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201. A Snapshot of the Most Recent Transthyretin Stabilizers.

Author

Marotta, Carlo, Ciccone, Lidia, Orlandini, Elisabetta, Rossello, Armando, and Nencetti, Susanna

Subjects
TRANSTHYRETIN, SYMPTOMS, RESEARCH personnel, CLINICAL trials, AMYLOIDOSIS
Abstract

In recent years, several strategies have been developed for the treatment of transthyretin-related amyloidosis, whose complex clinical manifestations involve cardiomyopathy and polyneuropathy. In view of this, transthyretin stabilizers represent a major cornerstone in treatment thanks to the introduction of tafamidis into therapy and the entry of acoramidis into clinical trials. However, the clinical treatment of transthyretin-related amyloidosis still presents several challenges, urging the development of new and improved therapeutics. Bearing this in mind, in this paper, the most promising among the recently published transthyretin stabilizers were reviewed. Their activity was described to provide some insights into their clinical potential, and crystallographic data were provided to explain their modes of action. Finally, structure–activity relationship studies were performed to give some guidance to future researchers aiming to synthesize new transthyretin stabilizers. Interestingly, some new details emerged with respect to the previously known general rules that guided the design of new compounds. [ABSTRACT FROM AUTHOR]

Published
2024
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202. Imagining ecopolis: Visions of ecofeminist political theology and ecocriticism in Latin America.

Author

ORREGO TORRES, Ely and ROSSELLO, Diego

Subjects
*POLITICAL theology, *POLITICAL community, *ECOCRITICISM, *CONSTITUTIONALISM, *THEOLOGY, *ECOFEMINISM, *FEMINIST theology
Abstract

Although often overlooked by mainstream accounts of political theology and ecocriticism in the Global North, powerful visions of an ecopolis have been emerging in Latin America. In this article, we review the status of mainstream approaches to notions such as subject, citizen, and personal dignity and put them in a critical dialogue with Latin American Ecofeminist Political Theologies (LAEPT). We argue that those notions, often conceived from a Western and anthropocentric perspective, show their limits when interrogated from the perspective of LAEPT. Accordingly, we suggest that their main contribution lies not only in their critique of the Western paradigm but also in advancing alternative conceptions of an ecologically conscious political community that considers the Earth as sacred, and nature as a reflection of the divine. We conclude that such conceptions can also be seen at work in the rights of nature enshrined in the so-called new Latin American Constitutionalism. [ABSTRACT FROM AUTHOR]

Published
2024
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203. A New Wound-Healing Tool Based on Glycyrrhiza glabra Extract-Loaded Ufasomes on Spanish Broom Dressings.

Author

Rossello, Simone, Mandrone, Manuela, Cerchiara, Teresa, Chiocchio, Ilaria, Rossi, Martina, Chinnici, Fabio, Sallustio, Valentina, Aponte, Maria, Blaiotta, Giuseppe, Luppi, Barbara, Abruzzo, Angela, Bigucci, Federica, and Cappadone, Concettina

Subjects
*LICORICE (Plant), *WOUND healing, *BIOACTIVE compounds, *HEALING, *FIBROBLASTS
Abstract

The development of innovative products for restoring skin integrity and promoting wound healing is still a challenge. The aim of this work was to evaluate an innovative Spanish broom wound dressing impregnated with Glycyrrhiza glabra extract-loaded ufasomes to improve wound healing. Ufasomes were characterized in terms of size, polydispersity index, entrapment efficiency, zeta potential, and stability. In addition, in vitro release studies and biocompatibility, biosafety, and scratch tests on WS1 fibroblasts were performed. The loaded ufasomes showed a nanometric size (<250 nm), good size distribution (lower than 0.3), and appropriate encapsulation efficiency (~67%). Moreover, the lipid vesicles showed good stability during the storage period and allowed for a slow release of glycyrrhizin, the main bioactive compound of the extract. Biological studies revealed that loaded vesicles are not cytotoxic, are hemocompatible, and lead to the complete closure of the scratch after about 33 h. To conclude, the results suggest that the developed dressings can be efficiently used to promote the healing process. [ABSTRACT FROM AUTHOR]

Published
2024
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204. Incremental value of C‐reactive protein to the MEESSI acute heart failure risk score.

Author

Wussler, Desiree, Belkin, Maria, Shrestha, Samyut, Wernicke, Hannah, Papachristou, Androniki, Nowak, Albina, Aliyeva, Fatima, Mork, Constantin, Strebel, Ivo, Huré, Gabrielle Valerie Francoi, Weil, Dominic, Michou, Eleni, Kozhuharov, Nikola, Gualandro, Danielle M., Puelacher, Christian, Miró, Oscar, Rossello, Xavier, Martín‐Sánchez, Francisco Javier, Pocock, Stuart J., and Goudev, Assen

Subjects
DISEASE risk factors, HEART failure patients, HEART failure, HOSPITAL emergency services, LOGISTIC regression analysis
Abstract

Aims: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI‐AHF) risk score, can be further improved by adding systemic inflammation as quantified by C‐reactive protein (CRP). Methods and results: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI‐AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30‐day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single‐centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30‐day mortality of the extended MEESSI model (c‐statistic 0.83, 95% confidence interval [CI] 0.79–0.87) was significantly higher compared to the recalibrated model (c‐statistic 0.79, 95% CI 0.75–0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81–1.19) and an intercept of 0.0 (95% CI −0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). Conclusions: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model. [ABSTRACT FROM AUTHOR]

Published
2024
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207. Enhancing energy harvesting by coupling monostable oscillators

Author

Rossello, J. I. Pena, Wio, H. S., Deza, R. R., and Hanggi, P.

Subjects
Nonlinear Sciences - Pattern Formation and Solitons, Condensed Matter - Statistical Mechanics, Physics - Computational Physics, 82C31
Abstract

The performance of a ring of linearly coupled, monostable nonlinear oscillators is optimized towards its goal of acting as energy harvester---through piezoelectric transduction---of mesoscopic fluctuations, which are modeled as Ornstein--Uhlenbeck noises. For a single oscillator, the maximum output voltage and overall efficiency are attained for a soft piecewise-linear potential (providing a weak attractive constant force) but they are still fairly large for a harmonic potential. When several harmonic springs are linearly and bidirectionally coupled to form a ring, it is found that counter-phase coupling can largely improve the performance while in-phase coupling worsens it. Moreover, it turns out that few (two or three) coupled units perform better than more., Comment: Accepted in EPJB, 5 pages

Published
2016
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208. New Hybrid Compounds Incorporating Natural Products as Multifunctional Agents against Alzheimer’s Disease

Author

Lidia Ciccone, Caterina Camodeca, Nicolò Tonali, Lucia Barlettani, Armando Rossello, Carole Fruchart Gaillard, Julia Kaffy, Giovanni Petrarolo, Concettina La Motta, Susanna Nencetti, and Elisabetta Orlandini

Subjects
neuroprotection, amyloid β (Aβ), chelating agents, antioxidant, Transthyretin, TTR, Pharmacy and materia medica, RS1-441
Abstract

A series of new hybrid derivatives 1a–c, 2a–c, 3a–c, 4a–c, 5a–c, inspired by nature, were synthesized and studied as multifunctional agents for the treatment of Alzheimer’s disease (AD). These compounds were designed to merge together the trifluoromethyl benzyloxyaminic bioactive moiety, previously identified, with different acids available in nature. The ability of the synthesized compounds to chelate biometals, such as Cu2+, Zn2+ and Fe2+, was studied by UV–Vis spectrometer, and through a preliminary screening their antioxidant activity was evaluated by DPPH. Then, selected compounds were tested by in vitro ABTS free radical method and ex vivo rat brain TBARS assay. Compounds 2a–c, combining the strongest antioxidant and biometal chelators activities, were studied for their ability to contrast Aβ1-40 fibrillization process. Finally, starting from the promising profile obtained for compound 2a, we evaluated if it could be able to induce a positive cross-interaction between transthyretin (TTR) and Aβ in presence and in absence of Cu2+.

Published
2023
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214. Breaking constraint of mammalian axial formulae

Author

Gabriel M. Hauswirth, Victoria C. Garside, Lisa S. F. Wong, Heidi Bildsoe, Jan Manent, Yi-Cheng Chang, Christian M. Nefzger, Jaber Firas, Joseph Chen, Fernando J. Rossello, Jose M. Polo, and Edwina McGlinn

Subjects
Science
Abstract

Vertebral column length and shape exhibits remarkable robustness within a species but diversity across species. Here the authors reveal the molecular logic constraining vertebral number in mouse and a novel role for posterior Hox genes in this context.

Published
2022
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221. Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged low-risk adults

Author

Fernández-Friera, Leticia, primary, García-Alvarez, Ana, additional, Oliva, Belen, additional, García-Lunar, Inés, additional, García, Iris, additional, Moreno-Arciniegas, Andrea, additional, Gómez-Talavera, Sandra, additional, Pérez-Herreras, Cristina, additional, Sánchez-González, Javier, additional, de Vega, Vicente Martinez, additional, Rossello, Xavier, additional, Bueno, Héctor, additional, Fernández-Ortiz, Antonio, additional, Ibañez, Borja, additional, Sanz, Javier, additional, and Fuster, Valentín, additional

Published
2024
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223. Multiple Carrier-Vehicle Travelling Salesman Problem

Author

Fahradyan, Tigran, Bono Rossello, Nicolas, Garone, Emanuele, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Mazal, Jan, editor, Fagiolini, Adriano, editor, and Vasik, Petr, editor

Published
2020
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228. Care and treatments related to intensive care unit–acquired muscle weakness: A cohort study

Author

Rodríguez Delgado, María Esther, Contreras Rodríguez, Antonia María, Cimiano, Ester Oreña, Guerrero, Alvaro Ortega, del Carmen, María, del Aguila, Martínez, Monsalve, Virginia Rodríguez, Cano Herrera, Carlos Leonardo, Masegosa Pérez, Juan Manuel, de la Cuesta, DeliaMaría González, Pardo Artero, María Inmaculada, Laseca, Marta Palacios, Cabello Casao, Ana Isabel, de Vera Bellostas, María BelénVicente, Martínez, Carmen Pérez, González, SheilaEscuder, Cisneros, Amelia Lezcano, Romeo, Antonio Miguel, Alegre, Isabel López, de San Pío, Emilia Romero, Alonso, Helena Fernández, Rodríguez Villanueva, Lara María, Suárez, Roberto Riaño, Cerviño, Begoña Sánchez, Santos, Sergio Carrasco, Arribas, Alicia San José, García, Miriam González, Tavio, Antonio Linares, García, Paz Álvarez, Hernández, Nuria Polo, Cosío, Lourdes Gómez, Loza, Isabel Pérez, Pérez, Ángela Suárez, Rebollo, Sonia Crespo, Camargo, Juan Carlos Muñoz, García, Julián García, Aguado, César Rojo, López, José Gómez, Bartolomé, Laura Sonseca, del Olmo Nuñez, Sonia, Mazo, Patricia García, Torre, Eduardo Siguero, Díez, Isabel Muñoz, Hito, Pilar Delgado, Garrido Martín, Mercedes Olalla, Vivó, Gemma Marín, Rovira, Maria del Mar Eseverri, Dobon, Montserrat Guillen, Esteve, Montserrat Aran, Rodríguez, Maribel Mirabete, Méndez, Albert Mariné, Fernández, Silvia Rodríguez, Sancho, Joan Rosselló, Lamas, Valeria Zafra, Delgado, Inmaculada Carmona, Arilla, Àngels Navarro, Esteva, Gustau Zariquiey, Bueno Luna, Angel Lucas, Brianso, Cristina Lerma, García, Rubén Gómez, Pascual, Bernat Planas, López, Marta Sabaté, Mayer Frutos, Ana Isabel, Escrihuela, Roser Roca, Albà, Gemma Torrents, Flores, Vanesa Garcia, Galmés, Joan Melis, Moral, Sandra Belmonte, Pellicer, Montserrat Grau, Eizmendi, Aintzane Ruiz, Moll, Carme Garriga, Bosch de Jaureguízar, Esteve, Guardia, Sergio Cordovilla, Espuela, Fidel López, Hinojal, Lara Mateos, Redondo Cantos, María Isabel, Redondo, Ma del Rosario Villar, Rey, Jesús Vila, Méndez, Susana Sánchez, Fernández, Yolanda García, Benítez Canosa, María Cristina, Álvarez, Mauricio Díaz, Cordo Isorna, José Ramón, Penín, Ángeles Estébez, Rial, Gloria Güeto, López, Esther Bouzas, Rivera, Susana Arias, Frade Mera y María Jesús Luengo Alarcia, María Jesús, Díaz, Noelia Regueiro, Carrasco Rodríguez-Rey, Luis Fernando, del Rosario Hernández García, María, Gómez, Gema Sala, Rubio, Javier Vecino, González, Saúl García, Sánchez, María del Mar Sánchez, Franco, Carmen Cruzado, Rivera, Beatriz Martín, Blanco, Rocío González, de la Ventana, Ana Belén Sánchez, Bravo Arcas, Maria Luisa, Lavela, Josefa Escobar, del Pilar Domingo Moreno, María, Arias, Mercedes García, Collado Saiz, Inmaculada Concepción, Nuevo, María Acevedo, Suárez, Alejandro Barrios, Zarza Bejarano, Francisco Javier, Pérez Muñoz, María Catalina, Rubio, Virginia Toribio, Chicharro, Patricia Martínez, Martínez, Alexandra Pascual, Pozo, Sergio López, Infante, Laura Sánchez, García, Verónica Ocaña, Medina, Daniel Menes, Cortázar, Ana Vadillo, Burgos, Gema Lendínez, Juntanez, Jesús Díaz, Godino Olivares, María Teresa, José Rodríguez Mondéjar, Juan, José Martínez Rojo, Francisco, Ruiz Martínez, María Vanessa, Celdrán, Daniel Linares, Molina, Antonio Ros, Sánchez, Javier Sáez, Martínez Oliva, José María, Gilar, Ana Bernal, Hernández García, María Belén, Ríos Cortés, Antonio Tomás, Méndez, Raquel Navarro, García, Sebastián Gil, Garre, Juan Sánchez, Linares, Miriam del Barrio, Viguria, Rosana Goñi, Santano, Raquel Aguirre, Díez, Ma Rosario García, Cilla, Laura Aparicio, Domingo, Mónica Delicado, Núñez, César Rodríguez, López, Ane Arrasate, Morán, Ángela Romero, Melgoso, Rosa Paños, Cerón, Mónica Yañez, Martínez, Amparo Mercado, Llopis, Beatriz Martínez, Vayá Albelda, María Josefa, Carbonell, Javier Inat, Senent, M.Rosario Alcayne, García, Fátima Giménez, Fernández Gonzaga, Eva Cristina, Puchol, Laura Febrer, Ortuño, Senén Berenguer, Martínez, María Pastor, Talavera, Dunia Valera, Rovira, María José Segrera, Revert, Yolanda Langa, Pozuelo, Maricruz Espí, de Diego, María Ángeles, Aspas, Beatriz Garijo, del Rosario Asensio García, María, Sánchez Muñoz, José Ramón, Sánchez, Quirico Martínez, Mateu, Ramón López, Raurell-Torredà, M., Arias-Rivera, S., Martí, J.D., Frade-Mera, M.J., Zaragoza-García, I., Gallart, E., Velasco-Sanz, T.R., San José-Arribas, A., and Blazquez-Martínez, E.

Published
2021
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232. The role of PI3Kα in cardioprotection

Author

Rossello Lozano, Francisco Javier

Subjects
616.1
Abstract

BACKGROUND: Ischaemic preconditioning (IPC) is an endogenous cardioprotective phenomenon, which can limit infarct size following ischaemia-reperfusion injury (IRI) through the activation of intracellular signalling pathways, such as the PI3K kinase cascade. Little is known about the individual roles of PI3K isoforms in IRI. This thesis aimed to elucidate the role of PI3Kα in cardioprotection. METHODS AND RESULTS. Initial studies focussed on establishing the Langendorff-perfused isolated heart model of mouse IRI, and the relative contribution of different lengths of ischemia and reperfusion to myocardial infarction was rigorously determined. The PI3K signalling cascade and its interaction with other pathways were also dissected before evaluating the role of PI3Kα. PI3Kα was shown to be critical in mediating IPC-induced heart protection against IRI. Using the ex vivo model of myocardial infarction, we showed that PI3Kα is required during the IPC reperfusion phase to reduce myocardial infarct size, whilst not mediating the effect during the trigger phase. These findings were confirmed in an in vivo setting. Using insulin as a canonical activator of PI3K, we also demonstrated that this isoform is not only necessary for IPC to confer cardioprotection, but sufficient for its specific activator to promote myocardial salvage against IRI. PI3Kα activation mediates its effect through the end-effector namely the mitochondrial permeability transition pore, as demonstrated by delaying its opening in primary isolated cardiomyocytes. Importantly, the PI3Kα protein levels are comparable between mouse and human heart tissue, and its activation can be modulated in both tissues. These last observations highlights the potential ability of PI3Kα to be translated into the clinical setting. CONCLUSIONS. These studies have clearly demonstrated that PI3Kα plays a crucial role at reperfusion. This suggests that strategies specifically enhancing the α isoform of PI3K, at reperfusion, could provide a direct target for clinical treatment of IRI.

Published
2017

233. Essays on the spillovers of the household environment on childhood development : domestic violence, health and education, and maternal working hours on children's wellbeing

Author

Rossello-Roig, M.

Subjects
330, HB Economic Theory, HN Social history and conditions. Social problems. Social reform, HQ The family. Marriage. Woman, RJ101 Child Health. Child health services
Abstract

This thesis contains three chapters that each study the spillover effects of two aspects of the child's household environment, Domestic Violence (chapter one and two) and Maternal Working Hours (chapter three). The first chapter looks at Children's Health, the second at Education Outcomes and the third looks at children's Well-Being. Understanding what influences a child's early development is of paramount importance as it explains future job market performance and success in life in general. All chapters exploit the data set UK Millennium Cohort Study (MCS), a longitudinal survey following around 19,000 children born in the UK in 2000-01. The first chapter studies the effect of Domestic Violence on children's health production function. We use waves 4 and 5 of the MCS, when children are aged 7 and 11, respectively. We find that there is a strong negative externality of living in a household where there is violence on children's parental-assessed health outcomes. Simultaneity between the child's health and the existence of Domestic Violence in the household makes it diffcult to establish a causal relationship, so we use an instrumental approach to address the potential bias caused by this. In particular, our results show that children exposed to Domestic Violence appear to be between 55% and 61% less likely to have their health rated as Excellent. Our results are robust and statistically significant across all specifications. Our paper not only sheds light on the negative impact of Domestic Violence on children's health but provides a robust quantification of this effect. This chapter is co-authored with Prof. Jofre-Bonet and Dr. Serra-Sastre. The second chapter studies the spillover effect on children's educational attainment of living in a household in which mothers are subject to Domestic Violence. To do so, we exploit measurements of the child's educational performance in English, Science, Mathematics, Physical Education, Creativity, and Information and Technology by the age of 7 and 11, available in the MCS. Our results suggest that growing up in a household where there is Domestic Violence has a negative impact on all educational outcomes. Our results are robust and hold when addressing several potential sources of sample selection bias. Children from domestically abused mothers lose around 0.20 standard deviations in English and 0.30 standard deviations in Mathematics scores at an age as early as 11 years. The cumulative negative effect is heterogenous across academic areas, being more pronounced for those subjects where past knowledge acquisition is essential (i.e., Mathematics and Science). This chapter is co-authored with Prof. Jofre-Bonet and Dr. Serra-Sastre. The third chapter investigates how maternal working status is connected to children's well-being at ages 7 and 11. The rapid increase of female participation in the labour market, along with the impact that well-being levels during childhood has on their psychological development and labour market outcomes later in adulthood, calls for a closer examination of this topic. To do so, we also exploit the MCS, which contains a very complete set of children's well-being outcomes and the intensity of the engagement of mothers with the labour market. To our knowledge, this is the first paper to use such a full array of children's well-being indicators and relate it to maternal labour supply. Our results show that in households in which mothers work fulltime, children are, on average, happier, less worried, as well as less likely to lose their temper. Further, we investigate whether child obesity, which has been related to children's well-being, is associated to the mother's working hours, the mother's commuting time and the father's employment status. We find that higher the number of working hours of the mother increases the likelihood of the child being obese at 7 and 11 years of age, in line with previous literature. This chapter is co-authored with Prof. Jofre-Bonet and Dr. Serra-Sastre.

Published
2017

234. Local clinical informatics investments are required for in silico biomarker generation across the globe: lessons learned from a secondary analysis of the PROP trial

Author

Juliet Torres, Satya D. Malla, Valentina Silveira, Luis Mainero, Catherine Czeisler, José L. Díaz-Rossello, Alejandro Maccarrone, Alexandria Medoro, Pablo Sanchez, Fernanda Blasina, and Jose J. Otero

Subjects
Public aspects of medicine, RA1-1270
Abstract

# Background Advances in statistical modelling and machine learning approaches, which can be deployed locally using open source programming languages, represent a unique opportunity to improve workflows and lower costs in health care across the globe through the creation of *in silico* biomarkers. The goal of this study was to extract meaningful data from the publicly available Prematurity and Respiratory Outcomes Program (PROP) trial data that could help generate useful clinical diagnostic aids with minimal cost for deployment in global healthcare settings. # Methods A cluster analysis of the PROP dataset was conducted. We generated a simple model using an open-source software platform that generates a growth prediction of patients born less than 30 weeks. We then obtained validation data from a Uruguayan hospital to test the capacity for deployment of the models. # Results Analysis revealed two main clusters of patients in the trial, with differentiation mainly based on the clinical and anthropomorphic measurements of birth gestational age, birth weight, and head circumference. The anthropometric measurements of daily weight, birth weight, head circumference, and birth gestational age were highly correlated with respiratory dysfunction and co-morbidities We note that deviation from this predicted growth curve in PROP patients was associated with culture-proven sepsis, and may represent a more sensitive anthropomorphic biomarker than the weight percentile systems routinely used globally such as Fenton curves. We found that early deviation from our projected growth model was highly associated with patient fatality. However, over long-term predictions, models trained on PROP clinical trial patients showed significantly more error in the Uruguayan patients. # Conclusions Although these prediction models built upon PROP data were not generalizable to Uruguayan patients, our data suggest that prediction models using simple anthropomorphic measurements, if trained on local patients, may be able to provide value as a low-cost in silico biomarker. We concluded that local investment in clinical informatics infrastructure is needed to train models based on locally extracted clinical data.

Published
2022
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235. Triglycerides and Residual Atherosclerotic Risk

Author

Raposeiras-Roubin, Sergio, Rosselló, Xavier, Oliva, Belén, Fernández-Friera, Leticia, Mendiguren, José M., Andrés, Vicente, Bueno, Héctor, Sanz, Javier, Martínez de Vega, Vicente, Abu-Assi, Emad, Iñiguez, Andrés, Fernández-Ortiz, Antonio, Ibáñez, Borja, and Fuster, Valentin

Published
2021
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239. Fibromyalgia Pain and Fatigue Symptoms in Spanish and U.S. Men

Author

Kueny, Angela, Montesó-Curto, Pilar, Lunn, Shannon, Mohabbat, Arya B., Clark, Stephanie, Luedtke, Connie, Vincent, Ann, Ruschak, Ilga, Mateu-Gil, María Luisa, Panisello-Chavarria, Maria Luisa, Rosselló, Lluís, Guerrero, Carme Campoy, Gonçalves, Alessandra Queiroga, Martín, Carina Aguilar, and Toussaint, Loren

Published
2021
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240. Pomegranate: A Source of Multifunctional Bioactive Compounds Potentially Beneficial in Alzheimer’s Disease

Author

Lidia Ciccone, Susanna Nencetti, Armando Rossello, and Elisabetta Orlandini

Subjects
Alzheimer’s disease, AD, pomegranate fruit, nutraceuticals, antioxidants, multifunctional compounds, Medicine, Pharmacy and materia medica, RS1-441
Abstract

Pomegranate fruit (PF) is a fruit rich in nutraceuticals. Nonedible parts of the fruit, especially peels, contain high amounts of bioactive components that have been largely used in traditional medicine, such as the Chinese, Unani, and Ayurvedic ones, for treating several diseases. Polyphenols such as anthocyanins, tannins, flavonoids, phenolic acids, and lignans are the major bioactive molecules present in PF. Therefore, PF is considered a source of natural multifunctional agents that exert simultaneously antioxidant, anti-inflammatory, antitumor, antidiabetic, cardiovascular, and neuroprotective activities. Recently, several studies have reported that the nutraceuticals contained in PF (seed, peel, and juice) have a potential beneficial role in Alzheimer’s disease (AD). Research suggests that the neuroprotective effect of PF is mostly due to its potent antioxidant and anti-inflammatory activities which contribute to attenuate the neuroinflammation associated with AD. Despite the numerous works conducted on PF, to date the mechanism by which PF acts in combatting AD is not completely known. Here, we summarize all the recent findings (in vitro and in vivo studies) related to the positive effects that PF and its bioactive components can have in the neurodegeneration processes occurring during AD. Moreover, considering the high biotransformation characteristics of the nutraceuticals present in PF, we propose to consider the chemical structure of its active metabolites as a source of inspiration to design new molecules with the same beneficial effects but less prone to be affected by the metabolic degradation process.

Published
2023
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241. Identification of N-Acyl Hydrazones as New Non-Zinc-Binding MMP-13 Inhibitors by Structure-Based Virtual Screening Studies and Chemical Optimization

Author

Doretta Cuffaro, Aleix Gimeno, Bianca Laura Bernardoni, Riccardo Di Leo, Gerard Pujadas, Santiago Garcia-Vallvé, Susanna Nencetti, Armando Rossello, and Elisa Nuti

Subjects
virtual screening, MMP-13 inhibitors, osteoarthritis, N-acyl hydrazones, protein-ligand docking, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1′ pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the µM range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new N-acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.

Published
2023
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242. Bacterial Zinc Metalloenzyme Inhibitors: Recent Advances and Future Perspectives

Author

Riccardo Di Leo, Doretta Cuffaro, Armando Rossello, and Elisa Nuti

Subjects
zinc metalloenzymes, LpxC, pseudolysin, thermolysin, antivirulence agents, Gram-negative bacteria, Organic chemistry, QD241-441
Abstract

Human deaths caused by Gram-negative bacteria keep rising due to the multidrug resistance (MDR) phenomenon. Therefore, it is a priority to develop novel antibiotics with different mechanisms of action. Several bacterial zinc metalloenzymes are becoming attractive targets since they do not show any similarities with the human endogenous zinc-metalloproteinases. In the last decades, there has been an increasing interest from both industry and academia in developing new inhibitors against those enzymes involved in lipid A biosynthesis, and bacteria nutrition and sporulation, e.g., UDP-[3-O-(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC), thermolysin (TLN), and pseudolysin (PLN). Nevertheless, targeting these bacterial enzymes is harder than expected and the lack of good clinical candidates suggests that more effort is needed. This review gives an overview of bacterial zinc metalloenzyme inhibitors that have been synthesized so far, highlighting the structural features essential for inhibitory activity and the structure–activity relationships. Our discussion may stimulate and help further studies on bacterial zinc metalloenzyme inhibitors as possible novel antibacterial drugs.

Published
2023
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245. Transcriptional signature in microglia associated with Aβ plaque phagocytosis

Author

Alexandra Grubman, Xin Yi Choo, Gabriel Chew, John F. Ouyang, Guizhi Sun, Nathan P. Croft, Fernando J. Rossello, Rebecca Simmons, Sam Buckberry, Dulce Vargas Landin, Jahnvi Pflueger, Teresa H. Vandekolk, Zehra Abay, Yichen Zhou, Xiaodong Liu, Joseph Chen, Michael Larcombe, John M. Haynes, Catriona McLean, Sarah Williams, Siew Yeen Chai, Trevor Wilson, Ryan Lister, Colin W. Pouton, Anthony W. Purcell, Owen J. L. Rackham, Enrico Petretto, and Jose M. Polo

Subjects
Science
Abstract

Microglia associated with Aβ plaques may have a distinct transcriptional signature compared to those in plaque-free areas of the brain in Alzheimer’s disease (AD) models. Here the authors show that amyloid plaque phagocytosis is associated with a specific microglia transcriptional signature in a mouse model of AD.

Published
2021
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246. FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy

Author

A. J. Wood, C. H. Lin, M. Li, K. Nishtala, S. Alaei, F. Rossello, C. Sonntag, L. Hersey, L. B. Miles, C. Krisp, S. Dudczig, A. J. Fulcher, S. Gibertini, P. J. Conroy, A. Siegel, M. Mora, P. Jusuf, N. H. Packer, and P. D. Currie

Subjects
Science
Abstract

FKRP mutations cause muscular dystrophies with varied clinical presentations. The target of FKRP is α-dystroglycan, but here the authors show that FKRP also directs sialylation of fibronectin, a process that is essential for recruitment o collagen to the muscle basement membrane.

Published
2021
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247. Compliance with the clinical guidelines for managing asthma by primary care physicians: An ambispective observational study

Author

Abedianzadeh Timar, Mohsen, Acha Domínguez, Jesús, Aguaviva Bascuñana, Jesus, Aguilar Martín, Ignacio, Ales Conejo, Francisco Ignacio, Alfaro González, Juan Vicente, Alfonso Landa, Patricia, Altés Boronat, Andrés, Álvarez Arriero, Jesús Joaquín, Álvarez Rojo, Juan Ángel, Vidal German, Allut, Amaro Cendón, Jesús, Amiano Arregui, María Teresa, Angulo Vallejo, Esther, Anton Álvarez, Juan José, Anton Ortega, Javier, Arconada Perez, Ana, Ardiaca Burgués, Lidia, Armario Vázquez, Juan Manuel, Arroyo Cubeiro, Amador, Aso Mendialdea, Koldo, Attardo, Francesca, Ávila de Tomás, José Francisco, Avinent Arnal, M. Jesús, Aznar Aguilar, Francisco, Aznar Tejero, Pilar, Baena Montilla, Emilio, Baeza López, José María, Barón Carrillo, Juan José, Bartolomé Resano, Rafael, Becoña de la Torre, Francisco, Benavent Martín, Isabel, Benedí Sánchez, María Teresa, Berrocal del Brío, José, Blanco Delgado, Antonio, Bleda Cano, Jesús, Boladeras Sabater, Josep, Bolívar Mantilla, Zenaida, Brito Brito, Elisenda, Burgos Parra, M. Rosario, Buxadé Martí, Isaac, Caballero Garcia, Juan Carlos, Cabañas Enríquez, Luis Fernando, Calviño Cerqueiro, Marcelino, Calvo Fernández, Juan, Calle Velles, Felipe, Camaro Zafra, Beatriz, Campomar Quetlas, Jaume, Capitán Jurado, Mónica, Cárdenas Joyanes, Dolores, Carles Bueso, Gonzalo, Carvajal Puente, Cristina, Casado Rodriguez, Cristina, Casanova García, Carlos, Castellà Cahiz, Santiago, Castellà Cuesta, Cristina, Castellano Martínez, Manuel Antonio, Catalán Félez, Rafael, Cavada García, Miguel Ángel, Cavada Velasco, Antonio, Cidra Gordillo, Jose Luis, Clemente Garcia, Julia, Collada Jiménez, José Luis, Cornejo Figueroa, Andrés, Cornejo Rodríguez, Roberto, Cuevas Morales, Julio, Curado-Moliní Álvarez, María Jesús, Daviña Romero, Susana, de Arriba Muñoz, Leonor, de la Flor Benítez, Manuel, de la Poza Abad, Mariam, de los Bueis Martinez, Gustavo, de Miguel Márquez, María Pía, de Pablo Martín, Jesús, Delgado Mora, Manuel, Díaz Mateo, Joaquín, Díaz Saborido, Almudena, Díez-Caballero Murua, María, Doganis Peppas, Constantino, Domínguez Alonso, Gonzalo, Domínguez Ávila, Julián, Domínguez González, María Nieves, Domínguez Hernández, María Isabel, Dosantos Hernández, Javier Oscar, Dueñas Buey, Aurelio, Eiris Cambre, M. Jesús, El Wafa Vaca, Yussef Abu, Enseñat Sanchez, Antonio Alberto, Esquerra Tuñí, Eulalia, Esteve Ribelles, José María, Estevez Barrondo, José Antonio, Estraviz Vidal, M. Dolores, Fajardo Salguero, Rosa María, Felipe Olivero, José Francisco, Fernández Bujía, María Luisa, Fernández Cano, Patricia, Fernández Cañaveras, M. Isabel, Fernández Fernández, Carmen, Fernández García, José Manuel, Fernández Gómez, Patricia, Fernández González, José María, Fernández Gutiérrez Denia, Irene, Fernández Huelga, M. Esther, Fernández Martin, Yolanda, Fernández Navarro, Francisco, Fernández Revuelta, Araceli, Fernández Toro, José María, Fernández-Pacheco Corchado, Luis María, Ferrándiz Miquel, Joaquín, Ferrari Piquero, Carmen, Ferrer García-Borrás, José María, Gago Fernandez, Carlos, Gago Gómez, Fernando, Galera de Ulierte, Luz Inmaculada, Gallegos Juárez, Ingrid, Garceran Azorín-Gómez, José Enrique, Garcés Romero, Carmen, García Alonso, Francisco Javier, García Cabana, Andres A., García Cano, Josefa, García Ceballos, Victoria Gema, García de Francisco, Sara, García Fuentes, Francisco, García Vázquez, Yolanda, García Collado, Sergio, García-Giralda Ruiz, Luis, García-Serrano Jiménez, Beatriz, Garrido Pérez, Montse, Garro Mendiolagaray, Jon Kepa, Gea Villar, Jorge, Genover Llimona, Teresa, Gil Moreno, Felipe, Gil Pastor, Javier Julián, Gispert Servitje, Adrià, Godoy García, Isidro Domingo, Gómez Martínez, Gabriel, Gómez Sanmiguel, Francisco Javier, Gómez Yelo, Jose, Gonzales Flores, Pedro Alejandro, González Hernández, Luis, Gonzálvez Rey, Jaime, Gorgues Comas, Roberto, Guillen Anton, María Victoria, Gutiérrez Almarza, Miguel Ángel, Gutiérrez Esteban, Jose Luis, Guzón Centeno, Marta, Hermoso Sabio, Antonio, Hernández Castellanos, Manuel, Hernández Pérez, Ana, Herranz Alfaro, Alfredo, Hinojosa Díaz, José Francisco, Iglesias Fernández, José, Intxausti Erdoiza, Iñaki, Izarra Páramo, Miriam, Jiménez Marcen, Ana Isabel, Jimeno Bernad, Rosa María, Jover Andreu, María José, Juan Alcaraz, Francisco Emilio, Labrador Arranz, Esther, Laencina López, Salvador, Lapuente Troncoso, Elena, Latorre Cásedas, Montserrat, Leal Hernández, Mariano, Ledesma Santiago, Lourdes, Lillo Bravo, Francisco Javier, Lizarribar Sans, Marta, Lobato Martínez, Rocío, López Alonso, Emilia Begoña, López Cruz, Urbano, López Chamon, Silvia, López de Viñaspre Muguerza, Ana Isabel, López Herranz, Ana Belén, López Marina, Víctor, López Ortiz, Francisco, López Silva, Mª Carmen, Lucas Boronat, José María, Lugo Ramos, Héctor Leonardo, Lutz Garcia, Erika, Llosa Ventura, Juan Luis, Macías Corbacho, Antonio, Magem Niubo, Juan, Mancilla las Heras, Diego, Maneu Juan, Alfonso, Manzano Jiménez, José, Mañes Vicente, Pascual, Maranges Comella, María Isabel, Marco Segarra, Emilio, María Tablado, Miguel Ángel, Marlasca Garcia, Juan Carlos, Martí Canales, Juan Carlos, Martín Clos, José, Martín de la Vega, Saúl, Martín Ruiz Lavela, Francisco, Martinez Aparicio, M. Desamparada, Martínez de Carnero Calzada, Rafael, Martinez González, Agustín, Martínez Jiménez, Juan Manuel, Martínez Laguna, Daniel, Martínez Mayora, María Teresa, Martinez Merodio, Pilar, Martínez Novoa, Luis, Martínez Ortega, Mireia, Martínez Rojas, Francisco, Martínez Rossello, Antonio, Meijome Sánchez, María del Carmen, Méndez-Cabeza Velázquez, Jesús, Méndez Maiques, Jose María, Misericordia Garcia, Santiago, Molina Cabildo, José, Molina Martínez, Luis Javier, Monge García, José Manuel, Montes Belloso, María Ester, Moreno Molina, Susana, Motos Díaz, Patrocinio, Mourelo Cereijo, Marta, Moyá Amengual, Ana, Muñoz Ruiz, Pedro José, Narváez Martín, José María, Navarro Luna, Juan Luis, Navarro Tarin, Fernando, Nicolau Grego, Jorge, Niño Azcarate, Cristina, Nova Alvarez, José, Núñez Cordón, Juan Carlos, Olagorta de Prado, Asunción, Oros Espinosa, Vicente, Ortega Pinilla, M. Concepción, Ortega Ruiz, María Paz, Osca Pellicer, David, Otamendi Murillo, Ana, Otero Mata, Manuel, Ouzzine Marín, Myriam, Paja Fano, Eduardo, Palacio Gonzalez, Domingo, Palau Oñate, Rosario, Pazos Garrido, Néstor, Pecharroman Fuente, Virginia, Peña Rosa, Jose Manuel, Peral Cabot, Francisco Javier, Pérez Barreto, Iván Yamir, Pérez Caballero, Isabel, Pérez Fernández, Maria del Carmen, Pérez Fernández, Antonio Luis, Pérez Gutiérrez, Esteban, Pérez Rios, Manuel, Petit Sánchez, José Manuel, Piñero Acin, Maria José, Pozuelos Estrada, Jerónimo, Prieto Cid, Manuel, Prieto Gutiérrez, Joaquín, Raga Casasus, José Vicente, Ramírez Espinosa, Manuel Francisco, Rebollo Hernamperez, Eduardo, Rey Rañal, Alejandra, Ribelles Villalba, Ricardo Sagunto, Rodas Peral, José Antonio, Rodil Martinez, Aurora, Rodríguez, Manuel, José, Rodríguez Calcaño, Enrique Emperador, Rodríguez Fernandez, Concepción, Rodríguez Galipienzo, José Miguel, Rodriguez Lois, Miguel Ángel, Rodríguez Partida, José Antonio, Roel Conde, Jaime, Roman Rodriguez, Miguel, Romero Caballero, Gregorio, Romero Hernández, Pedro, Rosales García, Luis Miguel, Royo del Río, Manuel, Ruiz Gomes, María, Ruiz Moruno, Francisco Javier, Ruiz Perez, Jaime, Salinero Acevedo, José Ramón, Sánchez Apresa, Manuel, Sanchez Calavera, María Antonia, Sánchez Garcia, Fernando, Sánchez Gutiérrez, Miguel Ángel, Sánchez Ibáñez, Antonio, Sánchez López, Eugenio, Sánchez Loureiro, Manuel, Sanchez Lozano, Ana, Sánchez Romero, Gregorio, Sánchez Ruano, Fernando, Sánchez Ruiz, Gabriela, Sánchez Sanchez, Froilán, Santiago Ayarza, Asier, Santos Bermejo, Juan Antonio, Sanz de Miguel, Elena, Sanz Sanz, Marta, Sanz Velasco, Carmelina, Sauco Colón, Inmaculada, Sedano García, José Ignacio, Segovia Castro, Luis, Senan Sanz, María Rosa, Serra Cabot, Pere, Serra Gallego, Marta, Serrano Tomás, Daniel, Sesma Aisa, Francisco Tomás, Seuba Garcés, Jordi, Soler David, Vicente, Soria Mesa, Jose Antonio, Sosa Álvarez, César, Suárez Pérez, María, Tafalla Martín, Antonio, Tamayo Ferriol, Thaimi, Tamayo Marín, José Luis, Thalamas Atienza, Juan Aitor, Toledo Muñoz, Ana María, Tomás-Rodo Massaneda, Lluis Miquel, Torres de Castro, Milko, Torres Martínez, Francisco Javier, Tovar Álvarez, Enrique, Ugarte Goñi, Ainhoa, Valle González, Irene, Vasco Mahillo, Sonia, Enrique José, Vázquez Seijas, Vericat Roure, Antonio, Villalba Parrado, Arelis, Villanueva Rebollo, Jose María, Villar Valgañon, Ricardo, Villena Masegosa, Vicente, Viñals Gigena, Montserrat, Viñas Cabrera, Lydia, Zarco Pinteño, David, Roman-Rodriguez, M., Molina-Paris, J., and Fernandez Sanchez, A.

Published
2021
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248. Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Author

Abedianzadeh Timar, Mohsen, Acha Domínguez, Jesús, Aguaviva Bascuñana, Jesus, Aguilar Martín, Ignacio, Ales Conejo, Francisco Ignacio, Alfaro González, Juan Vicente, Alfonso Landa, Patricia, Altés Boronat, Andrés, Álvarez Arriero, Jesús Joaquín, Álvarez Rojo, Juan Ángel, Vidal German, Allut, Amaro Cendón, Jesús, Amiano Arregui, María Teresa, Angulo Vallejo, Esther, Anton Álvarez, Juan José, Anton Ortega, Javier, Arconada Perez, Ana, Ardiaca Burgués, Lidia, Armario Vázquez, Juan Manuel, Arroyo Cubeiro, Amador, Aso Mendialdea, Koldo, Attardo, Francesca, Ávila de Tomás, José Francisco, Avinent Arnal, M. Jesús, Aznar Aguilar, Francisco, Aznar Tejero, Pilar, Baena Montilla, Emilio, Baeza López, José María, Barón Carrillo, Juan José, Bartolomé Resano, Rafael, Becoña de la Torre, Francisco, Benavent Martín, Isabel, Benedí Sánchez, María Teresa, Berrocal del Brío, José, Blanco Delgado, Antonio, Bleda Cano, Jesús, Boladeras Sabater, Josep, Bolívar Mantilla, Zenaida, Brito Brito, Elisenda, Burgos Parra, M. Rosario, Buxadé Martí, Isaac, Caballero Garcia, Juan Carlos, Cabañas Enríquez, Luis Fernando, Calviño Cerqueiro, Marcelino, Calvo Fernández, Juan, Calle Velles, Felipe, Camaro Zafra, Beatriz, Campomar Quetlas, Jaume, Capitán Jurado, Mónica, Cárdenas Joyanes, Dolores, Carles Bueso, Gonzalo, Carvajal Puente, Cristina, Casado Rodriguez, Cristina, Casanova García, Carlos, Castellà Cahiz, Santiago, Castellà Cuesta, Cristina, Castellano Martínez, Manuel Antonio, Catalán Félez, Rafael, Cavada García, Miguel Ángel, Cavada Velasco, Antonio, Cidra Gordillo, Jose Luis, Clemente Garcia, Julia, Collada Jiménez, José Luis, Cornejo Figueroa, Andrés, Cornejo Rodríguez, Roberto, Cuevas Morales, Julio, Curado-Moliní Álvarez, María Jesús, Daviña Romero, Susana, de Arriba Muñoz, Leonor, de la Flor Benítez, Manuel, de la Poza Abad, Mariam, de los Bueis Martinez, Gustavo, de Miguel Márquez, María Pía, de Pablo Martín, Jesús, Delgado Mora, Manuel, Díaz Mateo, Joaquín, Díaz Saborido, Almudena, Díez-Caballero Murua, María, Doganis Peppas, Constantino, Domínguez Alonso, Gonzalo, Domínguez Ávila, Julián, Domínguez González, María Nieves, Domínguez Hernández, María Isabel, Dosantos Hernández, Javier Oscar, Dueñas Buey, Aurelio, Eiris Cambre, M. Jesús, El Wafa Vaca, Yussef Abu, Enseñat Sanchez, Antonio Alberto, Esquerra Tuñí, Eulalia, Esteve Ribelles, José María, Estevez Barrondo, José Antonio, Estraviz Vidal, M. Dolores, Fajardo Salguero, Rosa María, Felipe Olivero, José Francisco, Fernández Bujía, María Luisa, Fernández Cano, Patricia, Fernández Cañaveras, M. Isabel, Fernández Fernández, Carmen, Fernández García, José Manuel, Fernández Gómez, Patricia, Fernández González, José María, Fernández Gutiérrez Denia, Irene, Fernández Huelga, M. Esther, Fernández Martin, Yolanda, Fernández Navarro, Francisco, Fernández Revuelta, Araceli, Fernández Toro, José María, Fernández-Pacheco Corchado, Luis María, Ferrándiz Miquel, Joaquín, Ferrari Piquero, Carmen, Ferrer García-Borrás, José María, Gago Fernandez, Carlos, Gago Gómez, Fernando, Galera de Ulierte, Luz Inmaculada, Gallegos Juárez, Ingrid, Garceran Azorín-Gómez, José Enrique, Garcés Romero, Carmen, García Alonso, Francisco Javier, García Cabana, Andres A., García Cano, Josefa, García Ceballos, Victoria Gema, García de Francisco, Sara, García Fuentes, Francisco, García Vázquez, Yolanda, García Collado, Sergio, García-Giralda Ruiz, Luis, García-Serrano Jiménez, Beatriz, Garrido Pérez, Montse, Garro Mendiolagaray, Jon Kepa, Gea Villar, Jorge, Genover Llimona, Teresa, Gil Moreno, Felipe, Gil Pastor, Javier Julián, Gispert Servitje, Adrià, Godoy García, Isidro Domingo, Gómez Martínez, Gabriel, Gómez Sanmiguel, Francisco Javier, Gómez Yelo, Jose, Gonzales Flores, Pedro Alejandro, González Hernández, Luis, Gonzálvez Rey, Jaime, Gorgues Comas, Roberto, Guillen Anton, María Victoria, Gutiérrez Almarza, Miguel Ángel, Gutiérrez Esteban, Jose Luis, Guzón Centeno, Marta, Hermoso Sabio, Antonio, Hernández Castellanos, Manuel, Hernández Pérez, Ana, Herranz Alfaro, Alfredo, Hinojosa Díaz, José Francisco, Iglesias Fernández, José, Intxausti Erdoiza, Iñaki, Izarra Páramo, Miriam, Jiménez Marcen, Ana Isabel, Jimeno Bernad, Rosa María, Jover Andreu, María José, Juan Alcaraz, Francisco Emilio, Labrador Arranz, Esther, Laencina López, Salvador, Lapuente Troncoso, Elena, Latorre Cásedas, Montserrat, Leal Hernández, Mariano, Ledesma Santiago, Lourdes, Lillo Bravo, Francisco Javier, Lizarribar Sans, Marta, Lobato Martínez, Rocío, López Alonso, Emilia Begoña, López Cruz, Urbano, López Chamon, Silvia, López de Viñaspre Muguerza, Ana Isabel, López Herranz, Ana Belén, López Marina, Víctor, López Ortiz, Francisco, López Silva, M.a Carmen, Lucas Boronat, José María, Lugo Ramos, Héctor Leonardo, Lutz Garcia, Erika, Llosa Ventura, Juan Luis, Macías Corbacho, Antonio, Magem Niubo, Juan, Mancilla las Heras, Diego, Maneu Juan, Alfonso, Manzano Jiménez, José, Mañes Vicente, Pascual, Maranges Comella, María Isabel, Marco Segarra, Emilio, María Tablado, Miguel Ángel, Marlasca Garcia, Juan Carlos, Martí Canales, Juan Carlos, Martín Clos, José, Martín de la Vega, Saúl, Martín Ruiz Lavela, Francisco, Martinez Aparicio, M. Desamparada, Martínez de Carnero Calzada, Rafael, Martinez González, Agustín, Martínez Jiménez, Juan Manuel, Martínez Laguna, Daniel, Martínez Mayora, María Teresa, Martinez Merodio, Pilar, Martínez Novoa, Luis, Martínez Ortega, Mireia, Martínez Rojas, Francisco, Martínez Rossello, Antonio, Meijome Sánchez, María del Carmen, Méndez-Cabeza Velázquez, Jesús, Méndez Maiques, Jose María, Misericordia Garcia, Santiago, Molina Cabildo, José, Molina Martínez, Luis Javier, Monge García, José Manuel, Montes Belloso, María Ester, Moreno Molina, Susana, Motos Díaz, Patrocinio, Mourelo Cereijo, Marta, Moyá Amengual, Ana, Muñoz Ruiz, Pedro José, Narváez Martín, José María, Navarro Luna, Juan Luis, Navarro Tarin, Fernando, Nicolau Grego, Jorge, Niño Azcarate, Cristina, Nova Alvarez, José, Núñez Cordón, Juan Carlos, Olagorta de Prado, Asunción, Oros Espinosa, Vicente, Ortega Pinilla, M. Concepción, Ortega Ruiz, María Paz, Osca Pellicer, David, Otamendi Murillo, Ana, Otero Mata, Manuel, Ouzzine Marín, Myriam, Paja Fano, Eduardo, Palacio Gonzalez, Domingo, Palau Oñate, Rosario, Pazos Garrido, Néstor, Pecharroman Fuente, Virginia, Peña Rosa, Jose Manuel, Peral Cabot, Francisco Javier, Pérez Barreto, Iván Yamir, Pérez Caballero, Isabel, Pérez Fernández, Maria del Carmen, Pérez Fernández, Antonio Luis, Pérez Gutiérrez, Esteban, Pérez Rios, Manuel, Petit Sánchez, José Manuel, Piñero Acin, Maria José, Pozuelos Estrada, Jerónimo, Prieto Cid, Manuel, Prieto Gutiérrez, Joaquín, Raga Casasus, José Vicente, Ramírez Espinosa, Manuel Francisco, Rebollo Hernamperez, Eduardo, Rey Rañal, Alejandra, Ribelles Villalba, Ricardo Sagunto, Rodas Peral, José Antonio, Rodil Martinez, Aurora, Rodríguez, Manuel, José, Rodríguez Calcaño, Enrique Emperador, Rodríguez Fernandez, Concepción, Rodríguez Galipienzo, José Miguel, Rodriguez Lois, Miguel Ángel, Rodríguez Partida, José Antonio, Roel Conde, Jaime, Roman Rodriguez, Miguel, Romero Caballero, Gregorio, Romero Hernández, Pedro, Rosales García, Luis Miguel, Royo del Río, Manuel, Ruiz Gomes, María, Ruiz Moruno, Francisco Javier, Ruiz Perez, Jaime, Salinero Acevedo, José Ramón, Sánchez Apresa, Manuel, Sanchez Calavera, María Antonia, Sánchez Garcia, Fernando, Sánchez Gutiérrez, Miguel Ángel, Sánchez Ibáñez, Antonio, Sánchez López, Eugenio, Sánchez Loureiro, Manuel, Sanchez Lozano, Ana, Sánchez Romero, Gregorio, Sánchez Ruano, Fernando, Sánchez Ruiz, Gabriela, Sánchez Sanchez, Froilán, Santiago Ayarza, Asier, Santos Bermejo, Juan Antonio, Sanz de Miguel, Elena, Sanz Sanz, Marta, Sanz Velasco, Carmelina, Sauco Colón, Inmaculada, Sedano García, José Ignacio, Segovia Castro, Luis, Senan Sanz, María Rosa, Serra Cabot, Pere, Serra Gallego, Marta, Serrano Tomás, Daniel, Sesma Aisa, Francisco Tomás, Seuba Garcés, Jordi, Soler David, Vicente, Soria Mesa, Jose Antonio, Sosa Álvarez, César, Suárez Pérez, María, Tafalla Martín, Antonio, Tamayo Ferriol, Thaimi, Tamayo Marín, José Luis, Thalamas Atienza, Juan Aitor, Toledo Muñoz, Ana María, Tomás-Rodo Massaneda, Lluis Miquel, Torres de Castro, Milko, Torres Martínez, Francisco Javier, Tovar Álvarez, Enrique, Ugarte Goñi, Ainhoa, Valle González, Irene, Vasco Mahillo, Sonia, Enrique José, Vázquez Seijas, Vericat Roure, Antonio, Villalba Parrado, Arelis, Villanueva Rebollo, Jose María, Villar Valgañon, Ricardo, Villena Masegosa, Vicente, Viñals Gigena, Montserrat, Viñas Cabrera, Lydia, Zarco Pinteño, David, Roman-Rodriguez, M., Molina-Paris, J., and Fernandez-Sanchez, A.

Published
2021
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249. New Monoclonal Antibodies to Defined Cell Surface Proteins on Human Pluripotent Stem Cells

Author

O'Brien, Carmel M, Chy, Hun S, Zhou, Qi, Blumenfeld, Shiri, Lambshead, Jack W, Liu, Xiaodong, Kie, Joshua, Capaldo, Bianca D, Chung, Tung‐Liang, Adams, Timothy E, Phan, Tram, Bentley, John D, McKinstry, William J, Oliva, Karen, McMurrick, Paul J, Wang, Yu‐Chieh, Rossello, Fernando J, Lindeman, Geoffrey J, Chen, Di, Jarde, Thierry, Clark, Amander T, Abud, Helen E, Visvader, Jane E, Nefzger, Christian M, Polo, Jose M, Loring, Jeanne F, and Laslett, Andrew L

Subjects
Medical Biotechnology, Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Cancer, Stem Cell Research - Induced Pluripotent Stem Cell, Breast Cancer, Regenerative Medicine, Stem Cell Research - Embryonic - Human, Stem Cell Research, Biotechnology, 1.1 Normal biological development and functioning, Underpinning research, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Generic health relevance, Animals, Antibodies, Monoclonal, Antigens, Surface, Cell Culture Techniques, Cell Differentiation, Cell Self Renewal, Down-Regulation, Embryoid Bodies, Flow Cytometry, Hematopoietic Stem Cells, Humans, Membrane Proteins, Mice, Octamer Transcription Factor-3, Pluripotent Stem Cells, Pluripotency, Human embryonic stem cells, Human iPS cells, Naive, Breast, Colorectal, Cell surface markers, Monoclonal antibodies, Technology, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences
Abstract

The study and application of human pluripotent stem cells (hPSCs) will be enhanced by the availability of well-characterized monoclonal antibodies (mAbs) detecting cell-surface epitopes. Here, we report generation of seven new mAbs that detect cell surface proteins present on live and fixed human ES cells (hESCs) and human iPS cells (hiPSCs), confirming our previous prediction that these proteins were present on the cell surface of hPSCs. The mAbs all show a high correlation with POU5F1 (OCT4) expression and other hPSC surface markers (TRA-160 and SSEA-4) in hPSC cultures and detect rare OCT4 positive cells in differentiated cell cultures. These mAbs are immunoreactive to cell surface protein epitopes on both primed and naive state hPSCs, providing useful research tools to investigate the cellular mechanisms underlying human pluripotency and states of cellular reprogramming. In addition, we report that subsets of the seven new mAbs are also immunoreactive to human bone marrow-derived mesenchymal stem cells (MSCs), normal human breast subsets and both normal and tumorigenic colorectal cell populations. The mAbs reported here should accelerate the investigation of the nature of pluripotency, and enable development of robust cell separation and tracing technologies to enrich or deplete for hPSCs and other human stem and somatic cell types. Stem Cells 2017;35:626-640.

Published
2017

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