.22), tomographic biomechanical index(P=0.91) and corneal stif fness parameter(SPA1, P=0.97). Significant inverse correlations were found between corneal thickness and CBI in STOK(r=-0.90, P<0.01) and LTOK groups(r=-0.71, P<0.01).CONCLUSION: OK does not seem to alter significantly the corneal biomechanical properties, but special care should be taken when analyzing biomechanical parameters influenced by corneal thickness such as amplitude of deformation, ARTh or CBI, because they change significantly after treatment but mainly due to the reduction and pachymetric progression induced by the corneal molding secondary to OK treatment.

关键词： overnight orthokeratology corneal biomechanics pachymetry corneal biomechanical index CorVis?ST tomographic biomechanical index

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Development of a modified predicted heat strain model for hot work environments

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International Journal of Mining Science and Technology 2020年第4期30卷 477-481页

作者： paloma Lazaro Moe Momayez Department of Mining and Geological Engineering The University of ArizonaTucsonAZ 85750USA

Excessive exposure to heat can lead to injuries,illness,and death among mineworkers.The actual cost of heat-related injuries and illnesses is unknown because of underreporting and lack of symptom recognition.Multi-factorial,evidence-based,and field-ready guidelines for identifying–and predicting–physiolo gical markers of heat strain are currently unavailable.The predicted heat strain(PHS)model,is the latest attempt by mining companies to aid in the evaluation and management of occupational heat exposures.The adopted algorithm relies on worksite environmental measurements and an estimate of individual metabolic rate for mine workers to provide an estimate of the workers’core temperature during a work shift.There are several known limitations of the PHS model,including the assumption that the subject worker is hydrated and fit.A modified PHS model was presented based on eight physical parameters that are measured at different intervals during a work shift;these parameters are air temperature,relative humidity,air velocity,radiation,metabolic rate,acclimatization,clothing insulation and posture.To validate the results,the predictions from the modified PHS model were compared with direct physiological measurements obtained from ingestible pills and heat stress monitors under different environmental and working conditions.

关键词： Predicted heat strain Hot underground mines Heat strain Heat stress

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Newly Described Components and Regulatory Mechanisms of Circadian Clock Function in Arabidopsis thaliana

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Molecular Plant 2012年第3期5卷 545-553页

作者： Manuel Adrian Troncoso-Ponce and paloma Mas Center for Research in Agricultural Genomics （CRAG） Parc de Recerca UAB Edifici CRAG Barcelona 08193 Spain

The circadian clock temporally coordinates plant growth and metabolism in close synchronization with the diurnal and seasonal environmental changes. Research over the last decade has identified a number of clock components and a variety of regulatory mechanisms responsible for the rhythmic oscillations in metabolic and physiological activities. At the core of the clock, transcriptional/translational feedback loops modulate the expression of a significant proportion of the genome. In this article, we briefly describe some of the very recent advances that have improved our understanding of clock organization and function in Arabidopsis thaliana. The new studies illustrate the role of clock protein complex for- mation on circadian gating of plant growth and identify alternative splicing as a new regulatory mechanism for clock function. Examination of key clock properties such as temperature compensation has also opened new avenues for func- tional research within the plant clockwork. The emerging connections between the circadian clock and metabolism, hor- mone signaling and response to biotic and abiotic stress also add new layers of complexity to the clock network and underscore the significance of the circadian clock regulating the daily life of plants.

关键词： circadian clock circadian rhythms Arabidopsis thaliana feedback loops.

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